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Factors influencing the success of exposure therapy for specific phobia: A systematic review
Journal Pre-proof Factors influencing the success of exposure therapy for specific phobia: A systematic review Joscha B¨ohnlein, Luisa Altegoer, Nina Kristin Muck, Kati Roesmann, Ronny Redlich, Udo Dannlowski, Elisabeth J. Leehr
PII:
S0149-7634(19)30404-X
DOI:
https://doi.org/10.1016/j.neubiorev.2019.12.009
Reference:
NBR 3622
To appear in:
Neuroscience and Biobehavioral Reviews
Received Date:
29 May 2019
Revised Date:
26 November 2019
Accepted Date:
6 December 2019
Please cite this article as: B¨ohnlein J, Altegoer L, Muck NK, Roesmann K, Redlich R, Dannlowski U, Leehr EJ, Factors influencing the success of exposure therapy for specific phobia: A systematic review, Neuroscience and Biobehavioral Reviews (2019), doi: https://doi.org/10.1016/j.neubiorev.2019.12.009
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Factors influencing the success of exposure therapy for specific phobia: A systematic review. Joscha Böhnlein1,*, Luisa Altegoer1, Nina Kristin Muck1, Kati Roesmann², Ronny Redlich1, Udo Dannlowski1, & Elisabeth J. Leehr1.
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Department of Psychiatry, University of Münster, Germany Institute for Biomagnetism and Biosignalanalysis, University of Münster, Germany
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Running Title: Influencing factors on Exposure Therapy in Specific Phobia
Abstract Word count: 172
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Most researched factors have not been studied enough to give concrete recommendations Factors enhancing inhibitory learning experience increase success most These are having a high self-efficacy, low trait anxiety, addressing disgust in the therapy, focusing on changing cognitions, changing contexts between ET sessions, focusing on heart rate changes and administering D-Cycloserine
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Article word count: 8436
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Highlights
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Number of tables: 3
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Joscha Böhnlein Department of Psychiatry University of Münster Albert-Schweitzer-Campus 1, Building A9 48149 Münster; Germany, Phone: +49251-83-51861 Email: [email protected]
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*Corresponding author:
ABSTRACT Although Exposure Therapy (ET) is the first-line treatment of Specific Phobia (SP), there is no clear consensus on which factors influence its success, and thus on how to conduct it
most efficiently. This review summarizes the current state of research regarding this topic. N=111 studies were in accordance with our eligibility criteria: participants had at least symptoms of SP, the intervention was ET and the study investigated a factor influencing its success. Best evidence for positive effects was found for low trait anxiety, high motivation and high self-efficacy before the ET, high cortisol levels and heart rate variation, evoking disgust additionally to anxiety, avoiding relaxation, focusing on cognitive changes, context variation, sleep, and memory-enhancing drugs. These factors may be conceptualized as modulating different aspects of learning as suggested in current models of ET that focus on
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inhibitory learning mechanisms. Limitations lie in the great heterogeneity concerning operationalization of factors and success. Based on these findings, we make suggestions for
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improvements in ET conduction and which factors should be researched in the future.
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Keywords: Specific Phobia, Exposure Therapy, Treatment outcome, Psychotherapy
1. INTRODUCTION Specific Phobias (SP) are some of the most prevalent psychiatric disorders, with adverse effects on patients’ everyday lives. Gustavsson (2011) numbers the total cost of anxiety disorders with over €70 billion. While anxiety disorders are the largest group of psychiatric disorders with a 12-month prevalence of 14.0%, SP is the most prevalent subgroup of these. With a 12-month prevalence of 6,4%, 22.7 million people are affected in Europe (Wittchen et al., 2011). Additionally, SP represents a risk factor for other psychiatric disorders: Patients with SP show a twofold risk of developing any anxiety disorder, depression, and any
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somatoform disorder (Trumpf et al., 2010). Subclinical anxiety is even more prevalent: Curtis, Magee, Eaton, Wittchen and Kessler (1998) show that 49,5% of a large US-American sample report a “lifetime occurrence of an unreasonably strong fear” of a specific stimulus.
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Current models of SP explain its development through different processes of conditioning and learning like classical and operant conditioning and model learning. This has been most
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prominently described by Rachmann (1977), and is still relevant to this day (Duits et al.,
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2015; Hamm, 2009; Lissek et al., 2005; Mineka and Zinbarg, 2006; Schweckendiek et al., 2011). Thus, a fear memory is formed (Foa and Kozak, 1986). In this fear structure, the feared (but harmless) stimulus is connected to the concepts of danger and corresponding
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reactions like panic, flight and physiological reactions like activity of the sympathetic nervous system. Extinction based-treatments such as Exposure Therapy (ET) were developed to
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lessen the effect of the fear structure by either replacing (Foa and Kozak, 1986), competing with (Foa and McNally, 1996) or inhibiting (Craske et al., 2014) it.
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Exposure Therapy (ET) is the latest of a group of therapy forms that evolved from Wolpe’s Systematic Desensitization (1954) in the early fifties of the last century. It has become the first-choice therapy form not only for specific phobia but for many different anxiety disorders (Bandelow et al., 2014) and, in slightly adjusted form, for other diseases like obsessivecompulsive disorder (Öst et al., 2015). Investigating the success of ET in patients with different anxiety disorders, Bandelow and colleagues (2015) find considerable pre-post effect sizes of d = 1.3. Modern variations of ET include Virtual Reality ET (VRET), which shows
comparable effect sizes in meta analyses and systematic reviews (Botella et al., 2017; Opriş et al., 2012). It is recommended as the first-choice treatment of specific phobias (Bandelow et al., 2014). But even though ET is seen as the most effective way to treat SP, it is not without its problems: In a systematic review for anxiety disorders in children and adolescents (excluding SP), James and colleagues (2015) call ET as the central intervention of a CognitiveBehavioral Therapy (CBT) “an effective treatment for childhood and adolescent anxiety
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disorders”. However, they could not show superiority to other treatments such as medication or other forms of psychotherapy, especially at follow-up. Additionally, about a fifth of anxiety disorders patients dropped out prematurely (James et al., 2015). Furthermore, a third of treatment completers have to be classified as non-responders, irrespective of the specific
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type of therapy (Craske and Mystkowski, 2006; Fernandez et al., 2015; Scholten et al., 2013; Taylor et al., 2012). Additionally, the underlying mechanisms of ET are not yet well
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understood and are subject of discussion (e.g. Craske et al., 2014; Rupp et al., 2017). Even
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seemingly basic aspects like the necessary length of a successful ET are not yet clear (Bandelow et al., 2014). Overall, factors discriminating a successful from an unsuccessful ET-outcome are controversially discussed (Lueken et al., 2016; Taylor et al., 2012), and
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there is a high degree of heterogeneity in proposed and executed minutiae. Some reviews have tackled the need for an overview of factors that contribute to the success (or the lack
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thereof) of ET, both within the patient as well as in the conduction of the ET: For example, Lueken and colleagues (2016) presented potential neurobiological markers predicting the
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success of ET in all subtypes of anxiety disorders. They show that there is evidence for the 5-HTTLPR/rs25531 variant as a predictive genetic marker, as well as anterior cingulate cortex (ACC) activity as a functional neuroimaging marker and cardiovascular flexibility as a third marker. Additionally, they emphasize the high methodological heterogeneity of included studies and call for more rigorous, standardized studies. To sum up, ET is the first-choice treatment for SP, but it is neither as effective nor as well understood as one would hope. In the following review, we want to help both practitioners as
well as scientists to improve the effectiveness and our understanding of ET. We will expand on these existing reviews by giving an overview over possible influencing factors on the success (or lack thereof) of ET in SP. We take the perspective that a successful ET can be seen in changed behavior (e.g. in a Behavioral Avoidance Test, BAT), changed cognitions (e.g. in a questionnaire), changed subjective fear (e.g. in lower Subjective Units of Distress, SUDs) or changed physiology (e.g. different heart rates when confronted with the feared stimulus). Ideally, a successful ET leads to changes in every one of these categories. Additionally, modern cognitive-behavioral models of exposure therapy like the “inhibitory
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learning” model by Craske and colleagues (Craske et al., 2008) state that ET works by enabling the patient to learn to inhibit their initial reaction to the feared stimulus. We therefore see these changes as a result of continuous learning processes that may take place before,
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during and after the ET itself. Hence, we divided potential influencing factors by their time of influence, i.e. if they play a part before, during or after the ET itself.
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The aim of this review is twofold: Firstly, we try to show concisely which of these factors or
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these categories are highly relevant when planning and conducting an ET for patients with specific phobia, which factors have a lower relevance and for which factors the verdict is still out. This would help optimize the treatment and thus response rates. Secondly, we aim to
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provide a current state of research in order to identify factors that should be investigated in
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2. METHODS This systematic review was conducted according to the PRISMA guidelines (Liberatî et al., 2009). To be eligible for inclusion in this review, articles had to adhere to the following inclusion PICOS (Participants, Intervention, Comparator, Outcome, Study Design) criteria (Liberatî et al., 2009):
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(a) Participants had to be humans affected with specific phobia or significant symptoms of specific phobia. Included studies had (1) a sample of patients with specific phobia according to objective and standardized measures or interviews according to DSM-III, DSM-III-R, DSMIV or ICD-10 criteria (spider phobia, SP). The criteria changed very little between the different
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versions of the DSM and ICD, especially concerning the core criteria of anxiety and avoidance of a specific object, distress, and realization by the individual that the fear is
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excessive. Hence, we did not make a difference between these classification systems. Furthermore, included studies used (2) a sample of participants with specific phobia
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according to self-report measures (e.g. Spider Phobia Questionnaire or Acrophobia Questionnaire), or (3) with symptoms of a specific phobia that did not fulfill the full criteria of a
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clinical diagnosis (e.g. significant fear and avoidance of a feared stimulus in a BAT) (subclinical specific phobia, sub-SP). Studies with less than 10 participants per experimental
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condition were excluded.
(b) The Intervention had to be any form of exposure therapy (in vivo or in virtual reality; those
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two forms will only be differentiated when it is the factor of interest). “Exposure therapy” is defined as any form of presenting the feared stimulus to the patient with the specific intent of reducing the emotional, cognitive, and somatic reaction to said stimulus. To ensure relevance of the presented results for ET as it is conducted today, studies conducting exposure with the instructed use of coping skills were excluded (e.g. systematic desensitization, see Rupp et al., 2017). An exception is made for studies that examine the effect of said coping skills and compare a therapy with versus a therapy without such skills.
Additionally, studies that presented the stimulus only in sensu were discarded due to the missing ability to standardize presentation. (c) Regarding the used comparator, only studies were included that measured within subject variables concerning their potential as a predictor of success or that had two groups that both underwent some form of ET that differed in one key aspect. (d) The outcome had to be a direct measure of treatment success (measured by questionnaires, behavioral outcome measures or standardized interviews), pre and post
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intervention, and the influence of the investigated factor. (e) Concerning study design, included studies are controlled experiments in a laboratory or a naturalistic environment as long as the design is experimental in nature (i.e. a ET is part of
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the study and not of another treatment). Excluded are case studies and reviews. As independent variable, we required a potential influencing factor or factors; the dependent
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variable was treatment success through exposure therapy.
We searched the databases PubMed and PsychInfo for studies published in peer-reviewed
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journals up to May 13th 2019 and performed hand searches in the reference lists of included studies. We used MeSH-Terms to search for studies with human subjects concerning
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specific phobia and exposure. Included studies had to be written in English, German, French or Spanish. We did not limit the age of the subjects.
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The PubMed Search Term was as follows:
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("phobic disorders"[MeSH Terms] NOT ("phobia, social"[MeSH Terms] OR (social[All Fields] AND ("anxiety"[MeSH Terms] OR "anxiety"[All Fields])))) AND ("exposure"[All Fields] AND "therapy"[All Fields] OR "exposure therapy"[All Fields] OR "Behavior Therapy"[Mesh] OR "exposure treatment"[All Fields] OR "exposure session"[All Fields] OR "fear modification"[All Fields] OR flooding OR "in vivo exposure"[All Fields] OR "imaginal exposure"[All Fields]) AND humans [Filter]
The search in PsychInfo was conducted in a way that mirrored the search in PubMed as closely as possible. JB screened studies found by the search terms for eligibility regarding title and abstract and, if deemed potentially relevant, subsequently assessed for eligibility according to the predefined PICOS criteria by JB and EJL in a full-text review. The interrater reliability was very high with a Pearson’s r = .927 (p <.001). A coding system (“Quality Score”, QS) on study characteristics was developed by JB and
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EJL based on the one used by Lueken and colleagues (2016) as well as the MERSQI criteria (Reed et al., 2007) to assess quality and risk of bias of included studies (see Table 1). Both JB and EJL rated all included studies based on this system. Values of five and lower can be
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seen as low, values of ten and above as high. Insert Table 1 here.
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We cannot eliminate the risk of bias in our results. We intentionally limited our search for
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relevant articles on well-known and respected databases with PubMed and PsychInfo. This, however, means that biases such as a publication bias are not only possible, but probable, all
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3. RESULTS We included 111 studies in our review. The flowchart that shows numbers for studies screened, assessed for eligibility and subsequently included in the review as well as the reasons for exclusions can be found in Figure 1.
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Insert Figure 1 here. A list of all the studies as well as relevant characteristics can be found in Table 2.
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Insert Table 2 here.
The following sections will present the included studies and their results that are most
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important for our research question. We will present our results divided into the aforementioned categories: before the ET, during ET, and after ET. Each of these categories
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is then subdivided into the subcategories “emotional”, “cognitions”, “behavioral”, and “physiological”.
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3.1 Before the ET
There were no researched factors in the behavioral category before the ET. In the emotional
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category, we did find three potential factors (trait anxiety with n=2 studies, motivation with n=2 studies and fear reactivation with n=2 studies), four potential cognitional factors (coping
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style with n=3 studies, self-efficacy with n=4 studies, perceived automaticity and irrationality of threatening cognitions with n=1 study and memory with n=1 study) and finally three potential factors on the physiological level (eyeblink startle response with n=1 study, cortisol levels with n=2 studies and comorbid disorders with n=1 study). 3.1.1. Emotional factors
Trait anxiety and motivation. Two studies (Muris et al., 1998; Rodriguez et al., 1999) found that higher trait anxiety scores lead to less success of ET. Furthermore, St-Jacques and colleagues (2010a) showed that motivation was crucial for success, especially “extrinsic integrated motivation” as described in the Self-Determination Theory (Deci and Ryan, 1985). O’Sullivan and colleagues (1976) corroborated this finding. Fear reactivation. Two studies tried improving ET by reactivating fear just before ET: While Hodgson and Rachman (1970) found an improvement by showing a video with horrific
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scenes that were however unrelated to the phobic objects just before implosion therapy, Shiban, Brutting, Pauli, & Mühlberger (2015a) could not replicate this finding in a much more recent study when reactivating the fear with the specific stimulus (spiders).
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3.1.2. Cognititive factors
Coping style. Two studies (Antony et al., 2001; Muris et al., 1993) did not find an impact of
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coping styles on the success of ET, differentiating between “blunters” (people that tend to avoid threat-related information) and “monitors” (people that actively seek out threat-related
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information). However, the follow-up study to one of these (Muris et al., 1995) did find that “blunting” lead to better results. The coping style did not change because of the treatment in
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the latter study.
Self-efficacy. Three studies found self-efficacy (both its level at the beginning and its change
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during the treatment) to be an important influencing factor concerning the success of ET (Bandura et al., 1977; Cote and Bouchard, 2009; Zoellner et al., 2000). Additionally, Williams
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and colleagues (1984) found that a therapy focused on improving self-efficacy was as successful as one with exposition only. Cote and Bouchard (2009) additionally found changes in dysfunctional beliefs to be significantly associated with treatment success. Automaticity and irrationality of cognitions. Mayer and colleagues (2000) found that while perceived automaticity of cognitions was not related to treatment success, perceived irrationality was: For participants who rated their own cognitions as more irrational, the treatment was more successful.
Memory. The aforementioned study of Zoellner and colleagues (2000) also suggests that better memory for the anxious response, but not the phobic stimulus itself, is correlated with better treatment success. 3.1.3. Physiological factors Eyeblink startle response. Results by de Jong and colleagues (1991) suggest that larger eyeblink startle response in response to white noise while being confronted with a live spider (compared to while confronted with a household object) before an ET was associated with
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higher success of ET. Cortisol levels. Lass-Hennemann and Michael (2014) find that, in their study, different cortisol levels in the morning compared to the evening explain differences in the success of ET
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conducted at these times due to enhanced extinction memory in the morning when cortisol levels are higher. Soravia and colleagues (2014) successfully used this finding by
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administrating cortisol prior to ET and thereby improving reduction of fear.
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Comorbidity. One study (Ollendick et al., 2010) found that, in adolescent patients with comorbid specific phobias and anxiety disorders, ET targeting one specific phobia had a positive influence on the severity of the other comorbid phobia or anxiety disorder.
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Furthermore, the success considering the targeted specific phobia was not affected by the existence of a comorbid anxiety disorder.
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3.2 During the ET
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Most of the researched potential factors take effect during the ET. We found five potential factors in the emotional category (within and between session habituation with n=4 studies, disgust with n=5 studies, disgust evocation with n=3 studies, relaxation as an addition with n=3 studies, Positive Valence Training with n=1 study), four potential factors in the cognitional category (presence with n=1 study, coping self-statements with n=1 study, adding cognitive parts to ET with n=7 studies and attentional focus guiding with n= 6 studies), nine potential factors in the behavioral category (spontaneously shown safety behavior with n=1
study, evoked safety behavior with n=6 studies, , sex of the therapist with n=1 study, context variation with n=7 studies, stimulus variation with n=4 studies, length with n=11 studies computer assistance with n=14 studies, motion simulation with n=1 study, and additional manipulation with n=3 studies) 3.2.1 Emotional factors Within- and between-session anxiety decrease. Two studies found a correlation between a measurable between session habituation (BSH) and within session habituation (WSH) on the
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one hand and overall success of the therapy on the other hand (Mühlberger et al., 2005a; Rachman and Levitt, 1988). Two more recent studies (with higher Quality Scores) did not find such a correlation (Baker et al., 2010; Busscher et al., 2015), especially when
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investigating long-term success.
Disgust. Regarding the relation between fear, disgust, and the success of ET, Smits and
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colleagues (2002) found that anxiety and disgust declined independently from each other (anxiety declined more than disgust), but they did not find that global disgust levels were
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changed nor that disgust levels prior to the ET had an impact on anxiety level reduction (or vice versa). Similarly, Olatunji and colleagues (2007) found that in their study participants
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with blood-injection—injury phobia (BII) found that anxiety declined more than disgust. However, in their study disgust and fear decline were not independent from each other. In
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two following studies, Olatunji et al. (2012, 2009) show fear and disgust and their respective decline to be independent from each other, with fear, but not disgust, being a significant
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predictor of treatment success (measured by a BAT). Contrary to this, Matthews, Naran & Kirkby (2015) found that in their study, both anxiety and disgust reduction predicted treatment success (behavioral avoidance). Disgust evocation. Another line of research did not only measure both disgust and anxiety, but directly evoke disgust in participants with specific phobias: Both Choplin and Carter (2011) and Olatunji and colleagues (2009) were able to evoke disgust and reach a significant reduction of both anxiety and disgust by only showing disgusting pictures. They found no
differences in treatment success (both behavioral and subjective) between a group exposed to a disgusting stimulus compared to a group exposed to an anxiety-inducing stimulus, although Choplin and Carter (2011) found the anxiety-condition to have more long-lasting effects on behavior. De Jong and colleagues (2000) tried to countercondition the disgust elicited by an exposure to a spider in spider phobic individuals by presenting explicitly nondisgusting stimuli after the ET. They found no added effect on treatment success. Relaxation. Mühlberger and colleagues (2001a) find that relaxation alone is not as successful
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in reducing anxiety as VRET alone is. Rimm and Medeiros (1970) find no enhancement by adding relaxation to ET, while McGlynn and colleagues (1999) even found a suppression of anxiety by a history of relaxation training.
Additional Positive Valence Training. Dour and colleagues (2016) suggest that Positive
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Valence Training, a training that tries to increase the valence of the feared stimulus, in this
Cognitive factors
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3.2.2
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case spiders, by pointing out their usefulness, can enhance the effect of ET.
Presence and coping self-statements. Krijn and colleagues (2004) could not find an impact of presence, i.e. the feeling of actually being in a real environment while being in a Virtual
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Reality, on the success of VRET. In another study, Krijn and colleagues (2007) showed that coping self-statements did not enhance the success of VRET.
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Adding Cognitive parts. One potential factor that drew much attention is the question whether ET with parts specifically addressing cognitions like cognitive preparation or cognitive tasks
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in the ET is more successful than ET without such parts. Raes and colleagues (2011) did not find an advantageous effect of explicitly addressing cognitions in the ET, but did find that success was mediated by cognitive changes. Similarly, Tardif (2019) and colleagues showed that in their study, changes in cognitive beliefs and self-efficacy were predictive of ET success. Kircanski and colleagues (2012) found only marginally better results of ET augmented by affect labeling but not by guided threat-reappraisal, with Tabibnia (2008) corroborating this result. Dee’s (1972) study suggests that instructions seem to help – albeit
not significantly. However, Bandura and colleagues (1974) argue that “induction aids”, such as a gradual exposure and company, help in exposure and lead to better results. Furthermore, Sloan and Telch (2002) as well as a study by Kamphuis and Telch (2000) suggests that guided threat-reappraisal helped. Additionally one study found that a treatment without a cognitive part is effective, but less so than a treatment with cognitive contents (Van Gerwen et al., 2006). Finally, Koch and colleagues (2004) found a treatment without cognitive part as effective, but it was perceived as more intrusive.
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Attentional Focus Guiding. Concerning attentional focus guiding: while one study finds that distraction is beneficial (Oliver and Page, 2008), three others find that distraction hinders extinction and lowers the success of ET (Dethier et al., 2015; Kamphuis and Telch, 2000; Telch et al., 2004). A third pair of studies find no effect of attentional focus guiding on
Behavioral factors
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3.2.3
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treatment success (Antony et al., 2001; Waters et al., 2014).
Safety Behavior. Rentz and colleagues (Rentz et al., 2003) found that the (not instructed,
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spontaneously shown) use of safety behavior was associated with less improvement. In contrast to this, four studies find either no drawback or even small advantages of explicitly
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instructing participants to use safety behavior (Deacon et al., 2010; Hood et al., 2010; Milosevic and Radomsky, 2008; Sy et al., 2011), and only one study found the expected
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disadvantage of an ET with instructed safety behavior (Sloan and Telch, 2002). Additionally, Wolitzky and Telch (2009) show that utilizing “fear antagonistic behavior”, which can be seen
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as a form of safety behavior or distraction from the feared stimulus, leads to better behavioral success and more generalization. Sex of therapist. O’Sullivan and Gilner (1976) found that the sex of the therapist is a factor; female therapists seem to be beneficial regardless of the sex of the patient. Context variation. Mystkowski and colleagues (2002) have shown that in their study, exposition to the feared stimulus in a context different to the one used in the ET leads to return of fear, which is not equivalent to fear relapse, but is a partial fear recovery after ET
(Rachman, 1989). Five studies suggest that using several contexts in the ET leads to less return of fear and generally better treatment success (Bandarian-Balooch et al., 2015; Shiban et al., 2015a, 2013; Vansteenwegen et al., 2007b, 2007a), but two studies (Rodriguez et al., 1999; Shiban et al., 2015b) could not find such an effect. Stimulus variation. Both last-mentioned studies also looked at the effect of varying the stimulus itself within the ET. This question was addressed by a total of three studies: One of these (Shiban et al., 2015b) suggest that varying the stimulus is beneficial, while the other
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two (Koch et al., 2004; Rodriguez et al., 1999) did not find a benefit of different stimuli. Length. When looking at the potential influence of length, one can further subdivide this
factor into three subcategories: number of sessions, length of the individual session and
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massed vs. expanding-spaced ET, which will be discussed in the following paragraphs.
In three different studies, Öst and his colleagues did not find any differences between a one-
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session and a five-session ET (Hellström et al., 1996; Öst et al., 2001, 1997), although their latest study suggests a slight advantage of the five-session treatment one year after the ET
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(Vika et al., 2009). When comparing higher numbers of sessions, Fraser and colleagues (2001) found no difference between participants getting three versus six sessions of
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vicarious exposure. Bornas and colleagues (2011) tackled the question differently by counting the numbers of sessions needed until they reached a successful reduction of
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subjective level of anxiety. Participants needed between one and seven sessions; the faster anxiety was reduced within the sessions, the fewer sessions were needed.
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Length of individual sessions has been researched in three studies: Miller and Levis (1971) found a superiority of 30- and 45-minute exposure sessions over 15-minute sessions. Rachmann and Lopatka (1988) showed that in their study, extending the ET over a point of acceptably reduced anxiety did not have an added effect on the success, and neither did stopping the ET before the point of acceptably reduced anxiety (SUDs at 0). Finally, Rodriguez et al. (1999) found that, in their study longer treatment duration predicted greater return of fear.
Lastly, Rowe and Craske (1998) tried to find differences between a massed ET and an ET with sessions spaced with more times between sessions. Although both forms of ET worked comparably well at first (the massed ET worked even slightly better), they found a return of fear in the massed ET group directly after the ET and at a 1-month follow-up. Computer assistance. A modern way of presenting the feared stimulus is by using computer assistance. But respective techniques seem to be either as good as or even inferior to in vivo ET: This was shown for video exposure (Öst et al., 1998), imagery exposure (Wiederhold et
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al., 2002, 2001), computer-aided ET (Tortella-Feliu et al., 2011) and internet-based therapies (Andersson et al., 2013, 2009). Additionally, Virtual Reality (VR) or Augmented Reality (AR), were either as effective (Botella et al., 2016; Emmelkamp et al., 2001; St-Jacques et al., 2010) or slightly inferior(Heading et al., 2001; Michaliszyn et al., 2010) than in vivo ET.
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However, the authors frequently name a lesser aversiveness (Botella et al., 2016) and lower costs, especially in the case of flight phobia (Emmelkamp et al., 2001), as advantages for VR
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or AR. When it comes to differences between specific ways of projecting the virtual reality,
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Krijn and colleagues (2004) do not find a difference between an ET with a head-mounted display (HMD) and a computer automatic virtual environment (CAVE). Mühlberger and
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colleagues (2005b) found no additional effect of motion simulation in VRET. Additional manipulation. Finally, three studies manipulated the stimulus in additional ways: Smith and colleagues (Smith et al., 1997) show that vicarious exposure to an irrelevant, not
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anxiety-inducing stimulus (i.e. training of the ET technique without the feared stimulus) does
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improve anxiety. Craske and colleagues (1991) varied the participant’s control over the length of an exposure and found no influence on the success of treatment. Shiban and colleagues (2016) showed that specific perceptual cues (i.e. presenting pictures of a closed door to claustrophobic participants) lead to better success of ET (measured by physiological parameters) than fear-related conceptual information (i.e. telling the participants that the door was closed). 3.2.4
Physiological factors
Heart rate. When investigating heart rate, systolic blood pressure and diastolic blood pressure, Hellström and Öst (1996) could not find any stable predictors for short- or longterm success of ET. Several other studies researched the connection between heart rate and ET success: While Bornas and colleagues (2007) could predict better success when combining heart rate variability with heart rate entropy, Alpers and Sell (2008) even showed that in their participants, heart rate at the start of ET alone correlated more with its success than measures of subjective anxiety. Bornas and colleagues (2011) added to this showing that “flexible patients” (i.e. patients with greater heart rate variability) improved more. In line
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with this, Busscher and colleagues (2013) showed that heart rate was a predictor for participants with high anxiety sensitivity, but less so for patients with low anxiety sensitivity. In a follow-up study (Bornas et al., 2012) that further discriminated between tonic and phasic
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heart rate, this finding was corroborated. However, two studies (Benoit Allen et al., 2015; Busscher et al., 2015) could not find correlations between long-term treatment success and
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heart rate reactivity or changes.
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Feedback of body reactions. Craske and colleagues (1995) gave participants corrective information on their bodily reactions (like explaining that shortness of breath did not lead to suffocation). While this lead to higher fear reduction in claustrophobics, the effect did not
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generalize and was not found in spider or snake phobic participants. However, two studies (Telch et al., 2000; Wiederhold et al., 2002) found that feedback of the heart rate did
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enhance the effect of ET, while one study could not find an influence of (visual or tactile) feedback (Tardif et al., 2019).
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Caffeine State. Mystkowski and colleagues (2003) showed that the “caffeine state”, i.e. how much coffee a participant drank, has an effect on post-ET anxiety in that a “caffeine state” differing to the one in the ET lead to greater return of fear. Anxiety-differing medication. A number of different medication was administered in studies to examine its effect on the success of ET. A study conducted by Meyerbroeker and colleagues (2012) could not find enhancing effects for Yohimbine Hydrochloride. For Quetiapine, an
effect was limited to physiological anxiety measurements (Diemer et al., 2013) but did not show in behavioral measurements or subjective ratings by the participants. For Benzodiazepines, a study even found a hindering effect for flight phobic participants (Wilhelm and Roth, 1997). Similarly, Oxytocin showed diminishing effects on success in one study (Acheson et al., 2015). Lastly, Naltrexone was not administered as a potential enhancement but rather to test the role of the opioid system: Both Merluzzi, Taylor, Boltwood, and Gotestam (1991) and Arntz, Merckelbach, & de Jong (1993) find that the administration of Naltrexone hinders reduction of anxiety in an ET, thus suggesting a role of the opioid system
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in its success. 3.3 After the ET
Only a few factors in this category have been researched, with one emotional (conditioned
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odor with n=1 study) and one cognitive factor (return of phobic cognitions with n=2 studies)
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and 3 physiological factors (neural activation with n=3 studies, sleep with n=2 studies and memory-enhancing medication with n=5 studies). Emotional factors
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3.3.1
Conditioned odor. Rihm et al. (2016) could not enhance the effect of an ET by re-
participants.
Cognitive factors
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3.3.2
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administrating an odor that was previously conditioned to a successful ET to their sleeping
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Return of phobic cognitions. Rodriguez and colleagues (1999) found evidence that “recovery of phobic cognitions”, i.e. an increase in phobic cognitions about the feared stimulus assessed with the Spider Beliefs Questionnaire (Arnoud Arntz et al., 1993), leads to less long-term success of ET. 3.3.3
Physiological factors
Neural activation. Hauner and colleagues (2012) show that the magnitude of the activation of a part of the visual cortex (a lingual cortex subregion) to specific fearful stimuli measured by
fMRI shortly after ET predicted long-term treatment success. Schienle and colleagues (2007) showed that successful ET correlated with a reduction in amygdala and insula reactivity to relevant pictures when success was measured with somatic panic symptoms and correlated with only amygdala changes when measured with arousal ratings in a BAT. Finally, Landowska and colleagues (2018) found no correlation between brain activity measured with functional Near-Infrared Spectroscopy (fNRIS) and subjective anxiety ratings in a group of acrophobic participants during a VRET.
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Sleep. Both Kleim and colleagues (2014) and Pace-Schott and colleagues (2012) showed that respectively 90 minutes or 12 hours of sleep lead to better post-therapy anxiety reductions.
Memory-enhancing mediation. The most-researched enhancing drug is D-Cycloserine, a
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partial agonist to the glutamatergic NMDA receptor (Hofmann, 2014) with heterogeneous
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results: While Smits and colleagues (2013) find that application of D-Cycloserine after a “successful” session, i.e. a session with within-session reduction of anxiety according to
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“Subjective Units of Distress (SUDs, but not after an “unsuccessful” one) seems to enhance the effect of the treatment in a group of height phobic individuals and Byrne et al. (2015)
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corroborate this finding in a group of children with varying specific phobias, Tart et al. (2013) do not find an enhancing effect of D-Cycloserine.
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Methylene Blue seems to have an effect that is comparable to that of D-Cycloserine, i.e. being effective after a successful, but counterproductive after an unsuccessful exposure
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session (Telch et al., 2014).
4. DISCUSSION The present review aimed to give an overview over factors spanning the time before, during and after the ET itself and their respective empiric corroboration. Before discussing the limitations and the conclusion of this review and giving concrete advice for clinicians and researchers on how to use the results in their respective work, we will summarize our results
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for different factors.
4.1. Summary of evidence
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4.1.1. Before the ET
At this point in time, one can only recommend considering two emotional factors before ET
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as factors influencing the success of ET: A low trait anxiety and a high motivation, both researched by two studies with acceptable QS. Coping stiles (3 studies with acceptable to
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high QS and mixed results) has not been shown to be relevant in an adequate number of studies.
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The fact that four studies with acceptable to high QSs point to self-efficacy being an important factor fits well with the results of the aforementioned study by Williams and
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colleagues (1984). No other cognitive factors emerged as good candidates for influencing the success of ET.
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For potential physiological influencing factors before ET, it must be said again that replication of findings is needed (especially for comorbidity, that has only been researched by one study with acceptable QS), albeit Cortisol levels seem to be the most promising candidate, with two promising studies with very high QSs finding and using a relationship between Cortisol levels and ET success. 4.1.2.
During the ET
When it comes to emotional factors during the ET, the literature summarized here calls into question if WSH and BSH are necessary, with two studies with lower QS finding a relationship, while to studies with higher QSs fail to do so. This concurs with the work by Craske and colleagues (Craske et al., 2008b), and with the results of a recent meta-analysis by Rupp and colleagues (Rupp et al., 2017). It remains entirely unclear whether disgust and its decline through an ET is independent from anxiety and whether it is a relevant predictor of ET success. Five studies, all with lower to medium QSs, come to very contradicting results. However, the three included studies with medium QSs (Choplin and Carter, 2011; de Jong et
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al., 2000; Olatunji et al., 2009) suggest that exposing to disgusting stimuli does also help reduce anxiety. Additionally, avoiding relaxation shows promise as a relevant factor in three studies with QSs ranging from low to high (McGlynn et al., 1999; Mühlberger et al., 2001b;
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Rimm and Medeiros, 1970).
Regarding cognitive factors during the ET, it seems clear that focusing on changes in fear-
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relevant cognitions during the ET improves the success rate of ET with a high number of
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studies, all with medium to high QSs, finding a relationship. However, we cannot specify the best kind of cognitive addition more precisely, as the different studies used very
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heterogeneous cognitive additions.
Going on to look at potential behavioral factors during the ET change of context - but not change of the stimulus itself - has emerged as a factor of success in ET, especially regarding
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long-term effects. Regarding length three studies with high QS found five sessions to be
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sufficient, with evidence from one high-quality study that five sessions is superior over one session when it comes to long-term effectiveness. Extending the time of individual sessions does not seem to improve the success. Virtual Reality Exposure Therapy (VRET) seems to be a viable option for the treatment of specific phobias: In most of the reviewed studies (that all have good QSs), it has shown superiority or at least no inferiority to other forms of treatment that have been used frequently when in vivo exposure was not possible or too aversive and seems to be a viable alternative
to in vivo ET. This finding is in line with newer reviews (Botella et al., 2017; Maples-Keller et al., 2017). Regarding physiological factors, there are several different measurements of heart rate activity that show potential as factors predicting treatment success, none of which has been studied in a satisfactory amount, even though all studies show medium to high QSs. Nonetheless, it seems clear that heart rate changes and differences are an important factor for the success of ET.
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4.1.3. After the ET Overall, factors influencing the success that take effect after ET play a comparably small role. Except for the return of phobic cognitions (with only one, medium to high quality study),
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no potential factors emerged in the emotional or cognition category. When it comes to additions concerning physiological aspects, best evidence exists for sleep as well as
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administering D-Cycloserine as being helpful (albeit only if it is administered with a successful ET; 3 studies with high QS). In their review concerning the use of cognitive
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enhancers in exposure-based therapies for several diseases, Singewald and colleagues (2015) come to a similar conclusion. See Hofmann (2014) for a guidelines for clinical practice
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of using D-Cycloserine as an enhancer of ET.
For an overview over the status of every factor included in this review, see table 3.
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Insert Table 3 here.
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4.2. Embedding our results into the theoretical background Our findings show only a handful of factors that definitely play a part in the success of ET. However, these factors can be integrated very well into the aforementioned Inhibitory Learning Approach by Craske (Craske et al., 2014, 2008). This approach states that patients develop secondary inhibitory associations to the feared stimuli; ET is thus successful when it provides patients with possibilities to build and strengthen these new associations (Craske et al., 2014). This theory differentiates itself from older models of the underlying mechanisms of
ET like the Pavlovian conditioning model in that it does not postulate an overwriting of the old associations but a building of separate, new associations. Thus, factors that enable maximum new learning and create an environment in which learning is possible help the most. In our review, these are: A high self-efficacy before the ET (Bandura et al., 1977; Cote and Bouchard, 2009; Williams et al., 1984; Zoellner et al., 2000), a low trait anxiety (Muris et al., 1998; Rodriguez et al., 1999), addressing disgust as well as anxiety when choosing the stimulus (Choplin and Carter, 2011; de Jong et al., 2000; Olatunji
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et al., 2009), focusing on changing phobia-specific cognitions (Bandura et al., 1974; Dee, 1972; Kamphuis and Telch, 2000; Kircanski et al., 2012; Koch et al., 2004; Raes et al., 2011; Sloan and Telch, 2002; Tabibnia et al., 2008; Tardif et al., 2019; Van Gerwen et al., 2006), changing contexts between ET sessions (Bandarian-Balooch et al., 2015; Mystkowski et al.,
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2002; Shiban et al., 2015a, 2013; Vansteenwegen et al., 2007b), focusing on heart rate changes (Alpers and Sell, 2008; Bornas et al., 2012, 2011, 2007; Busscher et al., 2013;
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Hellström and Öst, 1996), administering D-Cycloserine after a successful ET (Byrne et al.,
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2015; Smits et al., 2013; Tart et al., 2013) and sleeping after one (Kleim et al., 2014; Pace-
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Schott et al., 2012).
All of these factors help the patient build new associations with the feared stimulus: Either by
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enabling them to be more open to new experiences that violate existing expectancies concerning the feared stimulus (high self-efficacy and low trait anxiety), by “deepen the
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extinction” (Rescorla, 2006) in the case of addressing disgust additionally to anxiety and focusing on cognitions and heart rate change or by enabling reconsolidation (changing contexts, D-Cycloserine, and sleep). Nevertheless, some of the strategies to optimize ET proposed by Craske and colleagues are not corroborated by our findings, namely the call for variability of stimulus. Especially since most of the assumptions of the Inhibitory Learning Approach are met, it seems surprising that this is not the case for changing stimuli. One possible reason might be the focus of this
review on a very specific anxiety disorder, namely SP. SP is characterized by the fear of one specific stimulus. Thus, there might not be a need to generalize as much to other forms of the same feared stimulus. This also explains why the length and number of the ET sessions seem to play a smaller role. It is easier to learn new cognitions in the context of a specific phobia than in the context of other phobias or anxiety disorders. When an ET is successful in providing these new learning experiences, it does not need as much time or many repetitions for this learning experience to consolidate.
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Furthermore, our findings show that some factors only influence the success measured on one dimension (behavioral, subjective, physiological, or in clinicians’ ratings). This relationship between different levels of measurement of the success and different factors is
4.2.1
Perspective for clinical research
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not yet clear (Lambert and Ogles, 2009; Moustgaard et al., 2014).
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There is only a small number of sufficiently researched and corroborated factors influencing the success of ET in patients with specific phobia. Studies that aim to replicate previous
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results, with sufficiently sized and well-screened samples, are needed to further the understanding of what makes ET successful.
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Based on our findings, researchers wanting to select factors worthy of future research and to find good operationalizations should start at the underlying theoretical mechanisms. As
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already mentioned, factors that could help improve the learning experience in ET (e.g. by directing the patient’s attention on the new experience, limiting distractions and unnecessary
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parts of the ET) are more likely to be relevant factors of success than factors that stand in no connection to the learning experience. Agreeing on shared operationalizations of factors as well as shared measures of success, with a special focus of measuring long-term success, is of utmost importance for the advancement of the research field. Furthermore, studies show a huge difference in regard to the form of ET they use (OST, VRET and multi-session ET are used similarly often) and their inclusion and exclusion criteria. We presented studies that show that these different forms of
ET are comparable, as they are very similar to each other in terms of success and underlying mechanism. Nevertheless, an effort should be made in trying to mirror everyday practice in future studies and to use more comparable forms of ET to ensure generalizability. Lastly, we see the inclusion of participants with only mild anxiety as a big problem: This calls into question if the respective results are transferrable to clinical practice, where patients have comparably severe disorders and symptomatology. Studies with participants with clinical diagnoses sometimes come to different conclusions, not least
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because ET seems to be more effective with participants with more severe anxiety. Therefore, we argue that studies should try to include only participants with clinically significant specific phobia.
This is especially the case since once the question of who profits from ET most is answered,
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the question what to do with the ones who do not becomes even more pressing. This group
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of hard-to-treat patients might need a more optimized and individualized treatment. However, based on the current literature, it is hard to say how such optimizations should look like; more
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research is needed in this field. Some studies that try to fill this need: Studies like the one from Schwarzmeier and colleagues (Schwarzmeier et al., in press) try to identify these
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patients before a treatment begins. Future studies will have to show how to individualize therapy.
Perspective for clinical practice
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4.2.2
A conclusion for how to conduct ET with patients is very hard to draw. Nevertheless, some
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advice can be given.
All things considered, the literature shown here underlines that ET is a very effective form of treatment; even if both the mechanisms and the influencing factors still need to be put under scrutiny, a majority of the studies presented here shows an improvement in anxiety (subjectively, behaviorally and physiologically). It is thus superior to other forms of treatment for patients with SP.
ET should have the goal to expose the patient with the feared stimulus as fast and as direct as possible (while still taking the commitment of the patient into account) to ensure the best learning experience. Factors that have been shown to improve the learning experience are addressing disgust as well as anxiety (i.e.when building an anxiety hierarchy, therapists should also ask for especially disgust-inducing stimuli and take respective stimuli into consideration when choosing exposure stimuli), focusing onchanging cognitions in the ET (by concretely exploring cognitions before and after the ET to stress changes), changing context for different sessions, monitoring and addressing heart rate changes during the ET and sleep
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and/or D-Cycloserine after a (successful) ET. Lastly, ET should be conducted as close as possible to the current state of the art (Bandelow et al., 2014), since this is the form of ET that is best examined and the influence of all deviances from it are not yet clear.
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Some factors that we found to have an impact on the success of ET cannot be controlled by the clinician directly, mainly the motivation, self-efficacy and trait anxiety of their patients.
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However, we would argue that there is nevertheless merit in accounting for their influence:
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As we have said, ET is the therapy of choice even for patients with less chance of success. Clinicians should just be aware that success might take longer for patients with unfavorable attitudes or traits, and might want to address motivation and self-efficacy before starting with
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ET (e.g. by exploring and discussing potential dysfunctional cognitions that lead to these, or using techniques like Motivational Interviewing (Miller, 1983) to improve them. Moreover,
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specific adjustments and individual optimization might be necessary for this group of patients. As discussed, the nature of these optimizations is not yet clear, making this group
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of patients a particular challenge. 4.3 Limitations
A large number of factors have been researched in the literature, but most of them by only a very small number of studies. Additionally, a lot of potential factors have been operationalized very heterogeneously in different studies, leading to problems in comparing these studies even if the same factor was the object of interest. This leads to problems
especially when different potential factors (e.g. distraction and cognitive additions) influence each other. Finally, both the characterization of participants and the definition of success of ET differed greatly, further complicating comparison between studies. Additionally, a lot of studies do not take satisfactory follow-up measurements: Studies show that there is a considerable change in the reaction to an ET even 6 and 12 months after treatment, most widely studied in respect to the aforementioned concept of return of fear (Haaker et al., 2014), which often is disregarded in the presented literature.
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Many studies that looked at potential predictors of success of ET did not meet our inclusion criteria and were thus excluded from this review. Hence, it could be argued that with less rigid inclusion criteria, more predictors could have been unveiled and the picture for the predictors discussed here could have looked differently. Similarly, one could argue that we
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limited ourselves too much by only including studies regarding SP, and excluding other
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studies that, while conducting research on ET, did so with participants having (symptoms of) another phobia or anxiety disorder. But we think that, especially in the face of the number of
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different predictors discussed in the literature and the huge number of articles published in this area, it is of importance to adhere to strict quality standards to be able to get trustworthy
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results.
Furthermore, there is still considerable heterogeneity in our results. This heterogeneity raises
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the question whether our inclusion criteria were not strict enough: We included a number of articles that have a sample of participants with only light symptomatology or that measure the
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success (or lack thereof) of the ET in an unsatisfactory amount. However, we decided to include these studies in order to give a picture of the existing research that is as exhaustive as possible – as long as they fulfilled certain minimal criteria outlined in our PICOS criteria (see 2. Methods). Since all the included studies had to satisfy these inclusion criteria, we feel that reporting their results is not without merit even if their methodology leaves things to be desired. Additionally, we tried to make the reader aware of quality differences between included studies by reporting their respective QS.
Moreover, studies measured outcome in different ways, and some studies included several kinds of measuring outcome like subjective (e.g. via questionnaires), behavioral (e.g. with Behavioral Avoidance Tests), physiological (e.g. via measuring electrodermal activity) or professional (e.g. a rating by therapists). There is merit to every one of these kinds of measures, since they show different aspects of change that tend to be intercorrelated, but not equal to each other (Ogles et al., 1990). Hence, a combination is desirable to get a complete pictures as much as possible (Lonsdorf et al., 2017). This is why the QS is higher the more different kinds of measuring outcome were applied. In our review, eight included
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studies did only measure success in one of the aforementioned ways; all the other studies employed two or more ways.
Another problem in interpreting our results lies in the fact that there is a risk of bias across
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the included studies (see 2.Methods). This is especially disconcerting because oftentimes, one potential factor has only been researched by one team of researchers. For example,
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OST has been researched most actively by Öst and colleagues. This makes it hard to
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compare two factors with each other, given that the quality of the underlying research may differ. We again tried to tackle this problem with our Quality Score, which should give an
4.4 Conclusion
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insight into the quality of every study (albeit not being able to fully eliminate risk of bias).
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This review gives an overview over potential factors influencing the success of ET in patients with SP. Best evidence is shown for the following factors: low trait anxiety, high motivation
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and high self-efficacy before the ET, high cortisol levels and heart rate variation, evoking disgust additionally to anxiety, avoiding relaxation, focusing on cognitive changes, context variation, sleep, and memory-enhancing drugs. This review serves two purposes: Firstly, it helps practitioners in planning and conducting an ET with a high chance to succeed. Although conclusive evidence for many aspects is still missing, we nevertheless show that enabling to learn new associations with the feared stimulus should be the focus. Secondly, this review presents the challenges and the groundwork for future research: It shows the
need for unified operationalizations of both potential factors and the measurement of the outcome. It presents many potential factors that should be replicated in future studies and provides a theoretical background for other factors that can be researched in the future.
Funding and conflicts of interest The study was supported by grants of the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation; Collaborative Research Centre “Fear, Anxiety, Anxiety Disorders”
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SFB-TRR-58) projects Z2 and C09 to UD. There was no conflict of interest.
5
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Smits, J.A.J., Telch, M.J., Randall, P.K., 2002. An examination of the decline in fear and
Jo
disgust during exposure-based treatment. Behav. Res. Ther. 40, 1243–1253. Soravia, L.M., Heinrichs, M., Winzeler, L., Fisler, M., Schmitt, W., Horn, H., Dierks, T., Strik, W., Hofmann, S.G., de Quervain, D.J.-F., 2014. Glucocorticoids enhance in vivo exposure-based therapy of spider phobia. Depress. Anxiety 31, 429–435. https://doi.org/10.1002/da.22219 St-Jacques, J., Bouchard, S., Belanger, C., 2010a. Is virtual reality effective to motivate and raise interest in phobic children toward therapy? A clinical trial study of in vivo with in
virtuo versus in vivo only treatment exposure. J. Clin. Psychiatry 71, 924–931. https://doi.org/10.4088/JCP.08m04822blu St-Jacques, J., Bouchard, S., Belanger, C., 2010b. Is virtual reality effective to motivate and raise interest in phobic children toward therapy? A clinical trial study of in vivo with in virtuo versus in vivo only treatment exposure. J. Clin. Psychiatry 71, 924–931. https://doi.org/10.4088/JCP.08m04822blu Sy, J.T., Dixon, L.J., Lickel, J.J., Nelson, E.A., Deacon, B.J., 2011. Failure to replicate the
ro of
deleterious effects of safety behaviors in exposure therapy. Behav. Res. Ther. 49, 305– 314. https://doi.org/10.1016/j.brat.2011.02.005
Tabibnia, G., Lieberman, M.D., Craske, M.G., 2008. The Lasting Effect of Words on
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Feelings: Words May Facilitate Exposure Effects to Threatening Images. Emotion 8, 307–317. https://doi.org/10.1037/1528-3542.8.3.307
re
Tardif, N., Therrien, C.-É., Bouchard, S., 2019. Re-Examining Psychological Mechanisms
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Underlying Virtual Reality-Based Exposure for Spider Phobia. Cyberpsychology, Behav. Soc. Netw. 22, 39–45. https://doi.org/10.1089/cyber.2017.0711
na
Tart, C.D., Handelsman, P.R., DeBoer, L.B., Rosenfield, D., Pollack, M.H., Hofmann, S.G., Powers, M.B., Otto, M.W., Smits, J.A.J., 2013. Augmentation of exposure therapy with post-session administration of d-cycloserine. J. Psychiatr. Res. 47, 168–174.
ur
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Taylor, S., Abramowitz, J.S., McKay, D., 2012. Non-adherence and non-response in the treatment of anxiety disorders. J. Anxiety Disord. 26, 583–589. https://doi.org/10.1016/j.janxdis.2012.02.010
Telch, M.J., Bruchey, A.K., Rosenfield, D., Cobb, A.R., Smits, J., Pahl, S., Gonzalez-Lima, F., 2014. Effects of post-session administration of methylene blue on fear extinction and contextual memory in adults with claustrophobia. Am. J. Psychiatry 171, 1091–1098. https://doi.org/10.1176/appi.ajp.2014.13101407
Telch, M.J., Valentiner, D.P., Ilai, D., Petruzzi, D., Hehmsoth, M., 2000. The facilitative effects of heart-rate feedback in the emotional processing of claustrophobic fear. Behav. Res. Ther. 38, 373–387. Telch, M.J., Valentiner, D.P., Ilai, D., Young, P.R., Powers, M.B., Smits, J.A.J., 2004. Fear activation and distraction during the emotional processing of claustrophobic fear. J. Behav. Ther. Exp. Psychiatry 35, 219–232. https://doi.org/10.1016/j.jbtep.2004.03.004 Tortella-Feliu, M., Botella, C., Llabres, J., Breton-Lopez, J.M., del Amo, A.R., Banos, R.M.,
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Gelabert, J.M., 2011. Virtual reality versus computer-aided exposure treatments for fear of flying. Behav. Modif. 35, 3–30. https://doi.org/10.1177/0145445510390801
Trumpf, J., Margraf, J., Vriends, N., Meyer, A.H., Becker, E.S., 2010. Specific phobia predicts
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psychopathology in young women. Soc. Psychiatry Psychiatr. Epidemiol. 45, 1161– 1166. https://doi.org/10.1007/s00127-009-0159-5
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Van Gerwen, L.J., Spinhoven, P., Van Dyck, R., 2006. Behavioral and cognitive group
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Vansteenwegen, D., Vervliet, B., Hermans, D., Thewissen, R., Eelen, P., 2007a. Verbal, behavioural and physiological assessment of the generalization of exposure-based fear reduction in a spider-anxious population. Behav. Res. Ther. 45, 291–300.
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Vansteenwegen, D., Vervliet, B., Iberico, C., Baeyens, F., Van den Bergh, O., Hermans, D., 2007b. The repeated confrontation with videotapes of spiders in multiple contexts attenuates renewal of fear in spider-anxious students. Behav. Res. Ther. 45, 1169– 1179. https://doi.org/10.1016/j.brat.2006.08.023 Vika, M., Skaret, E., Raadal, M., Öst, L.G., Kvale, G., 2009. One- vs. five-session treatment of intra-oral injection phobia: a randomized clinical study. Eur. J. Oral Sci. 117, 279– 285. https://doi.org/10.1111/j.1600-0722.2009.00628.x
Waters, A.M., Farrell, L.J., Zimmer-Gembeck, M.J., Milliner, E., Tiralongo, E., Donovan, C.L., McConnell, H., Bradley, B.P., Mogg, K., Ollendick, T.H., 2014. Augmenting one-session treatment of children’s specific phobias with attention training to positive stimuli. Behav. Res. Ther. 62, 107–119. https://doi.org/10.1016/j.brat.2014.07.020 Wiederhold, B.K., Gevirtz, R.N., Spira, J.L., 2001. Virtual reality exposure therapy vs. imagery desensitization therapy in the treatment of flying phobia., in: Riva, G., Galimberti, C., Riva (Ed), G., Galimberti (Ed), C. (Eds.), Towards Cyberpsychology:
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Wiederhold, B.K., Jang, D.P., Gevirtz, R.G., Kim, S.I., Kim, I.Y., Wiederhold, M.D., 2002. The treatment of fear of flying: a controlled study of imaginal and virtual reality graded
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exposure therapy. IEEE Trans. Inf. Technol. Biomed. 6, 218–223.
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Wilhelm, F.H., Roth, W.T., 1997. Acute and delayed effects of alprazolam on flight phobics
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during exposure. Behav. Res. Ther. 35, 831–841.
Williams, S.L., Dooseman, G., Kleinfield, E., 1984. Comparative effectiveness of guided
505–518.
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mastery and exposure treatments for intractable phobias. J. Consult. Clin. Psychol. 52,
Wittchen, H.-U., Jacobi, F., Rehm, J., Gustavsson, A., Svensson, M., Jönsson, B., Olesen,
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J., Allgulander, C., Alonso, J., Faravelli, C., Fratiglioni, L., Jennum, P., Lieb, R., Maercker, A., van Os, J., Preisig, M., Salvador-Carulla, L., Simon, R., Steinhausen, H.-
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C., 2011. The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur. Neuropsychopharmacol. 21, 655–679. https://doi.org/10.1016/j.euroneuro.2011.07.018
Wolitzky-Taylor, K.B., Telch, M.J., 2009. Augmenting in vivo exposure with fear antagonistic actions: a preliminary test. Behav. Ther. 40, 57–71. https://doi.org/10.1016/j.beth.2007.12.006
Wolpe, J., 1954. Reciprocal Inhibition as the main basis of psychotherapeutic effects. Arch. Neurol. Psychiatry 72, 205. https://doi.org/10.1001/archneurpsyc.1954.02330020073007 Zoellner, L.A., Echiverri, A.M., Craske, M.G., 2000. Processing of phobic stimuli and its
Jo
ur
na
lP
re
-p
ro of
relationship to outcome. Behav. Res. Ther. 38, 921–931.
Identification
Figure 1. PRISMA flow chart for study inclusion.
Records identified through database searching: n=2619 (PubMed: n=2045; PsycInfo: n=573)
Screening
Records after duplicates removed: n=1938
Records excluded:
ro of
Records screened: n=1938
n=1386
Full-text articles excluded, with
lP
n=552
re
Eligibility
Full-text articles assessed for eligibility:
-p
reasons (n=441):
Included
Studies included in qualitative synthesis:
Jo
ur
na
n=111
wrong sample: n=142 Intervention does not meet criteria of exposition: n=115 n<10: n=63 no predictors as independent variable: n=43 short report: n=14 not an empirical study (i.e. review or case study): n=28 success of intervention is not measured: n=6 No or wrong control group (e.g. no ET in the control group): n=29 language: n=1
ro of
-p
re
lP
na
ur
Jo
Table 1 Quality and risk of bias assessment for studies researching factors influencing the success of Exposure Therapy in Specific Phobia 1 point
0.5 points
Independent sample
Yes
-
Sample size
≥20/condition
≥15/condition
Diagnosis secured
SCID or comparable
Questionnaire with clear cutoff AND BAT
Exclusion criteria
Reported
-
Concomitant Medication reported
No
-
Statistical control of possible confounders
Yes (or matched groups/ exclusion of confounders)
-
Standardized
Length or specific content not standardized, but manualized
Sample (0-3 points) No
re
Standardization
Behavioral measure
Yes
Physiological measure
Yes
Rating by professional
Randomization Blinding
Jo
RCT methodology (0-2 points)
-
Yes
-
Yes, exclusively
Yes, plus non-evidence based addition (medication etc.)
ur
Evidence-based treatment? (0-1 point)
na
Yes
lP
Outcome measures (0-4 points) Self-report
-p
Exposure Therapy (0-1 point)
ro of
Confounder Control (0-3 points)
Yes
-
Yes
-
Sum score study quality (0-14 points)
SCID: Structural Clinical Interview for DSM-IV; BAT= Behavioral Avoidance Test; RCT = Randomized Controlled Trial
Table 2 Included studies, their quality score and results ordered by the researched factors Topic
Author
Year
Treatment
Sample Size
Type of Specific Phobia
Main findings
Quality Score
Measure of success and evidence for use as predictor SR
B
Before the ET – emotional factors 1998
OST
36 women
Spider Phobia
The higher the trait anxiety scores, the less patients profited from behavior therapy.
7
-
-
Rodriguez, Craske, Mineka, & Hladek
1999
In vivo exposure
65 in 4 groups
Spider Phobia
Higher trait anxiety scores are associated with less successful therapy (increased return of fear)
9,5
-
-
2010
Exposure, in vivo only vs. VR plus in vivo
Spider Phobia
No increase in motivation through the use of VRET; significant impact of motivation (especially extrinsic integrated motivation) on subjective treatment success
9,25
+
see Computer assistance
Fear reactivation
Jo
see Sex of therapist
1976
31 children (8-15 years) in 2 groups
OST (15 minutes)
40 women in 4 groups
Snake Phobia
Significant impact of the motivation to change; interaction of motivation with modeling behavior
4,5
+
+
ur
O’Sullivan, & Gilner
lP
St-Jacques, Bouchard, & Bélanger
na
Motivation
re
see Context and stimulus variation, Length of the session, Recovery of phobic cognitions
ro of
Muris, Mayer, & Merckelbach
-p
Trait Anxiety
Hodgson, & Rachman
1970
Implosive therapy
50 in 5 groups
Snake Phobia
Improved effect of implosive therapy by showing horrifying images immediately but not delayed before implosion by imaging phobic images
5,5
Shiban, Brutting, Pauli, & Mühlberger
2015
VRET + In Vivo ET (one week later) with vs. without fear
32 in 2 groups
Spider Phobia
No group differences between people with fear reactivation prior to VR and in vivo exposure and
10,25
O
O
PH
PR
Author
Year
Treatment
Sample Size
Type of Specific Phobia
Main findings
Quality Score
Measure of success and evidence for use as predictor SR
B
PH
10
O
O
O
8
O
O
-p
Topic
No change of coping styles over the time (i. e. two years period), but better treatment results for blunting vs. monitoring
7,5
+
+
Snake Phobia
Self-efficacy as a uniformly accurate predictor of performance on tasks
7
+
+
+
O
activation
those without
Before the ET – cognitive factors 2001
60 in 4 groups
Spider Phobia
2 hours without distraction vs. 1 hour with and 1 hour without distraction
see Attentional focus guiding
No main effect of coping style, distraction nor their interaction on the short-term outcome
1993
OST
33
Spider Phobia
Muris, Merckelbach, & de Jong
1995
OST
36 women
Spider Phobia
Bandura, Adams, & Beyer
1977
Observation only vs. observation and imitation (=performance mastery experiences)
33 in 3 groups
Cote & Bouchard
2009
VRET
28
Spider Phobia
Best predictors of change in general outcomes and cardiac response: changes in perceived self-efficacy and dysfunctional beliefs; best predictor of change in behavioral avoidance: change in dysfunctional beliefs
10
lP
re
Muris, De Jong, Merckelbach, & van Zuuren
ur Jo
Self-efficacy
OST
ro of
Antony, McCabe, Leeuw, Sano, & Swinson
na
Coping Style
No substantial contribution of the coping style to short-term or long-term outcomes
Zoellner, Echiverry, & Craske
2000
2 sessions of in vivo exposure
46
Spider Phobia
Positive relationship of selfefficacy to better behavioral performance at post-treatment
7
Williams, Dooseman, & Kleinfield
1984
exposition vs. guided mastery exposition
32 in 3 groups
Driving Phobia, Acrophobia
Same effect of exposition and mastery/self-efficacy-oriented treatment regarding the duration of exposure and degree of inducement to confront threats
6,75
+
+
+
+
PR
Topic
Author
Year
Treatment
Sample Size
Type of Specific Phobia
Main findings
Quality Score
Measure of success and evidence for use as predictor SR
B
O/+
O/+
PH
PR
Mayer, Merckelbach, & Muris
2000
OST
39
Spider Phobia
Memory
Zoellner, Echiverry, & Craske
2000
2 sessions of in vivo exposure
46
Spider Phobia
41
Spider Phobia
Cortisol levels
Lass-Hennemann, & Michael
2014
OST in the morning vs. evening
lP
OST
7
+
Eyeblink startle response has a modest predictive effect, explaining 16% of the treatment effect
7
-
60 in 2 groups
Spider Phobia
Higher effectiveness of exposure therapy in the morning vs. evening; suggested underlying effect: higher endogenous cortisol levels in the morning group, enhancement of extinction memory by cortisol
12
(+)
2014
Jo
Soravia, Heinrichs, Winzeler, Fisler, Schmitt, Horn., …, & de Quervain
ur
na
1991
Better memory for the anxious response (but not the phobic stimulus) leads to better treatment success
re
Before the ET: physiological factors de Jong, Merckelbach, & Arntz
7
ro of
Perceived automaticity and irrationality of cognitions
Eyeblink startle response
No influence of self-received automaticity on treatment outcome; irrationality as predictor for treatment outcome (the more the fear is experienced as irrational, the higher the profit from the exposure therapy)
-p
rapidly; better effect of mastery (self-efficacy) model regarding restoring behavioral functioning and diminishing anxiety
Two sessions of in vivo exposurebased group therapy with vs. without Cortisol 1hr. before session
22 in 2 groups
Spider Phobia
Increased effectiveness by administrating Cortisol; significantly greater reduction in fear of spiders at follow-up, but not immediately after treatment
11
+
OST
100 youths
diverse
The presence of comorbid phobias or anxiety disorders did not affect treatment outcomes;
9,5
O
+
Before the ET: comorbid disorders Comorbid disorders
Ollendick, Öst, Reuterskiold, & Costa
2010
O
Topic
Author
Year
Treatment
Sample Size
Type of Specific Phobia
Main findings
Quality Score
Measure of success and evidence for use as predictor SR
B
PH
significant reductions in the clinical severity of other cooccurring specific phobias and related anxiety disorders through the treatment of the targeted specific phobias During the ET: emotional factors 2005
VRET
42 in 2 groups
Aviophobia
Rachman, & Levitt
1988
Diverse
74 in 4 groups
Claustrophobia
Baker, Mystkowski, Culver, Yi, Mortazavi, & Craske
2010
Two sessions of in vivo exposition
44
Acrophobia
see Heart rate
Disgust
Smits, Telch, & Randall
2002
8,75
+
Suggested relation between fear reduction and “habituation” (but not between initial levels of fear and “habituation”)
3,5
+
No consistent prediction of treatment outcome through the variables of the emotional processing theory; no support was found for initial fear activation (IFA) or within session habituation (WSH, fear subsides within sessions); measures of between session habituation (BSH, fear subsides between sessions) were predictive of short-term change, but these effects were attenuated at followup
7,75
?
O
?
-p
re
na ur 2015
Jo
Busscher, Spinhoven, & de Geus
Reductions in subjective fear ratings and HR reactions during VRET serve as significant predictors of therapy outcome
ro of
Mühlberger, Petrusek, Herrmann, & Pauli
lP
Within- and between session anxiety decrease
Two days of Cognitivebehavioural group treatment (CBGT) with VRET and in vivo exposure
79
Aviophobia
Association of within-flight habituation of HR reactivity and respiratory sinus arrhythmia reactivity and lower flight anxiety directly after the flight (shortterm), but not on long-term; low self-reported anxiety during in vivo flight exposure as the best predictor of successful long-term therapy outcome
10,5
+
30 min selfguided in vivo
27 women
Spider Phobia
Significant declines in spider fear and spider-specific disgust but not in global disgust sensitivity
7
O
+
O
O
PR
Topic
Author
Year
Treatment
Sample Size
Type of Specific Phobia
Main findings
Quality Score
Measure of success and evidence for use as predictor SR
exposure
30min. selfguided in vivo exposition
22
Blood-InjuryInjection Phobia
Olatunji, Ciesielski, Wolitzky-Taylor, Wentworth, & Viar
2012
Video exposition with or without disgust activation by showing clips of vomiting people
44 in 2 groups
Blood Injection and Injury Phobia
Olatunji, WolitzkyTaylor, Ciesielski, Armstrong, Etzel, & David
2009
Video exposition with or without disgust activation by showing disgusting pictures
Disgust evocation
Choplin, & Carter
Decline in fear and disgust across trials; fear as an independent predictor for behavior in the behavioral avoidance test, contrary to disgust (dependent on fear); initial fear during exposure as a predictor for fear and disgust in the behavioral avoidance test afterwards
8
O
O
-p
re
lP
?
Spider Phobia
Significant declines in fear and disgust through repeated exposure; reduction in disgust during exposure in the disgust activation condition remained significant after controlling for change in fear
8,75
O
O
Internet-delivered exposure (images); real vs. Hyper-real images
28 in two groups
Spider Phobia
Significant reductions in behavioral avoidance and selfreported phobic symptoms but no difference for real vs. hyperreal images, but both disgust and anxiety reduction are predictors for success
9
+
+
OST (40-90min)
30 in 2 groups
Spider Phobia
Significant decrease of fear, avoidance and disgust through exposure to disgust or fear stimuli; greater decrease in
7,25
?
?
na 2011
6,25
46 in 2 groups
ur
Jo
2015
Significant declines in disgust and especially fear across trials; decline in fear across trials; no significant effect of trial on disgust after control for change in fear; no moderation of the fear activation or reduction during exposure through global disgust sensitivity prior to exposure
ro of
2007
Matthews, Naran, & Kirkby
PH
through exposure; stronger decay for fear vs. disgust; no moderation of the level of fear activation or fear reduction during treatment through disgust levels at pretreatment
Olatunji, Smits, Connolly, Willems, & Lohr
see Disgust evocation
B
O
PR
Topic
Author
Year
Treatment
Sample Size
Type of Specific Phobia
Main findings
Quality Score
Measure of success and evidence for use as predictor SR
B
PH
+
avoidance behavior through exposure to fear stimuli Video exposition with or without disgust activation by showing disgusting pictures
46 in 2 groups
Spider Phobia
Exposure to a disgusting stimulus reduces disgust additionally to and more than fear; exposure to a feared stimulus shows the opposite pattern
8,75
+
+
de Jong, Vorage, & van den Hout
2000
OST with vs. without counterconditioning
34 in 2 groups
Spider Phobia
No additional effect of adding counterconditioning aspects to the exposure
8,5
O
O
Mühlberger, Herrmann, Wiedemann, Ellgring, & Pauli
2001
Four sessions of VRET vs. lengthy relaxation training session
40 in 2 groups
Aviophobia
Greater fear reduction through repeated VRET vs. relaxation;
10
-
Rimm, & Medeiros
1970
One session: relaxation only vs. participant modeling only vs. relaxation followed by participant modeling vs. control;
40 in 4 groups
Snake Phobia
Reduction of fear in the modeling conditions; no enhancement of the participant modeling exposure through relaxation
6
O
O
McGlynn, Moore, Lawyer, & Karg
1999
-p
-
na
lP
Relaxation
re
see Disgust
ro of
2009
Olatunji, WolitzkyTaylor, Ciesielski, Armstrong, Etzel, & David
20 in 2 groups
Snake Phobia
Reduced arousal and fear during in vivo exposures through relaxation training; relaxation working by lowering arousal throughout the course of exposure
8
-
-
20x38sec. exposition trials on 2 days (10/10) with vs. without positive valence training (at the end of day 1)
61 in 2 groups
Spider Phobia
Significant less subjective fear and less behavioral avoidance through positive valence training
6
+
+
Additional Positive Valence Training
Jo
ur
6 x 4min. in vivo exposition with vs. without relaxation training before
Dour, Brown, & Craske
During the ET: cognitive factors
2016
-
PR
Author
Year
Treatment
Sample Size
Type of Specific Phobia
Main findings
Quality Score
Measure of success and evidence for use as predictor SR
B O
Krijn, Emmelkamp, Biemond, De Wilde De Ligny, Schuemie, & Van Der Mast
2004
VRET using a head-mounted display (HMD – low presence) vs. a computer automatic virtual environment (CAVE – high presence)
37 in 3 groups
Acrophobia
Less experienced presence and anxiety during the first VRET session for early drop-outs; no relationship of presence and anxiety in treatment completers
9
O
Coping selfstatements
Krijn, Emmelkamp, Olafsson, Schuemie, & van der Mast
2007
VRET with vs. without production / activation of coping selfstatements
26 in 2 groups
Acrophobia
Reduction of anxiety of heights, avoidance of height situations and improvement of attitudes towards heights through VRET; no influence of adding selfstatements
8,5
O
CBT vs. Exposure only
Raes, Koster, Loeys, & De Raedt
2011
Behavioral vs. cognitivebehavioral OST
31 in 2 groups
Spider Phobia
Strong treatment effects and cognitive mediation of these effects in both conditions; mediation of exposure effects through cognition even without explicitly targeting those
9,5
O
O
Tardif, Therrien, & Bouchard
2019
30-minute VRET with visual vs. visual and tactical vs. visual, tactical, and haptic feedback
59 in 3 groups
Spider Phobia
Changes in self-reported selfefficacy and cognitive beliefs predicted ET success
9
+
+
OST (10 exposures, each lasting 38 seconds) focussing on affect-labelling vs. reappraisal vs. distraction
88 in 4 groups
Spider Phobia
Reduced skin conductance response in the post-test for the affect-labelling group; no differences in self-reported fear; greater reductions in fear responding by greater use of anxiety and fear words
8
O
O
ur
2012
Jo
Kircanski, Lieberman, & Craske
na
see Feedback to body sensations
lP
re
ro of
Presence
-p
Topic
Tabibnia, Liebermann, & Craske
2008
Exposure to picturs with no vs. negative vs. neutral labels
48 in 3 groups
Spider Phobia
Negative labels improved success when measured with skin conduction, but not with HR acceleration
9,5
Dee
1972
Taped implosive therapy with
58 in 5
Snake Phobia
Weak facilitating effect of instructions in reducing fear;
5,75
PH
+
?
?
?
PR
Author
Year
Treatment
Sample Size
different instructions vs. no instructions vs. control
groups
Type of Specific Phobia
Better improvement through guided threat reappraisal
7,5
+
+
Claustrophobia
Facilitating effect of guided threat reappraisal and detrimental effect of cognitive load task on fear reduction; highest fear reduction and lowest return of fear in the guided threat reappraisal condition
7,5
+
2002
6x5min. exposure only vs. with guided threat focus and reappraisal vs. with safetybehaviorutilization
46 in 3 groups
Claustrophobia
2000
6x5min. in vivo
Koch, Spates, &
lP
re
-p
ro of
Sloan, & Telch
58 in 4 groups
ur
na
Exposure only vs. with guided threat reappraisal vs. with a cognitive load distracter task vs. with both
2006
2004
B
+
Snake Phobia
Van Gerwen, Spinhoven, & Van Dyck
SR
+
36 in 3 groups
see Attentional focus guiding
Measure of success and evidence for use as predictor
6
Participant Modeling
Kamphuis, & Telch
Quality Score
Significant higher improvement of behavior and attitudes through medium or high number of performance/ induction aids (company, gradual exposure); highest generalization effect on some measures for moderate induction aids; no effect of number of facilitations on therapeutic efficacy
1974
see Safety Behavior
Main findings
retardation of fear reduction through the absence of any instructions; uncertainty about the efficacy of standardized, taped therapy
Bandura, Jeffery, & Wright
Jo
Topic
1-day behavioral (BGT) vs. 2-days cognitivebehavioral group treatment (CBGT); both conditions with information about flights, airplanes, etc.
150 in 3 groups
Aviophobia
Success of both treatment conditions; higher effectiveness of CBGT on subjective measures of fear and self-efficacy
10
+
?
Behavioral vs.
40 in 4
Phobia of small
No significant difference in the
9,5
?
O
PH
PR
Author
Year
Himle see Stimulus variation
Sample Size
Type of Specific Phobia
6,5
+
+
Return of distress through the activation of concepts unrelated to spiders (negative effect of distraction); decrease in emotional and avoidance responses between sessions through activation of concepts related to spiders
10
+
+
Claustrophobia
Facilitating effect of guided threat reappraisal and detrimental effect of cognitive load task on fear reduction; highest fear reduction and lowest return of fear in the guided threat reappraisal condition
7,5
+
2015
Image exposure only vs. with activation of concepts related vs. unrelated to spiders
66 in 3 groups
Spider Phobia
Kamphuis, & Telch
2000
6x5min. in vivo
58 in 4 groups
ur
re
na
Exposure only vs. with guided threat reappraisal vs. with a cognitive load distracter task vs. with both 30-minute selfguided exposure (1) with threatening vs. neutral words and (2) images only vs. with a cognitive load task
60 in 4 groups
Claustrophobia
Slower between-trial habituation and less fear reduction posttreatment when distracted during exposure; no effect of threat manipulation
8
-
-
OST
60 in 4 groups
Spider Phobia
No effect of distraction nor its interaction with coping style on the short-term outcome
10
O
O
2 hours without distraction vs. 1
PH
?
-p
ro of
Dethier, Bruneau, & Philippot
2001
B
Highest fear reduction in the (external) distraction condition; greatest decrease in the behavioral avoidance task and greatest increase in perceived control after treatment in the (external) distraction condition
Blood-InjuryInjection Phobia
Antony, McCabe, Leeuw, Sano, & Swinson
SR effectiveness of behavioral vs. cognitive-behavioral OST; behavioral OST perceived as more intrusive
50 in 5 groups
2004
Measure of success and evidence for use as predictor
animals and insects (spider, snake, rat/mouse, crawling insects)
Exposure only vs. with internal vs. external focus vs. external vs. internal distraction
Telch, Valentiner, Ilai, Young, Powers, & Smits
Quality Score
groups
2008
see CBT vs. Exposure only
Main findings
cognitivebehavioral OST with vs. without programmed generalization
Oliver, & Page
Jo
Attentional Focus Guiding
Treatment
lP
Topic
O
PR
Author
Year
Sample Size
Type of Specific Phobia
Quality Score
Measure of success and evidence for use as predictor SR
B
11
+
?
improvement of fear and avoidance in all conditions; less improvement through safety behavior utilization during treatment
7,5
-
-
2014
Attention Training towards positive stimuli (ATP) vs. control (ATC), both followed by OST
37 children in 2 groups
diverse
Rentz, Powers, Smits, Cougle, & Telch
2003
exposure in vivo (IV) vs. imaginal (IE) vs. active imaginal (AI)
82 in 3 groups
Cynophobia (Dog Phobia)
Deacon, Sy, Lickel, & Nelson
2010
6x5min. in vivo exposure with vs. without access to safety/coping aids during the first four exposure trials
33 in 2 groups
Claustrophobia
no reliable advantages or disadvantages of the availability of safety behavior
-p
7
O
Hood, Antony, Koerner, & Monson
2010
Exposure with vs. without safety behavior use (SBU vs. NSB)
43 in 2 groups
na
Spider Phobia
Faster approach in the SBU condition; small but significant decrease in approach distance at follow-up in the SBU condition
7,5
+
+
OST (45min.) with vs. without the use of safety gear
62 in 2 groups
Snake Phobia
Better approach during the exposure using safety behavior/gear; no differences in the follow-up behavioral avoidance test, significant improvement in fearful cognitions, subjective anxiety and distance of approach
8,5
+
O
6x max. 5min. in vivo exposure only vs. with safety behavior availability (SBA)
58 in 3 groups
Claustrophobia
Equal fear reduction in all conditions, but significantly greater improvement in selfefficacy and claustrophobic cognitions through SBU vs.
7
?
Sy, Dixon, Lickel, Nelson, & Deacon
lP
ur 2008
Jo
Milosevic, & Radomsky
2011
significantly greater reductions in danger expectancies and improved attention bias towards positive stimuli, but no differences in the clinician, parent or child-rated clinical outcomes
re
During the ET: behavioral factors Safety Behavior
Main findings
PH
PR
hour with and 1 hour without distraction
see Coping style
Waters, Farrell, Zimmer-Gembeck, Milliner, Tiralongo, Donovan, McConnell, Bradley, Mogg, & Ollendick
Treatment
ro of
Topic
?
-
Topic
Author
Year
Treatment
Sample Size
Type of Specific Phobia
vs. utilization (SBU) 46 in 3 groups
Claustrophobia
Wolitzky, & Telch
2009
6x6min. in vivo exposure with vs. without oppositional actions vs. placebo (pulsed audio-photic stimulation) vs. control
88 in 4 groups
Acrophobia
O’Sullivan & Gilner
1976
OST: 2 hours without distraction vs. 1 hour with and 1 hour without distraction
40 women in 4 groups
2002
Bandarian-Balooch, Neumann, & Boschen
2015
Shiban, Brütting, Pauli, & Mühlberger
2015a
B
7,5
-
-
10
+
PH
?
-p
Better fear extinction and generalization through the use of oppositional actions during exposure
Significant contribution of the perceived role consonance between the subject and the model to behavior change
4,5
+
46 in 4 groups
Spider Phobia
Return of fear in a new context in the follow up (1 week later); return of fear independent from perceptions of safety, danger, control and predictability
9
+
+
OST in one vs. three contexts
46 in 3 groups
Spider Phobia
One-context participants showed renewal of fear (behavioral, physiological and subjective), while this was attenuated in three contexts
8,5
+
+
+
VRET after vs. without fear reactivation with a live spider
32 in 2 groups
Spider Phobia
Long-term reduction of spider fear in both groups regardless of the fear reactivation
10,25
O
O
O
OST with different treatment contexts
ur
Mystkowski, Craske, & Echiverri
Jo
Context variation
SR
Snake Phobia
lP
see Motivation
Weakened effect of between-trial habituation through safetybehavior utilization; significantly more fear post-treatment and follow-up for the utilized safetybehavior condition
ro of
6x5min. exposure only vs. with guided threat focus and reappraisal vs. with safetybehaviorutilization
re
Sex of therapist
Measure of success and evidence for use as predictor
exposure only
2002
see CBT vs. Exposure only
Quality Score
na
Sloan, & Telch
Main findings
PR
Year
Treatment
Sample Size
Type of Specific Phobia
Quality Score
Measure of success and evidence for use as predictor SR
B +
PH
Shiban, Pauli, & Mühlberger
2013
4x 5 minuten VRET
40 in 2 groups
Spider Phobia
Extinction in multiple contexts was able to significantly reduce renewal compared to extinction in a single context
9,5
+
Vansteenwegen, Vervliet, Iberico, Baeyens, Van den Bergh, & Hermans
2007
Video exposition in one vs. three contexts
52 in 3 groups
Spider Phobia
Significant reduction of fear through extinction; generalization of extinction in the multiple but not in the single extinction group
6,5
+
Vansteenwegen, Vervliet, Hermans, Thewissen, & Eelen
2007
Three sessions of two hours of group in vivo exposure
26 in 2 groups
Spider Phobia
Enhancement of efficiency of exposure treatment in the long term through conducting treatment and tests in different contexts
7,5
+
+
+
Rodriguez, Craske, Mineka, & Hladek
1999
In vivo exposure
65 in 4 groups
Spider Phobia
No influence of context or stimulus on return of fear
9,5
O
O
O
2015
4x 5 minuten VRET
Attenuation of return of fear by multiple context exposure in VR short-term but not long-term;
11
O/+
O/+
9,5
O
O
lP 38 in 4 groups
Spider Phobia
na
Shiban, Schelhorn, Pauli, & Mühlberger
long-term effect of fear attenuation only in the multi stimuli single context group; higher benefit in the multiple stimuli condition in the behavioral avoidance test short- and longterm; no superiority of the combined multiple stimuli and contexts condition found
ur Jo
Koch, Spates, & Himle see CBT vs. Exposure only
+
re
see Trait anxiety, Length of the session, Recovery of phobic cognitions
Stimulus variation
Main findings
ro of
Context and stimulus variation
Author
-p
Topic
2004
Behavioral vs. cognitivebehavioral OST with vs. without programmed generalization
40 in 4 groups
Phobia of small animals and insects (spider, snake, rat/mouse, crawling insects)
No added effect through programmed generalization
PR
Year
Treatment
Sample Size
Type of Specific Phobia
Quality Score
Measure of success and evidence for use as predictor SR
B
One vs. five session(s) applied tension vs. one session tension only
30 in 3 groups
Blood Phobia
Significant improvement in all treatment conditions for shortand long-term; treatment of choice: one-session applied tension or tension only
11,5
O
O
Öst, L.-G., Brandberg, M., & Alm, T.
1997
One vs. five session(s) of exposure and cognitive restructuring (3hrs. massed vs. 6hrs. gradual treatment)
28 in 2 groups
Aviophobia
No differences between the conditions
9,5
O
O
Öst, Alm, Brandberg, & Breitholtz
2001
One vs. five session(s) of exposure vs. five sessions of cognitive therapy
46 in 4 groups
Claustrophobia
10
O
O
Vika, Skaret, Raadal, Öst, & Kvale
2009
One vs. five sessions of CBT by dentists (sensu Öst)
55 in 2 groups
Fraser, Kirkby, Daniels, Gilroy, & Montgomery
2001
ro of
1996
Significant treatment effect of one and five sessions of CBT performed by specially trained dentists; less anxiety for five sessions at the one-year follow up
10,25
?
?
30 in 2 groups
Significant treatment effect in both conditions; no significant differences between the threeand six-session groups; competence on the program already reached after three sessions (also in the six-sessions group)
10
O
O
na
2011
Computerassisted fear of flying treatment (CAFFT)
37
Aviophobia
The fewer the number of attended sessions, the faster the rate of change; significant correlation of HR variability and within-session rates of change (WSRC), faster improvement of people with higher HR variability
7,25
+
1971
6x 30min. in vivo
40 in 4
Snake Phobia
Same effect of the length of 0 vs. 30 vs. 45 minutes, better than 15
5,5
-
ur
3 vs. 6 sessions of CAVE Expo
PH
O
-p Intra-Oral Injection Phobia
see Heart rate
Miller, & Levis
Treatment success through all three conditions; no differences
Spider Phobia
Jo
Bornas, Gelabert, Llabres, Balle, & Tortela-Feliu
Length of the
Main findings
Hellstrom, Fellenius, & Öst
lP
Number of sessions
Author
re
Topic
+
-
PR
Author
Year
session
Treatment
Sample Size
exposition
groups
Type of Specific Phobia
Quality Score
Measure of success and evidence for use as predictor SR
B
PH
O
O
-
-
-
+
?
+
-
-
?
+
+
?
minutes; possible explanation (speculative!): reaching the highest amount of fear without time for tackling the fear and coping strategies
Rachman, & Lopatka
1988
One-session exposition with therapeutic modelling (undervs. full- vs. overlearning)
39 in 3 goups
Snake or Spider Phobia
Rodriguez, Craske, Mineka, & Hladek
1999
In vivo exposure
65 in 4 groups
Spider Phobia
Massed vs. expandingspaced ET (4 sessions in 1 day vs. 4 in 4 weeks)
31 in 2 groups
No benefit of extending the ET after reaching a level of no subjective fear
6,5
Longer treatment duration predicted higher chance of return of fear
Rowe, & Craske
1998
Computer assistance
Öst, Stridh, & Wolf
1998
Spider Phobia
Similar good effect of massed (ME) and expanding-spaced (ESE) exposure; significantly more habituation across exposure trials in the ME vs. ESE group; return of fear in the ME, but not in the ESE group
na
lP
Massed vs. expandingspaced exposure
re
-p
see Trait anxiety, Context and stimulus variation, Recovery of phobic cognitions
Main findings
ro of
Topic
103 in 4 groups
Spider Phobia
Significantly better effect through individual in vivo vs. group in vivo treatment vs. video treatment
Imaginal Exposure Therapy (IET) vs. VRET with vs. without physiological feedback
30 in 3 groups
Aviophobia
Higher effectiveness of VRGET vs. IET; possibly added efficacy through physiological feedback
Jo
ur
Self-help manual vs. video vs. group vs. individual exposure treatment
8,75
Wiederhold, Jang, Gevirtz, Kim, Kim, & Wiederhold
see Feedback to body reactions
2002
VR-Expo
9,25
PR
Author
Year
Treatment
Sample Size
Type of Specific Phobia
Main findings
Quality Score
Measure of success and evidence for use as predictor SR
B
2001
VRET with vs. without physiological feedback vs. imagery conditions
30 in 3 groups
Aviophobia
VR patients (irrespective of feedback) improved considerably more than imagery patients
9,75
+
+
Tortella-Feliu, Botella, Llabres, Breton-Lopez, del Amo, Banos, & Gelabert
2011
VRET vs. computer-aided exposure with (CAE-T) vs. without (CAE-SA) therapist’s assistance through exposure
60 in 3 groups
Aviophobia
Significant improvement in all conditions; no differences between groups
10
O
O
Andersson, G., Waara, J., Jonsson, U., Malmaeus, F., Carlbring, P., & Öst, L.-G
2013
OST vs. guided Internet-delivered self-help
30 in 2 groups
Snake phobia
?
+
Andersson, Waara, Jonsson, Malmeus, Carlbring, & Öst
2009
OST vs. guided Internet-delivered self-help
24 in 2 groups
Botella, Pérez-Ara, Bretón-López, Quero, GarcíaPalacios, & Banos
2016
one session of in vivo (IVE) vs. augmented reality exposure (ARE)
St-Jacques, Bouchard, & Bélanger see Motivation
2010
-p
re
9
?
-
50 in 2 groups
Small Animal Phobia
Improvement in both conditions; IVE more useful than ARE (posttreatment, but not at follow-up); ARE considered as less aversive, high acceptance by patients
12
-/?
+/?
VRET vs. VRET and exposure in vivo
10
Acrophobia
Effectiveness of both conditions; VRET effective, even with relatively cheap hard- and software on stand-alone computers currently on the market
2,5
O
O
Exposure, in vivo only vs. VR plus in vivo
31 children (8-15 years) in 2 groups
Spider Phobia
No increase in motivation and success through the use of VRET
9,25
O
lP
Good improvement in both conditions; better improvement for in vivo exposure, partially significant
na 2001
Improvement in both conditions; self-report shows no group effect; sig. interaction for BAT in favor of OST
Spider Phobia
ur
Emmelkamp, Bruynzeel, Drost, & van der Mast
ro of
Wiederhold, Gevirtz, & Spira
Jo
Topic
PH
PR
Topic
Author
Year
Treatment
Sample Size
Type of Specific Phobia
Main findings
Measure of success and evidence for use as predictor SR
B
9,5
-
-
2001
Prolonged singlesession treatment of live graded exposure (LGE) vs. computer-aided vicarious exposure (CAVE)
40 in 3 groups
Spider Phobia
Michaliszyn, Marchand, Bouchard, Martel, & Poirier-Bisson
2010
VRET vs. in vivo exposure
43 in 3 groups
Spider Phobia
Significant improvements in both groups; greater improvement on the Spider Beliefs Questionnaire for in vivo exposure
11
-
?
Krijn, Emmelkamp, Biemond, de Wilde de Ligny, Schuemie, & van der Mast
2004
VRET using a head-mounted display (HMD – low presence) vs. a computer automatic virtual environment (CAVE – high presence)
37 in 3 groups
Acrophobia
no relationship of presence and anxiety in treatment completers ; no effect of either using HMD or CAVE VRET
9
O
O
Motion simulation
Mühlberger, Wiedemann, & Pauli
2005
VRET with vs. without motion simulation
25 in 2 groups
Aviophobia
Stronger fear during VRET and slower habituation in the motion vs. no-motion group, but no differences in treatment outcome
8,5
O
Additional manipulation of the stimulus
Smith, Kirkby, Montgomery, & Daniels
1997
3x40minute computerdelivered treatment with relevant vs. irrelevant exposure, relevant with vs. without feedback
38 in 3 groups
Spider Phobia
Significant phobic improvement in all conditions; no significant effect of either relevance of exposure or manipulation of the onscreen feedback
8
O
6 exposure trials of max. two minutes
80 in 4 groups
Spider Phobia
No effect of perceived emotional control in general nor control over the duration of exposure on the fear levels, fear reduction, or fear prediction accuracy;
5
O
-p
PH
re
lP
na
ur
Jo 1991
ro of
Heading, Kirkby, Martin, Daniels, Gilroy, & Menzies
Craske, Bunt, Rapee, & Barlow
Significant improvement for the LGE group; no difference between the CAVE and waiting list control group (exception: subjective distress, little support for single-session CAVE treatment)
Quality Score
O
PR
Topic
Author
Year
Treatment
Sample Size
Type of Specific Phobia
Main findings
Quality Score
Measure of success and evidence for use as predictor SR
9
+
No identification of stable predictors for short- or long-term success; only significant predictors in single studies, seen as chance findings
10
O
O
Aviophobia
Patients with high HR variability improve more; HR variability only in combination with HR entropy as a significant predictor
10
+
+
Claustrophobia
Higher HR at the beginning of exposure as a predictor for better treatment outcome; HR correlates more with success than subjective measures
8
+
2016
4x 5min. VRET with pretreatment fear reaction activation by specific perceptual cues (C) vs. conceptual fearrelated information (I) vs. combination of both (CI)
38 in 3 groups
Claustrophobia
Hellstrom, & Öst
1996
OST vs. fivesession therapistguided exposure vs. self-directed exposure
138 (from four other studies)
Spider Phobia, Blood Phobia, Injection Phobia
Bornas, Gelabert, Llabres, Balle, &Tortella-Feliu
2007
Computerassisted fear of flying treatment (CAFFT)
33
Alpers, & Sell
2008
6x 30min. in vivo exposition
10
re
lP
na ur 2011
Jo
Bornas, Gelabert, Llabres, Balle, & Tortella-Feliu
Computerassisted fear of flying treatment (CAFFT)
37
Aviophobia
Significant correlation of HR variability and within-session rates of change (WSRC), faster improvement of people with higher HR variability
7,25
+
Cognitivebehavioural group treatment (CBGT)
50
Aviophobia
HR and parasympathetic activity is shown as a predictor for patients with high (but not for those with low) anxiety sensitivity
9,5
+
see Numbers of sessions
Busscher, Spinhoven, van Gerwen, & de Geus
2013
PH +
-p
During the ET: physiological factors Heart rate (HR)
Higher experienced initial selfreported fear through C; no significant enhancement through the combination (CI); higher fear habituation for C; differing physiological parameters in the groups, differing decreases in heart rate for claustrophobics throughout the conditions
ro of
Shiban, Peperkorn, Alpers, Pauli, & Mühlberger
B
PR
Topic
Author
Year
Treatment
Sample Size
Type of Specific Phobia
Main findings
Quality Score
Measure of success and evidence for use as predictor SR
Self- vs. therapistadministered CAFFT vs. VRET
20 in 2 groups
Aviophobia
Combination of HR variability and HR entropy as a predictor for success of treatment; lower tonic HR in the successful group; stronger decrease of the HR during the phasic level in the successful group (higher HR variability)
10,5
Benoit Allen, Allen, Austin, Waldron, & Ollendick
2015
OST
98 children
diverse
No change of cardiovascular reactivity through ET; no predictive power of cardiovascular reactivity
9,5
-
Busscher, Spinhoven, & de Geus
2015
Two days of Cognitivebehavioural group treatment (CBGT)
79
Aviophobia
Association of within-flight habituation of HR reactivity and respiratory sinus arrhythmia reactivity and lower flight anxiety directly after the flight (shortterm), but not on long-term
10,5
?
1995
Two sessions in vivo exposition plus relaxation vs. disconfirmation of misappraisals of bodily sensations
70 in 2 groups (49 snake / spider phobics, 21 claustrophobics)
Claustrophobia, Snake/Spider Phobia
Equal effect on basic beliefs about arousal sensations; improvement of claustrophobic fear reduction through disconfirmation of misappraisals of bodily sensations; little effect on snake/spider phobia; no generalization to nontargeted phobic situations or over time
9
-
6x5min. selfguided in vivo exposure only (EOC) vs. with heart rate feedback (HRF) vs. with paced tone control (PTC)
54 in 3 groups
Claustrophobia
Significant greater fear reduction and lower fear levels posttreatment through HRF; no higher levels of initial fear activation
7,75
+
Imaginal Exposure Therapy (IET) vs. VRET with vs. without
30 in 3 groups
Aviophobia
Higher effectiveness of VRET vs. IET; possibly higher efficacy of VRET through added physiological feedback
9,25
+
Telch, Valentiner, Ilai, Petruzzi, & Hehmsoth
2000
Wiederhold, Jang, Gevirtz, Kim, Kim, & Wiederhold see Computer
2002
-
-
+
+
PR +
-p re
lP
ur
na
Craske, Mohlman, Yi, Glover, & Valeri
ro of
2012
Jo
Feedback to body reactions
PH
+
Bornas, Riera del Amo, Tortella-Feliu, & Llabres
see Within and between session anxiety decrease
B
?
Topic
Author
Year
assistance
Treatment
Sample Size
Type of Specific Phobia
Main findings
Quality Score
Measure of success and evidence for use as predictor SR
B
9
-
-
+
PH
PR
physiological feedback VRET 2019
30-minute VRET with visual vs. visual and tactical vs. visual, tactical, and haptic feedback
59 in 3 groups
Spider Phobia
see CBT vs. Exposure only
No influence of the type of feedback on the success of VRET
ro of
Tardif, Therrien, & Bouchard
Mystkowski, Mineka, Vernon, & Zinbarg
2003
OST with vs. without caffeine
43 in 2 groups
Spider Phobia
Greater return of fear for a different caffeine state during treatment and follow-up
5,5
+
Yohimbine hycdrochloride (YOH)
Meyerbroeker, Powers, van Stegeren, & Emmelkamp
2012
VRET with vs. without YOH before exposure
45 in 2 groups
Aviophobia
No enhancing effect of the manipulation of the noradrenaline level through YOH in the used dosage (10mg)
10,5
O
Quetiapine
Diemer, Domschke, Mühlberger, Winter, Zavorotnyy, Notzon., …, & Zwanzger
2013
VRET with vs. without Quetiapine 8hrs. before exposure
58 in 2 groups
Spider Phobia
Quetiapine shows significant anxiolytic effects, but only on physiological ratings
11,5
O
+
Benzodiazepine
Wilhelm, & Roth
1997
OST with vs. without alprazolam before exposure
28 women in 2 groups
Aviophobia
Alprazolam increases physiological activation under acute stress conditions and hinders therapeutic effects of ET
8,25
-
-
Oxytocin
Acheson, Feifel, Kamenski, Mckinney, & Risbrough
2015
OST with vs. without pretreatment intranasal Oxytocine administration
23 in 2 groups
Spider Phobia
Self-report shows impeded treatment response; no significant effect on behavioral measures; less confidence in the treatment before treatment and lower ratings of therapeutic alliance for the Oxytocine
11
-
Naltrexone
Merluzzi, Taylor, Boltwood, & Gotestam
1991
Graded exposure with vs. without Naltrexone
30 in 2 groups
Spider Phobia
No differences concerning selfefficacy and cognitions, but higher anxiety in Naltrexone group
10
?
Arntz, Merckelbach,
1993
OST 2 hours
48 in 3
Spider Phobia
Hindering effect on ET through the induction of Naltrexone;
11,5
O
re
lP
na
ur
Jo
-p
Caffeine state
O
-
-
-
O
Topic
Author
Year
Treatment
Sample Size
& de Jong
Type of Specific Phobia
groups
Main findings
Quality Score
Measure of success and evidence for use as predictor SR
B
11
O
O
Return of phobic cognitions is associated with less successful outcome (increased return of fear)
-
-
+
PH
greater avoidance relapse through Naltrexone; no influence on emotional, cognitive and physiological measures
After the ET: emotional factors Rihm, Sollberger, Soravia, & Rasch
2016
2 in vivo expositions followed by 90min. sleep with vs. without odor vs. awake control group
54 in 3 groups
Spider Phobia
1999
in vivo exposure
65 in 4 groups
Spider Phobia
Rodriguez, Craske, Mineka, & Hladek
12
Spider Phobia
Individual differences in the magnitude of visual cortex activations shortly after therapy as a predictor for long-term success; stable reorganization of neural responses to initially feared stimuli in successful therapy
7,5
+
lP 2012
OST
Jo
ur
Hauner, Mineka, Voss, & Paller
na
After the ET: physiological factors Neural activation
9,5
re
see Trait anxiety, Context and stimulus variation, Length of the session
-p
After the ET: cognitive factors Recovery of phobic cognitions
No enhanced effect of sleep after exposition through presentation of a contextual odor
ro of
Conditioned odor
Schienle, Schafer, Hermann, Rohrmann, & Vaitl
2007
OST (ca. 4 hours)
14
Spider Phobia
Correlation between the reduction of subjective somatic panic symptoms and decrease of right amygdala activity in fMRI
9
+
Landowska, Roberts, Eachus, & Barrett
2018
VRET
14
Acrophobia
No correlation between subjective fear ratings and neural activation measured with fNRIS
6,75
-
-
PR
Topic
Author
Year
Treatment
Sample Size
Type of Specific Phobia
Main findings
Quality Score
Measure of success and evidence for use as predictor SR
Methylene blue
VRET (OST), afterwards 90min. sleep vs. awakefulness
40 in 2 groups
Spider Phobia
90 minutes of sleep lead to less anxiety in a post-therapy BAT and less catastrophic spiderrelated cognitions; the more stage 2 sleep, the better
9,25
+
Pace-Scott, Verga, Bennett, & Spencer
2012
14x1min. video exposure in the morning vs. in the evening, with vs. without sleep before delaymeasurement
66 in 4 groups
Spider Phobia
extinction augmentation and extinction generalization in the sleep-condition
6,5
+
Smits, Rosenfield, Otto, Powers, Hofmann, Telch, …, & Tart
2013
2x 30min. VRET with vs. without D-Cycloserine post session
29 in 2 groups
Acrophobia
D-Cycloserine appears to enhance the benefits of exposure treatment when applied after a successful session, but it seems to have detrimental effects when administered after inadequate/unsuccessful exposure sessions.
9,5
+
Byrne, Rapee, Richardson, Malhi, Jones, & Hudson
2015
OST with vs. without DCycloserine before the session
35 children (6-14years) in 2 groups
Dog and Spider Phobia
Less avoidance and less increase in fear through DCycloserine for a new stimulus in a new context; possible enhancement of ET and especially generalization in children and youths
8,5
Tart, Handelsman, Deboer, Rosenfield, Pollack, Hofmann, …, & Smits
2013
Telch, Bruchey, Rosenfield, Cobb, Smits, Pahl, & Gonzalez-Lima
PH
PR
+
+
-p re
na
lP
2014
ro of
2014
+
2x 30min. VRET with vs. without D-Cycloserine post session
29 in 2 groups
Acrophobia
No augmented efficacy of ET through the application of postsession D-Cycloserine
10
O
6x 5min. exposure trials with vs. without Methylene blue post session
42 in 2 groups
Claustrophobia
Methylene blue enhances memory and hinders return of fear after a successful ET, but has detrimental effects after an unsuccessful ET
11
+
ur
D-Cycloserine
Kleim, Wilhelm, Temp, Margraf, Wiederhold, & Rasch
Jo
Sleep
B
+
O
Quality Score: In case of differences between the two judges, the mean of the two scores is reported; measure of success: SR = Self report, B = behavioral measure, PH = physiological measure, PR = professional rating; Evidence for use as factor: + = good evidence for positive influence; - = good evidence for negative influence; o = evidence that it is not applicable as a predictor; ?= no conclusive evidence; OST: One Session Therapy sensu ÖST; ET: Exposure Therapy; fMRI: functional magnet resonance imaging; fNRIS: functional Near-Infrared Spectroscopy.
Table 3 Every researched factor and its current state in respect to its influence on the success of ET Factor Comment Factors that seem to have an influence on the success of ET Less trait anxiety leads to better ET results
Motivation
More motivation leads to better ET results
Self-efficacy
More self-efficacy leads to better ET results
Cortisol levels
Higher cortisol levels improve learning in ET
Disgust evocation
Evoking disgust additionally to anxiety improves ET results Relaxation hinders ET effectiveness
Relaxation
Addressing cognitive changes leads to better ET results
Adding cognitive parts Context variation
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Using different contexts leads to better ET results
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Trait anxiety
Heart rate
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HR plays a role, but it is unclear which measure best to use (variability, entropy, tonic vs. phasic HR…)
Sleeping after a successful ET leads to better results
Memory enhancing medication
Taking memory enhancing drugs (D-Cycloserine) leads to better long-term success
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Sleep
Potential factors that could have an influence on the success of ET (more research needed)
Eyeblink startle response
Less startle response after specific stimulus leads to better ET results Unclear if heightened feelings of disgust are independent of anxiety and if they play a role in ET success
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Disgust
Better memory leads to better ET results
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Memory
Higher perceived irrationality (but not automaticity) of thoughts leads to better ET results
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Automaticity/Irrationality of thoughts
Positive Valence Training seems to improve ET success
Positive Valence Training
Unclear relationship between showing safety behavior and ET success
Safety behavior
Female therapists lead to better success Massed ET leads to less ET success
Sex of therapist
Feedbacks leads to better ET success ET success does not generalize over different caffeine states
Massed ET feedback of heart rate
Medication hinders success of ET
Caffeine state Anxiety differing medication (given during ET) Return of phobic conditions
A return of phobic cognitions leads to less success of ET Higher visual cortex activation after ET leads to better long-term success
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Visual cortex activation
Factors that have no influence on the success of ET
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Comorbidity Within-session habituation/between-session habituation
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Factors that probably have no influence (more research needed)
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Fear reactivation coping style stimulus variation number of sessions (no improvement by more sessions) length of sessions (no improvement by longer ET sessions) computer assistance (no improvement over normal ET)
Presence Coping self-statements
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Attentional focus guiding Motion simulation
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Conditioned odor
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ET: Exposure Therapy; HR: Heart rate
PII:
S0149-7634(19)30404-X
DOI:
https://doi.org/10.1016/j.neubiorev.2019.12.009
Reference:
NBR 3622
To appear in:
Neuroscience and Biobehavioral Reviews
Received Date:
29 May 2019
Revised Date:
26 November 2019
Accepted Date:
6 December 2019
Please cite this article as: B¨ohnlein J, Altegoer L, Muck NK, Roesmann K, Redlich R, Dannlowski U, Leehr EJ, Factors influencing the success of exposure therapy for specific phobia: A systematic review, Neuroscience and Biobehavioral Reviews (2019), doi: https://doi.org/10.1016/j.neubiorev.2019.12.009
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier.
Factors influencing the success of exposure therapy for specific phobia: A systematic review. Joscha Böhnlein1,*, Luisa Altegoer1, Nina Kristin Muck1, Kati Roesmann², Ronny Redlich1, Udo Dannlowski1, & Elisabeth J. Leehr1.
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Department of Psychiatry, University of Münster, Germany Institute for Biomagnetism and Biosignalanalysis, University of Münster, Germany
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Running Title: Influencing factors on Exposure Therapy in Specific Phobia
Abstract Word count: 172
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Most researched factors have not been studied enough to give concrete recommendations Factors enhancing inhibitory learning experience increase success most These are having a high self-efficacy, low trait anxiety, addressing disgust in the therapy, focusing on changing cognitions, changing contexts between ET sessions, focusing on heart rate changes and administering D-Cycloserine
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Article word count: 8436
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Highlights
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Number of tables: 3
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Joscha Böhnlein Department of Psychiatry University of Münster Albert-Schweitzer-Campus 1, Building A9 48149 Münster; Germany, Phone: +49251-83-51861 Email: [email protected]
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*Corresponding author:
ABSTRACT Although Exposure Therapy (ET) is the first-line treatment of Specific Phobia (SP), there is no clear consensus on which factors influence its success, and thus on how to conduct it
most efficiently. This review summarizes the current state of research regarding this topic. N=111 studies were in accordance with our eligibility criteria: participants had at least symptoms of SP, the intervention was ET and the study investigated a factor influencing its success. Best evidence for positive effects was found for low trait anxiety, high motivation and high self-efficacy before the ET, high cortisol levels and heart rate variation, evoking disgust additionally to anxiety, avoiding relaxation, focusing on cognitive changes, context variation, sleep, and memory-enhancing drugs. These factors may be conceptualized as modulating different aspects of learning as suggested in current models of ET that focus on
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inhibitory learning mechanisms. Limitations lie in the great heterogeneity concerning operationalization of factors and success. Based on these findings, we make suggestions for
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improvements in ET conduction and which factors should be researched in the future.
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Keywords: Specific Phobia, Exposure Therapy, Treatment outcome, Psychotherapy
1. INTRODUCTION Specific Phobias (SP) are some of the most prevalent psychiatric disorders, with adverse effects on patients’ everyday lives. Gustavsson (2011) numbers the total cost of anxiety disorders with over €70 billion. While anxiety disorders are the largest group of psychiatric disorders with a 12-month prevalence of 14.0%, SP is the most prevalent subgroup of these. With a 12-month prevalence of 6,4%, 22.7 million people are affected in Europe (Wittchen et al., 2011). Additionally, SP represents a risk factor for other psychiatric disorders: Patients with SP show a twofold risk of developing any anxiety disorder, depression, and any
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somatoform disorder (Trumpf et al., 2010). Subclinical anxiety is even more prevalent: Curtis, Magee, Eaton, Wittchen and Kessler (1998) show that 49,5% of a large US-American sample report a “lifetime occurrence of an unreasonably strong fear” of a specific stimulus.
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Current models of SP explain its development through different processes of conditioning and learning like classical and operant conditioning and model learning. This has been most
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prominently described by Rachmann (1977), and is still relevant to this day (Duits et al.,
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2015; Hamm, 2009; Lissek et al., 2005; Mineka and Zinbarg, 2006; Schweckendiek et al., 2011). Thus, a fear memory is formed (Foa and Kozak, 1986). In this fear structure, the feared (but harmless) stimulus is connected to the concepts of danger and corresponding
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reactions like panic, flight and physiological reactions like activity of the sympathetic nervous system. Extinction based-treatments such as Exposure Therapy (ET) were developed to
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lessen the effect of the fear structure by either replacing (Foa and Kozak, 1986), competing with (Foa and McNally, 1996) or inhibiting (Craske et al., 2014) it.
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Exposure Therapy (ET) is the latest of a group of therapy forms that evolved from Wolpe’s Systematic Desensitization (1954) in the early fifties of the last century. It has become the first-choice therapy form not only for specific phobia but for many different anxiety disorders (Bandelow et al., 2014) and, in slightly adjusted form, for other diseases like obsessivecompulsive disorder (Öst et al., 2015). Investigating the success of ET in patients with different anxiety disorders, Bandelow and colleagues (2015) find considerable pre-post effect sizes of d = 1.3. Modern variations of ET include Virtual Reality ET (VRET), which shows
comparable effect sizes in meta analyses and systematic reviews (Botella et al., 2017; Opriş et al., 2012). It is recommended as the first-choice treatment of specific phobias (Bandelow et al., 2014). But even though ET is seen as the most effective way to treat SP, it is not without its problems: In a systematic review for anxiety disorders in children and adolescents (excluding SP), James and colleagues (2015) call ET as the central intervention of a CognitiveBehavioral Therapy (CBT) “an effective treatment for childhood and adolescent anxiety
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disorders”. However, they could not show superiority to other treatments such as medication or other forms of psychotherapy, especially at follow-up. Additionally, about a fifth of anxiety disorders patients dropped out prematurely (James et al., 2015). Furthermore, a third of treatment completers have to be classified as non-responders, irrespective of the specific
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type of therapy (Craske and Mystkowski, 2006; Fernandez et al., 2015; Scholten et al., 2013; Taylor et al., 2012). Additionally, the underlying mechanisms of ET are not yet well
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understood and are subject of discussion (e.g. Craske et al., 2014; Rupp et al., 2017). Even
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seemingly basic aspects like the necessary length of a successful ET are not yet clear (Bandelow et al., 2014). Overall, factors discriminating a successful from an unsuccessful ET-outcome are controversially discussed (Lueken et al., 2016; Taylor et al., 2012), and
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there is a high degree of heterogeneity in proposed and executed minutiae. Some reviews have tackled the need for an overview of factors that contribute to the success (or the lack
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thereof) of ET, both within the patient as well as in the conduction of the ET: For example, Lueken and colleagues (2016) presented potential neurobiological markers predicting the
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success of ET in all subtypes of anxiety disorders. They show that there is evidence for the 5-HTTLPR/rs25531 variant as a predictive genetic marker, as well as anterior cingulate cortex (ACC) activity as a functional neuroimaging marker and cardiovascular flexibility as a third marker. Additionally, they emphasize the high methodological heterogeneity of included studies and call for more rigorous, standardized studies. To sum up, ET is the first-choice treatment for SP, but it is neither as effective nor as well understood as one would hope. In the following review, we want to help both practitioners as
well as scientists to improve the effectiveness and our understanding of ET. We will expand on these existing reviews by giving an overview over possible influencing factors on the success (or lack thereof) of ET in SP. We take the perspective that a successful ET can be seen in changed behavior (e.g. in a Behavioral Avoidance Test, BAT), changed cognitions (e.g. in a questionnaire), changed subjective fear (e.g. in lower Subjective Units of Distress, SUDs) or changed physiology (e.g. different heart rates when confronted with the feared stimulus). Ideally, a successful ET leads to changes in every one of these categories. Additionally, modern cognitive-behavioral models of exposure therapy like the “inhibitory
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learning” model by Craske and colleagues (Craske et al., 2008) state that ET works by enabling the patient to learn to inhibit their initial reaction to the feared stimulus. We therefore see these changes as a result of continuous learning processes that may take place before,
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during and after the ET itself. Hence, we divided potential influencing factors by their time of influence, i.e. if they play a part before, during or after the ET itself.
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The aim of this review is twofold: Firstly, we try to show concisely which of these factors or
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these categories are highly relevant when planning and conducting an ET for patients with specific phobia, which factors have a lower relevance and for which factors the verdict is still out. This would help optimize the treatment and thus response rates. Secondly, we aim to
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provide a current state of research in order to identify factors that should be investigated in
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2. METHODS This systematic review was conducted according to the PRISMA guidelines (Liberatî et al., 2009). To be eligible for inclusion in this review, articles had to adhere to the following inclusion PICOS (Participants, Intervention, Comparator, Outcome, Study Design) criteria (Liberatî et al., 2009):
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(a) Participants had to be humans affected with specific phobia or significant symptoms of specific phobia. Included studies had (1) a sample of patients with specific phobia according to objective and standardized measures or interviews according to DSM-III, DSM-III-R, DSMIV or ICD-10 criteria (spider phobia, SP). The criteria changed very little between the different
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versions of the DSM and ICD, especially concerning the core criteria of anxiety and avoidance of a specific object, distress, and realization by the individual that the fear is
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excessive. Hence, we did not make a difference between these classification systems. Furthermore, included studies used (2) a sample of participants with specific phobia
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according to self-report measures (e.g. Spider Phobia Questionnaire or Acrophobia Questionnaire), or (3) with symptoms of a specific phobia that did not fulfill the full criteria of a
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clinical diagnosis (e.g. significant fear and avoidance of a feared stimulus in a BAT) (subclinical specific phobia, sub-SP). Studies with less than 10 participants per experimental
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condition were excluded.
(b) The Intervention had to be any form of exposure therapy (in vivo or in virtual reality; those
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two forms will only be differentiated when it is the factor of interest). “Exposure therapy” is defined as any form of presenting the feared stimulus to the patient with the specific intent of reducing the emotional, cognitive, and somatic reaction to said stimulus. To ensure relevance of the presented results for ET as it is conducted today, studies conducting exposure with the instructed use of coping skills were excluded (e.g. systematic desensitization, see Rupp et al., 2017). An exception is made for studies that examine the effect of said coping skills and compare a therapy with versus a therapy without such skills.
Additionally, studies that presented the stimulus only in sensu were discarded due to the missing ability to standardize presentation. (c) Regarding the used comparator, only studies were included that measured within subject variables concerning their potential as a predictor of success or that had two groups that both underwent some form of ET that differed in one key aspect. (d) The outcome had to be a direct measure of treatment success (measured by questionnaires, behavioral outcome measures or standardized interviews), pre and post
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intervention, and the influence of the investigated factor. (e) Concerning study design, included studies are controlled experiments in a laboratory or a naturalistic environment as long as the design is experimental in nature (i.e. a ET is part of
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the study and not of another treatment). Excluded are case studies and reviews. As independent variable, we required a potential influencing factor or factors; the dependent
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variable was treatment success through exposure therapy.
We searched the databases PubMed and PsychInfo for studies published in peer-reviewed
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journals up to May 13th 2019 and performed hand searches in the reference lists of included studies. We used MeSH-Terms to search for studies with human subjects concerning
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specific phobia and exposure. Included studies had to be written in English, German, French or Spanish. We did not limit the age of the subjects.
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The PubMed Search Term was as follows:
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("phobic disorders"[MeSH Terms] NOT ("phobia, social"[MeSH Terms] OR (social[All Fields] AND ("anxiety"[MeSH Terms] OR "anxiety"[All Fields])))) AND ("exposure"[All Fields] AND "therapy"[All Fields] OR "exposure therapy"[All Fields] OR "Behavior Therapy"[Mesh] OR "exposure treatment"[All Fields] OR "exposure session"[All Fields] OR "fear modification"[All Fields] OR flooding OR "in vivo exposure"[All Fields] OR "imaginal exposure"[All Fields]) AND humans [Filter]
The search in PsychInfo was conducted in a way that mirrored the search in PubMed as closely as possible. JB screened studies found by the search terms for eligibility regarding title and abstract and, if deemed potentially relevant, subsequently assessed for eligibility according to the predefined PICOS criteria by JB and EJL in a full-text review. The interrater reliability was very high with a Pearson’s r = .927 (p <.001). A coding system (“Quality Score”, QS) on study characteristics was developed by JB and
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EJL based on the one used by Lueken and colleagues (2016) as well as the MERSQI criteria (Reed et al., 2007) to assess quality and risk of bias of included studies (see Table 1). Both JB and EJL rated all included studies based on this system. Values of five and lower can be
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seen as low, values of ten and above as high. Insert Table 1 here.
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We cannot eliminate the risk of bias in our results. We intentionally limited our search for
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relevant articles on well-known and respected databases with PubMed and PsychInfo. This, however, means that biases such as a publication bias are not only possible, but probable, all
included
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3. RESULTS We included 111 studies in our review. The flowchart that shows numbers for studies screened, assessed for eligibility and subsequently included in the review as well as the reasons for exclusions can be found in Figure 1.
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Insert Figure 1 here. A list of all the studies as well as relevant characteristics can be found in Table 2.
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Insert Table 2 here.
The following sections will present the included studies and their results that are most
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important for our research question. We will present our results divided into the aforementioned categories: before the ET, during ET, and after ET. Each of these categories
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is then subdivided into the subcategories “emotional”, “cognitions”, “behavioral”, and “physiological”.
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3.1 Before the ET
There were no researched factors in the behavioral category before the ET. In the emotional
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category, we did find three potential factors (trait anxiety with n=2 studies, motivation with n=2 studies and fear reactivation with n=2 studies), four potential cognitional factors (coping
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style with n=3 studies, self-efficacy with n=4 studies, perceived automaticity and irrationality of threatening cognitions with n=1 study and memory with n=1 study) and finally three potential factors on the physiological level (eyeblink startle response with n=1 study, cortisol levels with n=2 studies and comorbid disorders with n=1 study). 3.1.1. Emotional factors
Trait anxiety and motivation. Two studies (Muris et al., 1998; Rodriguez et al., 1999) found that higher trait anxiety scores lead to less success of ET. Furthermore, St-Jacques and colleagues (2010a) showed that motivation was crucial for success, especially “extrinsic integrated motivation” as described in the Self-Determination Theory (Deci and Ryan, 1985). O’Sullivan and colleagues (1976) corroborated this finding. Fear reactivation. Two studies tried improving ET by reactivating fear just before ET: While Hodgson and Rachman (1970) found an improvement by showing a video with horrific
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scenes that were however unrelated to the phobic objects just before implosion therapy, Shiban, Brutting, Pauli, & Mühlberger (2015a) could not replicate this finding in a much more recent study when reactivating the fear with the specific stimulus (spiders).
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3.1.2. Cognititive factors
Coping style. Two studies (Antony et al., 2001; Muris et al., 1993) did not find an impact of
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coping styles on the success of ET, differentiating between “blunters” (people that tend to avoid threat-related information) and “monitors” (people that actively seek out threat-related
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information). However, the follow-up study to one of these (Muris et al., 1995) did find that “blunting” lead to better results. The coping style did not change because of the treatment in
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the latter study.
Self-efficacy. Three studies found self-efficacy (both its level at the beginning and its change
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during the treatment) to be an important influencing factor concerning the success of ET (Bandura et al., 1977; Cote and Bouchard, 2009; Zoellner et al., 2000). Additionally, Williams
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and colleagues (1984) found that a therapy focused on improving self-efficacy was as successful as one with exposition only. Cote and Bouchard (2009) additionally found changes in dysfunctional beliefs to be significantly associated with treatment success. Automaticity and irrationality of cognitions. Mayer and colleagues (2000) found that while perceived automaticity of cognitions was not related to treatment success, perceived irrationality was: For participants who rated their own cognitions as more irrational, the treatment was more successful.
Memory. The aforementioned study of Zoellner and colleagues (2000) also suggests that better memory for the anxious response, but not the phobic stimulus itself, is correlated with better treatment success. 3.1.3. Physiological factors Eyeblink startle response. Results by de Jong and colleagues (1991) suggest that larger eyeblink startle response in response to white noise while being confronted with a live spider (compared to while confronted with a household object) before an ET was associated with
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higher success of ET. Cortisol levels. Lass-Hennemann and Michael (2014) find that, in their study, different cortisol levels in the morning compared to the evening explain differences in the success of ET
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conducted at these times due to enhanced extinction memory in the morning when cortisol levels are higher. Soravia and colleagues (2014) successfully used this finding by
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administrating cortisol prior to ET and thereby improving reduction of fear.
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Comorbidity. One study (Ollendick et al., 2010) found that, in adolescent patients with comorbid specific phobias and anxiety disorders, ET targeting one specific phobia had a positive influence on the severity of the other comorbid phobia or anxiety disorder.
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Furthermore, the success considering the targeted specific phobia was not affected by the existence of a comorbid anxiety disorder.
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3.2 During the ET
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Most of the researched potential factors take effect during the ET. We found five potential factors in the emotional category (within and between session habituation with n=4 studies, disgust with n=5 studies, disgust evocation with n=3 studies, relaxation as an addition with n=3 studies, Positive Valence Training with n=1 study), four potential factors in the cognitional category (presence with n=1 study, coping self-statements with n=1 study, adding cognitive parts to ET with n=7 studies and attentional focus guiding with n= 6 studies), nine potential factors in the behavioral category (spontaneously shown safety behavior with n=1
study, evoked safety behavior with n=6 studies, , sex of the therapist with n=1 study, context variation with n=7 studies, stimulus variation with n=4 studies, length with n=11 studies computer assistance with n=14 studies, motion simulation with n=1 study, and additional manipulation with n=3 studies) 3.2.1 Emotional factors Within- and between-session anxiety decrease. Two studies found a correlation between a measurable between session habituation (BSH) and within session habituation (WSH) on the
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one hand and overall success of the therapy on the other hand (Mühlberger et al., 2005a; Rachman and Levitt, 1988). Two more recent studies (with higher Quality Scores) did not find such a correlation (Baker et al., 2010; Busscher et al., 2015), especially when
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investigating long-term success.
Disgust. Regarding the relation between fear, disgust, and the success of ET, Smits and
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colleagues (2002) found that anxiety and disgust declined independently from each other (anxiety declined more than disgust), but they did not find that global disgust levels were
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changed nor that disgust levels prior to the ET had an impact on anxiety level reduction (or vice versa). Similarly, Olatunji and colleagues (2007) found that in their study participants
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with blood-injection—injury phobia (BII) found that anxiety declined more than disgust. However, in their study disgust and fear decline were not independent from each other. In
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two following studies, Olatunji et al. (2012, 2009) show fear and disgust and their respective decline to be independent from each other, with fear, but not disgust, being a significant
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predictor of treatment success (measured by a BAT). Contrary to this, Matthews, Naran & Kirkby (2015) found that in their study, both anxiety and disgust reduction predicted treatment success (behavioral avoidance). Disgust evocation. Another line of research did not only measure both disgust and anxiety, but directly evoke disgust in participants with specific phobias: Both Choplin and Carter (2011) and Olatunji and colleagues (2009) were able to evoke disgust and reach a significant reduction of both anxiety and disgust by only showing disgusting pictures. They found no
differences in treatment success (both behavioral and subjective) between a group exposed to a disgusting stimulus compared to a group exposed to an anxiety-inducing stimulus, although Choplin and Carter (2011) found the anxiety-condition to have more long-lasting effects on behavior. De Jong and colleagues (2000) tried to countercondition the disgust elicited by an exposure to a spider in spider phobic individuals by presenting explicitly nondisgusting stimuli after the ET. They found no added effect on treatment success. Relaxation. Mühlberger and colleagues (2001a) find that relaxation alone is not as successful
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in reducing anxiety as VRET alone is. Rimm and Medeiros (1970) find no enhancement by adding relaxation to ET, while McGlynn and colleagues (1999) even found a suppression of anxiety by a history of relaxation training.
Additional Positive Valence Training. Dour and colleagues (2016) suggest that Positive
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Valence Training, a training that tries to increase the valence of the feared stimulus, in this
Cognitive factors
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3.2.2
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case spiders, by pointing out their usefulness, can enhance the effect of ET.
Presence and coping self-statements. Krijn and colleagues (2004) could not find an impact of presence, i.e. the feeling of actually being in a real environment while being in a Virtual
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Reality, on the success of VRET. In another study, Krijn and colleagues (2007) showed that coping self-statements did not enhance the success of VRET.
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Adding Cognitive parts. One potential factor that drew much attention is the question whether ET with parts specifically addressing cognitions like cognitive preparation or cognitive tasks
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in the ET is more successful than ET without such parts. Raes and colleagues (2011) did not find an advantageous effect of explicitly addressing cognitions in the ET, but did find that success was mediated by cognitive changes. Similarly, Tardif (2019) and colleagues showed that in their study, changes in cognitive beliefs and self-efficacy were predictive of ET success. Kircanski and colleagues (2012) found only marginally better results of ET augmented by affect labeling but not by guided threat-reappraisal, with Tabibnia (2008) corroborating this result. Dee’s (1972) study suggests that instructions seem to help – albeit
not significantly. However, Bandura and colleagues (1974) argue that “induction aids”, such as a gradual exposure and company, help in exposure and lead to better results. Furthermore, Sloan and Telch (2002) as well as a study by Kamphuis and Telch (2000) suggests that guided threat-reappraisal helped. Additionally one study found that a treatment without a cognitive part is effective, but less so than a treatment with cognitive contents (Van Gerwen et al., 2006). Finally, Koch and colleagues (2004) found a treatment without cognitive part as effective, but it was perceived as more intrusive.
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Attentional Focus Guiding. Concerning attentional focus guiding: while one study finds that distraction is beneficial (Oliver and Page, 2008), three others find that distraction hinders extinction and lowers the success of ET (Dethier et al., 2015; Kamphuis and Telch, 2000; Telch et al., 2004). A third pair of studies find no effect of attentional focus guiding on
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3.2.3
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treatment success (Antony et al., 2001; Waters et al., 2014).
Safety Behavior. Rentz and colleagues (Rentz et al., 2003) found that the (not instructed,
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spontaneously shown) use of safety behavior was associated with less improvement. In contrast to this, four studies find either no drawback or even small advantages of explicitly
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instructing participants to use safety behavior (Deacon et al., 2010; Hood et al., 2010; Milosevic and Radomsky, 2008; Sy et al., 2011), and only one study found the expected
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disadvantage of an ET with instructed safety behavior (Sloan and Telch, 2002). Additionally, Wolitzky and Telch (2009) show that utilizing “fear antagonistic behavior”, which can be seen
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as a form of safety behavior or distraction from the feared stimulus, leads to better behavioral success and more generalization. Sex of therapist. O’Sullivan and Gilner (1976) found that the sex of the therapist is a factor; female therapists seem to be beneficial regardless of the sex of the patient. Context variation. Mystkowski and colleagues (2002) have shown that in their study, exposition to the feared stimulus in a context different to the one used in the ET leads to return of fear, which is not equivalent to fear relapse, but is a partial fear recovery after ET
(Rachman, 1989). Five studies suggest that using several contexts in the ET leads to less return of fear and generally better treatment success (Bandarian-Balooch et al., 2015; Shiban et al., 2015a, 2013; Vansteenwegen et al., 2007b, 2007a), but two studies (Rodriguez et al., 1999; Shiban et al., 2015b) could not find such an effect. Stimulus variation. Both last-mentioned studies also looked at the effect of varying the stimulus itself within the ET. This question was addressed by a total of three studies: One of these (Shiban et al., 2015b) suggest that varying the stimulus is beneficial, while the other
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two (Koch et al., 2004; Rodriguez et al., 1999) did not find a benefit of different stimuli. Length. When looking at the potential influence of length, one can further subdivide this
factor into three subcategories: number of sessions, length of the individual session and
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massed vs. expanding-spaced ET, which will be discussed in the following paragraphs.
In three different studies, Öst and his colleagues did not find any differences between a one-
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session and a five-session ET (Hellström et al., 1996; Öst et al., 2001, 1997), although their latest study suggests a slight advantage of the five-session treatment one year after the ET
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(Vika et al., 2009). When comparing higher numbers of sessions, Fraser and colleagues (2001) found no difference between participants getting three versus six sessions of
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vicarious exposure. Bornas and colleagues (2011) tackled the question differently by counting the numbers of sessions needed until they reached a successful reduction of
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subjective level of anxiety. Participants needed between one and seven sessions; the faster anxiety was reduced within the sessions, the fewer sessions were needed.
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Length of individual sessions has been researched in three studies: Miller and Levis (1971) found a superiority of 30- and 45-minute exposure sessions over 15-minute sessions. Rachmann and Lopatka (1988) showed that in their study, extending the ET over a point of acceptably reduced anxiety did not have an added effect on the success, and neither did stopping the ET before the point of acceptably reduced anxiety (SUDs at 0). Finally, Rodriguez et al. (1999) found that, in their study longer treatment duration predicted greater return of fear.
Lastly, Rowe and Craske (1998) tried to find differences between a massed ET and an ET with sessions spaced with more times between sessions. Although both forms of ET worked comparably well at first (the massed ET worked even slightly better), they found a return of fear in the massed ET group directly after the ET and at a 1-month follow-up. Computer assistance. A modern way of presenting the feared stimulus is by using computer assistance. But respective techniques seem to be either as good as or even inferior to in vivo ET: This was shown for video exposure (Öst et al., 1998), imagery exposure (Wiederhold et
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al., 2002, 2001), computer-aided ET (Tortella-Feliu et al., 2011) and internet-based therapies (Andersson et al., 2013, 2009). Additionally, Virtual Reality (VR) or Augmented Reality (AR), were either as effective (Botella et al., 2016; Emmelkamp et al., 2001; St-Jacques et al., 2010) or slightly inferior(Heading et al., 2001; Michaliszyn et al., 2010) than in vivo ET.
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However, the authors frequently name a lesser aversiveness (Botella et al., 2016) and lower costs, especially in the case of flight phobia (Emmelkamp et al., 2001), as advantages for VR
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or AR. When it comes to differences between specific ways of projecting the virtual reality,
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Krijn and colleagues (2004) do not find a difference between an ET with a head-mounted display (HMD) and a computer automatic virtual environment (CAVE). Mühlberger and
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colleagues (2005b) found no additional effect of motion simulation in VRET. Additional manipulation. Finally, three studies manipulated the stimulus in additional ways: Smith and colleagues (Smith et al., 1997) show that vicarious exposure to an irrelevant, not
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anxiety-inducing stimulus (i.e. training of the ET technique without the feared stimulus) does
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improve anxiety. Craske and colleagues (1991) varied the participant’s control over the length of an exposure and found no influence on the success of treatment. Shiban and colleagues (2016) showed that specific perceptual cues (i.e. presenting pictures of a closed door to claustrophobic participants) lead to better success of ET (measured by physiological parameters) than fear-related conceptual information (i.e. telling the participants that the door was closed). 3.2.4
Physiological factors
Heart rate. When investigating heart rate, systolic blood pressure and diastolic blood pressure, Hellström and Öst (1996) could not find any stable predictors for short- or longterm success of ET. Several other studies researched the connection between heart rate and ET success: While Bornas and colleagues (2007) could predict better success when combining heart rate variability with heart rate entropy, Alpers and Sell (2008) even showed that in their participants, heart rate at the start of ET alone correlated more with its success than measures of subjective anxiety. Bornas and colleagues (2011) added to this showing that “flexible patients” (i.e. patients with greater heart rate variability) improved more. In line
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with this, Busscher and colleagues (2013) showed that heart rate was a predictor for participants with high anxiety sensitivity, but less so for patients with low anxiety sensitivity. In a follow-up study (Bornas et al., 2012) that further discriminated between tonic and phasic
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heart rate, this finding was corroborated. However, two studies (Benoit Allen et al., 2015; Busscher et al., 2015) could not find correlations between long-term treatment success and
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heart rate reactivity or changes.
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Feedback of body reactions. Craske and colleagues (1995) gave participants corrective information on their bodily reactions (like explaining that shortness of breath did not lead to suffocation). While this lead to higher fear reduction in claustrophobics, the effect did not
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generalize and was not found in spider or snake phobic participants. However, two studies (Telch et al., 2000; Wiederhold et al., 2002) found that feedback of the heart rate did
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enhance the effect of ET, while one study could not find an influence of (visual or tactile) feedback (Tardif et al., 2019).
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Caffeine State. Mystkowski and colleagues (2003) showed that the “caffeine state”, i.e. how much coffee a participant drank, has an effect on post-ET anxiety in that a “caffeine state” differing to the one in the ET lead to greater return of fear. Anxiety-differing medication. A number of different medication was administered in studies to examine its effect on the success of ET. A study conducted by Meyerbroeker and colleagues (2012) could not find enhancing effects for Yohimbine Hydrochloride. For Quetiapine, an
effect was limited to physiological anxiety measurements (Diemer et al., 2013) but did not show in behavioral measurements or subjective ratings by the participants. For Benzodiazepines, a study even found a hindering effect for flight phobic participants (Wilhelm and Roth, 1997). Similarly, Oxytocin showed diminishing effects on success in one study (Acheson et al., 2015). Lastly, Naltrexone was not administered as a potential enhancement but rather to test the role of the opioid system: Both Merluzzi, Taylor, Boltwood, and Gotestam (1991) and Arntz, Merckelbach, & de Jong (1993) find that the administration of Naltrexone hinders reduction of anxiety in an ET, thus suggesting a role of the opioid system
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in its success. 3.3 After the ET
Only a few factors in this category have been researched, with one emotional (conditioned
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odor with n=1 study) and one cognitive factor (return of phobic cognitions with n=2 studies)
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and 3 physiological factors (neural activation with n=3 studies, sleep with n=2 studies and memory-enhancing medication with n=5 studies). Emotional factors
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3.3.1
Conditioned odor. Rihm et al. (2016) could not enhance the effect of an ET by re-
participants.
Cognitive factors
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3.3.2
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administrating an odor that was previously conditioned to a successful ET to their sleeping
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Return of phobic cognitions. Rodriguez and colleagues (1999) found evidence that “recovery of phobic cognitions”, i.e. an increase in phobic cognitions about the feared stimulus assessed with the Spider Beliefs Questionnaire (Arnoud Arntz et al., 1993), leads to less long-term success of ET. 3.3.3
Physiological factors
Neural activation. Hauner and colleagues (2012) show that the magnitude of the activation of a part of the visual cortex (a lingual cortex subregion) to specific fearful stimuli measured by
fMRI shortly after ET predicted long-term treatment success. Schienle and colleagues (2007) showed that successful ET correlated with a reduction in amygdala and insula reactivity to relevant pictures when success was measured with somatic panic symptoms and correlated with only amygdala changes when measured with arousal ratings in a BAT. Finally, Landowska and colleagues (2018) found no correlation between brain activity measured with functional Near-Infrared Spectroscopy (fNRIS) and subjective anxiety ratings in a group of acrophobic participants during a VRET.
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Sleep. Both Kleim and colleagues (2014) and Pace-Schott and colleagues (2012) showed that respectively 90 minutes or 12 hours of sleep lead to better post-therapy anxiety reductions.
Memory-enhancing mediation. The most-researched enhancing drug is D-Cycloserine, a
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partial agonist to the glutamatergic NMDA receptor (Hofmann, 2014) with heterogeneous
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results: While Smits and colleagues (2013) find that application of D-Cycloserine after a “successful” session, i.e. a session with within-session reduction of anxiety according to
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“Subjective Units of Distress (SUDs, but not after an “unsuccessful” one) seems to enhance the effect of the treatment in a group of height phobic individuals and Byrne et al. (2015)
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corroborate this finding in a group of children with varying specific phobias, Tart et al. (2013) do not find an enhancing effect of D-Cycloserine.
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Methylene Blue seems to have an effect that is comparable to that of D-Cycloserine, i.e. being effective after a successful, but counterproductive after an unsuccessful exposure
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session (Telch et al., 2014).
4. DISCUSSION The present review aimed to give an overview over factors spanning the time before, during and after the ET itself and their respective empiric corroboration. Before discussing the limitations and the conclusion of this review and giving concrete advice for clinicians and researchers on how to use the results in their respective work, we will summarize our results
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for different factors.
4.1. Summary of evidence
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4.1.1. Before the ET
At this point in time, one can only recommend considering two emotional factors before ET
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as factors influencing the success of ET: A low trait anxiety and a high motivation, both researched by two studies with acceptable QS. Coping stiles (3 studies with acceptable to
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high QS and mixed results) has not been shown to be relevant in an adequate number of studies.
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The fact that four studies with acceptable to high QSs point to self-efficacy being an important factor fits well with the results of the aforementioned study by Williams and
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colleagues (1984). No other cognitive factors emerged as good candidates for influencing the success of ET.
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For potential physiological influencing factors before ET, it must be said again that replication of findings is needed (especially for comorbidity, that has only been researched by one study with acceptable QS), albeit Cortisol levels seem to be the most promising candidate, with two promising studies with very high QSs finding and using a relationship between Cortisol levels and ET success. 4.1.2.
During the ET
When it comes to emotional factors during the ET, the literature summarized here calls into question if WSH and BSH are necessary, with two studies with lower QS finding a relationship, while to studies with higher QSs fail to do so. This concurs with the work by Craske and colleagues (Craske et al., 2008b), and with the results of a recent meta-analysis by Rupp and colleagues (Rupp et al., 2017). It remains entirely unclear whether disgust and its decline through an ET is independent from anxiety and whether it is a relevant predictor of ET success. Five studies, all with lower to medium QSs, come to very contradicting results. However, the three included studies with medium QSs (Choplin and Carter, 2011; de Jong et
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al., 2000; Olatunji et al., 2009) suggest that exposing to disgusting stimuli does also help reduce anxiety. Additionally, avoiding relaxation shows promise as a relevant factor in three studies with QSs ranging from low to high (McGlynn et al., 1999; Mühlberger et al., 2001b;
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Rimm and Medeiros, 1970).
Regarding cognitive factors during the ET, it seems clear that focusing on changes in fear-
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relevant cognitions during the ET improves the success rate of ET with a high number of
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studies, all with medium to high QSs, finding a relationship. However, we cannot specify the best kind of cognitive addition more precisely, as the different studies used very
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heterogeneous cognitive additions.
Going on to look at potential behavioral factors during the ET change of context - but not change of the stimulus itself - has emerged as a factor of success in ET, especially regarding
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long-term effects. Regarding length three studies with high QS found five sessions to be
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sufficient, with evidence from one high-quality study that five sessions is superior over one session when it comes to long-term effectiveness. Extending the time of individual sessions does not seem to improve the success. Virtual Reality Exposure Therapy (VRET) seems to be a viable option for the treatment of specific phobias: In most of the reviewed studies (that all have good QSs), it has shown superiority or at least no inferiority to other forms of treatment that have been used frequently when in vivo exposure was not possible or too aversive and seems to be a viable alternative
to in vivo ET. This finding is in line with newer reviews (Botella et al., 2017; Maples-Keller et al., 2017). Regarding physiological factors, there are several different measurements of heart rate activity that show potential as factors predicting treatment success, none of which has been studied in a satisfactory amount, even though all studies show medium to high QSs. Nonetheless, it seems clear that heart rate changes and differences are an important factor for the success of ET.
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4.1.3. After the ET Overall, factors influencing the success that take effect after ET play a comparably small role. Except for the return of phobic cognitions (with only one, medium to high quality study),
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no potential factors emerged in the emotional or cognition category. When it comes to additions concerning physiological aspects, best evidence exists for sleep as well as
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administering D-Cycloserine as being helpful (albeit only if it is administered with a successful ET; 3 studies with high QS). In their review concerning the use of cognitive
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enhancers in exposure-based therapies for several diseases, Singewald and colleagues (2015) come to a similar conclusion. See Hofmann (2014) for a guidelines for clinical practice
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of using D-Cycloserine as an enhancer of ET.
For an overview over the status of every factor included in this review, see table 3.
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Insert Table 3 here.
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4.2. Embedding our results into the theoretical background Our findings show only a handful of factors that definitely play a part in the success of ET. However, these factors can be integrated very well into the aforementioned Inhibitory Learning Approach by Craske (Craske et al., 2014, 2008). This approach states that patients develop secondary inhibitory associations to the feared stimuli; ET is thus successful when it provides patients with possibilities to build and strengthen these new associations (Craske et al., 2014). This theory differentiates itself from older models of the underlying mechanisms of
ET like the Pavlovian conditioning model in that it does not postulate an overwriting of the old associations but a building of separate, new associations. Thus, factors that enable maximum new learning and create an environment in which learning is possible help the most. In our review, these are: A high self-efficacy before the ET (Bandura et al., 1977; Cote and Bouchard, 2009; Williams et al., 1984; Zoellner et al., 2000), a low trait anxiety (Muris et al., 1998; Rodriguez et al., 1999), addressing disgust as well as anxiety when choosing the stimulus (Choplin and Carter, 2011; de Jong et al., 2000; Olatunji
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et al., 2009), focusing on changing phobia-specific cognitions (Bandura et al., 1974; Dee, 1972; Kamphuis and Telch, 2000; Kircanski et al., 2012; Koch et al., 2004; Raes et al., 2011; Sloan and Telch, 2002; Tabibnia et al., 2008; Tardif et al., 2019; Van Gerwen et al., 2006), changing contexts between ET sessions (Bandarian-Balooch et al., 2015; Mystkowski et al.,
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2002; Shiban et al., 2015a, 2013; Vansteenwegen et al., 2007b), focusing on heart rate changes (Alpers and Sell, 2008; Bornas et al., 2012, 2011, 2007; Busscher et al., 2013;
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Hellström and Öst, 1996), administering D-Cycloserine after a successful ET (Byrne et al.,
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2015; Smits et al., 2013; Tart et al., 2013) and sleeping after one (Kleim et al., 2014; Pace-
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Schott et al., 2012).
All of these factors help the patient build new associations with the feared stimulus: Either by
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enabling them to be more open to new experiences that violate existing expectancies concerning the feared stimulus (high self-efficacy and low trait anxiety), by “deepen the
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extinction” (Rescorla, 2006) in the case of addressing disgust additionally to anxiety and focusing on cognitions and heart rate change or by enabling reconsolidation (changing contexts, D-Cycloserine, and sleep). Nevertheless, some of the strategies to optimize ET proposed by Craske and colleagues are not corroborated by our findings, namely the call for variability of stimulus. Especially since most of the assumptions of the Inhibitory Learning Approach are met, it seems surprising that this is not the case for changing stimuli. One possible reason might be the focus of this
review on a very specific anxiety disorder, namely SP. SP is characterized by the fear of one specific stimulus. Thus, there might not be a need to generalize as much to other forms of the same feared stimulus. This also explains why the length and number of the ET sessions seem to play a smaller role. It is easier to learn new cognitions in the context of a specific phobia than in the context of other phobias or anxiety disorders. When an ET is successful in providing these new learning experiences, it does not need as much time or many repetitions for this learning experience to consolidate.
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Furthermore, our findings show that some factors only influence the success measured on one dimension (behavioral, subjective, physiological, or in clinicians’ ratings). This relationship between different levels of measurement of the success and different factors is
4.2.1
Perspective for clinical research
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not yet clear (Lambert and Ogles, 2009; Moustgaard et al., 2014).
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There is only a small number of sufficiently researched and corroborated factors influencing the success of ET in patients with specific phobia. Studies that aim to replicate previous
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results, with sufficiently sized and well-screened samples, are needed to further the understanding of what makes ET successful.
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Based on our findings, researchers wanting to select factors worthy of future research and to find good operationalizations should start at the underlying theoretical mechanisms. As
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already mentioned, factors that could help improve the learning experience in ET (e.g. by directing the patient’s attention on the new experience, limiting distractions and unnecessary
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parts of the ET) are more likely to be relevant factors of success than factors that stand in no connection to the learning experience. Agreeing on shared operationalizations of factors as well as shared measures of success, with a special focus of measuring long-term success, is of utmost importance for the advancement of the research field. Furthermore, studies show a huge difference in regard to the form of ET they use (OST, VRET and multi-session ET are used similarly often) and their inclusion and exclusion criteria. We presented studies that show that these different forms of
ET are comparable, as they are very similar to each other in terms of success and underlying mechanism. Nevertheless, an effort should be made in trying to mirror everyday practice in future studies and to use more comparable forms of ET to ensure generalizability. Lastly, we see the inclusion of participants with only mild anxiety as a big problem: This calls into question if the respective results are transferrable to clinical practice, where patients have comparably severe disorders and symptomatology. Studies with participants with clinical diagnoses sometimes come to different conclusions, not least
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because ET seems to be more effective with participants with more severe anxiety. Therefore, we argue that studies should try to include only participants with clinically significant specific phobia.
This is especially the case since once the question of who profits from ET most is answered,
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the question what to do with the ones who do not becomes even more pressing. This group
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of hard-to-treat patients might need a more optimized and individualized treatment. However, based on the current literature, it is hard to say how such optimizations should look like; more
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research is needed in this field. Some studies that try to fill this need: Studies like the one from Schwarzmeier and colleagues (Schwarzmeier et al., in press) try to identify these
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patients before a treatment begins. Future studies will have to show how to individualize therapy.
Perspective for clinical practice
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4.2.2
A conclusion for how to conduct ET with patients is very hard to draw. Nevertheless, some
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advice can be given.
All things considered, the literature shown here underlines that ET is a very effective form of treatment; even if both the mechanisms and the influencing factors still need to be put under scrutiny, a majority of the studies presented here shows an improvement in anxiety (subjectively, behaviorally and physiologically). It is thus superior to other forms of treatment for patients with SP.
ET should have the goal to expose the patient with the feared stimulus as fast and as direct as possible (while still taking the commitment of the patient into account) to ensure the best learning experience. Factors that have been shown to improve the learning experience are addressing disgust as well as anxiety (i.e.when building an anxiety hierarchy, therapists should also ask for especially disgust-inducing stimuli and take respective stimuli into consideration when choosing exposure stimuli), focusing onchanging cognitions in the ET (by concretely exploring cognitions before and after the ET to stress changes), changing context for different sessions, monitoring and addressing heart rate changes during the ET and sleep
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and/or D-Cycloserine after a (successful) ET. Lastly, ET should be conducted as close as possible to the current state of the art (Bandelow et al., 2014), since this is the form of ET that is best examined and the influence of all deviances from it are not yet clear.
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Some factors that we found to have an impact on the success of ET cannot be controlled by the clinician directly, mainly the motivation, self-efficacy and trait anxiety of their patients.
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However, we would argue that there is nevertheless merit in accounting for their influence:
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As we have said, ET is the therapy of choice even for patients with less chance of success. Clinicians should just be aware that success might take longer for patients with unfavorable attitudes or traits, and might want to address motivation and self-efficacy before starting with
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ET (e.g. by exploring and discussing potential dysfunctional cognitions that lead to these, or using techniques like Motivational Interviewing (Miller, 1983) to improve them. Moreover,
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specific adjustments and individual optimization might be necessary for this group of patients. As discussed, the nature of these optimizations is not yet clear, making this group
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of patients a particular challenge. 4.3 Limitations
A large number of factors have been researched in the literature, but most of them by only a very small number of studies. Additionally, a lot of potential factors have been operationalized very heterogeneously in different studies, leading to problems in comparing these studies even if the same factor was the object of interest. This leads to problems
especially when different potential factors (e.g. distraction and cognitive additions) influence each other. Finally, both the characterization of participants and the definition of success of ET differed greatly, further complicating comparison between studies. Additionally, a lot of studies do not take satisfactory follow-up measurements: Studies show that there is a considerable change in the reaction to an ET even 6 and 12 months after treatment, most widely studied in respect to the aforementioned concept of return of fear (Haaker et al., 2014), which often is disregarded in the presented literature.
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Many studies that looked at potential predictors of success of ET did not meet our inclusion criteria and were thus excluded from this review. Hence, it could be argued that with less rigid inclusion criteria, more predictors could have been unveiled and the picture for the predictors discussed here could have looked differently. Similarly, one could argue that we
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limited ourselves too much by only including studies regarding SP, and excluding other
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studies that, while conducting research on ET, did so with participants having (symptoms of) another phobia or anxiety disorder. But we think that, especially in the face of the number of
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different predictors discussed in the literature and the huge number of articles published in this area, it is of importance to adhere to strict quality standards to be able to get trustworthy
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results.
Furthermore, there is still considerable heterogeneity in our results. This heterogeneity raises
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the question whether our inclusion criteria were not strict enough: We included a number of articles that have a sample of participants with only light symptomatology or that measure the
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success (or lack thereof) of the ET in an unsatisfactory amount. However, we decided to include these studies in order to give a picture of the existing research that is as exhaustive as possible – as long as they fulfilled certain minimal criteria outlined in our PICOS criteria (see 2. Methods). Since all the included studies had to satisfy these inclusion criteria, we feel that reporting their results is not without merit even if their methodology leaves things to be desired. Additionally, we tried to make the reader aware of quality differences between included studies by reporting their respective QS.
Moreover, studies measured outcome in different ways, and some studies included several kinds of measuring outcome like subjective (e.g. via questionnaires), behavioral (e.g. with Behavioral Avoidance Tests), physiological (e.g. via measuring electrodermal activity) or professional (e.g. a rating by therapists). There is merit to every one of these kinds of measures, since they show different aspects of change that tend to be intercorrelated, but not equal to each other (Ogles et al., 1990). Hence, a combination is desirable to get a complete pictures as much as possible (Lonsdorf et al., 2017). This is why the QS is higher the more different kinds of measuring outcome were applied. In our review, eight included
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studies did only measure success in one of the aforementioned ways; all the other studies employed two or more ways.
Another problem in interpreting our results lies in the fact that there is a risk of bias across
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the included studies (see 2.Methods). This is especially disconcerting because oftentimes, one potential factor has only been researched by one team of researchers. For example,
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OST has been researched most actively by Öst and colleagues. This makes it hard to
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compare two factors with each other, given that the quality of the underlying research may differ. We again tried to tackle this problem with our Quality Score, which should give an
4.4 Conclusion
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insight into the quality of every study (albeit not being able to fully eliminate risk of bias).
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This review gives an overview over potential factors influencing the success of ET in patients with SP. Best evidence is shown for the following factors: low trait anxiety, high motivation
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and high self-efficacy before the ET, high cortisol levels and heart rate variation, evoking disgust additionally to anxiety, avoiding relaxation, focusing on cognitive changes, context variation, sleep, and memory-enhancing drugs. This review serves two purposes: Firstly, it helps practitioners in planning and conducting an ET with a high chance to succeed. Although conclusive evidence for many aspects is still missing, we nevertheless show that enabling to learn new associations with the feared stimulus should be the focus. Secondly, this review presents the challenges and the groundwork for future research: It shows the
need for unified operationalizations of both potential factors and the measurement of the outcome. It presents many potential factors that should be replicated in future studies and provides a theoretical background for other factors that can be researched in the future.
Funding and conflicts of interest The study was supported by grants of the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation; Collaborative Research Centre “Fear, Anxiety, Anxiety Disorders”
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SFB-TRR-58) projects Z2 and C09 to UD. There was no conflict of interest.
5
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Schweckendiek, J., Klucken, T., Merz, C.J., Tabbert, K., Walter, B., Ambach, W., Vaitl, D., Stark, R., 2011. Weaving the (neuronal) web: Fear learning in spider phobia.
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Shiban, Y., Brutting, J., Pauli, P., Mühlberger, A., 2015a. Fear reactivation prior to exposure therapy: does it facilitate the effects of VR exposure in a randomized clinical sample? J. Behav. Ther. Exp. Psychiatry 46, 133–140. https://doi.org/10.1016/j.jbtep.2014.09.009 Shiban, Y., Pauli, P., Mühlberger, A., 2013. Effect of multiple context exposure on renewal in spider phobia. Behav. Res. Ther. 51, 68–74. https://doi.org/10.1016/j.brat.2012.10.007
Shiban, Y., Peperkorn, H.M., Alpers, G.W., Pauli, P., Mühlberger, A., 2016. Influence of perceptual cues and conceptual information on the activation and reduction of claustrophobic fear. J. Behav. Ther. Exp. Psychiatry 51, 19–26. https://doi.org/10.1016/j.jbtep.2015.11.002 Shiban, Y., Schelhorn, I., Pauli, P., Mühlberger, A., 2015b. Effect of combined multiple contexts and multiple stimuli exposure in spider phobia: A randomized clinical trial in virtual reality. Behav. Res. Ther. 71, 45–53. https://doi.org/10.1016/j.brat.2015.05.014
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Smith, K.L., Kirkby, K.C., Montgomery, I.M., Daniels, B.A., 1997. Computer-delivered
modeling of exposure for spider phobia: relevant versus irrelevant exposure. J. Anxiety
re
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Smits, J.A.J., Hofmann, S.G., Rosenfield, D., DeBoer, L.B., Costa, P.T., Simon, N.M.,
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na
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ur
Smits, J.A.J., Telch, M.J., Randall, P.K., 2002. An examination of the decline in fear and
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disgust during exposure-based treatment. Behav. Res. Ther. 40, 1243–1253. Soravia, L.M., Heinrichs, M., Winzeler, L., Fisler, M., Schmitt, W., Horn, H., Dierks, T., Strik, W., Hofmann, S.G., de Quervain, D.J.-F., 2014. Glucocorticoids enhance in vivo exposure-based therapy of spider phobia. Depress. Anxiety 31, 429–435. https://doi.org/10.1002/da.22219 St-Jacques, J., Bouchard, S., Belanger, C., 2010a. Is virtual reality effective to motivate and raise interest in phobic children toward therapy? A clinical trial study of in vivo with in
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Tabibnia, G., Lieberman, M.D., Craske, M.G., 2008. The Lasting Effect of Words on
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re
Tardif, N., Therrien, C.-É., Bouchard, S., 2019. Re-Examining Psychological Mechanisms
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na
Tart, C.D., Handelsman, P.R., DeBoer, L.B., Rosenfield, D., Pollack, M.H., Hofmann, S.G., Powers, M.B., Otto, M.W., Smits, J.A.J., 2013. Augmentation of exposure therapy with post-session administration of d-cycloserine. J. Psychiatr. Res. 47, 168–174.
ur
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Taylor, S., Abramowitz, J.S., McKay, D., 2012. Non-adherence and non-response in the treatment of anxiety disorders. J. Anxiety Disord. 26, 583–589. https://doi.org/10.1016/j.janxdis.2012.02.010
Telch, M.J., Bruchey, A.K., Rosenfield, D., Cobb, A.R., Smits, J., Pahl, S., Gonzalez-Lima, F., 2014. Effects of post-session administration of methylene blue on fear extinction and contextual memory in adults with claustrophobia. Am. J. Psychiatry 171, 1091–1098. https://doi.org/10.1176/appi.ajp.2014.13101407
Telch, M.J., Valentiner, D.P., Ilai, D., Petruzzi, D., Hehmsoth, M., 2000. The facilitative effects of heart-rate feedback in the emotional processing of claustrophobic fear. Behav. Res. Ther. 38, 373–387. Telch, M.J., Valentiner, D.P., Ilai, D., Young, P.R., Powers, M.B., Smits, J.A.J., 2004. Fear activation and distraction during the emotional processing of claustrophobic fear. J. Behav. Ther. Exp. Psychiatry 35, 219–232. https://doi.org/10.1016/j.jbtep.2004.03.004 Tortella-Feliu, M., Botella, C., Llabres, J., Breton-Lopez, J.M., del Amo, A.R., Banos, R.M.,
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Vansteenwegen, D., Vervliet, B., Iberico, C., Baeyens, F., Van den Bergh, O., Hermans, D., 2007b. The repeated confrontation with videotapes of spiders in multiple contexts attenuates renewal of fear in spider-anxious students. Behav. Res. Ther. 45, 1169– 1179. https://doi.org/10.1016/j.brat.2006.08.023 Vika, M., Skaret, E., Raadal, M., Öst, L.G., Kvale, G., 2009. One- vs. five-session treatment of intra-oral injection phobia: a randomized clinical study. Eur. J. Oral Sci. 117, 279– 285. https://doi.org/10.1111/j.1600-0722.2009.00628.x
Waters, A.M., Farrell, L.J., Zimmer-Gembeck, M.J., Milliner, E., Tiralongo, E., Donovan, C.L., McConnell, H., Bradley, B.P., Mogg, K., Ollendick, T.H., 2014. Augmenting one-session treatment of children’s specific phobias with attention training to positive stimuli. Behav. Res. Ther. 62, 107–119. https://doi.org/10.1016/j.brat.2014.07.020 Wiederhold, B.K., Gevirtz, R.N., Spira, J.L., 2001. Virtual reality exposure therapy vs. imagery desensitization therapy in the treatment of flying phobia., in: Riva, G., Galimberti, C., Riva (Ed), G., Galimberti (Ed), C. (Eds.), Towards Cyberpsychology:
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Wilhelm, F.H., Roth, W.T., 1997. Acute and delayed effects of alprazolam on flight phobics
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Wolitzky-Taylor, K.B., Telch, M.J., 2009. Augmenting in vivo exposure with fear antagonistic actions: a preliminary test. Behav. Ther. 40, 57–71. https://doi.org/10.1016/j.beth.2007.12.006
Wolpe, J., 1954. Reciprocal Inhibition as the main basis of psychotherapeutic effects. Arch. Neurol. Psychiatry 72, 205. https://doi.org/10.1001/archneurpsyc.1954.02330020073007 Zoellner, L.A., Echiverri, A.M., Craske, M.G., 2000. Processing of phobic stimuli and its
Jo
ur
na
lP
re
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ro of
relationship to outcome. Behav. Res. Ther. 38, 921–931.
Identification
Figure 1. PRISMA flow chart for study inclusion.
Records identified through database searching: n=2619 (PubMed: n=2045; PsycInfo: n=573)
Screening
Records after duplicates removed: n=1938
Records excluded:
ro of
Records screened: n=1938
n=1386
Full-text articles excluded, with
lP
n=552
re
Eligibility
Full-text articles assessed for eligibility:
-p
reasons (n=441):
Included
Studies included in qualitative synthesis:
Jo
ur
na
n=111
wrong sample: n=142 Intervention does not meet criteria of exposition: n=115 n<10: n=63 no predictors as independent variable: n=43 short report: n=14 not an empirical study (i.e. review or case study): n=28 success of intervention is not measured: n=6 No or wrong control group (e.g. no ET in the control group): n=29 language: n=1
ro of
-p
re
lP
na
ur
Jo
Table 1 Quality and risk of bias assessment for studies researching factors influencing the success of Exposure Therapy in Specific Phobia 1 point
0.5 points
Independent sample
Yes
-
Sample size
≥20/condition
≥15/condition
Diagnosis secured
SCID or comparable
Questionnaire with clear cutoff AND BAT
Exclusion criteria
Reported
-
Concomitant Medication reported
No
-
Statistical control of possible confounders
Yes (or matched groups/ exclusion of confounders)
-
Standardized
Length or specific content not standardized, but manualized
Sample (0-3 points) No
re
Standardization
Behavioral measure
Yes
Physiological measure
Yes
Rating by professional
Randomization Blinding
Jo
RCT methodology (0-2 points)
-
Yes
-
Yes, exclusively
Yes, plus non-evidence based addition (medication etc.)
ur
Evidence-based treatment? (0-1 point)
na
Yes
lP
Outcome measures (0-4 points) Self-report
-p
Exposure Therapy (0-1 point)
ro of
Confounder Control (0-3 points)
Yes
-
Yes
-
Sum score study quality (0-14 points)
SCID: Structural Clinical Interview for DSM-IV; BAT= Behavioral Avoidance Test; RCT = Randomized Controlled Trial
Table 2 Included studies, their quality score and results ordered by the researched factors Topic
Author
Year
Treatment
Sample Size
Type of Specific Phobia
Main findings
Quality Score
Measure of success and evidence for use as predictor SR
B
Before the ET – emotional factors 1998
OST
36 women
Spider Phobia
The higher the trait anxiety scores, the less patients profited from behavior therapy.
7
-
-
Rodriguez, Craske, Mineka, & Hladek
1999
In vivo exposure
65 in 4 groups
Spider Phobia
Higher trait anxiety scores are associated with less successful therapy (increased return of fear)
9,5
-
-
2010
Exposure, in vivo only vs. VR plus in vivo
Spider Phobia
No increase in motivation through the use of VRET; significant impact of motivation (especially extrinsic integrated motivation) on subjective treatment success
9,25
+
see Computer assistance
Fear reactivation
Jo
see Sex of therapist
1976
31 children (8-15 years) in 2 groups
OST (15 minutes)
40 women in 4 groups
Snake Phobia
Significant impact of the motivation to change; interaction of motivation with modeling behavior
4,5
+
+
ur
O’Sullivan, & Gilner
lP
St-Jacques, Bouchard, & Bélanger
na
Motivation
re
see Context and stimulus variation, Length of the session, Recovery of phobic cognitions
ro of
Muris, Mayer, & Merckelbach
-p
Trait Anxiety
Hodgson, & Rachman
1970
Implosive therapy
50 in 5 groups
Snake Phobia
Improved effect of implosive therapy by showing horrifying images immediately but not delayed before implosion by imaging phobic images
5,5
Shiban, Brutting, Pauli, & Mühlberger
2015
VRET + In Vivo ET (one week later) with vs. without fear
32 in 2 groups
Spider Phobia
No group differences between people with fear reactivation prior to VR and in vivo exposure and
10,25
O
O
PH
PR
Author
Year
Treatment
Sample Size
Type of Specific Phobia
Main findings
Quality Score
Measure of success and evidence for use as predictor SR
B
PH
10
O
O
O
8
O
O
-p
Topic
No change of coping styles over the time (i. e. two years period), but better treatment results for blunting vs. monitoring
7,5
+
+
Snake Phobia
Self-efficacy as a uniformly accurate predictor of performance on tasks
7
+
+
+
O
activation
those without
Before the ET – cognitive factors 2001
60 in 4 groups
Spider Phobia
2 hours without distraction vs. 1 hour with and 1 hour without distraction
see Attentional focus guiding
No main effect of coping style, distraction nor their interaction on the short-term outcome
1993
OST
33
Spider Phobia
Muris, Merckelbach, & de Jong
1995
OST
36 women
Spider Phobia
Bandura, Adams, & Beyer
1977
Observation only vs. observation and imitation (=performance mastery experiences)
33 in 3 groups
Cote & Bouchard
2009
VRET
28
Spider Phobia
Best predictors of change in general outcomes and cardiac response: changes in perceived self-efficacy and dysfunctional beliefs; best predictor of change in behavioral avoidance: change in dysfunctional beliefs
10
lP
re
Muris, De Jong, Merckelbach, & van Zuuren
ur Jo
Self-efficacy
OST
ro of
Antony, McCabe, Leeuw, Sano, & Swinson
na
Coping Style
No substantial contribution of the coping style to short-term or long-term outcomes
Zoellner, Echiverry, & Craske
2000
2 sessions of in vivo exposure
46
Spider Phobia
Positive relationship of selfefficacy to better behavioral performance at post-treatment
7
Williams, Dooseman, & Kleinfield
1984
exposition vs. guided mastery exposition
32 in 3 groups
Driving Phobia, Acrophobia
Same effect of exposition and mastery/self-efficacy-oriented treatment regarding the duration of exposure and degree of inducement to confront threats
6,75
+
+
+
+
PR
Topic
Author
Year
Treatment
Sample Size
Type of Specific Phobia
Main findings
Quality Score
Measure of success and evidence for use as predictor SR
B
O/+
O/+
PH
PR
Mayer, Merckelbach, & Muris
2000
OST
39
Spider Phobia
Memory
Zoellner, Echiverry, & Craske
2000
2 sessions of in vivo exposure
46
Spider Phobia
41
Spider Phobia
Cortisol levels
Lass-Hennemann, & Michael
2014
OST in the morning vs. evening
lP
OST
7
+
Eyeblink startle response has a modest predictive effect, explaining 16% of the treatment effect
7
-
60 in 2 groups
Spider Phobia
Higher effectiveness of exposure therapy in the morning vs. evening; suggested underlying effect: higher endogenous cortisol levels in the morning group, enhancement of extinction memory by cortisol
12
(+)
2014
Jo
Soravia, Heinrichs, Winzeler, Fisler, Schmitt, Horn., …, & de Quervain
ur
na
1991
Better memory for the anxious response (but not the phobic stimulus) leads to better treatment success
re
Before the ET: physiological factors de Jong, Merckelbach, & Arntz
7
ro of
Perceived automaticity and irrationality of cognitions
Eyeblink startle response
No influence of self-received automaticity on treatment outcome; irrationality as predictor for treatment outcome (the more the fear is experienced as irrational, the higher the profit from the exposure therapy)
-p
rapidly; better effect of mastery (self-efficacy) model regarding restoring behavioral functioning and diminishing anxiety
Two sessions of in vivo exposurebased group therapy with vs. without Cortisol 1hr. before session
22 in 2 groups
Spider Phobia
Increased effectiveness by administrating Cortisol; significantly greater reduction in fear of spiders at follow-up, but not immediately after treatment
11
+
OST
100 youths
diverse
The presence of comorbid phobias or anxiety disorders did not affect treatment outcomes;
9,5
O
+
Before the ET: comorbid disorders Comorbid disorders
Ollendick, Öst, Reuterskiold, & Costa
2010
O
Topic
Author
Year
Treatment
Sample Size
Type of Specific Phobia
Main findings
Quality Score
Measure of success and evidence for use as predictor SR
B
PH
significant reductions in the clinical severity of other cooccurring specific phobias and related anxiety disorders through the treatment of the targeted specific phobias During the ET: emotional factors 2005
VRET
42 in 2 groups
Aviophobia
Rachman, & Levitt
1988
Diverse
74 in 4 groups
Claustrophobia
Baker, Mystkowski, Culver, Yi, Mortazavi, & Craske
2010
Two sessions of in vivo exposition
44
Acrophobia
see Heart rate
Disgust
Smits, Telch, & Randall
2002
8,75
+
Suggested relation between fear reduction and “habituation” (but not between initial levels of fear and “habituation”)
3,5
+
No consistent prediction of treatment outcome through the variables of the emotional processing theory; no support was found for initial fear activation (IFA) or within session habituation (WSH, fear subsides within sessions); measures of between session habituation (BSH, fear subsides between sessions) were predictive of short-term change, but these effects were attenuated at followup
7,75
?
O
?
-p
re
na ur 2015
Jo
Busscher, Spinhoven, & de Geus
Reductions in subjective fear ratings and HR reactions during VRET serve as significant predictors of therapy outcome
ro of
Mühlberger, Petrusek, Herrmann, & Pauli
lP
Within- and between session anxiety decrease
Two days of Cognitivebehavioural group treatment (CBGT) with VRET and in vivo exposure
79
Aviophobia
Association of within-flight habituation of HR reactivity and respiratory sinus arrhythmia reactivity and lower flight anxiety directly after the flight (shortterm), but not on long-term; low self-reported anxiety during in vivo flight exposure as the best predictor of successful long-term therapy outcome
10,5
+
30 min selfguided in vivo
27 women
Spider Phobia
Significant declines in spider fear and spider-specific disgust but not in global disgust sensitivity
7
O
+
O
O
PR
Topic
Author
Year
Treatment
Sample Size
Type of Specific Phobia
Main findings
Quality Score
Measure of success and evidence for use as predictor SR
exposure
30min. selfguided in vivo exposition
22
Blood-InjuryInjection Phobia
Olatunji, Ciesielski, Wolitzky-Taylor, Wentworth, & Viar
2012
Video exposition with or without disgust activation by showing clips of vomiting people
44 in 2 groups
Blood Injection and Injury Phobia
Olatunji, WolitzkyTaylor, Ciesielski, Armstrong, Etzel, & David
2009
Video exposition with or without disgust activation by showing disgusting pictures
Disgust evocation
Choplin, & Carter
Decline in fear and disgust across trials; fear as an independent predictor for behavior in the behavioral avoidance test, contrary to disgust (dependent on fear); initial fear during exposure as a predictor for fear and disgust in the behavioral avoidance test afterwards
8
O
O
-p
re
lP
?
Spider Phobia
Significant declines in fear and disgust through repeated exposure; reduction in disgust during exposure in the disgust activation condition remained significant after controlling for change in fear
8,75
O
O
Internet-delivered exposure (images); real vs. Hyper-real images
28 in two groups
Spider Phobia
Significant reductions in behavioral avoidance and selfreported phobic symptoms but no difference for real vs. hyperreal images, but both disgust and anxiety reduction are predictors for success
9
+
+
OST (40-90min)
30 in 2 groups
Spider Phobia
Significant decrease of fear, avoidance and disgust through exposure to disgust or fear stimuli; greater decrease in
7,25
?
?
na 2011
6,25
46 in 2 groups
ur
Jo
2015
Significant declines in disgust and especially fear across trials; decline in fear across trials; no significant effect of trial on disgust after control for change in fear; no moderation of the fear activation or reduction during exposure through global disgust sensitivity prior to exposure
ro of
2007
Matthews, Naran, & Kirkby
PH
through exposure; stronger decay for fear vs. disgust; no moderation of the level of fear activation or fear reduction during treatment through disgust levels at pretreatment
Olatunji, Smits, Connolly, Willems, & Lohr
see Disgust evocation
B
O
PR
Topic
Author
Year
Treatment
Sample Size
Type of Specific Phobia
Main findings
Quality Score
Measure of success and evidence for use as predictor SR
B
PH
+
avoidance behavior through exposure to fear stimuli Video exposition with or without disgust activation by showing disgusting pictures
46 in 2 groups
Spider Phobia
Exposure to a disgusting stimulus reduces disgust additionally to and more than fear; exposure to a feared stimulus shows the opposite pattern
8,75
+
+
de Jong, Vorage, & van den Hout
2000
OST with vs. without counterconditioning
34 in 2 groups
Spider Phobia
No additional effect of adding counterconditioning aspects to the exposure
8,5
O
O
Mühlberger, Herrmann, Wiedemann, Ellgring, & Pauli
2001
Four sessions of VRET vs. lengthy relaxation training session
40 in 2 groups
Aviophobia
Greater fear reduction through repeated VRET vs. relaxation;
10
-
Rimm, & Medeiros
1970
One session: relaxation only vs. participant modeling only vs. relaxation followed by participant modeling vs. control;
40 in 4 groups
Snake Phobia
Reduction of fear in the modeling conditions; no enhancement of the participant modeling exposure through relaxation
6
O
O
McGlynn, Moore, Lawyer, & Karg
1999
-p
-
na
lP
Relaxation
re
see Disgust
ro of
2009
Olatunji, WolitzkyTaylor, Ciesielski, Armstrong, Etzel, & David
20 in 2 groups
Snake Phobia
Reduced arousal and fear during in vivo exposures through relaxation training; relaxation working by lowering arousal throughout the course of exposure
8
-
-
20x38sec. exposition trials on 2 days (10/10) with vs. without positive valence training (at the end of day 1)
61 in 2 groups
Spider Phobia
Significant less subjective fear and less behavioral avoidance through positive valence training
6
+
+
Additional Positive Valence Training
Jo
ur
6 x 4min. in vivo exposition with vs. without relaxation training before
Dour, Brown, & Craske
During the ET: cognitive factors
2016
-
PR
Author
Year
Treatment
Sample Size
Type of Specific Phobia
Main findings
Quality Score
Measure of success and evidence for use as predictor SR
B O
Krijn, Emmelkamp, Biemond, De Wilde De Ligny, Schuemie, & Van Der Mast
2004
VRET using a head-mounted display (HMD – low presence) vs. a computer automatic virtual environment (CAVE – high presence)
37 in 3 groups
Acrophobia
Less experienced presence and anxiety during the first VRET session for early drop-outs; no relationship of presence and anxiety in treatment completers
9
O
Coping selfstatements
Krijn, Emmelkamp, Olafsson, Schuemie, & van der Mast
2007
VRET with vs. without production / activation of coping selfstatements
26 in 2 groups
Acrophobia
Reduction of anxiety of heights, avoidance of height situations and improvement of attitudes towards heights through VRET; no influence of adding selfstatements
8,5
O
CBT vs. Exposure only
Raes, Koster, Loeys, & De Raedt
2011
Behavioral vs. cognitivebehavioral OST
31 in 2 groups
Spider Phobia
Strong treatment effects and cognitive mediation of these effects in both conditions; mediation of exposure effects through cognition even without explicitly targeting those
9,5
O
O
Tardif, Therrien, & Bouchard
2019
30-minute VRET with visual vs. visual and tactical vs. visual, tactical, and haptic feedback
59 in 3 groups
Spider Phobia
Changes in self-reported selfefficacy and cognitive beliefs predicted ET success
9
+
+
OST (10 exposures, each lasting 38 seconds) focussing on affect-labelling vs. reappraisal vs. distraction
88 in 4 groups
Spider Phobia
Reduced skin conductance response in the post-test for the affect-labelling group; no differences in self-reported fear; greater reductions in fear responding by greater use of anxiety and fear words
8
O
O
ur
2012
Jo
Kircanski, Lieberman, & Craske
na
see Feedback to body sensations
lP
re
ro of
Presence
-p
Topic
Tabibnia, Liebermann, & Craske
2008
Exposure to picturs with no vs. negative vs. neutral labels
48 in 3 groups
Spider Phobia
Negative labels improved success when measured with skin conduction, but not with HR acceleration
9,5
Dee
1972
Taped implosive therapy with
58 in 5
Snake Phobia
Weak facilitating effect of instructions in reducing fear;
5,75
PH
+
?
?
?
PR
Author
Year
Treatment
Sample Size
different instructions vs. no instructions vs. control
groups
Type of Specific Phobia
Better improvement through guided threat reappraisal
7,5
+
+
Claustrophobia
Facilitating effect of guided threat reappraisal and detrimental effect of cognitive load task on fear reduction; highest fear reduction and lowest return of fear in the guided threat reappraisal condition
7,5
+
2002
6x5min. exposure only vs. with guided threat focus and reappraisal vs. with safetybehaviorutilization
46 in 3 groups
Claustrophobia
2000
6x5min. in vivo
Koch, Spates, &
lP
re
-p
ro of
Sloan, & Telch
58 in 4 groups
ur
na
Exposure only vs. with guided threat reappraisal vs. with a cognitive load distracter task vs. with both
2006
2004
B
+
Snake Phobia
Van Gerwen, Spinhoven, & Van Dyck
SR
+
36 in 3 groups
see Attentional focus guiding
Measure of success and evidence for use as predictor
6
Participant Modeling
Kamphuis, & Telch
Quality Score
Significant higher improvement of behavior and attitudes through medium or high number of performance/ induction aids (company, gradual exposure); highest generalization effect on some measures for moderate induction aids; no effect of number of facilitations on therapeutic efficacy
1974
see Safety Behavior
Main findings
retardation of fear reduction through the absence of any instructions; uncertainty about the efficacy of standardized, taped therapy
Bandura, Jeffery, & Wright
Jo
Topic
1-day behavioral (BGT) vs. 2-days cognitivebehavioral group treatment (CBGT); both conditions with information about flights, airplanes, etc.
150 in 3 groups
Aviophobia
Success of both treatment conditions; higher effectiveness of CBGT on subjective measures of fear and self-efficacy
10
+
?
Behavioral vs.
40 in 4
Phobia of small
No significant difference in the
9,5
?
O
PH
PR
Author
Year
Himle see Stimulus variation
Sample Size
Type of Specific Phobia
6,5
+
+
Return of distress through the activation of concepts unrelated to spiders (negative effect of distraction); decrease in emotional and avoidance responses between sessions through activation of concepts related to spiders
10
+
+
Claustrophobia
Facilitating effect of guided threat reappraisal and detrimental effect of cognitive load task on fear reduction; highest fear reduction and lowest return of fear in the guided threat reappraisal condition
7,5
+
2015
Image exposure only vs. with activation of concepts related vs. unrelated to spiders
66 in 3 groups
Spider Phobia
Kamphuis, & Telch
2000
6x5min. in vivo
58 in 4 groups
ur
re
na
Exposure only vs. with guided threat reappraisal vs. with a cognitive load distracter task vs. with both 30-minute selfguided exposure (1) with threatening vs. neutral words and (2) images only vs. with a cognitive load task
60 in 4 groups
Claustrophobia
Slower between-trial habituation and less fear reduction posttreatment when distracted during exposure; no effect of threat manipulation
8
-
-
OST
60 in 4 groups
Spider Phobia
No effect of distraction nor its interaction with coping style on the short-term outcome
10
O
O
2 hours without distraction vs. 1
PH
?
-p
ro of
Dethier, Bruneau, & Philippot
2001
B
Highest fear reduction in the (external) distraction condition; greatest decrease in the behavioral avoidance task and greatest increase in perceived control after treatment in the (external) distraction condition
Blood-InjuryInjection Phobia
Antony, McCabe, Leeuw, Sano, & Swinson
SR effectiveness of behavioral vs. cognitive-behavioral OST; behavioral OST perceived as more intrusive
50 in 5 groups
2004
Measure of success and evidence for use as predictor
animals and insects (spider, snake, rat/mouse, crawling insects)
Exposure only vs. with internal vs. external focus vs. external vs. internal distraction
Telch, Valentiner, Ilai, Young, Powers, & Smits
Quality Score
groups
2008
see CBT vs. Exposure only
Main findings
cognitivebehavioral OST with vs. without programmed generalization
Oliver, & Page
Jo
Attentional Focus Guiding
Treatment
lP
Topic
O
PR
Author
Year
Sample Size
Type of Specific Phobia
Quality Score
Measure of success and evidence for use as predictor SR
B
11
+
?
improvement of fear and avoidance in all conditions; less improvement through safety behavior utilization during treatment
7,5
-
-
2014
Attention Training towards positive stimuli (ATP) vs. control (ATC), both followed by OST
37 children in 2 groups
diverse
Rentz, Powers, Smits, Cougle, & Telch
2003
exposure in vivo (IV) vs. imaginal (IE) vs. active imaginal (AI)
82 in 3 groups
Cynophobia (Dog Phobia)
Deacon, Sy, Lickel, & Nelson
2010
6x5min. in vivo exposure with vs. without access to safety/coping aids during the first four exposure trials
33 in 2 groups
Claustrophobia
no reliable advantages or disadvantages of the availability of safety behavior
-p
7
O
Hood, Antony, Koerner, & Monson
2010
Exposure with vs. without safety behavior use (SBU vs. NSB)
43 in 2 groups
na
Spider Phobia
Faster approach in the SBU condition; small but significant decrease in approach distance at follow-up in the SBU condition
7,5
+
+
OST (45min.) with vs. without the use of safety gear
62 in 2 groups
Snake Phobia
Better approach during the exposure using safety behavior/gear; no differences in the follow-up behavioral avoidance test, significant improvement in fearful cognitions, subjective anxiety and distance of approach
8,5
+
O
6x max. 5min. in vivo exposure only vs. with safety behavior availability (SBA)
58 in 3 groups
Claustrophobia
Equal fear reduction in all conditions, but significantly greater improvement in selfefficacy and claustrophobic cognitions through SBU vs.
7
?
Sy, Dixon, Lickel, Nelson, & Deacon
lP
ur 2008
Jo
Milosevic, & Radomsky
2011
significantly greater reductions in danger expectancies and improved attention bias towards positive stimuli, but no differences in the clinician, parent or child-rated clinical outcomes
re
During the ET: behavioral factors Safety Behavior
Main findings
PH
PR
hour with and 1 hour without distraction
see Coping style
Waters, Farrell, Zimmer-Gembeck, Milliner, Tiralongo, Donovan, McConnell, Bradley, Mogg, & Ollendick
Treatment
ro of
Topic
?
-
Topic
Author
Year
Treatment
Sample Size
Type of Specific Phobia
vs. utilization (SBU) 46 in 3 groups
Claustrophobia
Wolitzky, & Telch
2009
6x6min. in vivo exposure with vs. without oppositional actions vs. placebo (pulsed audio-photic stimulation) vs. control
88 in 4 groups
Acrophobia
O’Sullivan & Gilner
1976
OST: 2 hours without distraction vs. 1 hour with and 1 hour without distraction
40 women in 4 groups
2002
Bandarian-Balooch, Neumann, & Boschen
2015
Shiban, Brütting, Pauli, & Mühlberger
2015a
B
7,5
-
-
10
+
PH
?
-p
Better fear extinction and generalization through the use of oppositional actions during exposure
Significant contribution of the perceived role consonance between the subject and the model to behavior change
4,5
+
46 in 4 groups
Spider Phobia
Return of fear in a new context in the follow up (1 week later); return of fear independent from perceptions of safety, danger, control and predictability
9
+
+
OST in one vs. three contexts
46 in 3 groups
Spider Phobia
One-context participants showed renewal of fear (behavioral, physiological and subjective), while this was attenuated in three contexts
8,5
+
+
+
VRET after vs. without fear reactivation with a live spider
32 in 2 groups
Spider Phobia
Long-term reduction of spider fear in both groups regardless of the fear reactivation
10,25
O
O
O
OST with different treatment contexts
ur
Mystkowski, Craske, & Echiverri
Jo
Context variation
SR
Snake Phobia
lP
see Motivation
Weakened effect of between-trial habituation through safetybehavior utilization; significantly more fear post-treatment and follow-up for the utilized safetybehavior condition
ro of
6x5min. exposure only vs. with guided threat focus and reappraisal vs. with safetybehaviorutilization
re
Sex of therapist
Measure of success and evidence for use as predictor
exposure only
2002
see CBT vs. Exposure only
Quality Score
na
Sloan, & Telch
Main findings
PR
Year
Treatment
Sample Size
Type of Specific Phobia
Quality Score
Measure of success and evidence for use as predictor SR
B +
PH
Shiban, Pauli, & Mühlberger
2013
4x 5 minuten VRET
40 in 2 groups
Spider Phobia
Extinction in multiple contexts was able to significantly reduce renewal compared to extinction in a single context
9,5
+
Vansteenwegen, Vervliet, Iberico, Baeyens, Van den Bergh, & Hermans
2007
Video exposition in one vs. three contexts
52 in 3 groups
Spider Phobia
Significant reduction of fear through extinction; generalization of extinction in the multiple but not in the single extinction group
6,5
+
Vansteenwegen, Vervliet, Hermans, Thewissen, & Eelen
2007
Three sessions of two hours of group in vivo exposure
26 in 2 groups
Spider Phobia
Enhancement of efficiency of exposure treatment in the long term through conducting treatment and tests in different contexts
7,5
+
+
+
Rodriguez, Craske, Mineka, & Hladek
1999
In vivo exposure
65 in 4 groups
Spider Phobia
No influence of context or stimulus on return of fear
9,5
O
O
O
2015
4x 5 minuten VRET
Attenuation of return of fear by multiple context exposure in VR short-term but not long-term;
11
O/+
O/+
9,5
O
O
lP 38 in 4 groups
Spider Phobia
na
Shiban, Schelhorn, Pauli, & Mühlberger
long-term effect of fear attenuation only in the multi stimuli single context group; higher benefit in the multiple stimuli condition in the behavioral avoidance test short- and longterm; no superiority of the combined multiple stimuli and contexts condition found
ur Jo
Koch, Spates, & Himle see CBT vs. Exposure only
+
re
see Trait anxiety, Length of the session, Recovery of phobic cognitions
Stimulus variation
Main findings
ro of
Context and stimulus variation
Author
-p
Topic
2004
Behavioral vs. cognitivebehavioral OST with vs. without programmed generalization
40 in 4 groups
Phobia of small animals and insects (spider, snake, rat/mouse, crawling insects)
No added effect through programmed generalization
PR
Year
Treatment
Sample Size
Type of Specific Phobia
Quality Score
Measure of success and evidence for use as predictor SR
B
One vs. five session(s) applied tension vs. one session tension only
30 in 3 groups
Blood Phobia
Significant improvement in all treatment conditions for shortand long-term; treatment of choice: one-session applied tension or tension only
11,5
O
O
Öst, L.-G., Brandberg, M., & Alm, T.
1997
One vs. five session(s) of exposure and cognitive restructuring (3hrs. massed vs. 6hrs. gradual treatment)
28 in 2 groups
Aviophobia
No differences between the conditions
9,5
O
O
Öst, Alm, Brandberg, & Breitholtz
2001
One vs. five session(s) of exposure vs. five sessions of cognitive therapy
46 in 4 groups
Claustrophobia
10
O
O
Vika, Skaret, Raadal, Öst, & Kvale
2009
One vs. five sessions of CBT by dentists (sensu Öst)
55 in 2 groups
Fraser, Kirkby, Daniels, Gilroy, & Montgomery
2001
ro of
1996
Significant treatment effect of one and five sessions of CBT performed by specially trained dentists; less anxiety for five sessions at the one-year follow up
10,25
?
?
30 in 2 groups
Significant treatment effect in both conditions; no significant differences between the threeand six-session groups; competence on the program already reached after three sessions (also in the six-sessions group)
10
O
O
na
2011
Computerassisted fear of flying treatment (CAFFT)
37
Aviophobia
The fewer the number of attended sessions, the faster the rate of change; significant correlation of HR variability and within-session rates of change (WSRC), faster improvement of people with higher HR variability
7,25
+
1971
6x 30min. in vivo
40 in 4
Snake Phobia
Same effect of the length of 0 vs. 30 vs. 45 minutes, better than 15
5,5
-
ur
3 vs. 6 sessions of CAVE Expo
PH
O
-p Intra-Oral Injection Phobia
see Heart rate
Miller, & Levis
Treatment success through all three conditions; no differences
Spider Phobia
Jo
Bornas, Gelabert, Llabres, Balle, & Tortela-Feliu
Length of the
Main findings
Hellstrom, Fellenius, & Öst
lP
Number of sessions
Author
re
Topic
+
-
PR
Author
Year
session
Treatment
Sample Size
exposition
groups
Type of Specific Phobia
Quality Score
Measure of success and evidence for use as predictor SR
B
PH
O
O
-
-
-
+
?
+
-
-
?
+
+
?
minutes; possible explanation (speculative!): reaching the highest amount of fear without time for tackling the fear and coping strategies
Rachman, & Lopatka
1988
One-session exposition with therapeutic modelling (undervs. full- vs. overlearning)
39 in 3 goups
Snake or Spider Phobia
Rodriguez, Craske, Mineka, & Hladek
1999
In vivo exposure
65 in 4 groups
Spider Phobia
Massed vs. expandingspaced ET (4 sessions in 1 day vs. 4 in 4 weeks)
31 in 2 groups
No benefit of extending the ET after reaching a level of no subjective fear
6,5
Longer treatment duration predicted higher chance of return of fear
Rowe, & Craske
1998
Computer assistance
Öst, Stridh, & Wolf
1998
Spider Phobia
Similar good effect of massed (ME) and expanding-spaced (ESE) exposure; significantly more habituation across exposure trials in the ME vs. ESE group; return of fear in the ME, but not in the ESE group
na
lP
Massed vs. expandingspaced exposure
re
-p
see Trait anxiety, Context and stimulus variation, Recovery of phobic cognitions
Main findings
ro of
Topic
103 in 4 groups
Spider Phobia
Significantly better effect through individual in vivo vs. group in vivo treatment vs. video treatment
Imaginal Exposure Therapy (IET) vs. VRET with vs. without physiological feedback
30 in 3 groups
Aviophobia
Higher effectiveness of VRGET vs. IET; possibly added efficacy through physiological feedback
Jo
ur
Self-help manual vs. video vs. group vs. individual exposure treatment
8,75
Wiederhold, Jang, Gevirtz, Kim, Kim, & Wiederhold
see Feedback to body reactions
2002
VR-Expo
9,25
PR
Author
Year
Treatment
Sample Size
Type of Specific Phobia
Main findings
Quality Score
Measure of success and evidence for use as predictor SR
B
2001
VRET with vs. without physiological feedback vs. imagery conditions
30 in 3 groups
Aviophobia
VR patients (irrespective of feedback) improved considerably more than imagery patients
9,75
+
+
Tortella-Feliu, Botella, Llabres, Breton-Lopez, del Amo, Banos, & Gelabert
2011
VRET vs. computer-aided exposure with (CAE-T) vs. without (CAE-SA) therapist’s assistance through exposure
60 in 3 groups
Aviophobia
Significant improvement in all conditions; no differences between groups
10
O
O
Andersson, G., Waara, J., Jonsson, U., Malmaeus, F., Carlbring, P., & Öst, L.-G
2013
OST vs. guided Internet-delivered self-help
30 in 2 groups
Snake phobia
?
+
Andersson, Waara, Jonsson, Malmeus, Carlbring, & Öst
2009
OST vs. guided Internet-delivered self-help
24 in 2 groups
Botella, Pérez-Ara, Bretón-López, Quero, GarcíaPalacios, & Banos
2016
one session of in vivo (IVE) vs. augmented reality exposure (ARE)
St-Jacques, Bouchard, & Bélanger see Motivation
2010
-p
re
9
?
-
50 in 2 groups
Small Animal Phobia
Improvement in both conditions; IVE more useful than ARE (posttreatment, but not at follow-up); ARE considered as less aversive, high acceptance by patients
12
-/?
+/?
VRET vs. VRET and exposure in vivo
10
Acrophobia
Effectiveness of both conditions; VRET effective, even with relatively cheap hard- and software on stand-alone computers currently on the market
2,5
O
O
Exposure, in vivo only vs. VR plus in vivo
31 children (8-15 years) in 2 groups
Spider Phobia
No increase in motivation and success through the use of VRET
9,25
O
lP
Good improvement in both conditions; better improvement for in vivo exposure, partially significant
na 2001
Improvement in both conditions; self-report shows no group effect; sig. interaction for BAT in favor of OST
Spider Phobia
ur
Emmelkamp, Bruynzeel, Drost, & van der Mast
ro of
Wiederhold, Gevirtz, & Spira
Jo
Topic
PH
PR
Topic
Author
Year
Treatment
Sample Size
Type of Specific Phobia
Main findings
Measure of success and evidence for use as predictor SR
B
9,5
-
-
2001
Prolonged singlesession treatment of live graded exposure (LGE) vs. computer-aided vicarious exposure (CAVE)
40 in 3 groups
Spider Phobia
Michaliszyn, Marchand, Bouchard, Martel, & Poirier-Bisson
2010
VRET vs. in vivo exposure
43 in 3 groups
Spider Phobia
Significant improvements in both groups; greater improvement on the Spider Beliefs Questionnaire for in vivo exposure
11
-
?
Krijn, Emmelkamp, Biemond, de Wilde de Ligny, Schuemie, & van der Mast
2004
VRET using a head-mounted display (HMD – low presence) vs. a computer automatic virtual environment (CAVE – high presence)
37 in 3 groups
Acrophobia
no relationship of presence and anxiety in treatment completers ; no effect of either using HMD or CAVE VRET
9
O
O
Motion simulation
Mühlberger, Wiedemann, & Pauli
2005
VRET with vs. without motion simulation
25 in 2 groups
Aviophobia
Stronger fear during VRET and slower habituation in the motion vs. no-motion group, but no differences in treatment outcome
8,5
O
Additional manipulation of the stimulus
Smith, Kirkby, Montgomery, & Daniels
1997
3x40minute computerdelivered treatment with relevant vs. irrelevant exposure, relevant with vs. without feedback
38 in 3 groups
Spider Phobia
Significant phobic improvement in all conditions; no significant effect of either relevance of exposure or manipulation of the onscreen feedback
8
O
6 exposure trials of max. two minutes
80 in 4 groups
Spider Phobia
No effect of perceived emotional control in general nor control over the duration of exposure on the fear levels, fear reduction, or fear prediction accuracy;
5
O
-p
PH
re
lP
na
ur
Jo 1991
ro of
Heading, Kirkby, Martin, Daniels, Gilroy, & Menzies
Craske, Bunt, Rapee, & Barlow
Significant improvement for the LGE group; no difference between the CAVE and waiting list control group (exception: subjective distress, little support for single-session CAVE treatment)
Quality Score
O
PR
Topic
Author
Year
Treatment
Sample Size
Type of Specific Phobia
Main findings
Quality Score
Measure of success and evidence for use as predictor SR
9
+
No identification of stable predictors for short- or long-term success; only significant predictors in single studies, seen as chance findings
10
O
O
Aviophobia
Patients with high HR variability improve more; HR variability only in combination with HR entropy as a significant predictor
10
+
+
Claustrophobia
Higher HR at the beginning of exposure as a predictor for better treatment outcome; HR correlates more with success than subjective measures
8
+
2016
4x 5min. VRET with pretreatment fear reaction activation by specific perceptual cues (C) vs. conceptual fearrelated information (I) vs. combination of both (CI)
38 in 3 groups
Claustrophobia
Hellstrom, & Öst
1996
OST vs. fivesession therapistguided exposure vs. self-directed exposure
138 (from four other studies)
Spider Phobia, Blood Phobia, Injection Phobia
Bornas, Gelabert, Llabres, Balle, &Tortella-Feliu
2007
Computerassisted fear of flying treatment (CAFFT)
33
Alpers, & Sell
2008
6x 30min. in vivo exposition
10
re
lP
na ur 2011
Jo
Bornas, Gelabert, Llabres, Balle, & Tortella-Feliu
Computerassisted fear of flying treatment (CAFFT)
37
Aviophobia
Significant correlation of HR variability and within-session rates of change (WSRC), faster improvement of people with higher HR variability
7,25
+
Cognitivebehavioural group treatment (CBGT)
50
Aviophobia
HR and parasympathetic activity is shown as a predictor for patients with high (but not for those with low) anxiety sensitivity
9,5
+
see Numbers of sessions
Busscher, Spinhoven, van Gerwen, & de Geus
2013
PH +
-p
During the ET: physiological factors Heart rate (HR)
Higher experienced initial selfreported fear through C; no significant enhancement through the combination (CI); higher fear habituation for C; differing physiological parameters in the groups, differing decreases in heart rate for claustrophobics throughout the conditions
ro of
Shiban, Peperkorn, Alpers, Pauli, & Mühlberger
B
PR
Topic
Author
Year
Treatment
Sample Size
Type of Specific Phobia
Main findings
Quality Score
Measure of success and evidence for use as predictor SR
Self- vs. therapistadministered CAFFT vs. VRET
20 in 2 groups
Aviophobia
Combination of HR variability and HR entropy as a predictor for success of treatment; lower tonic HR in the successful group; stronger decrease of the HR during the phasic level in the successful group (higher HR variability)
10,5
Benoit Allen, Allen, Austin, Waldron, & Ollendick
2015
OST
98 children
diverse
No change of cardiovascular reactivity through ET; no predictive power of cardiovascular reactivity
9,5
-
Busscher, Spinhoven, & de Geus
2015
Two days of Cognitivebehavioural group treatment (CBGT)
79
Aviophobia
Association of within-flight habituation of HR reactivity and respiratory sinus arrhythmia reactivity and lower flight anxiety directly after the flight (shortterm), but not on long-term
10,5
?
1995
Two sessions in vivo exposition plus relaxation vs. disconfirmation of misappraisals of bodily sensations
70 in 2 groups (49 snake / spider phobics, 21 claustrophobics)
Claustrophobia, Snake/Spider Phobia
Equal effect on basic beliefs about arousal sensations; improvement of claustrophobic fear reduction through disconfirmation of misappraisals of bodily sensations; little effect on snake/spider phobia; no generalization to nontargeted phobic situations or over time
9
-
6x5min. selfguided in vivo exposure only (EOC) vs. with heart rate feedback (HRF) vs. with paced tone control (PTC)
54 in 3 groups
Claustrophobia
Significant greater fear reduction and lower fear levels posttreatment through HRF; no higher levels of initial fear activation
7,75
+
Imaginal Exposure Therapy (IET) vs. VRET with vs. without
30 in 3 groups
Aviophobia
Higher effectiveness of VRET vs. IET; possibly higher efficacy of VRET through added physiological feedback
9,25
+
Telch, Valentiner, Ilai, Petruzzi, & Hehmsoth
2000
Wiederhold, Jang, Gevirtz, Kim, Kim, & Wiederhold see Computer
2002
-
-
+
+
PR +
-p re
lP
ur
na
Craske, Mohlman, Yi, Glover, & Valeri
ro of
2012
Jo
Feedback to body reactions
PH
+
Bornas, Riera del Amo, Tortella-Feliu, & Llabres
see Within and between session anxiety decrease
B
?
Topic
Author
Year
assistance
Treatment
Sample Size
Type of Specific Phobia
Main findings
Quality Score
Measure of success and evidence for use as predictor SR
B
9
-
-
+
PH
PR
physiological feedback VRET 2019
30-minute VRET with visual vs. visual and tactical vs. visual, tactical, and haptic feedback
59 in 3 groups
Spider Phobia
see CBT vs. Exposure only
No influence of the type of feedback on the success of VRET
ro of
Tardif, Therrien, & Bouchard
Mystkowski, Mineka, Vernon, & Zinbarg
2003
OST with vs. without caffeine
43 in 2 groups
Spider Phobia
Greater return of fear for a different caffeine state during treatment and follow-up
5,5
+
Yohimbine hycdrochloride (YOH)
Meyerbroeker, Powers, van Stegeren, & Emmelkamp
2012
VRET with vs. without YOH before exposure
45 in 2 groups
Aviophobia
No enhancing effect of the manipulation of the noradrenaline level through YOH in the used dosage (10mg)
10,5
O
Quetiapine
Diemer, Domschke, Mühlberger, Winter, Zavorotnyy, Notzon., …, & Zwanzger
2013
VRET with vs. without Quetiapine 8hrs. before exposure
58 in 2 groups
Spider Phobia
Quetiapine shows significant anxiolytic effects, but only on physiological ratings
11,5
O
+
Benzodiazepine
Wilhelm, & Roth
1997
OST with vs. without alprazolam before exposure
28 women in 2 groups
Aviophobia
Alprazolam increases physiological activation under acute stress conditions and hinders therapeutic effects of ET
8,25
-
-
Oxytocin
Acheson, Feifel, Kamenski, Mckinney, & Risbrough
2015
OST with vs. without pretreatment intranasal Oxytocine administration
23 in 2 groups
Spider Phobia
Self-report shows impeded treatment response; no significant effect on behavioral measures; less confidence in the treatment before treatment and lower ratings of therapeutic alliance for the Oxytocine
11
-
Naltrexone
Merluzzi, Taylor, Boltwood, & Gotestam
1991
Graded exposure with vs. without Naltrexone
30 in 2 groups
Spider Phobia
No differences concerning selfefficacy and cognitions, but higher anxiety in Naltrexone group
10
?
Arntz, Merckelbach,
1993
OST 2 hours
48 in 3
Spider Phobia
Hindering effect on ET through the induction of Naltrexone;
11,5
O
re
lP
na
ur
Jo
-p
Caffeine state
O
-
-
-
O
Topic
Author
Year
Treatment
Sample Size
& de Jong
Type of Specific Phobia
groups
Main findings
Quality Score
Measure of success and evidence for use as predictor SR
B
11
O
O
Return of phobic cognitions is associated with less successful outcome (increased return of fear)
-
-
+
PH
greater avoidance relapse through Naltrexone; no influence on emotional, cognitive and physiological measures
After the ET: emotional factors Rihm, Sollberger, Soravia, & Rasch
2016
2 in vivo expositions followed by 90min. sleep with vs. without odor vs. awake control group
54 in 3 groups
Spider Phobia
1999
in vivo exposure
65 in 4 groups
Spider Phobia
Rodriguez, Craske, Mineka, & Hladek
12
Spider Phobia
Individual differences in the magnitude of visual cortex activations shortly after therapy as a predictor for long-term success; stable reorganization of neural responses to initially feared stimuli in successful therapy
7,5
+
lP 2012
OST
Jo
ur
Hauner, Mineka, Voss, & Paller
na
After the ET: physiological factors Neural activation
9,5
re
see Trait anxiety, Context and stimulus variation, Length of the session
-p
After the ET: cognitive factors Recovery of phobic cognitions
No enhanced effect of sleep after exposition through presentation of a contextual odor
ro of
Conditioned odor
Schienle, Schafer, Hermann, Rohrmann, & Vaitl
2007
OST (ca. 4 hours)
14
Spider Phobia
Correlation between the reduction of subjective somatic panic symptoms and decrease of right amygdala activity in fMRI
9
+
Landowska, Roberts, Eachus, & Barrett
2018
VRET
14
Acrophobia
No correlation between subjective fear ratings and neural activation measured with fNRIS
6,75
-
-
PR
Topic
Author
Year
Treatment
Sample Size
Type of Specific Phobia
Main findings
Quality Score
Measure of success and evidence for use as predictor SR
Methylene blue
VRET (OST), afterwards 90min. sleep vs. awakefulness
40 in 2 groups
Spider Phobia
90 minutes of sleep lead to less anxiety in a post-therapy BAT and less catastrophic spiderrelated cognitions; the more stage 2 sleep, the better
9,25
+
Pace-Scott, Verga, Bennett, & Spencer
2012
14x1min. video exposure in the morning vs. in the evening, with vs. without sleep before delaymeasurement
66 in 4 groups
Spider Phobia
extinction augmentation and extinction generalization in the sleep-condition
6,5
+
Smits, Rosenfield, Otto, Powers, Hofmann, Telch, …, & Tart
2013
2x 30min. VRET with vs. without D-Cycloserine post session
29 in 2 groups
Acrophobia
D-Cycloserine appears to enhance the benefits of exposure treatment when applied after a successful session, but it seems to have detrimental effects when administered after inadequate/unsuccessful exposure sessions.
9,5
+
Byrne, Rapee, Richardson, Malhi, Jones, & Hudson
2015
OST with vs. without DCycloserine before the session
35 children (6-14years) in 2 groups
Dog and Spider Phobia
Less avoidance and less increase in fear through DCycloserine for a new stimulus in a new context; possible enhancement of ET and especially generalization in children and youths
8,5
Tart, Handelsman, Deboer, Rosenfield, Pollack, Hofmann, …, & Smits
2013
Telch, Bruchey, Rosenfield, Cobb, Smits, Pahl, & Gonzalez-Lima
PH
PR
+
+
-p re
na
lP
2014
ro of
2014
+
2x 30min. VRET with vs. without D-Cycloserine post session
29 in 2 groups
Acrophobia
No augmented efficacy of ET through the application of postsession D-Cycloserine
10
O
6x 5min. exposure trials with vs. without Methylene blue post session
42 in 2 groups
Claustrophobia
Methylene blue enhances memory and hinders return of fear after a successful ET, but has detrimental effects after an unsuccessful ET
11
+
ur
D-Cycloserine
Kleim, Wilhelm, Temp, Margraf, Wiederhold, & Rasch
Jo
Sleep
B
+
O
Quality Score: In case of differences between the two judges, the mean of the two scores is reported; measure of success: SR = Self report, B = behavioral measure, PH = physiological measure, PR = professional rating; Evidence for use as factor: + = good evidence for positive influence; - = good evidence for negative influence; o = evidence that it is not applicable as a predictor; ?= no conclusive evidence; OST: One Session Therapy sensu ÖST; ET: Exposure Therapy; fMRI: functional magnet resonance imaging; fNRIS: functional Near-Infrared Spectroscopy.
Table 3 Every researched factor and its current state in respect to its influence on the success of ET Factor Comment Factors that seem to have an influence on the success of ET Less trait anxiety leads to better ET results
Motivation
More motivation leads to better ET results
Self-efficacy
More self-efficacy leads to better ET results
Cortisol levels
Higher cortisol levels improve learning in ET
Disgust evocation
Evoking disgust additionally to anxiety improves ET results Relaxation hinders ET effectiveness
Relaxation
Addressing cognitive changes leads to better ET results
Adding cognitive parts Context variation
-p
Using different contexts leads to better ET results
ro of
Trait anxiety
Heart rate
re
HR plays a role, but it is unclear which measure best to use (variability, entropy, tonic vs. phasic HR…)
Sleeping after a successful ET leads to better results
Memory enhancing medication
Taking memory enhancing drugs (D-Cycloserine) leads to better long-term success
lP
Sleep
Potential factors that could have an influence on the success of ET (more research needed)
Eyeblink startle response
Less startle response after specific stimulus leads to better ET results Unclear if heightened feelings of disgust are independent of anxiety and if they play a role in ET success
Jo
Disgust
Better memory leads to better ET results
ur
Memory
Higher perceived irrationality (but not automaticity) of thoughts leads to better ET results
na
Automaticity/Irrationality of thoughts
Positive Valence Training seems to improve ET success
Positive Valence Training
Unclear relationship between showing safety behavior and ET success
Safety behavior
Female therapists lead to better success Massed ET leads to less ET success
Sex of therapist
Feedbacks leads to better ET success ET success does not generalize over different caffeine states
Massed ET feedback of heart rate
Medication hinders success of ET
Caffeine state Anxiety differing medication (given during ET) Return of phobic conditions
A return of phobic cognitions leads to less success of ET Higher visual cortex activation after ET leads to better long-term success
ro of
Visual cortex activation
Factors that have no influence on the success of ET
lP
Comorbidity Within-session habituation/between-session habituation
re
Factors that probably have no influence (more research needed)
-p
Fear reactivation coping style stimulus variation number of sessions (no improvement by more sessions) length of sessions (no improvement by longer ET sessions) computer assistance (no improvement over normal ET)
Presence Coping self-statements
na
Attentional focus guiding Motion simulation
ur
Conditioned odor
Jo
ET: Exposure Therapy; HR: Heart rate