Group cognitive-behavioral therapy for patients with epilepsy and comorbid depression and anxiety

Epilepsy & Behavior 20 (2011) 83–88

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Epilepsy & Behavior j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / ye b e h

Group cognitive-behavioral therapy for patients with epilepsy and comorbid depression and anxiety S. Macrodimitris a,b,c, J. Wershler a,c,d,⁎, M. Hatfield a, K. Hamilton e, B. Backs-Dermott d, K. Mothersill c,d, C. Baxter f,g, S. Wiebe a,b a

Clinical Neurosciences, Alberta Health Services, Calgary, AB, Canada Clinical Neurosciences, University of Calgary, Calgary, AB, Canada Psychology, University of Calgary, Calgary, AB, Canada d Outpatient Mental Health Program, Alberta Health Services, Calgary, AB, Canada e Forensic Assessment and Outpatient Services, Alberta Health Services, Calgary, AB, Canada f Active Treatment Team, Alberta Health Services, Calgary, AB, Canada g Psychiatry, University of Calgary, Calgary, AB, Canada b c

a r t i c l e

i n f o

Article history: Received 24 August 2010 Revised 26 October 2010 Accepted 27 October 2010 Available online 4 December 2010 Keywords: Cognitive-behavioral therapy Group Epilepsy Depression Anxiety

a b s t r a c t Clinical Practice Guidelines for depression and anxiety recommend cognitive-behavioral therapy (CBT) as an equivalent and sometimes more effective treatment than medication. The limited research investigating CBT for anxiety and depression in epilepsy demonstrates mixed results. Described here is a pilot project using an existing group CBT intervention for symptoms of depression and/or anxiety, CBT Basics II, in patients with epilepsy. Eighteen patients with epilepsy, referred by neurologists to address depression and/or anxiety symptoms, completed the 10-week group. Results demonstrated improvements in depression, anxiety, negative automatic thoughts, and cognitive therapy knowledge and skills. The group was generally acceptable to patients as indicated by good attendance rates and only one dropout. This pilot project demonstrates that group CBT is a feasible, acceptable, and promising intervention for patients with epilepsy and comorbid depression and anxiety symptoms. © 2010 Elsevier Inc. All rights reserved.

1. Introduction Research consistently demonstrates that depression and anxiety disorders are more prevalent in patients with chronic medical conditions [1,2]. In patients with epilepsy, rates of depression are estimated at 9–22% in community settings and 27–58% in tertiary care epilepsy centers [3,4], compared with 4.5% estimated in the general population in Canada [5]. Anxiety disorders are also more prevalent in patients with epilepsy: rates are estimated at 2.5–6.5% in the general population [6] compared with 15–25% in patients with epilepsy [7]. Despite the preponderance of depression and anxiety in patients with epilepsy, research demonstrates that these disorders are frequently left untreated [8,9]. Cognitive-behavioral therapy (CBT) is recommended by Clinical Practice Guidelines for treatment of depression [10,11] and anxiety [12–14]. This is based on previous research that has consistently found CBT to be an efficacious treatment [15–20]. Although medication can

⁎ Corresponding author. Outpatient Mental Health, Sheldon M. Chumir Centre, Calgary, AB T2R 0X7, Canada. Fax: + 1 403 955 6688. E-mail address: [email protected] (J. Wershler). 1525-5050/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2010.10.028

produce more immediate treatment effects [15], CBT demonstrates superior relapse prevention rates compared with medication treatments [15,16,21]. When CBT is combined with mindfulness meditation, additional reductions in symptoms of depression and anxiety [22–29], as well as reduced risk of relapse [30–32], particularly for those with more chronic depression [33,34], have been found. A major limitation to CBT acknowledged in Clinical Practice Guidelines (CPGs) is its limited accessibility [13,35]. This is an important problem for patients with epilepsy. While many epilepsy centers have access to a consulting psychiatrist and a neuropsychologist, neither typically offering CBT as a treatment option [36]. The limited research investigating CBT for the treatment of anxiety [37], depression [38], and adjustment-related issues (e.g., seizure fear) [39] in epilepsy demonstrates that CBT is also an effective treatment for patients with epilepsy with these comorbid problems. However, this research has significant limitations. First, it typically reports individual treatment [40] or case studies [37], rather than group interventions [see 41,42 for exceptions]; the latter could be more efficient and provide improved accessibility to CBT. Second, there is a preponderance of research studying the influence of CBT interventions on reducing seizure severity or frequency [41,43], rather than on reducing comorbid psychiatric issues. This may account for some negative findings for

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psychological symptom change in patients with epilepsy in this literature [e.g., 42,44]. Finally, only a few studies [38,43] used a randomized, waitlist-control method to test the effectiveness of CBT. Thus, further research is required to determine whether CBT is effective for managing depression, anxiety, and adjustment-related problems in individuals with epilepsy, and whether providing CBT in a group format is effective and acceptable to patients with epilepsy. The primary objective of this study was to pilot an existing 10-session group CBT program GCBT, CBT Basics II [45,46], for use with patients with epilepsy with comorbid depression and/or anxiety symptoms. This group program is similar to other innovative CBT programs [47–53] that target diagnostically heterogeneous (i.e., those presenting with depression, anxiety, or both) patients and have been associated with symptom reduction. We hoped to demonstrate proofof-principle for this group program as a likely effective and feasible means of providing CBT to patients with epilepsy, toward future development and integration of this program into regular clinical services. Specific research questions were: 1. Is GCBT effective for reducing symptoms of depression, anxiety, and negative automatic thoughts in patients with epilepsy? 2. Can a 10-session GCBT program increase knowledge of CBT concepts and skills in patients with epilepsy? 3. Is GCBT acceptable to patients with epilepsy, as measured by number approached versus number who agreed to attend the group (i.e., recruitment attrition rate), number of overall sessions attended, and patient satisfaction with treatment?

Table 1 Demographic characteristics of group completers. n Marital status Single Married/common-law Separated/divorced Education Some high school High school graduate Some trade school or college Trade school or college graduate University undergraduate degree Employment Full-time/part-time paid Disability Student Not currently working Psychotropic medicationsa Antidepressant Anxiolytic Anticonvulsantb Antipsychotic Sleep medication Reason for referral Depression symptoms only Anxiety symptoms only Both depression and anxiety symptoms

% 9 7 2

50.0 38.9 11.1

4 6 3 2 3

22.2 33.3 16.7 11.1 16.7

7 6 1 4

38.9 33.3 5.6 22.2

5 3 10 1 3

27.8 16.7 55.6 5.6 16.7

2 4 12

11.1 22.2 66.7

a Psychotropic medications indicate medications currently being taken at the beginning of CBT Basics II. b Anticonvulsant medication was used in all cases for the purpose of controlling seizure disorders.

2. Methods 2.1. Participants Eighteen patients with epilepsy (11 women, 7 men; mean age = 41.22 years, SD = 11.48), referred by neurologists to address depression (n = 2), anxiety (n = 4), or both depression and anxiety (n = 12) symptoms, completed the group (i.e., attended at least 6 of 10 sessions and completed both pre- and posttest questionnaires). One additional participant was recruited but dropped out after the first session. The 18 group completers were part of one of three pilot groups with five to seven participants in each group. Table 1 summarizes the demographic characteristics of the sample. 2.2. Procedure Fig. 1 depicts the primary procedures used in the pilot project, including recruitment, inclusion/exclusion criteria, and symptom evaluation measures. All participants were recruited from the Calgary Epilepsy Programme Clinical Psychology Service waiting list. Interviews were conducted by telephone by the Calgary Epilepsy Programme clinical psychologist (S.M.) and a social worker (M.H.) to screen for inclusion and exclusion criteria. Thirty-eight patients with epilepsy were contacted by telephone and invited to participate in the group. Nineteen (50% of those contacted) met our criteria, were available for the duration of the group, and agreed to participate. CBT Basics II [45,46] is a weekly 10-session group program for depression and/or anxiety. Standard CBT skills for anxiety and depression treatment, based on evidence-based literature, treatment manuals, and patient resources [31,54–60], were used to create the group program. Sessions 1–4 focus on behavioral interventions; sessions 5–7 focus on cognitive techniques; sessions 8 and 9 on advanced behavioral skills; and session 10 on relapse prevention. Each session incorporates mindfulness meditation, which, as indicated previously, has been demonstrated to further reduce anxiety and depression symptoms in standard CBT interventions [e.g., 23, 24] and to reduce depression relapse rates in those who also learned CBT skills [e.g., 30, 31]. This form of meditation teaches patients to focus their

thinking in the present moment [30] rather than on the past (i.e., depression-related thoughts are often “past focused”) or the future (i.e., anxiety-related thoughts are often “future focused”). Table 2 summarizes the session content and goals in more detail. The program is also further described for a shorter (six-session) version of the group [61]. Participants attended one of three group sessions between February 2008 and June 2010. Groups were conducted weekly for 2 hours and began with a review of the agenda for the session and a 30-minute mindfulness meditation exercise. Sessions ended with a summary of the skills learned and a homework assignment based on the new skill. Opportunity for skill practice and discussion was provided during each group. The materials were based on the standard group program previously developed for general mental health patients [45,46,61]. However, examples were modified to fit key problem areas identified for patients with epilepsy (e.g., anxiety secondary to the unpredictable nature of seizures, depression secondary to activity restriction that may be imposed by a seizure diagnosis). Participants were provided with workbooks and a meditation CD for practice between sessions. The group was run by a psychologist (S.M.) and a social worker (M.H.), who are both experienced cognitive-behavioral therapists. Participants were aware that they were required to complete at least 6 of 10 sessions to obtain maximum benefit from the group. This cutoff was established because each session builds on previously presented information and allows for practice of skills. A similar rate of attendance was also the criterion for group completion for the six-session version of the group, and it was found that participants benefited from this intervention [61]. They were also encouraged to contact the therapists between sessions if they were struggling with learning a new skill. Finally, the leaders met with each of the participants individually following the group to review their pre–post symptom questionnaires and ensure that appropriate follow-up was in place for those who required additional support for depression and/or anxiety following the group. A research assistant entered the information into SPSS Version15.0 and scored the pre- and postgroup questionnaires. The study was approved by the University of Calgary Conjoint Health Research Ethics Board, and all individuals provided informed consent.

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Fig. 1. Summary of the procedure used for gathering participants for the CBT Basics II group.

2.3. Measures Standard demographic information was collected from participants as part of their questionnaire package, administered at session 1. This included date of birth, age, gender, marital status, education level, and employment status. 2.3.1. Primary referral reason and treatment information Psychiatric symptoms were identified by neurologists and nurses referring patients with epilepsy to the Clinical Psychology Service using a standard referral form. Referral sources checked boxes next

to key symptoms that applied to the patient being referred, with options including: adjustment/quality of life issues, depression, anxiety, trauma, anger/hostility, bipolar disorder, personality disorder, paranoia/ psychotic disorder, and nonepileptic events/conversion disorder. This form also requires physicians and/or nurses to indicate whether the patient has cognitive impairments and to list all the patient's medications (psychiatric and antiepileptic). A semistructured telephone screen for the inclusion and exclusion criteria (see Fig. 1) was developed to identify patients who were eligible for the group. In addition, participants were asked basic screening questions from the Structured Clinical Interview for the

Table 2 CBT Basics II group structure and content. Session No.

Session focus

1

Orientation to CBT model and group; activity–mood monitor Goal: To build awareness of maladaptive behaviors/activities and their contribution to depression and anxiety symptoms Behavioral skills: activity scheduling (depression) Goal: To build in rewarding activities, in a stepwise manner, to combat depression symptoms Behavioral skills: exposure (anxiety) Goal: To create a hierarchy of feared situations that patients will slowly challenge themselves with until the situation provokes little anxiety (starting with least feared situations) Cognitive skills: thought monitoring Goal: To build awareness of maladaptive thoughts and their contribution to depression and anxiety symptoms Cognitive skills: thought restructuring Goal: To learn to balance thinking toward a more realistic (rather than very negative or positive) view Behavioral experiments: testing balanced thoughts Goal: To create experiments that assist patients with testing more realistic thoughts that they do not completely believe Action plans: problem solving Goal: To create action plans toward changing problematic issues that surface as patterns and require modification toward improved mood Relapse prevention Goal: To review primary skills learned and self-awareness of key triggers, maladaptive behaviors, and maladaptive thought patterns that can contribute to mood problems; to establish an action plan for continued progress following group

2 3

4 5–7 8 9 10

Note. Each session began with 30 minutes of mindfulness meditation.

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DSM-IV [62] to ensure that their depression or anxiety symptoms were primary and causing enough distress to warrant treatment. These screening questions do not provide enough information to determine if participants meet full criteria for a depressive or anxiety disorder; therefore, specific psychiatric diagnoses were not captured as part of this pilot project (see Discussion for further information). Rather, “reason for referral” and confirmation of primary anxiety, depression, or adjustment-related anxiety/depression through the telephone screen were used as the main indicators of the primary presenting psychiatric issue. The acceptability of the CBT Basics II group program to patients with epilepsy was assessed through (1) enrollment/attrition rate (i.e., n contacted vs n participated); (2) reason for not participating; (3) session attendance; and (4) dropout rates. We also explored feedback about the satisfaction with the group experience provided by participants after conclusion of the group. The following provides a brief description of the main symptom measures used in this pilot project. 2.3.2. Beck Depression Inventory II The Beck Depression Inventory II (BDI-II) is a 21-item self-report depression symptom measure [63]. Each item is answered on a 0 to 3 intensity scale (maximum score = 63). The BDI-II has high internal consistency (α = 0.92, outpatient sample). The BDI-II has frequently been used to measure depression symptoms in individuals with epilepsy [39,64–68]. 2.3.3. Beck Anxiety Inventory The Beck Anxiety Inventory (BAI) is a 21-item scale measuring severity of anxiety (panic) symptoms on a 4-point scale (0 to 3, maximum score = 63) [69]. The BAI has excellent internal consistency (α = 0.94). The BAI has frequently been used to measure anxiety symptoms in individuals with epilepsy [39,65,66,68]. 2.3.4. Automatic Thoughts Questionnaire The Automatic Thoughts Questionnaire (ATQ) is a 30-item measure of automatic negative thoughts or self-statements that are common in depression and are targeted in CBT interventions [70]. Items are scored on a Likert scale ranging from 1 (not at all) to 5 (all the time). The ATQ has excellent internal consistency (α = 0.97). 2.3.5. Cognitive Therapy Awareness Scale The Cognitive Therapy Awareness Scale (CTAS) is a 40-item selfreport true/false scale designed to measure acquisition of cognitive therapy concepts [71]. This is the only measure available in the literature for this type of assessment. The psychometric properties of the scale have not been extensively investigated. 2.3.6. Feedback form/Client Satisfaction Questionnaire For the first group, participants were asked to complete an openended feedback form about their experience with the group. For the second and third groups, the Client Satisfaction Questionnaire (CSQ), a standardized eight-item therapy evaluation measure, was completed. Each item is rated from 1 to 4, with higher scores indicating increased satisfaction. The CSQ has excellent internal consistency (α = 0.93) [72]. 3. Results Paired-sample t tests were used to explore changes in affective symptoms and cognitive therapy skill acquisition that occurred over the course of the intervention. Results are summarized in Table 3. There were improvements in depression, anxiety, and negative automatic thoughts. Increases in cognitive therapy knowledge were also observed. Regarding acceptability of the group program to patients with epilepsy, only one (2.6%) of all potential participants contacted (n = 38)

Table 3 Means, SD, and paired-sample t tests of mean differences before and after the CBT Basics II group. Pregroup

BDI-II BAI ATQ CTASa

Postgroup

Test of mean differences

Mean

SD

Mean

SD

t

P

27.83 24.67 78.28 24.56

11.29 15.65 32.80 4.73

13.89 15.78 58.83 27.50

9.55 9.78 21.16 4.23

6.44 2.88 4.15 –2.86

b 0.001 0.010 0.001 0.011

Note. BDI-II, Beck Depression Inventory II, scores range from 0 to 63; BAI, Beck Anxiety Inventory, scores range from 0 to 63; ATQ, Automatic Thoughts Questionnaire, scores range from 30 to 150; CTAS, Cognitive Therapy Awareness Scale, scores range from 0 to 40. a Higher scores represent improvements for this scale.

said he or she would not participate in a group program. Two (5.3%) other potential participants contacted did not participate because their symptoms decreased without intervention while they were on the Clinical Psychology Service waiting list. Seven (18.4%) were unable to attend the program on the day and time established and were placed back on the waiting list. Other reasons for not attending the group were: not meeting group criteria (n = 2, 5.3%); barriers to attending group (i.e., no transportation, n = 2, 5.3%); did not return calls when the group leaders followed up on referrals (n =3, 7.9%); received other treatment while on waitlist (n = 1, 2.6%); or unknown (i.e., confirmed attendance but did not attend the first session, n =1, 2.6%). Participants attended an average of 8 sessions (range= 6–10) and there was only one individual (5.2%) who dropped out. Feedback from the first group (n = 7 participants) indicated that participants benefited from all aspects of the program, but particularly the behavioral technique of scheduling rewarding daily activities. Regarding the cognitive strategies, a common theme reported by participants was that their anxious thoughts about seizures were typically based on evidence of negative events that occurred secondary to seizures in the past. Participants with previous significant injuries secondary to seizures had difficulty balancing their anxiety-based thinking about seizures even when only a small minority of previous seizures may have caused injury. With respect to ways to improve the group, three (42.9%) believed the group should have been longer and four (57.1%) said the sessions were “too rushed.” For the second (n = 6 participants) and third (n = 5 participants) groups, the CSQ demonstrated that 10 participants (90.9%) were mostly or very satisfied with the group, whereas only one (9.1%) was indifferent or mildly dissatisfied. The majority of participants (n = 10, 90.9%) identified that the group helped them with their problems. Among the participants who completed the group (n = 18), the majority (88.9%) reported that they would recommend the group to other patients. 4. Discussion This article reports a pilot project implemented to enhance accessibility to cognitive-behavioral therapy (CBT) for patients with epilepsy with comorbid symptoms of depression and/or anxiety. The first objective of this study was to establish proof-of-principle for the effectiveness of the group, which we explored by assessing pre–post symptom change for anxiety, depression, and negative automatic thoughts. Results demonstrated statistically significant improvements in depression symptoms, anxiety symptoms, and negative automatic thoughts. The improvements demonstrated on all symptom measures indicate that this program is a promising intervention for improving symptoms of depression and anxiety in patients with epilepsy. The second objective was to investigate whether a 10-week group CBT intervention could facilitate cognitive therapy knowledge/skill acquisition. The significant improvement found in CBT skills and knowledge over the course of the intervention provides support for

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the ability of this type of intervention to facilitate knowledge and skill acquisition of CBT concepts. A third and final objective of our pilot project was to determine whether the group would be acceptable to patients with epilepsy, as measured by recruitment attrition (i.e., number approached vs number who agreed to attend the group), number of overall sessions attended, and patient satisfaction with treatment. Our recruitment attrition rate of 50% was higher than the average recruitment attrition rate for group therapy reported in the literature (~40%) [47,73]. However, the main reason potential participants did not agree to participate in our pilot project was conflicts with the time and day of the group (all groups were run on a weekday during the day), and not because they did not accept a group format for treatment. In our future work, we plan to offer the group at different times of the day to try to identify the optimal time for patient attendance. Regarding the other aspects of our group acceptability assessment, only one participant dropped out of the group. A meta-analysis exploring psychotherapy dropout reports an average 46.86% dropout rate across all therapy modalities [i.e., group and individual therapy, [74]. Although we can partly attribute our 94.7% retention rate to the acceptability of the group to participants, this also probably reflects the retention benefits secondary to our contacting participants when they did not attend a session. This is not typical practice in psychotherapy and certainly is not always feasible in busy clinical practices. This additional patient contact also likely influenced the high rate of group session attendance, averaging 8 of 10 sessions across all group members. Finally, in terms of satisfaction, participants were asked on their evaluation form whether they would recommend the program to other patients with epilepsy. All but two participants said that they would, which suggests that participants received at least enough benefit from the program to recommend it to others. Regarding limitations, as a pilot project with a small sample size, we cannot be certain that the effectiveness of the program will be demonstrated with larger sample sizes. In addition, no epilepsy-specific depression and anxiety measures are available, so the measures used were designed for use in the general population. It is possible that some of the symptoms may overlap with symptoms of epilepsy/seizures (e.g., feelings of fear on the BAI could be directly caused by seizures) and the side effects of seizures (e.g., fatigue on the BDI-II). However, the use of the BDI-II and BAI is based on precedent set in other research exploring comorbid psychiatric problems in epilepsy, as indicated in the Measures section. In addition, recent research in individuals with other medical problems (i.e., myocardial infarction) demonstrated that somatic symptom scores, as measured on the BDI-II, were not significantly different from somatic symptom scores of psychiatric outpatients or university students [75], suggesting that the overlap of medical symptoms and symptoms of depression may not be as significant as often assumed. Additionally, we have not demonstrated that this program can be applied specifically as a treatment for depression or anxiety; we can only identify that it provided symptom improvement and increases in CBT knowledge. This is because we did not assess patients to determine whether they met full criteria for a Major Depressive Disorder or an Anxiety Disorder. However, we established that all participants were determined, by the referring neurologist or nurse, and by a brief semistructured telephone interview, to have symptoms of depression and/or anxiety that were significant enough to warrant intervention. In the future, we hope to obtain additional funding to determine psychiatric diagnosis using a structured diagnostic interview. We also hope to obtain follow-up information (e.g., 1 month, 6 months, 12 months) to determine whether symptoms remain reduced over time. Another limitation of this pilot project was related to the minimal information collected about the patients’ seizure disorders other than confirming that they had an epilepsy diagnosis and did not experience nonepileptic events. Previous research applying CBT to patients with epilepsy explored whether seizure frequency was reduced as a result of

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CBT intervention [40,41,43]. Because the primary purpose of the current project was to explore the effectiveness of GCBT for reducing comorbid depression and anxiety symptoms, we did not assess change in seizure frequency from pre- and postgroup. However, we recognize that seizure frequency is closely tied to psychological adjustment issues and believe it is important to explore whether seizure frequency might influence responsiveness to the group program. Information regarding the type, severity, and age at onset of epilepsy will also be collected in the future, as these epilepsy-related factors could also have implications for the outcome of the intervention. Additionally, in the future we will assess quality of life to determine if participation in this group intervention can have positive impacts on the quality of life in individuals with epilepsy. Acknowledgements This project was funded by a Hotchkiss Brain Institute Clinical Research Unit Pilot Project Funding Grant, 2008–2010. An earlier version of this article was awarded the Canadian League Against Epilepsy (CLAE) Allied Health Worker Research Award, October 2009. The abstract for this article was published as part of the Proceedings, 2008 Annual Meeting of the American Epilepsy Society, Seattle, WA. A poster based on this abstract was presented at this meeting on December 7, 2008. References [1] Taylor RR. Cognitive behavioral therapy for chronic illness and disability. Berlin: Springer; 2005. [2] Taylor SE. Health psychology. 5th ed. New York: McGraw–Hill; 2000. [3] Kanner AM. Depression in epilepsy: prevalence, clinical semiology, pathogenic mechanisms, and treatment. Biol Psychiatry 2003;54:388–98. [4] Schmitz B. Depression and mania in patients with epilepsy. Epilepsia 2005;46(Suppl 4): 45–9. [5] Patten SB, Beck CA. Major depression and mental health care utilization in Canada: 1994 to 2000. Can J Psychiatry 2004;49:303–9. [6] American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Arlington, VA: American Psychiatric Publ.; 1994. [7] Harden CL. Depression and anxiety in epilepsy patients. Epilepsy Behav 2002;3(3, Pt 1): 296. [8] Barry JJ, Jones JE. What is effective treatment of depression in people with epilepsy? Epilepsy Behav 2005;6:520–8. [9] Thompson AW, Miller JW, Katon W, Chaytor N, Ciechanowski P. Sociodemographic and clinical factors associated with depression in epilepsy. Epilepsy Behav 2009;14:655–60. [10] NICE Guideline: depression (amended). Management of depression in primary and secondary care. London: National Institute for Health and Clinical Excellence; 2007. p. 67. [11] Royal Australian and New Zealand College of Psychiatrists Clinical Practice Guidelines Team for Depression. Australian and New Zealand clinical practice guidelines for the treatment of depression. Aust NZ J Psychiatry 2004;38:389–407. [12] Quick reference guide (amended): Anxiety: Management of anxiety (panic disorder with or without agoraphobia and generalized anxiety disorder) in adults in primary, secondary, and community care. London: National Institute for Health and Clinical Excellence; 2007. [13] Royal Australian and New Zealand College of Psychiatrists Clinical Practice Guidelines Team for Panic Disorder and Agoraphobia Team. Australian and New Zealand clinical practice guidelines for the treatment of panic disorder and agoraphobia. Aust NZ J Psychiatry 2003;37:641–56. [14] Canadian Psychiatric Association. Clinical practice guidelines: management of anxiety disorders. Can J Psychiatry 2006;51(Suppl 2):1–92S. [15] Antonuccio DO, Thomas M, Danton WG. A cost-effectiveness analysis of cognitive behavior therapy and fluoxetine (Prozac) in the treatment of depression. Behav Ther 1997;28:187–210. [16] Otto MW, Pollack MH, Maki KM. Empirically supported treatments for panic disorder: costs, benefits, and stepped care. J Consult Clin Psychol 2000;68:556–63. [17] Diefenbach GJ, Abramowitz JS, Norberg MM, Tolin DF. Changes in quality of life following cognitive-behavioral therapy for obsessive–compulsive disorder. Behav Res Ther 2007;45:3060–8. [18] Heldt E, Manfro GG, Kipper L, Blaya C, Isolan L, Otto MW. One-year follow-up of pharmacotherapy-resistant patients with panic disorder treated with cognitivebehavior therapy: outcome and predictors of remission. Behav Res Ther 2006;44: 657–65. [19] Lynch D, Laws K, McKenna P. Cognitive behavioural therapy for major psychiatric disorder: does it really work? A meta-analytical review of well-controlled trials. Psychol Med A J Res Psychiatry Allied Sci 2010;40:9–24. [20] Stewart RE, Chambless DL. Cognitive-behavioral therapy for adult anxiety disorders in clinical practice: a meta-analysis of effectiveness studies. J Consult Clin Psychol 2009;77:595–606.

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