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Prophylactic antidepressant treatment following acute coronary syndrome: A systematic review of randomized controlled trials
Journal of Psychiatric Research 94 (2017) 186e193
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Journal of Psychiatric Research journal homepage: www.elsevier.com/locate/psychires
Prophylactic antidepressant treatment following acute coronary syndrome: A systematic review of randomized controlled trials € genur a, 1 Ole G. Christiansen a, Michael T. Madsen a, b, *, Erik Simonsen a, b, 1, Ismail Go a b
Center for Surgical Science, Zealand University Hospital, Denmark Psychiatric Research Unit, Region Zealand, Denmark
a r t i c l e i n f o
a b s t r a c t
Article history: Received 5 December 2016 Received in revised form 10 July 2017 Accepted 17 July 2017
Major depressive disorder is significantly increased in patients following acute coronary syndrome resulting in twofold increased mortality compared with patients without depression. The depression diagnosis is often missed leading to considerable undertreatment. This systematic review assesses the current evidence of primary prophylactic treatment of depression in patients after acute coronary syndrome. The study protocol was prospectively registered at PROSPERO (registration number CRD42015025587). A systematic review were conducted and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Embase, PsychINFO, CINAHL, and Cochran Library was searched. Two independent reviewers screened the records. The inclusion criteria were randomized controlled trials on adult patients with acute coronary syndrome treated prophylactically with an antidepressant intervention of any kind. A validated assessment tool should measure depression and depressive symptoms. Languages were limited to articles written in English. Six articles were included. Four studies utilized different components of case and disease management, health coaching, or relaxational audiotapes as intervention compared with usual care or with no formal program of rehabilitation. None of the studies showed any significant prophylactic effect against depression. One study with a program of health education and counselling and another study with a pharmacological antidepressant showed significant prophylactic effect on depression and depressive symptoms. All six included studies were associated with high risk of bias. There is not strong evidence of the effects of any type of routine antidepressant prophylaxis in patients following acute coronary syndrome. Further high quality studies are warranted. © 2017 Elsevier Ltd. All rights reserved.
Keywords: Acute coronary syndrome Depression Preventive Prophylaxis Antidepressant Anxiety
Contents 1. 2. 3.
4. 5.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187 Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 188 3.1. Risk of bias assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189 3.2. Outcome description . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191 Declaration of conflicting interests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192 Author contributions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192
* Corresponding author. Center for Surgical Science, Zealand University Hospital, Lykkebækvej 1, 4600 Køge, Denmark. E-mail address: [email protected] (M.T. Madsen). 1 €genur have shared last authorship. Erik Simonsen and Ismail Go http://dx.doi.org/10.1016/j.jpsychires.2017.07.016 0022-3956/© 2017 Elsevier Ltd. All rights reserved.
O.G. Christiansen et al. / Journal of Psychiatric Research 94 (2017) 186e193
1. Introduction Major depressive disorder was significantly increased in patients following acute coronary syndrome (ACS) (Thombs et al., 2006; Jiang et al., 2002) with a rate ratio of 1.28 compared with a comparable reference population (Osler et al., 2016). The prevalence of depression (13,7%) was constant at least 18 months following myocardial infarction (Hanssen et al., 2009). The risk of depression was comparable to the risk in patients after stroke after controlling for sex, age, and level of handicap (hazard ratio (HR) 1.08; p ¼ 0.72) (Aben et al., 2003). Other register-based literature has shown prevalence of depression to be higher in patients following stroke compared to myocardial infarction (Jorgensen et al., 2016a). The prevalence of antidepressant prescription has increased considerably during the last decades, reaching 10e15% by 2005 in patients after ACS (Czarny et al., 2011). A nationwide Danish retrospective cohort study found that 12% of patients were treated with antidepressants within two years after their ACS e almost two times more than those without ACS (Jorgensen et al., 2016b). Recurrent or new onset depression in patients with ACS had higher mortality rates than patients with no depression (Osler et al., 2016; Meijer et al., 2011; van Melle et al., 2004). A recent patient level meta-analysis showed that hazard ratios for the association between post-myocardial infarction depression and all-cause mortality was 1.32 (95% CI 1.26e1.38, P < 0.001) but was attenuated after adjustment for disease severity (HR ¼ 1.23) (Meijer et al., 2013). However, depression was still an independent risk factor for all-cause mortality and cardiovascular events, which was acknowledged by the American Heart Association (Lichtman et al., 2014), who has made recommendations for screening of depression following ACS (Lichtman et al., 2008). The pathophysiology of post-ACS depression remains unclear and several mechanisms have been put forth (Jiang et al., 2002; Carney et al., 2002) including dysfunction of the autonomic nervous system, heart rate variability and an increase of the inflammation response (Jiang et al., 2002; Huffman et al., 2013; Carney and Freedland, 2009; Carney et al., 2005; Poole et al., 2011; Ross, 1999; Kaptoge et al., 2014; Pizzi et al., 2010; Howren et al., 2009). Cytokines have been associated with atherosclerotic plaque formation, progression, and rupture; and as such they were major contributors to the pathogenesis of coronary artery disease and myocardial infarction (Huffman et al., 2013). Depression have also been linked to increased levels of interleukins (especially CRP, IL-1, and IL-6), both in patients with and without a history of cardiac disease (Pizzi et al., 2010; Howren et al., 2009). Platelet activity and aggregation is yet another possible link between depression and ischemic heart disease as serotonin plays an important role in platelet function (Pizzi et al., 2009). Of potential direct mechanisms, Huffman J.C. et al (Huffman et al., 2013). mention neural-immune interaction via the serotonin receptors effect on cardiac outcomes, and increased cytokines which may elevate the degradation of tryptophan (precursor to serotonin) resulting in overall lover serotonin levels (Huffman et al., 2013). Besides the association between post-ACS depression and mortality, patients suffering from depression related to ACS were less likely to engage in health promoting behaviours, including maintenance of a healthy diet, regular exercise, adherence to medications (Rieckmann et al., 2006; Carney et al., 1995; May et al., 2010), stress reduction, and completion of cardiac rehabilitation programs following myocardial infarction (Blumenthal et al., 1982; Ziegelstein et al., 2000). This was associated with an increased risk of cardiac events (Gehi et al., 2007; Wessel et al., 2004). Patients with cardiac disease and clinical depression, who were hospitalized and treated for their depression on the other hand showed
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enhanced effect on adherence to diet, exercise, and medication (Bauer et al., 2012). Thus, suggesting these negative behavioural factors would be modifiable with the correct treatment. Moderate to severe depression were found to be significantly under-recognized and undertreated among patients with ACS (Amin et al., 2006; Huffman et al., 2006), which leads to patients receiving inadequate treatment. In the general population studies suggests that, despite the severity and possible complications of depression, only half of those with depression will seek professional help (World Health Organization, 2000). Given the high risk of patients developing depression and the problems inherent with diagnosing depression, there is increasing interest in prophylactic therapies that may prevent abnormal mood and improve outcome after ACS. The aim of this current systematic review was to review the prophylactic treatment of depression in patients after ACS. 2. Method The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines (Liberati et al., 2009). The systematic review was registered on PROSPERO (Booth et al., 2011a, 2011b) with registration number: CRD42015025587. We used the following PICOS (P: population, I: intervention, C: comparator/control, O: outcomes, S: study design) (Liberati et al., 2009) when constructing the eligibility criteria and the search strategy; P: humans, adults, 18 years, diagnosed with ACS, I: antidepressant treatment of any kind, C: placebo or active treatment, O: depression and depressive symptoms, and S: randomized controlled trails (RCT). Studies in English comparing pharmaceutical agents with placebo, psychotherapy against standard care, or any other antidepressant treatment against standard care to prevent depression in patients with ACS were included. No restriction on dose, administration, timing of the intervention, or to other outcomes being assessed in the studies was chosen. The search was carried out using PubMed, Embase, PsycINFO, CINAHL, and the Cochrane Library (PubMed: 1966 - now, Embase: 1974 - now, PsycINFO: 1806 - now, CINAHL: 1981 - now, Cochrane Library: date of inception - now). Contact with the study authors was made if the data were not extractable from text or figures in the article. The search was conducted on 19th of December 2015. The same search terms were use in the databases, however, the mesh terms were modified to fit to the search criteria of the respective databases. No limits were set for language; thus all records were manually screened with regard to being English. No limits were set with regard to the years of publication. No attempt was made to include potential ongoing trials. The reference list of all included studies was manually reviewed to identify additional relevant studies. The exact search terms for PubMed were: (coronary artery disease OR ischemic heart disease OR myocardial infarction OR acute myocardial infarction OR unstable angina OR acute coronary syndrome OR coronary bypass surgery OR atherosclerosis) AND (antidepressant OR tricyclic antidepressant OR selective serotonin reuptake inhibitor OR serotonin-noradrenaline reuptake inhibitor OR noradrenergic and specific serotonergic antidepressants OR mono amino oxidase inhibitors OR melatonin OR agomelatine OR Psychotherapy OR Psychological intervention OR Cognitive behavioural therapy OR psychodynamic psychotherapy OR interpersonal psychotherapy OR intervention OR counselling OR mindfulness OR family therapy OR psychosocial intervention OR stress management OR behavioural OR social support OR exercise) AND (prevention OR primary prevention OR secondary prevention OR tertiary prevention OR prophylactic OR prophylaxis) AND (depression OR depressive symptoms OR depressive disorder OR mood OR mood disorder).
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After removal of duplicates two independent reviewers (OGC, MTM) screened title and abstract for full-text evaluation according to inclusion and exclusion criteria mentioned above. Any discrepancies were resolved through discussion until consensus was reached. Upon full-text evaluation the reference list of the selected articles was scanned for further literature. Covidence, a web-based review software platform (Vertitas Health Innovation Ltd., 2015), was utilized as a blinded screening tool. Data on participant characteristics, interventions, and trial methodology were extracted. Two authors (OGC, MTM) assessed the methodological quality of the included studies by using the Cochrane Handbook for Systematic Review of Interventions' Risk of bias assessment tool (Higgins et al., 2011). Trial protocols for all included studies were searched for in two trial registers: clinical trials.gov and WHOs Trials Search, and published protocol articles were consulted if available. Information on bias assessment was used in the overall data synthesis to characterize the quality of the included studies. Our outcome was the measurement of depression and/or depressive symptoms, regardless of whether this was assessed as a primary, secondary, or tertiary outcome in the studies. The outcome measure had to be a validated clinician-administered or self-rating questionnaire with known and validated psychometric properties and with the main focus on diagnosing and/or measuring depression. Results had to be reported in the manuscript
in means (standard deviation, SD) or median (interquartile range, IQR/range). 3. Results A total of 1780 records were identified in the databases searched (PubMed ¼ 887 hits, Embase ¼ 532 hits, PsycINFO ¼ 31 hits, CINAHL ¼ 108 hits, and Cochrane Library ¼ 222 hits) of which six were included in the final qualitative synthesis (Elliott, 1994; Hansen et al., 2012; Hunger et al., 2015; Johnston et al., 1999; Kirchberger et al., 2015; O'Neil et al., 2014) (Fig. 1). Three articles included in the screening process were found during thorough search of the reference lists of the included literature, of which two were included in the final synthesis. Of the six studies included one was a randomized, double blinded, placebo-controlled trial with a pharmacological antidepressant intervention (Hansen et al., 2012). Four of the included studies showed no significant prophylactic effect against depression (Elliott, 1994; Hunger et al., 2015; Kirchberger et al., 2015; O'Neil et al., 2014). The four non-significant studies utilized different components of case and disease management, health coaching, or relaxational audiotapes as intervention compared with usual care or with no formal program of rehabilitation. Two studies with a program of health education and counselling or a pharmacological antidepressant, respectively, showed significant
IdenƟficaƟon
PRISMA Flow Diagram
Records idenƟfied through database (Pubmed, Embase, PSYCinfo, CINAHL, and Coharane library) (n = 1780)
AddiƟonal records idenƟfied through other sources (n = 3)
Eligibility
Screening
Records aŌer duplicates (215) removed (n = 1568)
Records screened at Ɵtle and abstract level (n = 1568)
Full-text arƟcles assessed for eligibility (n = 58)
Included
Studies included in qualitaƟve synthesis (n = 6)
Studies included in quanƟtaƟve synthesis (meta-analysis) (n = 0) Fig. 1. PRISMA flow diagram.
Records excluded (n = 1509)
Full-text arƟcles excluded, with reasons (n = 52): - AnƟdepressants not given as prophylacƟc (n = 4) - Other study design than RCT or cross-over trial (n = 6) - No original data (n = 13) - Wrong outcome (n = 6) - Wrong paƟent populaƟon (n = 22) - ArƟcle not published in English (n = 2) - Data not published as mean/median (n = 0)
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prophylactic effect on depression and depressive symptoms (Hansen et al., 2012; Johnston et al., 1999). Evaluation of individual treatment components were difficult due to inadequate descriptions of treatment. The number of included patients ranged from 56 to 430, predominantly male with an average age from 56 to 75 years. Psychological assessment was conducted at baseline and at follow-up, which ranged from inpatient regime (Elliott, 1994) and up to 3 years after discharge (Kirchberger et al., 2015) (Table 1). Three different depression assessment scales were used in the six trials, the most commonly used measure was the Hospital Anxiety and Depression Scale (HADS) (Elliott, 1994; Johnston et al., 1999; O'Neil et al., 2014), which also allowed the studies to report on anxiety. Only one study used a diagnostic interview in the form of Hamilton Depression Rating Scale (HAM-D) as the assessment of depression (Hansen et al., 2012). Included patients were diagnosed with acute myocardial infarction only (Hunger et al., 2015; Johnston et al., 1999; Kirchberger et al., 2015; O'Neil et al., 2014), or with unstable angina pectoris (Elliott, 1994; Hansen et al., 2012) and one study included patients undergoing coronary artery bypass grafting following ACS (Hansen et al., 2012). 3.1. Risk of bias assessment The risk of bias assessment of the included studies is presented in Fig. 2. Two studies failed to describe the method used to generate the random sequence (Elliott, 1994; Johnston et al., 1999). These studies were also at high risk of bias in allocation concealment and blinding of outcome assessors (Elliott, 1994; Johnston et al., 1999). Blinding of participants and personnel was only adequately described in Hansen et al. (2012). Only one study (Johnston et al., 1999) did not have high risk of attrition bias, whereas all other included studies struggled with many dropouts or exclusions, who were not adequately accounted for (Elliott, 1994; Hansen et al., 2012; Hunger et al., 2015; Kirchberger et al., 2015; O'Neil et al., 2014). All studies performed patient recruitment from cardiology departments at major hospitals in Western countries with a participation rate of eligible patients from 10% (Johnston et al., 1999) to 67% (Hansen et al., 2012). One study did not account for participation and loss to follow-up (Elliott, 1994), and thus with high risk of selection bias, and another did not account for a 70,9% loss to follow-up over a three year period (Kirchberger et al., 2015). Three articles accounted for loss to follow-up and found no statistical differences at baseline between treatment completers and non-completers (Hansen et al., 2012; Johnston et al., 1999; O'Neil et al., 2014). Two studies had problems with selective outcome reporting bias (Hansen et al., 2012; O'Neil et al., 2014), and we were unable to locate the protocol and assess the reporting bias of two
Fig. 2. Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
studies, which therefore was considered as unclear bias (Elliott, 1994; Johnston et al., 1999). Other sources of biases not addressed in the other domains in the bias assessment tool included funding bias, which in one study was assessed as high (Elliott, 1994).
3.2. Outcome description Two of the six included studies reported an overall reduction of depression in the intervention group compared with the control group (Hansen et al., 2012; Johnston et al., 1999). The DECARD
Table 1 Patient characteristics and study design. Study
Study design
Population n (randomized ptt)
Age (mean ± SD)
Sex (M/F) %
Diagnosis
Time of measurement since diagnosis
Elliott, 1994
RCT, 3 arm
56 (56)
60,6
71,4/28,6
UAP, AMI
Hansen et al., 2012
RCT
239 (240)
63,70 ± 12,22
63,2/36,8
Hunger et al., 2015
RCT
252 (326)
75,40 ± 5,99
62,6/37,4
UAP, AMI, CABG AMI
Johnston et al., 1999
RCT, 3 arm
100 (100)
55,98 ± 8,54
65/35
AMI
Kirchberger et al., 2015
RCT
199 (326)
75,40 ± 5,99
62,6/37,4
AMI
O'Neil et al., 2014
RCT
297 (430)
60,79 ± 10,73
79,1/20,9
AMI
<24 h after diagnosis, final intervention within CCU Baseline within eight weeks after ACS and eight visits over 12 months Shortly before discharge and one year after discharge In CCU, two weeks, two months, six months, and one year after discharge. Shortly before discharge and three years after discharge Within two weeks after discharge and 6 months after baseline
n, number of patients; ptt, patients; SD, standard deviation; M/F, male/female; RCT, randomized controlled trial; UAP, unstable angina pectoris; AMI, acute myocardial infarction; CCU, coronary care unit; CABG, coronary artery bypass grafting; ACS, acute coronary syndrome.
O'Neil et al., 2014
STAI, State Trait Anxiety Inventory; HADS, Hospital Anxiety and Depression Scale (-A, anxiety score); LAAS, Linear Analogue Anxiety Scale; ICD-10, International Classification of Diseases, version 10; mg, milligram; HAM-D, Hamilton Depression Rating Scale; N/A, not available; GDS, Geriatric Depression Scale; MI, myocardial infarction; inpt, inpatient group; ext, extended group.
Depression p ¼ 0,11. Anxiety p < 0,05 Yes No Usual care HADS Scripted telephone health coaching sessions Dec 2007eJan 2009
N/A No Sep 2008eMay 2010 Combination of components from case- Usual care GDS management and disease-management
Time to first unplanned readmission to hospital or death HADS Kirchberger et al., 2015
Yes Yes I) Program of education and counselling No formal HADS program or II) Extended for eight sessions
N/A No
ICD-10 depression, moderate or severe Hunger et al., 2015 Time to first unplanned readmission to hospital or death Johnston et al., 1999 Knowledge about MI Hansen et al., 2012
Anxiety; STAI, HADS, LAAS Elliott, 1994
Jan 1992eFeb 1993
N/A Yes
Music group: STAI ***p < 0,001, HASD-A *p < 0,01. Muscle group: LAAS p < 0,01. 80% relative reduction of depression Yes No
Sessions by audiotape players with a) Usual care HADS light classical music or b) Verbal instructions for muscle relaxation Nov 2004eDec 2007 5 mg escitalopram once daily for 1 week Placebo HAM-D and then 10 mg once daily Sep 2008eMay 2010 Combination of components from case- Usual care GDS management and disease-management
Intervention Recruitment period Primary outcome
Table 2 Outcome and measurements.
Two out of six studies reported a statistically significant prophylactic difference in depression between intervention and control groups (Hansen et al., 2012; Johnston et al., 1999). The DECARD study (Hansen et al., 2012) showed that prophylactically administered escitalopram resulted in a significant reduction in depression. Likewise, cardiac rehabilitation (Johnston et al., 1999) with counselling and an educational program was also found to have a significant antidepressant effect. The quality of the studies was questionable, since both trials were at high risk of bias in several items. Four studies showed no effect on reduction of depression in the intervention group compared with the control group (Elliott, 1994; Hunger et al., 2015; Kirchberger et al., 2015; O'Neil et al., 2014). Interventions were very heterogenic, vaguely described, and multiple different tools of depression assessment were used. The general quality of the studies was questionable with one or more items at a high risk of bias in all included trials. We did not have the results to complete a meta-analysis, as the included studies were heterogenic in measurements, interventions, and follow-up periods. Therefore it was not possible to apply a statistical method, i. a. a forest plot, to account for publication bias. As mentioned no attempt was made to include ongoing results as written apriori in the protocol, which is a limitation to the current study. A recent systematic review on comorbid depression and myocardial infarction found that collaborative care resulted in a small but significant reduction in depressive symptoms (standardised mean differences 0.31; 95% CI -0.43 to 0.19, p < 0.001) (Tully and Baumeister, 2015), and depression remission was significant by six months. Collaborative care was defined by a multiprofessional approach to patient care delivered by a physician and at least one other health professional such as a psychiatrist of psychologist, involving a structured patient management plan with interventions and scheduled patient follow-ups. Collaborative care was associated with a significant reduction in anxiety symptoms and an improvement in mental quality of life (Tully and
Control
4. Discussion
Unknown
Overall effect: Overall effect: Results if positive Depression: Anxiety measurement Depression instrument
(Depression in patients with Acute Coronary Disease) study showed an overall effect of 10 mg escitalopram administrated prophylactically to patients with a 6.8% absolute risk reduction (80% relative reduction) of depressive symptoms corresponding to a number needed to treat of 15 in 1 year to prevent one episode of depression (Hansen et al., 2012). Cardiac rehabilitation (counselling and education) had a significant prophylactic antidepressant effect during 12 months follow-up with a HADS score after one year of 3.43 and 2.8 for the inpatient and extended group respectively compared with 5.9 for the control group giving a relative reduction in depression scores of 42% and 51% in the inpatient and extended group respectively (p < 0.05) (Johnston et al., 1999). The remaining four studies did not show an overall reduction in depression or depressive symptoms in the intervention group compared with the control group (Elliott, 1994; Hunger et al., 2015; Kirchberger et al., 2015; O'Neil et al., 2014). The interventions of these studies were very heterogenic but characterized by case and disease management such as nurse counselling. The one-year follow-up of the KORINNA study showed a borderline significant overall effect (p ¼ 0.0519), but after the result was adjusted by stratification and the baseline variables the result ceased to be significant (p ¼ 0.1233) (Hunger et al., 2015). Furthermore, three studies reported a significant reduction in anxiety (measured with HADS) in the intervention group compared with the control group (Elliott, 1994; Johnston et al., 1999; O'Neil et al., 2014) (see Table 2).
Depression: 2 months: I) inpt p < 0,01, II) ext p < 0,001. 6 months: p < 0,005. 12 months: p < 0,05 Anxiety: 2 months: I) inpt p < 0,001, II) ext p < 0,02. 6 months: p < 0,02. 12 months: no difference
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Study
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Baumeister, 2015). However, these results reached the same conclusions as our current review showing that a major heterogeneity resides within these randomized controlled trials in the depression and myocardial infarction patients, and therefore, the outcomes were difficult to compare. Selective Serotonin Reuptake Inhibitors (SSRI) combined with cognitive behavioural therapy have shown to be effective in decreasing depression and improve social support in patients with coronary heart disease (Huffman et al., 2006; Berkman et al., 2003). This raise support to the hypothesis of the DECARD study (Hansen et al., 2012), which utilizes the SSRI escitalopram to prevent development of depression. SSRIs have previously been associated with a reduced risk of myocardial infarction due to the inhibitory effect on platelet aggregation (Pizzi et al., 2009; Sauer et al., 2001; Serebruany et al., 2001) and is generally considered safe (Wade et al., 2006; Muldoon, 1996). Specific concerns regarding cardiotoxicity of escitalopram has been raised nonetheless. Data indicate a positive correlation between high citalopram doses and ECG abnormalities and co-existing factors, including cardiac disease, may predispose to cardiac toxicity (Cooke and Waring, 2013). Thus, prophylactic treatment with SSRI is not without risk. Serious debate was raised whether prophylactic treatment of depression in patients with ACS in general and treatment with antidepressants specially is the correct choice of treatment (Thombs and Ziegelstein, 2012). Researchers critically examined the DECARD study (Hansen et al., 2009, 2012). It was questioned whether these findings could be reproduced and pointed out that the magnitude of effect was far beyond what could be expected in a reasonably powered study (Thombs and Ziegelstein, 2012). DECARD was significantly underpowered since the observed rate of depression in the study population was lower than the a priori assumed (Hansen et al., 2012). Furthermore, the fidelity of the DECARD study was questioned as the study failed to report on a primary outcome described in the published protocol, the HAM-D score (Thombs and Ziegelstein, 2012; Hansen et al., 2009). Therefore, it was concluded as a high risk of reporting bias. This review solely included studies using validated clinicianadministered or self-rating questionnaires with known psychometric properties and with a specific main focus on diagnosing and/ or measuring depression. This was done to improve both the internal and external validity of the review. HADS has been found to perform well in assessing the symptom severity and caseness of anxiety disorders and depression (Bjelland et al., 2002; Martin et al., 2003). Three included studies utilized HADS and all reported a significant reduction in anxiety (Elliott, 1994; Johnston et al., 1999; O'Neil et al., 2014). The prevalence of anxiety among patients hospitalized after ACS has been reported >40% (Lane et al., 2002; Mayou et al., 2000) and comorbid with depression in 90% of the cases (Denollet et al., 2006). Patients were at high risk of adverse psychological outcomes and decreased quality-of-life during the first year (Lane et al., 2002), but little is known about the mechanism behind anxiety. Anxiety after ACS has not received as much attention as post-ACS depression and as such represent a research area in urgent need of attention (Mavrides and Nemeroff, 2013) and in light of the prophylactic effect shown in the above mentioned studies this might represent a relevant area of research. A limitation of the literature is the multiple case-finding instruments used to identify patients with depression. Major discrepancies in prevalence of depression in an ACS population have been shown whether using self-reporting questionnaires or structured clinical interview (Thombs et al., 2006). Using a structured clinical interview, the golden standard of diagnosing depression, a meta-analysis showed a prevalence of 19.8%, which was higher than the prevalence of possible (15.5%) and probable (7.3%) clinical
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depression using HADS and the prevalence using the Beck Depression Index was 31.1% (Thombs et al., 2006). These discrepancies reflect some of the inherent challenges in evaluating symptoms of depression in general and among patients with an acute medical illness. A review of depression screening in primary care showed that a diagnostic interview was the best instrument, due to the relatively low positive predictive value of a positive screening by questionnaire (Williams et al., 2002). If a clear and valid consensus of methods in diagnosing and screening patients for depression after ACS existed the current review would have had a higher internal validity. Future research would benefit from applying both diagnostic interviews and validated selfadministered instruments making comparability of studies more accessible. Interventions in the included studies were similarly very heterogenic, ranging from music therapy over telephone counselling, education, and pharmacological interventions with doubtful or no significant effect. Future studies investigating prophylactic interventions against depression could benefit from applying interventions with known anti-depressive effect such as cognitive behavioural therapy, psychodynamic psychotherapies, and SSRIs as discussed earlier (Huffman et al., 2006; Robinson et al., 1990; Dobson, 1989; Dickens et al., 2013; Abbass et al., 2014). Furthermore, studies suggested beneficial effects of melatonin treatment in patients with major depressive disorder (Pandi-Perumal et al., 2009) and significantly reduced the risk of depressive symptoms (Hansen et al., 2014), and a close link between melatonin secretion disturbance and depressed mood have been shown (Pandi-Perumal et al., 2009; Bumb et al., 2016). This could prove an interesting topic to investigate in the future. Future studies should design the study with depressive symptoms as the primary outcome. When investigating pharmacological intervention a proper design with double-blinding can be applied. However, using a prophylactic antidepressant treatment with possible side effect should be considered carefully. In the current review we chose only to include studies treating patients with ACS as oppose to patients with known ischaemic heart disease or coronary heart disease. This was chosen to get a homogeneous population with a clear time to event relationships: incident depression following ACS. Had we included e.g. patients with stabile angina, the patient population would be more heterogenic and the time to event relationship would have been unclear. Patients with stable angina share the same pathological disease (i.e. atherosclerotic plaques in the coronary arteries) as ACS patients; however, the ACS (plaque rupture) is an acute event, which triggers an increase in incident depression. This review was limited to patients, who were not predisposed with depression at baseline. This was to ensure that the shown effect were prophylaxis of depression following the acute stress of ACS and to exclude any recurrence of depression at the time of measurement. We chose to include patients with an ACS treated with coronary artery bypass grafting as the primary revascularizing treatment. This was done although these patients may have experienced a different physiological trauma (surgical trauma) than the myocardial infarction patients treated with percutaneous coronary intervention or pharmacological treatment only. The patient categories have been shown to respond similarly to stress management treatment programme (Trzcieniecka-Green and Steptoe, 1996). 5. Conclusion We did not find general evidence to support prophylactic treatment of depression following ACS. In the light of the heterogeneity of the included studies and the low quality of the evidence we believe further studies are warranted. As many of the included studies were relatively small in size, larger studies should be
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conducted to exclude the possibility of type II error. Therefore, welldesigned, and adequately reported RCTs in groups of patients with ACS more representative of usual clinical practice are needed. These trials should include validated depression measurement instruments and carefully consider the ethical aspects of prophylactic pharmacological antidepressant treatment. In summary, this systematic review does not support any specific routine prophylaxis of depression in ACS patients until further data are available. Declaration of conflicting interests The Authors declare that there is no conflict of interest. Author contributions OGC contributed to design, contributed to acquisition, analysis, and interpretation, drafted the manuscript, and gave final approval. MTM contributed to conception and design, contributed to acquisition and interpretation, revised the manuscript, and gave final approval. MTM acted as corresponding author. ES and IG contributed to conception and design, revised the manuscript, and gave final approval. The authors agreed to be accountable for all aspects of work ensuring integrity and accuracy. OGC and MTM have agreed on a shared first authorship. References Abbass, A.A., Kisely, S.R., Town, J.M., Leichsenring, F., Driessen, E., De Maat, S., et al., 2014. Short-term psychodynamic psychotherapies for common mental disorders. Cochrane Database Syst. Rev. 7, CD004687. Aben, I., Verhey, F., Strik, J., Lousberg, R., Lodder, J., Honig, A., 2003. A comparative study into the one year cumulative incidence of depression after stroke and myocardial infarction. J. Neurol. Neurosurg. Psychiatry 74 (5), 581e585. Amin, A.A., Jones, A.M., Nugent, K., Rumsfeld, J.S., Spertus, J.A., 2006. The prevalence of unrecognized depression in patients with acute coronary syndrome. Am. Heart J. 152 (5), 928e934. Bauer, L.K., Caro, M.A., Beach, S.R., Mastromauro, C.A., Lenihan, E., Januzzi, J.L., et al., 2012. Effects of depression and anxiety improvement on adherence to medication and health behaviors in recently hospitalized cardiac patients. Am. J. Cardiol. 109 (9), 1266e1271. Berkman, L.F., Blumenthal, J., Burg, M., Carney, R.M., Catellier, D., Cowan, M.J., et al., 2003. Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the enhancing recovery in coronary heart disease patients (ENRICHED) randomized trial. JAMA 289 (23), 3106e3116. Bjelland, I., Dahl, A.A., Haug, T.T., Neckelmann, D., 2002. The validity of the Hospital Anxiety and Depression Scale. An updated literature review. J. Psychosom. Res. 52 (2), 69e77. Blumenthal, J.A., Williams, R.S., Wallace, A.G., Williams Jr., R.B., Needles, T.L., 1982. Physiological and psychological variables predict compliance to prescribed exercise therapy in patients recovering from myocardial infarction. Psychosom. Med. 44 (6), 519e527. Booth, A., Clarke, M., Ghersi, D., Moher, D., Petticrew, M., Stewart, L., 2011. Establishing a minimum dataset for prospective registration of systematic reviews: an international consultation. PLoS One 6 (11), e27319. Booth, A., Clarke, M., Ghersi, D., Moher, D., Petticrew, M., Stewart, L., 2011. An international registry of systematic-review protocols. Lancet 377 (9760), 108e109. Bumb, J.M., Enning, F., Mueller, J.K., van der List, T., Rohleder, C., Findeisen, P., et al., 2016. Differential melatonin alterations in cerebrospinal fluid and serum of patients with major depressive disorder and bipolar disorder. Compr. Psychiatry 68, 34e39. Carney, R.M., Freedland, K.E., 2009. Depression and heart rate variability in patients with coronary heart disease. Cleve Clin. J. Med. 76 (Suppl. 2), S13eS17. Carney, R.M., Freedland, K.E., Eisen, S.A., Rich, M.W., Jaffe, A.S., 1995. Major depression and medication adherence in elderly patients with coronary artery disease. Health Psychol. 14 (1), 88e90. Carney, R.M., Freedland, K.E., Miller, G.E., Jaffe, A.S., 2002. Depression as a risk factor for cardiac mortality and morbidity: a review of potential mechanisms. J. Psychosom. Res. 53 (4), 897e902. Carney, R.M., Blumenthal, J.A., Freedland, K.E., Stein, P.K., Howells, W.B., Berkman, L.F., et al., 2005. Low heart rate variability and the effect of depression on post-myocardial infarction mortality. Arch. Intern Med. 165 (13), 1486e1491. Cooke, M.J., Waring, W.S., 2013. Citalopram and cardiac toxicity. Eur. J. Clin. Pharmacol. 69 (4), 755e760.
Czarny, M.J., Arthurs, E., Coffie, D.F., Smith, C., Steele, R.J., Ziegelstein, R.C., et al., 2011. Prevalence of antidepressant prescription or use in patients with acute coronary syndrome: a systematic review. PLoS One 6 (11), e27671. Denollet, J., Strik, J.J., Lousberg, R., Honig, A., 2006. Recognizing increased risk of depressive comorbidity after myocardial infarction: looking for 4 symptoms of anxiety-depression. Psychother. Psychosom. 75 (6), 346e352. Dickens, C., Cherrington, A., Adeyemi, I., Roughley, K., Bower, P., Garrett, C., et al., 2013. Characteristics of psychological interventions that improve depression in people with coronary heart disease: a systematic review and meta-regression. Psychosom. Med. 75 (2), 211e221. Dobson, K.S., 1989. A meta-analysis of the efficacy of cognitive therapy for depression. J. Consult Clin. Psychol. 57 (3), 414e419. Elliott, D., 1994. The effects of music and muscle relaxation on patient anxiety in a coronary care unit. Heart Lung 23 (1), 27e35. Gehi, A.K., Ali, S., Na, B., Whooley, M.A., 2007. Self-reported medication adherence and cardiovascular events in patients with stable coronary heart disease: the heart and soul study. Arch. Intern Med. 167 (16), 1798e1803. Hansen, B.H., Hanash, J.A., Rasmussen, A., Hansen, J.F., Birket-Smith, M., 2009. Rationale, design and methodology of a double-blind, randomized, placebocontrolled study of escitalopram in prevention of Depression in Acute Coronary Syndrome (DECARD). Trials 10, 20. Hansen, B.H., Hanash, J.A., Rasmussen, A., Hansen, J.F., Andersen, N.L., Nielsen, O.W., et al., 2012. Effects of escitalopram in prevention of depression in patients with acute coronary syndrome (DECARD). J. Psychosom. Res. 72 (1), 11e16. Hansen, M.V., Andersen, L.T., Madsen, M.T., Hageman, I., Rasmussen, L.S., Bokmand, S., et al., 2014. Effect of melatonin on depressive symptoms and anxiety in patients undergoing breast cancer surgery: a randomized, doubleblind, placebo-controlled trial. Breast Cancer Res. Treat. 145 (3), 683e695. Hanssen, T.A., Nordrehaug, J.E., Eide, G.E., Bjelland, I., Rokne, B., 2009. Anxiety and depression after acute myocardial infarction: an 18-month follow-up study with repeated measures and comparison with a reference population. Eur. J. Cardiovasc Prev. Rehabil. 16 (6), 651e659. Higgins, J.P., Altman, D.G., Gotzsche, P.C., Juni, P., Moher, D., Oxman, A.D., et al., 2011. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 343, d5928. Howren, M.B., Lamkin, D.M., Suls, J., 2009. Associations of depression with Creactive protein, IL-1, and IL-6: a meta-analysis. Psychosom. Med. 71 (2), 171e186. Huffman, J.C., Smith, F.A., Blais, M.A., Beiser, M.E., Januzzi, J.L., Fricchione, G.L., 2006. Recognition and treatment of depression and anxiety in patients with acute myocardial infarction. Am. J. Cardiol. 98 (3), 319e324. Huffman, J.C., Celano, C.M., Beach, S.R., Motiwala, S.R., Januzzi, J.L., 2013. Depression and cardiac disease: epidemiology, mechanisms, and diagnosis. Cardiovasc Psychiatry Neurol. 2013, 695925. Hunger, M., Kirchberger, I., Holle, R., Seidl, H., Kuch, B., Wende, R., et al., 2015. Does nurse-based case management for aged myocardial infarction patients improve risk factors, physical functioning and mental health? The KORINNA trial. Eur. J. Prev. Cardiol. 22 (4), 442e450. Jiang, W., Krishnan, R.R., O'Connor, C.M., 2002. Depression and heart disease: evidence of a link, and its therapeutic implications. CNS Drugs 16 (2), 111e127. Johnston, M., Foulkes, J., Johnston, D.W., Pollard, B., Gudmundsdottir, H., 1999. Impact on patients and partners of inpatient and extended cardiac counseling and rehabilitation: a controlled trial. Psychosom. Med. 61 (2), 225e233. Jorgensen, T.S., Wium-Andersen, I.K., Wium-Andersen, M.K., Jorgensen, M.B., Prescott, E., Maartensson, S., et al., 2016. Incidence of depression after stroke, and associated risk factors and mortality outcomes, in a large cohort of Danish patients. JAMA Psychiatry 73 (10), 1032e1040. Jorgensen, T.S., Martensson, S., Ibfelt, E.H., Jorgensen, M.B., Wium-Andersen, I.K., Wium-Andersen, M.K., et al., 2016. Time trend in depression diagnoses among acute coronary syndrome patients and a reference population from 2001 to 2009 in Denmark. Nord. J. Psychiatry 70 (5), 335e341. Kaptoge, S., Seshasai, S.R., Gao, P., Freitag, D.F., Butterworth, A.S., Borglykke, A., et al., 2014. Inflammatory cytokines and risk of coronary heart disease: new prospective study and updated meta-analysis. Eur. Heart J. 35 (9), 578e589. Kirchberger, I., Hunger, M., Stollenwerk, B., Seidl, H., Burkhardt, K., Kuch, B., et al., 2015. Effects of a 3-year nurse-based case management in aged patients with acute myocardial infarction on rehospitalisation, mortality, risk factors, physical functioning and mental health. a secondary analysis of the randomized controlled KORINNA study. PLoS One 10 (3), e0116693. Lane, D., Carroll, D., Ring, C., Beevers, D.G., Lip, G.Y., 2002. The prevalence and persistence of depression and anxiety following myocardial infarction. Br. J. Health Psychol. 7 (Pt 1), 11e21. Liberati, A., Altman, D.G., Tetzlaff, J., Mulrow, C., Gotzsche, P.C., Ioannidis, J.P., et al., 2009. The PRISMA statement for reporting systematic reviews and metaanalyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339, b2700. Lichtman, J.H., Bigger Jr., J.T., Blumenthal, J.A., Frasure-Smith, N., Kaufmann, P.G., Lesperance, F., et al., 2008. Depression and coronary heart disease: recommendations for screening, referral, and treatment: a science advisory from the American heart association prevention committee of the council on cardiovascular nursing, council on clinical cardiology, council on epidemiology and prevention, and interdisciplinary council on quality of care and outcomes research: endorsed by the American psychiatric association. Circulation 118 (17), 1768e1775. Lichtman, J.H., Froelicher, E.S., Blumenthal, J.A., Carney, R.M., Doering, L.V., Frasure-
O.G. Christiansen et al. / Journal of Psychiatric Research 94 (2017) 186e193 Smith, N., et al., 2014. Depression as a risk factor for poor prognosis among patients with acute coronary syndrome: systematic review and recommendations: a scientific statement from the American Heart Association. Circulation 129 (12), 1350e1369. Martin, C.R., Lewin, R.J., Thompson, D.R., 2003. A confirmatory factor analysis of the Hospital Anxiety and Depression Scale in coronary care patients following acute myocardial infarction. Psychiatry Res. 120 (1), 85e94. Mavrides, N., Nemeroff, C., 2013. Treatment of depression in cardiovascular disease. Depress Anxiety 30 (4), 328e341. May, H.T., Sheng, X., Catinella, A.P., Horne, B.D., Carlquist, J.F., Joy, E., 2010. Antilipidemic adherence post-coronary artery disease diagnosis among those with and without an ICD-9 diagnosis of depression. J. Psychosom. Res. 69 (2), 169e174. Mayou, R.A., Gill, D., Thompson, D.R., Day, A., Hicks, N., Volmink, J., et al., 2000. Depression and anxiety as predictors of outcome after myocardial infarction. Psychosom. Med. 62 (2), 212e219. Meijer, A., Conradi, H.J., Bos, E.H., Thombs, B.D., van Melle, J.P., de Jonge, P., 2011. Prognostic association of depression following myocardial infarction with mortality and cardiovascular events: a meta-analysis of 25 years of research. Gen. Hosp. Psychiatry 33 (3), 203e216. Meijer, A., Conradi, H.J., Bos, E.H., Anselmino, M., Carney, R.M., Denollet, J., et al., 2013. Adjusted prognostic association of depression following myocardial infarction with mortality and cardiovascular events: individual patient data meta-analysis. Br. J. Psychiatry 203 (2), 90e102. Muldoon, C., 1996. The safety and tolerability of citalopram. Int. Clin. Psychopharmacol. 11 (Suppl. 1), 35e40. O'Neil, A., Hawkes, A.L., Atherton, J.J., Patrao, T.A., Sanderson, K., Wolfe, R., et al., 2014. Telephone-delivered health coaching improves anxiety outcomes after myocardial infarction: the ‘ProActive Heart’ trial. Eur. J. Prev. Cardiol. 21 (1), 30e38. Osler, M., Martensson, S., Wium-Andersen, I.K., Prescott, E., Andersen, P.K., Jorgensen, T.S., et al., 2016. Depression after first hospital admission for acute coronary syndrome: a study of time of onset and impact on survival. Am. J. Epidemiol. 183 (3), 218e226. Pandi-Perumal, S.R., Moscovitch, A., Srinivasan, V., Spence, D.W., Cardinali, D.P., Brown, G.M., 2009. Bidirectional communication between sleep and circadian rhythms and its implications for depression: lessons from agomelatine. Prog. Neurobiol. 88 (4), 264e271. Pizzi, C., Mancini, S., Angeloni, L., Fontana, F., Manzoli, L., Costa, G.M., 2009. Effects of selective serotonin reuptake inhibitor therapy on endothelial function and inflammatory markers in patients with coronary heart disease. Clin. Pharmacol. Ther. 86 (5), 527e532. Pizzi, C., Manzoli, L., Mancini, S., Bedetti, G., Fontana, F., Costa, G.M., 2010. Autonomic nervous system, inflammation and preclinical carotid atherosclerosis in depressed subjects with coronary risk factors. Atherosclerosis 212 (1), 292e298. Poole, L., Dickens, C., Steptoe, A., 2011. The puzzle of depression and acute coronary
193
syndrome: reviewing the role of acute inflammation. J. Psychosom. Res. 71 (2), 61e68. Rieckmann, N., Kronish, I.M., Haas, D., Gerin, W., Chaplin, W.F., Burg, M.M., et al., 2006. Persistent depressive symptoms lower aspirin adherence after acute coronary syndromes. Am. Heart J. 152 (5), 922e927. Robinson, L.A., Berman, J.S., Neimeyer, R.A., 1990. Psychotherapy for the treatment of depression: a comprehensive review of controlled outcome research. Psychol. Bull. 108 (1), 30e49. Ross, R., 1999. Atherosclerosisean inflammatory disease. N. Engl. J. Med. 340 (2), 115e126. Sauer, W.H., Berlin, J.A., Kimmel, S.E., 2001. Selective serotonin reuptake inhibitors and myocardial infarction. Circulation 104 (16), 1894e1898. Serebruany, V.L., Gurbel, P.A., O'Connor, C.M., 2001. Platelet inhibition by sertraline and N-desmethylsertraline: a possible missing link between depression, coronary events, and mortality benefits of selective serotonin reuptake inhibitors. Pharmacol. Res. 43 (5), 453e462. Thombs, B.D., Ziegelstein, R.C., 2012. When prevention is a bad idea: problems with the DECARD trial and the premise behind it. J. Psychosom. Res. 72 (5), 333e335. Thombs, B.D., Bass, E.B., Ford, D.E., Stewart, K.J., Tsilidis, K.K., Patel, U., et al., 2006. Prevalence of depression in survivors of acute myocardial infarction. J. Gen. Intern Med. 21 (1), 30e38. Trzcieniecka-Green, A., Steptoe, A., 1996. The effects of stress management on the quality of life of patients following acute myocardial infarction or coronary bypass surgery. Eur. Heart J. 17 (11), 1663e1670. Tully, P.J., Baumeister, H., 2015. Collaborative care for comorbid depression and coronary heart disease: a systematic review and meta-analysis of randomised controlled trials. BMJ Open 5 (12), e009128. van Melle, J.P., de Jonge, P., Spijkerman, T.A., Tijssen, J.G., Ormel, J., van Veldhuisen, D.J., et al., 2004. Prognostic association of depression following myocardial infarction with mortality and cardiovascular events: a meta-analysis. Psychosom. Med. 66 (6), 814e822. Vertitas Health Innovation Ltd, 2015. Covidence online systematic review platform. Available from: https://www.covidence.org. Wade, A., Despiegel, N., Heldbo Reines, E., 2006. Escitalopram in the long-term treatment of major depressive disorder. Ann. Clin. Psychiatry 18 (2), 83e89. Wessel, T.R., Arant, C.B., Olson, M.B., Johnson, B.D., Reis, S.E., Sharaf, B.L., et al., 2004. Relationship of physical fitness vs body mass index with coronary artery disease and cardiovascular events in women. JAMA 292 (10), 1179e1187. Williams Jr., J.W., Pignone, M., Ramirez, G., Perez Stellato, C., 2002. Identifying depression in primary care: a literature synthesis of case-finding instruments. Gen. Hosp. Psychiatry 24 (4), 225e237. World Health Organization, 2000. The World Health Report 2000: Health systems: improving performance. World Health Organization, 2000, Geneve. Ziegelstein, R.C., Fauerbach, J.A., Stevens, S.S., Romanelli, J., Richter, D.P., Bush, D.E., 2000. Patients with depression are less likely to follow recommendations to reduce cardiac risk during recovery from a myocardial infarction. Arch. Intern Med. 160 (12), 1818e1823.
Contents lists available at ScienceDirect
Journal of Psychiatric Research journal homepage: www.elsevier.com/locate/psychires
Prophylactic antidepressant treatment following acute coronary syndrome: A systematic review of randomized controlled trials € genur a, 1 Ole G. Christiansen a, Michael T. Madsen a, b, *, Erik Simonsen a, b, 1, Ismail Go a b
Center for Surgical Science, Zealand University Hospital, Denmark Psychiatric Research Unit, Region Zealand, Denmark
a r t i c l e i n f o
a b s t r a c t
Article history: Received 5 December 2016 Received in revised form 10 July 2017 Accepted 17 July 2017
Major depressive disorder is significantly increased in patients following acute coronary syndrome resulting in twofold increased mortality compared with patients without depression. The depression diagnosis is often missed leading to considerable undertreatment. This systematic review assesses the current evidence of primary prophylactic treatment of depression in patients after acute coronary syndrome. The study protocol was prospectively registered at PROSPERO (registration number CRD42015025587). A systematic review were conducted and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Embase, PsychINFO, CINAHL, and Cochran Library was searched. Two independent reviewers screened the records. The inclusion criteria were randomized controlled trials on adult patients with acute coronary syndrome treated prophylactically with an antidepressant intervention of any kind. A validated assessment tool should measure depression and depressive symptoms. Languages were limited to articles written in English. Six articles were included. Four studies utilized different components of case and disease management, health coaching, or relaxational audiotapes as intervention compared with usual care or with no formal program of rehabilitation. None of the studies showed any significant prophylactic effect against depression. One study with a program of health education and counselling and another study with a pharmacological antidepressant showed significant prophylactic effect on depression and depressive symptoms. All six included studies were associated with high risk of bias. There is not strong evidence of the effects of any type of routine antidepressant prophylaxis in patients following acute coronary syndrome. Further high quality studies are warranted. © 2017 Elsevier Ltd. All rights reserved.
Keywords: Acute coronary syndrome Depression Preventive Prophylaxis Antidepressant Anxiety
Contents 1. 2. 3.
4. 5.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187 Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 188 3.1. Risk of bias assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189 3.2. Outcome description . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191 Declaration of conflicting interests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192 Author contributions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192
* Corresponding author. Center for Surgical Science, Zealand University Hospital, Lykkebækvej 1, 4600 Køge, Denmark. E-mail address: [email protected] (M.T. Madsen). 1 €genur have shared last authorship. Erik Simonsen and Ismail Go http://dx.doi.org/10.1016/j.jpsychires.2017.07.016 0022-3956/© 2017 Elsevier Ltd. All rights reserved.
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1. Introduction Major depressive disorder was significantly increased in patients following acute coronary syndrome (ACS) (Thombs et al., 2006; Jiang et al., 2002) with a rate ratio of 1.28 compared with a comparable reference population (Osler et al., 2016). The prevalence of depression (13,7%) was constant at least 18 months following myocardial infarction (Hanssen et al., 2009). The risk of depression was comparable to the risk in patients after stroke after controlling for sex, age, and level of handicap (hazard ratio (HR) 1.08; p ¼ 0.72) (Aben et al., 2003). Other register-based literature has shown prevalence of depression to be higher in patients following stroke compared to myocardial infarction (Jorgensen et al., 2016a). The prevalence of antidepressant prescription has increased considerably during the last decades, reaching 10e15% by 2005 in patients after ACS (Czarny et al., 2011). A nationwide Danish retrospective cohort study found that 12% of patients were treated with antidepressants within two years after their ACS e almost two times more than those without ACS (Jorgensen et al., 2016b). Recurrent or new onset depression in patients with ACS had higher mortality rates than patients with no depression (Osler et al., 2016; Meijer et al., 2011; van Melle et al., 2004). A recent patient level meta-analysis showed that hazard ratios for the association between post-myocardial infarction depression and all-cause mortality was 1.32 (95% CI 1.26e1.38, P < 0.001) but was attenuated after adjustment for disease severity (HR ¼ 1.23) (Meijer et al., 2013). However, depression was still an independent risk factor for all-cause mortality and cardiovascular events, which was acknowledged by the American Heart Association (Lichtman et al., 2014), who has made recommendations for screening of depression following ACS (Lichtman et al., 2008). The pathophysiology of post-ACS depression remains unclear and several mechanisms have been put forth (Jiang et al., 2002; Carney et al., 2002) including dysfunction of the autonomic nervous system, heart rate variability and an increase of the inflammation response (Jiang et al., 2002; Huffman et al., 2013; Carney and Freedland, 2009; Carney et al., 2005; Poole et al., 2011; Ross, 1999; Kaptoge et al., 2014; Pizzi et al., 2010; Howren et al., 2009). Cytokines have been associated with atherosclerotic plaque formation, progression, and rupture; and as such they were major contributors to the pathogenesis of coronary artery disease and myocardial infarction (Huffman et al., 2013). Depression have also been linked to increased levels of interleukins (especially CRP, IL-1, and IL-6), both in patients with and without a history of cardiac disease (Pizzi et al., 2010; Howren et al., 2009). Platelet activity and aggregation is yet another possible link between depression and ischemic heart disease as serotonin plays an important role in platelet function (Pizzi et al., 2009). Of potential direct mechanisms, Huffman J.C. et al (Huffman et al., 2013). mention neural-immune interaction via the serotonin receptors effect on cardiac outcomes, and increased cytokines which may elevate the degradation of tryptophan (precursor to serotonin) resulting in overall lover serotonin levels (Huffman et al., 2013). Besides the association between post-ACS depression and mortality, patients suffering from depression related to ACS were less likely to engage in health promoting behaviours, including maintenance of a healthy diet, regular exercise, adherence to medications (Rieckmann et al., 2006; Carney et al., 1995; May et al., 2010), stress reduction, and completion of cardiac rehabilitation programs following myocardial infarction (Blumenthal et al., 1982; Ziegelstein et al., 2000). This was associated with an increased risk of cardiac events (Gehi et al., 2007; Wessel et al., 2004). Patients with cardiac disease and clinical depression, who were hospitalized and treated for their depression on the other hand showed
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enhanced effect on adherence to diet, exercise, and medication (Bauer et al., 2012). Thus, suggesting these negative behavioural factors would be modifiable with the correct treatment. Moderate to severe depression were found to be significantly under-recognized and undertreated among patients with ACS (Amin et al., 2006; Huffman et al., 2006), which leads to patients receiving inadequate treatment. In the general population studies suggests that, despite the severity and possible complications of depression, only half of those with depression will seek professional help (World Health Organization, 2000). Given the high risk of patients developing depression and the problems inherent with diagnosing depression, there is increasing interest in prophylactic therapies that may prevent abnormal mood and improve outcome after ACS. The aim of this current systematic review was to review the prophylactic treatment of depression in patients after ACS. 2. Method The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines (Liberati et al., 2009). The systematic review was registered on PROSPERO (Booth et al., 2011a, 2011b) with registration number: CRD42015025587. We used the following PICOS (P: population, I: intervention, C: comparator/control, O: outcomes, S: study design) (Liberati et al., 2009) when constructing the eligibility criteria and the search strategy; P: humans, adults, 18 years, diagnosed with ACS, I: antidepressant treatment of any kind, C: placebo or active treatment, O: depression and depressive symptoms, and S: randomized controlled trails (RCT). Studies in English comparing pharmaceutical agents with placebo, psychotherapy against standard care, or any other antidepressant treatment against standard care to prevent depression in patients with ACS were included. No restriction on dose, administration, timing of the intervention, or to other outcomes being assessed in the studies was chosen. The search was carried out using PubMed, Embase, PsycINFO, CINAHL, and the Cochrane Library (PubMed: 1966 - now, Embase: 1974 - now, PsycINFO: 1806 - now, CINAHL: 1981 - now, Cochrane Library: date of inception - now). Contact with the study authors was made if the data were not extractable from text or figures in the article. The search was conducted on 19th of December 2015. The same search terms were use in the databases, however, the mesh terms were modified to fit to the search criteria of the respective databases. No limits were set for language; thus all records were manually screened with regard to being English. No limits were set with regard to the years of publication. No attempt was made to include potential ongoing trials. The reference list of all included studies was manually reviewed to identify additional relevant studies. The exact search terms for PubMed were: (coronary artery disease OR ischemic heart disease OR myocardial infarction OR acute myocardial infarction OR unstable angina OR acute coronary syndrome OR coronary bypass surgery OR atherosclerosis) AND (antidepressant OR tricyclic antidepressant OR selective serotonin reuptake inhibitor OR serotonin-noradrenaline reuptake inhibitor OR noradrenergic and specific serotonergic antidepressants OR mono amino oxidase inhibitors OR melatonin OR agomelatine OR Psychotherapy OR Psychological intervention OR Cognitive behavioural therapy OR psychodynamic psychotherapy OR interpersonal psychotherapy OR intervention OR counselling OR mindfulness OR family therapy OR psychosocial intervention OR stress management OR behavioural OR social support OR exercise) AND (prevention OR primary prevention OR secondary prevention OR tertiary prevention OR prophylactic OR prophylaxis) AND (depression OR depressive symptoms OR depressive disorder OR mood OR mood disorder).
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After removal of duplicates two independent reviewers (OGC, MTM) screened title and abstract for full-text evaluation according to inclusion and exclusion criteria mentioned above. Any discrepancies were resolved through discussion until consensus was reached. Upon full-text evaluation the reference list of the selected articles was scanned for further literature. Covidence, a web-based review software platform (Vertitas Health Innovation Ltd., 2015), was utilized as a blinded screening tool. Data on participant characteristics, interventions, and trial methodology were extracted. Two authors (OGC, MTM) assessed the methodological quality of the included studies by using the Cochrane Handbook for Systematic Review of Interventions' Risk of bias assessment tool (Higgins et al., 2011). Trial protocols for all included studies were searched for in two trial registers: clinical trials.gov and WHOs Trials Search, and published protocol articles were consulted if available. Information on bias assessment was used in the overall data synthesis to characterize the quality of the included studies. Our outcome was the measurement of depression and/or depressive symptoms, regardless of whether this was assessed as a primary, secondary, or tertiary outcome in the studies. The outcome measure had to be a validated clinician-administered or self-rating questionnaire with known and validated psychometric properties and with the main focus on diagnosing and/or measuring depression. Results had to be reported in the manuscript
in means (standard deviation, SD) or median (interquartile range, IQR/range). 3. Results A total of 1780 records were identified in the databases searched (PubMed ¼ 887 hits, Embase ¼ 532 hits, PsycINFO ¼ 31 hits, CINAHL ¼ 108 hits, and Cochrane Library ¼ 222 hits) of which six were included in the final qualitative synthesis (Elliott, 1994; Hansen et al., 2012; Hunger et al., 2015; Johnston et al., 1999; Kirchberger et al., 2015; O'Neil et al., 2014) (Fig. 1). Three articles included in the screening process were found during thorough search of the reference lists of the included literature, of which two were included in the final synthesis. Of the six studies included one was a randomized, double blinded, placebo-controlled trial with a pharmacological antidepressant intervention (Hansen et al., 2012). Four of the included studies showed no significant prophylactic effect against depression (Elliott, 1994; Hunger et al., 2015; Kirchberger et al., 2015; O'Neil et al., 2014). The four non-significant studies utilized different components of case and disease management, health coaching, or relaxational audiotapes as intervention compared with usual care or with no formal program of rehabilitation. Two studies with a program of health education and counselling or a pharmacological antidepressant, respectively, showed significant
IdenƟficaƟon
PRISMA Flow Diagram
Records idenƟfied through database (Pubmed, Embase, PSYCinfo, CINAHL, and Coharane library) (n = 1780)
AddiƟonal records idenƟfied through other sources (n = 3)
Eligibility
Screening
Records aŌer duplicates (215) removed (n = 1568)
Records screened at Ɵtle and abstract level (n = 1568)
Full-text arƟcles assessed for eligibility (n = 58)
Included
Studies included in qualitaƟve synthesis (n = 6)
Studies included in quanƟtaƟve synthesis (meta-analysis) (n = 0) Fig. 1. PRISMA flow diagram.
Records excluded (n = 1509)
Full-text arƟcles excluded, with reasons (n = 52): - AnƟdepressants not given as prophylacƟc (n = 4) - Other study design than RCT or cross-over trial (n = 6) - No original data (n = 13) - Wrong outcome (n = 6) - Wrong paƟent populaƟon (n = 22) - ArƟcle not published in English (n = 2) - Data not published as mean/median (n = 0)
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prophylactic effect on depression and depressive symptoms (Hansen et al., 2012; Johnston et al., 1999). Evaluation of individual treatment components were difficult due to inadequate descriptions of treatment. The number of included patients ranged from 56 to 430, predominantly male with an average age from 56 to 75 years. Psychological assessment was conducted at baseline and at follow-up, which ranged from inpatient regime (Elliott, 1994) and up to 3 years after discharge (Kirchberger et al., 2015) (Table 1). Three different depression assessment scales were used in the six trials, the most commonly used measure was the Hospital Anxiety and Depression Scale (HADS) (Elliott, 1994; Johnston et al., 1999; O'Neil et al., 2014), which also allowed the studies to report on anxiety. Only one study used a diagnostic interview in the form of Hamilton Depression Rating Scale (HAM-D) as the assessment of depression (Hansen et al., 2012). Included patients were diagnosed with acute myocardial infarction only (Hunger et al., 2015; Johnston et al., 1999; Kirchberger et al., 2015; O'Neil et al., 2014), or with unstable angina pectoris (Elliott, 1994; Hansen et al., 2012) and one study included patients undergoing coronary artery bypass grafting following ACS (Hansen et al., 2012). 3.1. Risk of bias assessment The risk of bias assessment of the included studies is presented in Fig. 2. Two studies failed to describe the method used to generate the random sequence (Elliott, 1994; Johnston et al., 1999). These studies were also at high risk of bias in allocation concealment and blinding of outcome assessors (Elliott, 1994; Johnston et al., 1999). Blinding of participants and personnel was only adequately described in Hansen et al. (2012). Only one study (Johnston et al., 1999) did not have high risk of attrition bias, whereas all other included studies struggled with many dropouts or exclusions, who were not adequately accounted for (Elliott, 1994; Hansen et al., 2012; Hunger et al., 2015; Kirchberger et al., 2015; O'Neil et al., 2014). All studies performed patient recruitment from cardiology departments at major hospitals in Western countries with a participation rate of eligible patients from 10% (Johnston et al., 1999) to 67% (Hansen et al., 2012). One study did not account for participation and loss to follow-up (Elliott, 1994), and thus with high risk of selection bias, and another did not account for a 70,9% loss to follow-up over a three year period (Kirchberger et al., 2015). Three articles accounted for loss to follow-up and found no statistical differences at baseline between treatment completers and non-completers (Hansen et al., 2012; Johnston et al., 1999; O'Neil et al., 2014). Two studies had problems with selective outcome reporting bias (Hansen et al., 2012; O'Neil et al., 2014), and we were unable to locate the protocol and assess the reporting bias of two
Fig. 2. Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
studies, which therefore was considered as unclear bias (Elliott, 1994; Johnston et al., 1999). Other sources of biases not addressed in the other domains in the bias assessment tool included funding bias, which in one study was assessed as high (Elliott, 1994).
3.2. Outcome description Two of the six included studies reported an overall reduction of depression in the intervention group compared with the control group (Hansen et al., 2012; Johnston et al., 1999). The DECARD
Table 1 Patient characteristics and study design. Study
Study design
Population n (randomized ptt)
Age (mean ± SD)
Sex (M/F) %
Diagnosis
Time of measurement since diagnosis
Elliott, 1994
RCT, 3 arm
56 (56)
60,6
71,4/28,6
UAP, AMI
Hansen et al., 2012
RCT
239 (240)
63,70 ± 12,22
63,2/36,8
Hunger et al., 2015
RCT
252 (326)
75,40 ± 5,99
62,6/37,4
UAP, AMI, CABG AMI
Johnston et al., 1999
RCT, 3 arm
100 (100)
55,98 ± 8,54
65/35
AMI
Kirchberger et al., 2015
RCT
199 (326)
75,40 ± 5,99
62,6/37,4
AMI
O'Neil et al., 2014
RCT
297 (430)
60,79 ± 10,73
79,1/20,9
AMI
<24 h after diagnosis, final intervention within CCU Baseline within eight weeks after ACS and eight visits over 12 months Shortly before discharge and one year after discharge In CCU, two weeks, two months, six months, and one year after discharge. Shortly before discharge and three years after discharge Within two weeks after discharge and 6 months after baseline
n, number of patients; ptt, patients; SD, standard deviation; M/F, male/female; RCT, randomized controlled trial; UAP, unstable angina pectoris; AMI, acute myocardial infarction; CCU, coronary care unit; CABG, coronary artery bypass grafting; ACS, acute coronary syndrome.
O'Neil et al., 2014
STAI, State Trait Anxiety Inventory; HADS, Hospital Anxiety and Depression Scale (-A, anxiety score); LAAS, Linear Analogue Anxiety Scale; ICD-10, International Classification of Diseases, version 10; mg, milligram; HAM-D, Hamilton Depression Rating Scale; N/A, not available; GDS, Geriatric Depression Scale; MI, myocardial infarction; inpt, inpatient group; ext, extended group.
Depression p ¼ 0,11. Anxiety p < 0,05 Yes No Usual care HADS Scripted telephone health coaching sessions Dec 2007eJan 2009
N/A No Sep 2008eMay 2010 Combination of components from case- Usual care GDS management and disease-management
Time to first unplanned readmission to hospital or death HADS Kirchberger et al., 2015
Yes Yes I) Program of education and counselling No formal HADS program or II) Extended for eight sessions
N/A No
ICD-10 depression, moderate or severe Hunger et al., 2015 Time to first unplanned readmission to hospital or death Johnston et al., 1999 Knowledge about MI Hansen et al., 2012
Anxiety; STAI, HADS, LAAS Elliott, 1994
Jan 1992eFeb 1993
N/A Yes
Music group: STAI ***p < 0,001, HASD-A *p < 0,01. Muscle group: LAAS p < 0,01. 80% relative reduction of depression Yes No
Sessions by audiotape players with a) Usual care HADS light classical music or b) Verbal instructions for muscle relaxation Nov 2004eDec 2007 5 mg escitalopram once daily for 1 week Placebo HAM-D and then 10 mg once daily Sep 2008eMay 2010 Combination of components from case- Usual care GDS management and disease-management
Intervention Recruitment period Primary outcome
Table 2 Outcome and measurements.
Two out of six studies reported a statistically significant prophylactic difference in depression between intervention and control groups (Hansen et al., 2012; Johnston et al., 1999). The DECARD study (Hansen et al., 2012) showed that prophylactically administered escitalopram resulted in a significant reduction in depression. Likewise, cardiac rehabilitation (Johnston et al., 1999) with counselling and an educational program was also found to have a significant antidepressant effect. The quality of the studies was questionable, since both trials were at high risk of bias in several items. Four studies showed no effect on reduction of depression in the intervention group compared with the control group (Elliott, 1994; Hunger et al., 2015; Kirchberger et al., 2015; O'Neil et al., 2014). Interventions were very heterogenic, vaguely described, and multiple different tools of depression assessment were used. The general quality of the studies was questionable with one or more items at a high risk of bias in all included trials. We did not have the results to complete a meta-analysis, as the included studies were heterogenic in measurements, interventions, and follow-up periods. Therefore it was not possible to apply a statistical method, i. a. a forest plot, to account for publication bias. As mentioned no attempt was made to include ongoing results as written apriori in the protocol, which is a limitation to the current study. A recent systematic review on comorbid depression and myocardial infarction found that collaborative care resulted in a small but significant reduction in depressive symptoms (standardised mean differences 0.31; 95% CI -0.43 to 0.19, p < 0.001) (Tully and Baumeister, 2015), and depression remission was significant by six months. Collaborative care was defined by a multiprofessional approach to patient care delivered by a physician and at least one other health professional such as a psychiatrist of psychologist, involving a structured patient management plan with interventions and scheduled patient follow-ups. Collaborative care was associated with a significant reduction in anxiety symptoms and an improvement in mental quality of life (Tully and
Control
4. Discussion
Unknown
Overall effect: Overall effect: Results if positive Depression: Anxiety measurement Depression instrument
(Depression in patients with Acute Coronary Disease) study showed an overall effect of 10 mg escitalopram administrated prophylactically to patients with a 6.8% absolute risk reduction (80% relative reduction) of depressive symptoms corresponding to a number needed to treat of 15 in 1 year to prevent one episode of depression (Hansen et al., 2012). Cardiac rehabilitation (counselling and education) had a significant prophylactic antidepressant effect during 12 months follow-up with a HADS score after one year of 3.43 and 2.8 for the inpatient and extended group respectively compared with 5.9 for the control group giving a relative reduction in depression scores of 42% and 51% in the inpatient and extended group respectively (p < 0.05) (Johnston et al., 1999). The remaining four studies did not show an overall reduction in depression or depressive symptoms in the intervention group compared with the control group (Elliott, 1994; Hunger et al., 2015; Kirchberger et al., 2015; O'Neil et al., 2014). The interventions of these studies were very heterogenic but characterized by case and disease management such as nurse counselling. The one-year follow-up of the KORINNA study showed a borderline significant overall effect (p ¼ 0.0519), but after the result was adjusted by stratification and the baseline variables the result ceased to be significant (p ¼ 0.1233) (Hunger et al., 2015). Furthermore, three studies reported a significant reduction in anxiety (measured with HADS) in the intervention group compared with the control group (Elliott, 1994; Johnston et al., 1999; O'Neil et al., 2014) (see Table 2).
Depression: 2 months: I) inpt p < 0,01, II) ext p < 0,001. 6 months: p < 0,005. 12 months: p < 0,05 Anxiety: 2 months: I) inpt p < 0,001, II) ext p < 0,02. 6 months: p < 0,02. 12 months: no difference
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Study
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Baumeister, 2015). However, these results reached the same conclusions as our current review showing that a major heterogeneity resides within these randomized controlled trials in the depression and myocardial infarction patients, and therefore, the outcomes were difficult to compare. Selective Serotonin Reuptake Inhibitors (SSRI) combined with cognitive behavioural therapy have shown to be effective in decreasing depression and improve social support in patients with coronary heart disease (Huffman et al., 2006; Berkman et al., 2003). This raise support to the hypothesis of the DECARD study (Hansen et al., 2012), which utilizes the SSRI escitalopram to prevent development of depression. SSRIs have previously been associated with a reduced risk of myocardial infarction due to the inhibitory effect on platelet aggregation (Pizzi et al., 2009; Sauer et al., 2001; Serebruany et al., 2001) and is generally considered safe (Wade et al., 2006; Muldoon, 1996). Specific concerns regarding cardiotoxicity of escitalopram has been raised nonetheless. Data indicate a positive correlation between high citalopram doses and ECG abnormalities and co-existing factors, including cardiac disease, may predispose to cardiac toxicity (Cooke and Waring, 2013). Thus, prophylactic treatment with SSRI is not without risk. Serious debate was raised whether prophylactic treatment of depression in patients with ACS in general and treatment with antidepressants specially is the correct choice of treatment (Thombs and Ziegelstein, 2012). Researchers critically examined the DECARD study (Hansen et al., 2009, 2012). It was questioned whether these findings could be reproduced and pointed out that the magnitude of effect was far beyond what could be expected in a reasonably powered study (Thombs and Ziegelstein, 2012). DECARD was significantly underpowered since the observed rate of depression in the study population was lower than the a priori assumed (Hansen et al., 2012). Furthermore, the fidelity of the DECARD study was questioned as the study failed to report on a primary outcome described in the published protocol, the HAM-D score (Thombs and Ziegelstein, 2012; Hansen et al., 2009). Therefore, it was concluded as a high risk of reporting bias. This review solely included studies using validated clinicianadministered or self-rating questionnaires with known psychometric properties and with a specific main focus on diagnosing and/ or measuring depression. This was done to improve both the internal and external validity of the review. HADS has been found to perform well in assessing the symptom severity and caseness of anxiety disorders and depression (Bjelland et al., 2002; Martin et al., 2003). Three included studies utilized HADS and all reported a significant reduction in anxiety (Elliott, 1994; Johnston et al., 1999; O'Neil et al., 2014). The prevalence of anxiety among patients hospitalized after ACS has been reported >40% (Lane et al., 2002; Mayou et al., 2000) and comorbid with depression in 90% of the cases (Denollet et al., 2006). Patients were at high risk of adverse psychological outcomes and decreased quality-of-life during the first year (Lane et al., 2002), but little is known about the mechanism behind anxiety. Anxiety after ACS has not received as much attention as post-ACS depression and as such represent a research area in urgent need of attention (Mavrides and Nemeroff, 2013) and in light of the prophylactic effect shown in the above mentioned studies this might represent a relevant area of research. A limitation of the literature is the multiple case-finding instruments used to identify patients with depression. Major discrepancies in prevalence of depression in an ACS population have been shown whether using self-reporting questionnaires or structured clinical interview (Thombs et al., 2006). Using a structured clinical interview, the golden standard of diagnosing depression, a meta-analysis showed a prevalence of 19.8%, which was higher than the prevalence of possible (15.5%) and probable (7.3%) clinical
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depression using HADS and the prevalence using the Beck Depression Index was 31.1% (Thombs et al., 2006). These discrepancies reflect some of the inherent challenges in evaluating symptoms of depression in general and among patients with an acute medical illness. A review of depression screening in primary care showed that a diagnostic interview was the best instrument, due to the relatively low positive predictive value of a positive screening by questionnaire (Williams et al., 2002). If a clear and valid consensus of methods in diagnosing and screening patients for depression after ACS existed the current review would have had a higher internal validity. Future research would benefit from applying both diagnostic interviews and validated selfadministered instruments making comparability of studies more accessible. Interventions in the included studies were similarly very heterogenic, ranging from music therapy over telephone counselling, education, and pharmacological interventions with doubtful or no significant effect. Future studies investigating prophylactic interventions against depression could benefit from applying interventions with known anti-depressive effect such as cognitive behavioural therapy, psychodynamic psychotherapies, and SSRIs as discussed earlier (Huffman et al., 2006; Robinson et al., 1990; Dobson, 1989; Dickens et al., 2013; Abbass et al., 2014). Furthermore, studies suggested beneficial effects of melatonin treatment in patients with major depressive disorder (Pandi-Perumal et al., 2009) and significantly reduced the risk of depressive symptoms (Hansen et al., 2014), and a close link between melatonin secretion disturbance and depressed mood have been shown (Pandi-Perumal et al., 2009; Bumb et al., 2016). This could prove an interesting topic to investigate in the future. Future studies should design the study with depressive symptoms as the primary outcome. When investigating pharmacological intervention a proper design with double-blinding can be applied. However, using a prophylactic antidepressant treatment with possible side effect should be considered carefully. In the current review we chose only to include studies treating patients with ACS as oppose to patients with known ischaemic heart disease or coronary heart disease. This was chosen to get a homogeneous population with a clear time to event relationships: incident depression following ACS. Had we included e.g. patients with stabile angina, the patient population would be more heterogenic and the time to event relationship would have been unclear. Patients with stable angina share the same pathological disease (i.e. atherosclerotic plaques in the coronary arteries) as ACS patients; however, the ACS (plaque rupture) is an acute event, which triggers an increase in incident depression. This review was limited to patients, who were not predisposed with depression at baseline. This was to ensure that the shown effect were prophylaxis of depression following the acute stress of ACS and to exclude any recurrence of depression at the time of measurement. We chose to include patients with an ACS treated with coronary artery bypass grafting as the primary revascularizing treatment. This was done although these patients may have experienced a different physiological trauma (surgical trauma) than the myocardial infarction patients treated with percutaneous coronary intervention or pharmacological treatment only. The patient categories have been shown to respond similarly to stress management treatment programme (Trzcieniecka-Green and Steptoe, 1996). 5. Conclusion We did not find general evidence to support prophylactic treatment of depression following ACS. In the light of the heterogeneity of the included studies and the low quality of the evidence we believe further studies are warranted. As many of the included studies were relatively small in size, larger studies should be
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conducted to exclude the possibility of type II error. Therefore, welldesigned, and adequately reported RCTs in groups of patients with ACS more representative of usual clinical practice are needed. These trials should include validated depression measurement instruments and carefully consider the ethical aspects of prophylactic pharmacological antidepressant treatment. In summary, this systematic review does not support any specific routine prophylaxis of depression in ACS patients until further data are available. Declaration of conflicting interests The Authors declare that there is no conflict of interest. Author contributions OGC contributed to design, contributed to acquisition, analysis, and interpretation, drafted the manuscript, and gave final approval. MTM contributed to conception and design, contributed to acquisition and interpretation, revised the manuscript, and gave final approval. MTM acted as corresponding author. ES and IG contributed to conception and design, revised the manuscript, and gave final approval. The authors agreed to be accountable for all aspects of work ensuring integrity and accuracy. OGC and MTM have agreed on a shared first authorship. References Abbass, A.A., Kisely, S.R., Town, J.M., Leichsenring, F., Driessen, E., De Maat, S., et al., 2014. Short-term psychodynamic psychotherapies for common mental disorders. Cochrane Database Syst. Rev. 7, CD004687. Aben, I., Verhey, F., Strik, J., Lousberg, R., Lodder, J., Honig, A., 2003. A comparative study into the one year cumulative incidence of depression after stroke and myocardial infarction. J. Neurol. Neurosurg. Psychiatry 74 (5), 581e585. Amin, A.A., Jones, A.M., Nugent, K., Rumsfeld, J.S., Spertus, J.A., 2006. The prevalence of unrecognized depression in patients with acute coronary syndrome. Am. Heart J. 152 (5), 928e934. Bauer, L.K., Caro, M.A., Beach, S.R., Mastromauro, C.A., Lenihan, E., Januzzi, J.L., et al., 2012. Effects of depression and anxiety improvement on adherence to medication and health behaviors in recently hospitalized cardiac patients. Am. J. Cardiol. 109 (9), 1266e1271. Berkman, L.F., Blumenthal, J., Burg, M., Carney, R.M., Catellier, D., Cowan, M.J., et al., 2003. Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the enhancing recovery in coronary heart disease patients (ENRICHED) randomized trial. JAMA 289 (23), 3106e3116. Bjelland, I., Dahl, A.A., Haug, T.T., Neckelmann, D., 2002. The validity of the Hospital Anxiety and Depression Scale. An updated literature review. J. Psychosom. Res. 52 (2), 69e77. Blumenthal, J.A., Williams, R.S., Wallace, A.G., Williams Jr., R.B., Needles, T.L., 1982. Physiological and psychological variables predict compliance to prescribed exercise therapy in patients recovering from myocardial infarction. Psychosom. Med. 44 (6), 519e527. Booth, A., Clarke, M., Ghersi, D., Moher, D., Petticrew, M., Stewart, L., 2011. Establishing a minimum dataset for prospective registration of systematic reviews: an international consultation. PLoS One 6 (11), e27319. Booth, A., Clarke, M., Ghersi, D., Moher, D., Petticrew, M., Stewart, L., 2011. An international registry of systematic-review protocols. Lancet 377 (9760), 108e109. Bumb, J.M., Enning, F., Mueller, J.K., van der List, T., Rohleder, C., Findeisen, P., et al., 2016. Differential melatonin alterations in cerebrospinal fluid and serum of patients with major depressive disorder and bipolar disorder. Compr. Psychiatry 68, 34e39. Carney, R.M., Freedland, K.E., 2009. Depression and heart rate variability in patients with coronary heart disease. Cleve Clin. J. Med. 76 (Suppl. 2), S13eS17. Carney, R.M., Freedland, K.E., Eisen, S.A., Rich, M.W., Jaffe, A.S., 1995. Major depression and medication adherence in elderly patients with coronary artery disease. Health Psychol. 14 (1), 88e90. Carney, R.M., Freedland, K.E., Miller, G.E., Jaffe, A.S., 2002. Depression as a risk factor for cardiac mortality and morbidity: a review of potential mechanisms. J. Psychosom. Res. 53 (4), 897e902. Carney, R.M., Blumenthal, J.A., Freedland, K.E., Stein, P.K., Howells, W.B., Berkman, L.F., et al., 2005. Low heart rate variability and the effect of depression on post-myocardial infarction mortality. Arch. Intern Med. 165 (13), 1486e1491. Cooke, M.J., Waring, W.S., 2013. Citalopram and cardiac toxicity. Eur. J. Clin. Pharmacol. 69 (4), 755e760.
Czarny, M.J., Arthurs, E., Coffie, D.F., Smith, C., Steele, R.J., Ziegelstein, R.C., et al., 2011. Prevalence of antidepressant prescription or use in patients with acute coronary syndrome: a systematic review. PLoS One 6 (11), e27671. Denollet, J., Strik, J.J., Lousberg, R., Honig, A., 2006. Recognizing increased risk of depressive comorbidity after myocardial infarction: looking for 4 symptoms of anxiety-depression. Psychother. Psychosom. 75 (6), 346e352. Dickens, C., Cherrington, A., Adeyemi, I., Roughley, K., Bower, P., Garrett, C., et al., 2013. Characteristics of psychological interventions that improve depression in people with coronary heart disease: a systematic review and meta-regression. Psychosom. Med. 75 (2), 211e221. Dobson, K.S., 1989. A meta-analysis of the efficacy of cognitive therapy for depression. J. Consult Clin. Psychol. 57 (3), 414e419. Elliott, D., 1994. The effects of music and muscle relaxation on patient anxiety in a coronary care unit. Heart Lung 23 (1), 27e35. Gehi, A.K., Ali, S., Na, B., Whooley, M.A., 2007. Self-reported medication adherence and cardiovascular events in patients with stable coronary heart disease: the heart and soul study. Arch. Intern Med. 167 (16), 1798e1803. Hansen, B.H., Hanash, J.A., Rasmussen, A., Hansen, J.F., Birket-Smith, M., 2009. Rationale, design and methodology of a double-blind, randomized, placebocontrolled study of escitalopram in prevention of Depression in Acute Coronary Syndrome (DECARD). Trials 10, 20. Hansen, B.H., Hanash, J.A., Rasmussen, A., Hansen, J.F., Andersen, N.L., Nielsen, O.W., et al., 2012. Effects of escitalopram in prevention of depression in patients with acute coronary syndrome (DECARD). J. Psychosom. Res. 72 (1), 11e16. Hansen, M.V., Andersen, L.T., Madsen, M.T., Hageman, I., Rasmussen, L.S., Bokmand, S., et al., 2014. Effect of melatonin on depressive symptoms and anxiety in patients undergoing breast cancer surgery: a randomized, doubleblind, placebo-controlled trial. Breast Cancer Res. Treat. 145 (3), 683e695. Hanssen, T.A., Nordrehaug, J.E., Eide, G.E., Bjelland, I., Rokne, B., 2009. Anxiety and depression after acute myocardial infarction: an 18-month follow-up study with repeated measures and comparison with a reference population. Eur. J. Cardiovasc Prev. Rehabil. 16 (6), 651e659. Higgins, J.P., Altman, D.G., Gotzsche, P.C., Juni, P., Moher, D., Oxman, A.D., et al., 2011. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 343, d5928. Howren, M.B., Lamkin, D.M., Suls, J., 2009. Associations of depression with Creactive protein, IL-1, and IL-6: a meta-analysis. Psychosom. Med. 71 (2), 171e186. Huffman, J.C., Smith, F.A., Blais, M.A., Beiser, M.E., Januzzi, J.L., Fricchione, G.L., 2006. Recognition and treatment of depression and anxiety in patients with acute myocardial infarction. Am. J. Cardiol. 98 (3), 319e324. Huffman, J.C., Celano, C.M., Beach, S.R., Motiwala, S.R., Januzzi, J.L., 2013. Depression and cardiac disease: epidemiology, mechanisms, and diagnosis. Cardiovasc Psychiatry Neurol. 2013, 695925. Hunger, M., Kirchberger, I., Holle, R., Seidl, H., Kuch, B., Wende, R., et al., 2015. Does nurse-based case management for aged myocardial infarction patients improve risk factors, physical functioning and mental health? The KORINNA trial. Eur. J. Prev. Cardiol. 22 (4), 442e450. Jiang, W., Krishnan, R.R., O'Connor, C.M., 2002. Depression and heart disease: evidence of a link, and its therapeutic implications. CNS Drugs 16 (2), 111e127. Johnston, M., Foulkes, J., Johnston, D.W., Pollard, B., Gudmundsdottir, H., 1999. Impact on patients and partners of inpatient and extended cardiac counseling and rehabilitation: a controlled trial. Psychosom. Med. 61 (2), 225e233. Jorgensen, T.S., Wium-Andersen, I.K., Wium-Andersen, M.K., Jorgensen, M.B., Prescott, E., Maartensson, S., et al., 2016. Incidence of depression after stroke, and associated risk factors and mortality outcomes, in a large cohort of Danish patients. JAMA Psychiatry 73 (10), 1032e1040. Jorgensen, T.S., Martensson, S., Ibfelt, E.H., Jorgensen, M.B., Wium-Andersen, I.K., Wium-Andersen, M.K., et al., 2016. Time trend in depression diagnoses among acute coronary syndrome patients and a reference population from 2001 to 2009 in Denmark. Nord. J. Psychiatry 70 (5), 335e341. Kaptoge, S., Seshasai, S.R., Gao, P., Freitag, D.F., Butterworth, A.S., Borglykke, A., et al., 2014. Inflammatory cytokines and risk of coronary heart disease: new prospective study and updated meta-analysis. Eur. Heart J. 35 (9), 578e589. Kirchberger, I., Hunger, M., Stollenwerk, B., Seidl, H., Burkhardt, K., Kuch, B., et al., 2015. Effects of a 3-year nurse-based case management in aged patients with acute myocardial infarction on rehospitalisation, mortality, risk factors, physical functioning and mental health. a secondary analysis of the randomized controlled KORINNA study. PLoS One 10 (3), e0116693. Lane, D., Carroll, D., Ring, C., Beevers, D.G., Lip, G.Y., 2002. The prevalence and persistence of depression and anxiety following myocardial infarction. Br. J. Health Psychol. 7 (Pt 1), 11e21. Liberati, A., Altman, D.G., Tetzlaff, J., Mulrow, C., Gotzsche, P.C., Ioannidis, J.P., et al., 2009. The PRISMA statement for reporting systematic reviews and metaanalyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339, b2700. Lichtman, J.H., Bigger Jr., J.T., Blumenthal, J.A., Frasure-Smith, N., Kaufmann, P.G., Lesperance, F., et al., 2008. Depression and coronary heart disease: recommendations for screening, referral, and treatment: a science advisory from the American heart association prevention committee of the council on cardiovascular nursing, council on clinical cardiology, council on epidemiology and prevention, and interdisciplinary council on quality of care and outcomes research: endorsed by the American psychiatric association. Circulation 118 (17), 1768e1775. Lichtman, J.H., Froelicher, E.S., Blumenthal, J.A., Carney, R.M., Doering, L.V., Frasure-
O.G. Christiansen et al. / Journal of Psychiatric Research 94 (2017) 186e193 Smith, N., et al., 2014. Depression as a risk factor for poor prognosis among patients with acute coronary syndrome: systematic review and recommendations: a scientific statement from the American Heart Association. Circulation 129 (12), 1350e1369. Martin, C.R., Lewin, R.J., Thompson, D.R., 2003. A confirmatory factor analysis of the Hospital Anxiety and Depression Scale in coronary care patients following acute myocardial infarction. Psychiatry Res. 120 (1), 85e94. Mavrides, N., Nemeroff, C., 2013. Treatment of depression in cardiovascular disease. Depress Anxiety 30 (4), 328e341. May, H.T., Sheng, X., Catinella, A.P., Horne, B.D., Carlquist, J.F., Joy, E., 2010. Antilipidemic adherence post-coronary artery disease diagnosis among those with and without an ICD-9 diagnosis of depression. J. Psychosom. Res. 69 (2), 169e174. Mayou, R.A., Gill, D., Thompson, D.R., Day, A., Hicks, N., Volmink, J., et al., 2000. Depression and anxiety as predictors of outcome after myocardial infarction. Psychosom. Med. 62 (2), 212e219. Meijer, A., Conradi, H.J., Bos, E.H., Thombs, B.D., van Melle, J.P., de Jonge, P., 2011. Prognostic association of depression following myocardial infarction with mortality and cardiovascular events: a meta-analysis of 25 years of research. Gen. Hosp. Psychiatry 33 (3), 203e216. Meijer, A., Conradi, H.J., Bos, E.H., Anselmino, M., Carney, R.M., Denollet, J., et al., 2013. Adjusted prognostic association of depression following myocardial infarction with mortality and cardiovascular events: individual patient data meta-analysis. Br. J. Psychiatry 203 (2), 90e102. Muldoon, C., 1996. The safety and tolerability of citalopram. Int. Clin. Psychopharmacol. 11 (Suppl. 1), 35e40. O'Neil, A., Hawkes, A.L., Atherton, J.J., Patrao, T.A., Sanderson, K., Wolfe, R., et al., 2014. Telephone-delivered health coaching improves anxiety outcomes after myocardial infarction: the ‘ProActive Heart’ trial. Eur. J. Prev. Cardiol. 21 (1), 30e38. Osler, M., Martensson, S., Wium-Andersen, I.K., Prescott, E., Andersen, P.K., Jorgensen, T.S., et al., 2016. Depression after first hospital admission for acute coronary syndrome: a study of time of onset and impact on survival. Am. J. Epidemiol. 183 (3), 218e226. Pandi-Perumal, S.R., Moscovitch, A., Srinivasan, V., Spence, D.W., Cardinali, D.P., Brown, G.M., 2009. Bidirectional communication between sleep and circadian rhythms and its implications for depression: lessons from agomelatine. Prog. Neurobiol. 88 (4), 264e271. Pizzi, C., Mancini, S., Angeloni, L., Fontana, F., Manzoli, L., Costa, G.M., 2009. Effects of selective serotonin reuptake inhibitor therapy on endothelial function and inflammatory markers in patients with coronary heart disease. Clin. Pharmacol. Ther. 86 (5), 527e532. Pizzi, C., Manzoli, L., Mancini, S., Bedetti, G., Fontana, F., Costa, G.M., 2010. Autonomic nervous system, inflammation and preclinical carotid atherosclerosis in depressed subjects with coronary risk factors. Atherosclerosis 212 (1), 292e298. Poole, L., Dickens, C., Steptoe, A., 2011. The puzzle of depression and acute coronary
193
syndrome: reviewing the role of acute inflammation. J. Psychosom. Res. 71 (2), 61e68. Rieckmann, N., Kronish, I.M., Haas, D., Gerin, W., Chaplin, W.F., Burg, M.M., et al., 2006. Persistent depressive symptoms lower aspirin adherence after acute coronary syndromes. Am. Heart J. 152 (5), 922e927. Robinson, L.A., Berman, J.S., Neimeyer, R.A., 1990. Psychotherapy for the treatment of depression: a comprehensive review of controlled outcome research. Psychol. Bull. 108 (1), 30e49. Ross, R., 1999. Atherosclerosisean inflammatory disease. N. Engl. J. Med. 340 (2), 115e126. Sauer, W.H., Berlin, J.A., Kimmel, S.E., 2001. Selective serotonin reuptake inhibitors and myocardial infarction. Circulation 104 (16), 1894e1898. Serebruany, V.L., Gurbel, P.A., O'Connor, C.M., 2001. Platelet inhibition by sertraline and N-desmethylsertraline: a possible missing link between depression, coronary events, and mortality benefits of selective serotonin reuptake inhibitors. Pharmacol. Res. 43 (5), 453e462. Thombs, B.D., Ziegelstein, R.C., 2012. When prevention is a bad idea: problems with the DECARD trial and the premise behind it. J. Psychosom. Res. 72 (5), 333e335. Thombs, B.D., Bass, E.B., Ford, D.E., Stewart, K.J., Tsilidis, K.K., Patel, U., et al., 2006. Prevalence of depression in survivors of acute myocardial infarction. J. Gen. Intern Med. 21 (1), 30e38. Trzcieniecka-Green, A., Steptoe, A., 1996. The effects of stress management on the quality of life of patients following acute myocardial infarction or coronary bypass surgery. Eur. Heart J. 17 (11), 1663e1670. Tully, P.J., Baumeister, H., 2015. Collaborative care for comorbid depression and coronary heart disease: a systematic review and meta-analysis of randomised controlled trials. BMJ Open 5 (12), e009128. van Melle, J.P., de Jonge, P., Spijkerman, T.A., Tijssen, J.G., Ormel, J., van Veldhuisen, D.J., et al., 2004. Prognostic association of depression following myocardial infarction with mortality and cardiovascular events: a meta-analysis. Psychosom. Med. 66 (6), 814e822. Vertitas Health Innovation Ltd, 2015. Covidence online systematic review platform. Available from: https://www.covidence.org. Wade, A., Despiegel, N., Heldbo Reines, E., 2006. Escitalopram in the long-term treatment of major depressive disorder. Ann. Clin. Psychiatry 18 (2), 83e89. Wessel, T.R., Arant, C.B., Olson, M.B., Johnson, B.D., Reis, S.E., Sharaf, B.L., et al., 2004. Relationship of physical fitness vs body mass index with coronary artery disease and cardiovascular events in women. JAMA 292 (10), 1179e1187. Williams Jr., J.W., Pignone, M., Ramirez, G., Perez Stellato, C., 2002. Identifying depression in primary care: a literature synthesis of case-finding instruments. Gen. Hosp. Psychiatry 24 (4), 225e237. World Health Organization, 2000. The World Health Report 2000: Health systems: improving performance. World Health Organization, 2000, Geneve. Ziegelstein, R.C., Fauerbach, J.A., Stevens, S.S., Romanelli, J., Richter, D.P., Bush, D.E., 2000. Patients with depression are less likely to follow recommendations to reduce cardiac risk during recovery from a myocardial infarction. Arch. Intern Med. 160 (12), 1818e1823.