Journal of Affective Disorders

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1 Journal of Affective Disorders 123 (2010) Contents lists available at ScienceDirect Journal of Affective Disorders journal homepage: Research report Relief of Chronic or Resistant Depression (Re-ChORD): A pragmatic, randomized, open-treatment trial of an integrative program intervention for chronic depression Greg Murray a, Erin E. Michalak b, Auby Axler b, David Yaxley b, Brenda Hayashi b, Åsa Westrin c, John S. Ogrodniczuk b, Edwin M. Tam b, Lakshmi N. Yatham b, Raymond W. Lam b, a Faculty of Life and Social Sciences, Swinburne University of Technology, Melbourne, Australia b Department of Psychiatry, University of British Columbia, Vancouver, Canada c Department of Psychiatry, University of Lund, Sweden article info abstract Article history: Received 20 May 2009 Received in revised form 6 October 2009 Accepted 12 October 2009 Available online 5 November 2009 Keywords: Psychosocial treatments Remission Interpersonal psychotherapy Occupational therapy Chronic depression ] Background: Chronic depression is a particularly disabling mood disorder and treatment outcomes are poor with either psychotherapy or pharmacotherapy alone. There is growing evidence that an integrative treatment approach may be optimal. A novel multi-modal, multidisciplinary treatment program, Re-ChORD, was developed at the University of British Columbia and evaluated in this pilot study. Methods: Re-ChORD consisted of guidelines-based medication management, and group-based interpersonal psychotherapy and occupational therapy. A randomized, parallel-groups, opentreatment trial was conducted comparing Re-ChORD to treatment as usual (TAU). Inclusion criteria were current depression (17-item Ham-D 15) and a diagnosis of a chronic depressive disorder. The primary outcome variable was clinical remission (17-item Ham-D 7) at 4 month assessment. Results: A total of 64 patients were randomised to Re-ChORD (N=34) and TAU (N=30). Under both intention to treat (ITT) and completer analyses, the remission rate was significantly higher in the Re-ChORD than TAU groups. Treatment effect size for remission was of medium magnitude (22.2% and 29.6% over TAU under ITT and completer analyses). Limitations: We did not collect sufficient follow-up data to investigate maintenance of gains. Re-ChORD shares elements with other combined treatments, and the present positive findings cannot be interpreted as being specific to the Re-ChORD program. Conclusions: Consistent with growing evidence that integrative treatments are necessary for chronic depressive disorders, Re-ChORD was demonstrated in this pilot study to produce significantly greater rates of remission than treatment as usual. A larger-scale trial is warranted Elsevier B.V. All rights reserved. 1. Introduction Clinical depression is archetypically an episodic/remitting condition, but there is increasing awareness of the prevalence Corresponding author. University of BC, 2255 Wesbrook Mall, Vancouver, Canada V6T 2A1. Tel.: ; fax: address: r.lam@ubc.ca (R.W. Lam). and impact of chronic depressive disorders (Judd, 1997; Klein, 2008). Depressive disorders with a chronic course (consensually defined as 2 years or more) are estimated to make up one third of all cases (Keller et al., 1995; Kessler et al., 1994), and are particularly disabling. Chronic depression is associated with increased comorbidity, poorer subjective wellbeing, greater service use and higher rates of suicidality compared to episodic depression (Arnow and Constantino, 2003). Indeed, much of /$ see front matter 2009 Elsevier B.V. All rights reserved. doi: /j.jad

2 244 G. Murray et al. / Journal of Affective Disorders 123 (2010) the disability associated with depression may be accounted for by chronic depression (Berndt et al., 2000; Gelenberg et al., 2003). Five subtypes of chronic depression are recognised in the DSM-IV (APA, 2000) dysthymic disorder, dysthymic disorder with superimposed major depressive episode ( double depression ), recurrent major depressive disorder (MDD) with incomplete interepisode recovery, MDD (chronic type) and major depressive episode with partial recovery. The validity of these categorical subtypes has been questioned (McCullough et al., 2003), and newer literature suggests that a dimension of severity across disorders, ranging from pure dysthymic disorder to chronic MDD has implications for treatment outcome (Klein, 2008). It is widely agreed that chronic depression is more difficult to treat than episodic major depression but knowledge about optimal treatment approaches is developing (Arnow et al., 2007; Markowitz et al., 2005; Michalak and Lam, 2002). Several classes of antidepressant medication have been demonstrated efficacious, safe and tolerable for acute-phase treatment of pure dysthymic disorder and double depression. As reviewed by Kocsis (2003), intent-to-treat response rates of 45 55% and remission rates of 25 35% have been found in placebo-controlled randomized clinical trials. Not surprisingly, this research has also shown that spontaneous remission rates from drug or placebo are lower for chronic depression than for its purely episodic counterpart. Because of its quasi-characterological presentation, early literature favoured psychotherapy as the preferred treatment for chronic depression (Akiskal et al., 1980; Markowitz, 1994). Studies comparing psychotherapy to medication have not supported this position: Pharmacotherapy is associated with equivalent outcomes to psychotherapy in the treatment of chronic major depression (De Maat et al., 2006), and in fact may show some advantage over psychotherapy in the treatment of less severe dysthymic disorder (Arnow and Constantino, 2003; Imel et al., 2008). The moderate effects of monotherapy treatments (pharmacotherapy or psychotherapy) and the complex, longstanding nature of chronic depression suggests that an integrative treatment approach may be optimal. Indeed, there is evidence that interventions combining medication with psychotherapy may be superior to either treatment in isolation. In a highly cited study, Keller et al. (2000) compared treatment with nefazodone, the Cognitive Behavioral Analysis System of Psychotherapy (CBASP, McCullough, 2003), or the combination, in chronic MDD, double depression or recurrent MDD with incomplete remission (N=681). After 12 weeks of treatment, response rates were significantly higher for the combination (85%) than for CBASP (52%) or nefazodone (55%) alone. Psychosocial outcome was also significantly superior in the combined treatment group (Hirschfeld et al., 2002), as was time to remission (Manber et al., 2008). More recently, Schramm et al. (2008) reported superior efficacy for Interpersonal Psychotherapy (IPT) plus pharmacotherapy over usual clinical inpatient management in a smaller inpatient sample with chronic MDD. Findings in relation to combination treatment for less severe chronic depression are more equivocal. For example, in the treatment of a large primary care cohort with dysthymic disorder, Browne et al. (2002) found combined sertraline plus IPT and sertraline alone to be superior to IPT alone, but differences between the combined treatment and sertraline were not significant. On the other hand, significant advantages for the combined treatment were found in relation to health service utilization, and smaller studies have found combined treatment to be associated with lower dropout rates (Mello et al., 2001) and greater functional improvement (Ravindran et al., 1999). Research into the addition of psychotherapy to medication has also been limited by potentially insufficient dose/duration of psychotherapy (Arnow and Constantino, 2003; Browne et al., 2002) and insufficient power given the likely shared placebo component of pharmacotherapy and psychotherapy (see Jindal and Thase, 2003). Existing research into the treatment of chronic depression is largely restricted to assessment of efficacy (Michalak and Lam, 2002). Studies have applied strict inclusion criteria and have tended to assess single antidepressant agents. Several studies have been conducted in patients with dysthymic disorder in primary care populations, which represents a less severely ill sample, or in patients who were not resistant to treatment. Such situations do not reflect typical clinical settings, where many patients with chronic depression have severe symptoms, additional comorbid conditions, and poor response to previous antidepressant trials. Pragmatic research is therefore required to evaluate the feasibility and effectiveness of naturalistic treatment strategies that can be applied in real world, outpatient settings. To meet the heterogenic needs of patients with chronic depression, an integrative treatment program, called Relief of Chronic or Resistant Depression (Re-ChORD) was developed at the Mood Disorders Centre (MDC), University of British Colombia (UBC). Re-ChORD is a multi-modal, multi-disciplinary treatment program addressing the biological, psychological, and social problems associated with chronic depression. The present pilot study was designed as a randomized, parallelgroups, open-treatment test of the hypothesis that the Re- ChORD program is more effective than treatment as usual (TAU). Based on findings about the prognostic significance of residual symptoms (Rush et al., 2006), rate of clinical remission was chosen as the primary outcome variable. It was also predicted that Re-ChORD would generate significantly greater decreases in depressive symptoms and improvements in functional measures relative to baseline. 2. Methods 2.1. Study population Patients aged were referred to the MDC at UBC Hospital by community psychiatrists, community mental health teams and family physicians. Some patients were referred from inpatient units or emergency rooms, but all were treated as outpatients. Inclusion criteria included a DSM- IV diagnosis of chronic MDD, dysthymic disorder with superimposed MDD (double depression), or MDD in partial remission with an episode duration of 2 years or more. Although dysthymic disorder was not formally excluded, it was unlikely that patients with dysthymic disorder alone would be referred, as they are usually treated in primary care. Patients entering the study were currently depressed, with a minimum score of 15 on the 17-item version of the Hamilton

3 G. Murray et al. / Journal of Affective Disorders 123 (2010) Depression Rating Scale (Ham-D, Williams et al., 1988), indicating depression of at least moderate severity. Exclusion criteria were limited to enhance generalisability to common clinical populations, but the following were excluded: diagnoses of bipolar I disorder, rapid cycling episodes, chronic psychotic disorders, active substance abuse/dependence, severe personality disorder, acute suicidal risk or electroconvulsive therapy within 3 months. Older patients (>65 years) were also excluded Re-ChORD Re-ChORD is an intensive, time-limited outpatient program of 4 months duration. The major components of Re- ChORD are medication management, group-based interpersonal psychotherapy, and group occupational therapy (OT) Medication management There is no consensus as to the most effective medication strategies for chronic or resistant depression (Trivedi and Kleiber, 2001). Therefore, patients were treated using individualized medication regimens informed by evidenced-based recommendations (Kennedy et al., 2001). Treatment history, tolerability, concurrent medications, comorbidity, drug drug interactions, adherence issues, and symptom profiles were taken into account (Lam, 2001). Interventions included augmentation strategies (e.g., lithium and atypical antipsychotics) and combination antidepressant strategies (Lam et al., 2002). Patients were seen by MDC psychiatrists for medication management on a weekly or bi-weekly basis as required, at which times adverse and side effects were monitored, and issues affecting adherence addressed Group interpersonal psychotherapy Interpersonal psychotherapy (IPT) was developed to address the interpersonal issues associated with depression (Klerman et al., 1984). IPT is a time-limited psychotherapy employing a semi-structured format. In the NIMH Collaborative Study of Depression, IPT was found as effective as tricylic antidepressants and cognitive behavioural therapy (Elkin et al., 1989). Subsequent comparative studies have supported the efficacy of IPT for MDD (Segal et al., 2001). In Re-ChORD, IPT is delivered in a group format (Wilfley et al., 2000) for sixteen 90- minute sessions. The content of IPT-G parallels individual IPT, viz., selection of target goals, encouragement of disclosure, problem clarification, encouragement of self-efficacy, and attention to positive emotional/social interactions. Following completion of the IPT-G program, patients meet for follow-up maintenance sessions on a monthly basis, as needed. In the present study, IPT-G therapists (AA, DY) were psychiatrists trained by the project leaders and fidelity was ensured by live observation and feedback from a senior psychotherapist Occupational therapy The OT component of Re-ChORD addresses the significant occupational and social dysfunction of chronic depression. Using the Occupational Performance Model and the standardized Canadian Occupational Performance Measure (COPM, McColl et al., 2000; Toomey et al., 1995), the therapist (BH) aims to prioritize occupational performance issues, identify strengths, resources and occupational barriers, negotiate targeted outcomes and interface with employers (Egan et al., 1998). Ten to twelve sessions were conducted once a week in a group format Study protocol The study was approved by the UBC Clinical Research Ethics Board, but the study was not registered at a clinical trial registration site because it was completed before such registration was required. Patients were competent to provide written informed consent. All patients underwent a comprehensive assessment by a multidisciplinary team. The assessment included a consult by a board-certified psychiatrist, a Mini International Neuropsychiatric Interview (MINI, Sheehan et al, 1998), administered by a trained interviewer, and the COPM administered by an occupational therapist. Diagnoses were assigned according to research team consensus using all available data. The primary measures of depression were drawn from clinician rating on the Ham-D at baseline. Patients also completed self-rated measures of depression (see Section 2.4). Following assessment, patients were randomized to one of two conditions: Re-ChORD or Treatment As Usual (TAU) by the referring physician. Patients were randomly allocated to treatment condition in blocks of six and stratified for depression severity as measured by the baseline Ham-D score (moderate, 15 21; severe, 22 and higher). Allocation was concealed by use of opaque, tamper-proof envelopes which were only opened after a patient had been logged into the study registry. After randomization, treatment was conducted openly. In the TAU condition, referring physicians received a detailed consultation report including baseline diagnostic assessments and recommendations for further medication and/or psychotherapeutic management. These patients were then treated using available services in the community. In the Re-ChORD condition, patients entered the full program, as outlined, for 4 months. Treatment effects were assessed on the Ham-D by raters blind to treatment allocation at an interview 4 months post-baseline, and by patient-rated measures Materials In addition to the primary Ham-D measure, effectiveness was assessed on a range of patient self-report instruments. Subjective levels of depression were measured on the Beck Depression Inventory, second edition (BDI-II, Beck et al., 1996), common psychiatric symptoms were measured on the Hopkins Symptom Checklist (HSCL, Derogatis et al., 1974) Data analysis The primary outcome measure was remission, operationalised as Ham-D 17 7 measured at the 4-month assessment. Secondary analyses focused on change from baseline: dichotomous clinical response ( 50% improvement on Ham-D 17) and continuous change in BDI-II and HSCL scores. Binary dependent variables were analysed using logistic regression (adjusted for baseline Ham-D), continuous change from baseline was analysed using repeated measures ANOVA. All analyses were conducted from both intent to treat (ITT, last observation carried forward, including baseline) and completer viewpoints.

4 246 G. Murray et al. / Journal of Affective Disorders 123 (2010) Results 3.1. Baseline patient characteristics A total of 64 patients were randomized to Re-ChORD (N=34) and TAU (N=30) groups (Table 1). The two groups did not differ on gender (70.6% and 73.3% female in Re-ChORD and TAU groups respectively, χ 2 =.059, n.s.) or age (M=46.9 and M=43.3, respectively, F(1,57)=2.11, n.s.). Completion rates also did not differ between the groups: At the 4-month assessment, Ham-D data was available for 27 (79.4%) and 27 (90.0%) patients in the Re-ChORD and TAU groups respectively (χ 2 =1.36, n.s.). As shown in the upper panel of Table 2, the proportion of patients meeting criteria for remission was greater in Re- ChORD than TAU. Binary logistic regressions (both main effect, and adjusting for baseline Ham-D) found the treatment effect to be significant under both ITT and completer analyses. 1 Data in the lower panel show a trend for clinical response ( 50% improvement over baseline) to be more common in the Treatment group, but this effect reached significance only in the completers analyses. As shown in Table 3, there was a trend for greater improvement in BDI-II and HSCL scores in the Re-ChORD group. Effects were of medium magnitude, but differences did not reach significance in ITT or completer analyses. 4. Discussion Existing research into the treatment of chronic depression provides growing evidence that combination treatments are efficacious for this singularly disabling mood disorder. The present study sought to build on earlier work by providing a pilot investigation of the real-world effectiveness of Re- ChORD, a novel integrative treatment program. As hypothesised, rates of remission were significantly higher for patients completing Re-ChORD compared with those receiving TAU. Re-ChORD was also significantly superior in more conservative ITT analyses of remission rates. Amongst treatment completers, binary response to treatment was also significantly higher in the Re-ChORD group, but this trend did not reach significance in ITT analyses. Non-significant trends towards superiority of Re-ChORD were also seen in continuous measures of patient-reported change in depression and other symptoms. Effect sizes for improvement of remission rates with Re- ChORD were of medium magnitude. In ITT analyses, the proportion of patients remitting in Re-ChORD was 22.2% greater than TAU; the corresponding figure for completers was 29.6%. By way of comparison, it has been estimated that across all treatments, adjunctive psychotherapy adds approximately 20% to remission rates beyond the specific effect of pharmacotherapy and shared placebo effects in combination treatment of chronic/non-chronic depression (Jindal and Thase, 2003). It seems reasonable to conclude, therefore, that Re-ChORD's effect on remission rates was both statistically and clinically significant in this pragmatic design. 1 Ham-D 17 ITT had a p value of.05 for Group, which reached significance when baseline Ham-D was covaried. Table 1 Clinical characteristics at baseline. Treatment as usual (N =30) Re-ChORD (N=34) Recurrent episodes (%) 24 (80%) 26 (76%) Bipolar II (%) 3 (10%) 7 (21%) Comorbidity Dysthymic disorder (%) 2 (7%) 1 (3%) Anxiety disorders (%) 8 (27%) 13 (38%) Personality disorders (%) 4 (13%) 10 (29%) Number of episodes (±SD) 4.1± ±3.6 Age of first episode (±SD) 25.8± ±7.8 Current episode duration (months) 27.5 ± ±9.8 (±SD) Number of failed medication trials 2.9± ±1.1 (±SD) Previous psychotherapy (%) 25 (83%) 30 (88%) Past electroconvulsive therapy (%) 9 (30%) 9 (26%) Secondary analyses of binary response to treatment ( 50% improvement in Ham-D over baseline) found smaller effect sizes in favour of Re-ChORD: a significant difference of 25.9% amongst completers and a non-significant 16.6% in ITT. The weaker experimental effect on response compared to remission is uncommon (although see, Barrett et al., 2001, for the same pattern), and is best explained statistically the relatively low baseline levels of depression in the present design rendered remission easier to achieve than 50% reduction over baseline. Analyses of patient reported symptoms on the BDI-II and HSCL showed non-significant trends towards the superiority of Re-ChORD over TAU. As noted by Jindal and Thase (2003), growing recognition of the large placebo component in all depression treatments compels reconsideration of power in outcome studies. Type II error (false negative findings) cannot be ruled out in the interpretation of the non-significant smallmedium effects in this pilot investigation. Remission rates across TAU and Re-ChORD were smaller than those found in existing randomized trials of combination treatments versus TAU. For example, Schramm et al. (2008) found remission rates in the TAU arm of 31.6% (compared with 14.8% here) and in combined IPT/pharmacotherapy treatment of 66.7% (compared with 44.4% for Re-ChORD). The most likely explanation for this divergence is the fact that effect sizes typically decrease as research moves from efficacy to effectiveness basis (Henggeler, 2004; Rowland and Goss, 2000): it is the real-world complexity of patients and their treatments that explains the relatively moderate effects for both of the present treatments. This pilot study had a number of limitations. First, maintenance of remission for at least 2 4 weeks has been proposed as the best outcome measure for chronic depression (Kocsis, 2003), so future tests of Re-ChORD should include a maintenance phase. A maintenance phase would also permit investigation of psychosocial functioning and quality of life effects, which may lag behind symptom relief (Michalak et al., 2008). Second, a significant proportion of participants did not complete treatment, and little is known about the determinants of dropout in this population (Arnow et al., 2007). Third, Re- ChORD is an integrative multi-modal treatment program, so it is unclear which individual or combination of components (guidelines-concordant medication management, IPT-G, or OT) contributes most to the therapeutic effects. Re-CHORD also

5 G. Murray et al. / Journal of Affective Disorders 123 (2010) Table 2 Cross-tabulation of outcome by group. Outcome Measure TAU (n, %) Re-ChORD (n, %) Total (n, %) Binary logistic regression group effect Binary logistic regression group effect adjusted for baseline Ham-D Remission Ham-D 17 ITT ( 7) (N=64) Yes 4, 13.3% 12, 35.3% 16, 25.0% Beta=1.27, p=.050 Beta=1.29, p=.047 No 26, 86.7% 22, 64.7% 48, 75.0% Ham-D 17 Completers ( 7) (N=54) Yes 4, 14.8% 12, 44.4% 16, 29.6% Beta=1.53, p=.022 Beta=1.54, p=.021 No 23, 85.2% 15, 55.6% 38, 70.4% Response Ham-D 17 ITT (N=64) Yes 5, 16.7% 12, 35.3% 17, 26.6% Beta=1.00, p=.099 Beta=.99, p=.105 No 25, 83.3% 22, 64.7% 47, 73.4% Ham-D 17 Completers (N=54) Yes 5, 18.5% 12, 44.4% 17, 31.5% Beta=1.25, p=.045 Beta=1.25, p=.047 No 22, 81.5% 15, 55.6% 37, 68.5% TAU, Treatment as Usual; Re-CHORD, Relief of Chronic or Resistant Depression program; Ham-D, Hamilton Depression Rating Scale; ITT, Intent to Treat. Table 3 Change (Visit 1 Visit 4) in patient-rated depression and symptom scores by group. Measure TAU ReCHORD Total Repeated measures Effect size ANOVA group effect (M, SD) (M, SD) (M, SD) ΔBDI-II ITT (N=56) 4.84 (9.13) 8.13 (13.05) 6.66 (11.49) F (1,54)=1.14, p= ΔBDI-II Completers (N=34) 8.07 (10.73) (14.56) (13.09) F (1,32)=1.34, p= ΔHSCL ITT (N=56) 1.77 (10.16) 4.23 (10.36) 3.13 (10.25) F (1,54)=.79, p= ΔHSCL Completers (N=25) 3.40 (14.16) (14.59) 7.01 (14.58) F (1,23)=1.71, p= Note: Effect size calculated as standardised mean difference relative to TAU group standard deviation. TAU, Treatment as Usual; Re-CHORD, Relief of Chronic or Resistant Depression program; ANOVA, analysis of variance; SD, standard deviation; BDI-II, Beck Depression Inventory II; HSCL, Hopkins Symptom Checklist; ITT, Intent to Treat. likely shares active psychotherapeutic elements with the other combined treatments known to be efficacious for chronic depression (viz., pharmacotherapy plus IPT/CBASP), and only direct investigation of change processes will determine which elements are necessary for the clinical effect. In addition, a placebo condition was not compared, so we cannot exclude the possibility of non-specific factors (e.g., increased attention, scheduling of visits, etc) as contributors to outcome. Finally, the present design was underpowered to investigate moderators of outcome. 5. Conclusions Research into the treatment of chronic depression is fragmented by issues of diagnosis, severity, type of treatment (s), duration, phase of illness etc. However, a growing number of efficacy and effectiveness trials provide evidence for a combination of pharmacotherapy and psychotherapy as the optimal approach, especially at the more severe end of the chronic depression spectrum. Within its limitations, the present pilot study adds to this literature by providing initial evidence for the real-world effectiveness of a novel multimodal intervention, Re-ChORD. Important questions remain about the active components of Re-ChORD, especially in relation to other efficacious combined approaches, and a larger-scale investigation is warranted. Role of funding source This study was funded by a research grant from the VGH and UBC Hospital Foundation. Erin Michalak is supported by a Michael Smith Scholar Award from the Michael Smith Foundation for Health Research and a Canadian Institutes of Health Research New Investigator Award. The funding sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. Conflict of interest Dr. Lam is on Speaker/Advisory Boards for, or has received research funds from: Advanced Neuromodulation Systems Inc., AstraZeneca, Brain- Cells Inc., Biovail, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Research Foundation, Eli Lilly, Janssen, Litebook Company Ltd., Lundbeck, Lundbeck Institute, Mathematics of Informatics Technology and Advanced Computing Systems, Michael Smith Foundation for Health Research, Servier, Takeda, UBC Institute of Mental Health/Coast Capital Savings, and Wyeth. Dr. Yatham is on Speaker/Advisory Boards for, or has received research funds from: AstraZeneca, Bristol Myers Squibb, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, Eli Lilly, GlaxoSmithKline, Janssen, Michael Smith Foundation for Health Research, Pfizer, Servier, and the Stanley Foundation. Dr. Michalak has received research funds from: Michael Smith Foundation for Health Research and the Canadian Institutes of Health Research. All other authors declare that they have no conflicts of interest. Acknowledgements This study was funded by a research grant from the VGH and UBC Hospital Foundation. Erin Michalak is supported by a Michael Smith Scholar Award from the Michael Smith Foundation for Health Research and a Canadian Institutes of Health Research New Investigator Award. The authors thank Dr. K. Roy MacKenzie for his invaluable assistance in designing the trial, training the therapists and monitoring the delivery of IPT. References Akiskal, H.S., Rosenthal, T.L., Haykal, R.F., Lemmi, H., Rosenthal, R.H., Scott- Strauss, A., Characterological depressions. Clinical and sleep EEG findings separating 'subaffective dysthymias' from 'character spectrum disorders'. Arch. Gen. Psychiatry 37 (7), American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders: DSM-IV-TR, (4th Text Revision Ed.). Author, Washington, DC.

6 248 G. Murray et al. / Journal of Affective Disorders 123 (2010) Arnow, B.A., Constantino, M.J., Effectiveness of psychotherapy and combination treatment for chronic depression. J. Clin. Psychol. 59 (8), Arnow, B.A., Blasey, C., Manber, R., Constantino, M.J., Markowitz, J.C., Klein, D.N., et al., Dropouts versus completers among chronically depressed outpatients. J. Affect. Disord. 97 (1 3), Barrett, J.E., Williams, J.W., Oxman, T.E., Frank, E., Katon, W., Sullivan, M., et al., Treatment of dysthmia and minor depression in primary care: a randomized trial in patients aged years. J. Fam. Pract. 50, Beck, A.T., Steer, R.A., Brown, G.K., Manual for the Beck Depression Inventory, 2nd edition. The Psychological Corporation, San Antonio, TX. Berndt, E.R., Koran, L.M., Finkelstein, S.N., Gelenberg, A.J., Kornstein, S.G., Miller, I.M., et al., Lost human capital from early-onset chronic depression. Am. J. Psychiatry 157 (6), Browne, G., Steiner, M., Roberts, J., Gafni, A., Byrne, C., Dunn, E., et al., Sertraline and/or interpersonal psychotherapy for patients with dysthymic disorder in primary care: 6-month comparison with longitudinal 2- year follow-up of effectiveness and costs. J. Affect. Disord. 68 (2 3), De Maat, S., Dekker, J., Schoevers, R., De Jonghe, F., Relative efficacy of psychotherapy and pharmacotherapy in the treatment of depression: a meta-analysis. Psychother. Res. 16, Derogatis, L.R., Lipman, R.S., Rickels, K., et al., The Hopkins Symptom Checklist (HSCL): a self-report symptom inventory. Behav. Sci. 19, Egan, M., Dubouloz, C.J., von Zweck, C., Vallerand, J., The client-centred evidence-based practice of occupational therapy. Can. J. Occup. Ther. 65, Elkin, I., Shea, M.T., Watkins, J.T., Imber, S.D., Sotsky, S.M., Collins, J.F., et al., National Institute of Mental Health Treatment of Depression Collaborative Research Program. General effectiveness of treatments. Arch. Gen. Psychiatry 46 (11), Discussion 983. Gelenberg,A.J.,Trivedi,M.H.,Rush,A.J.,Thase,M.E.,Howland,R.,Klein,D.N., et al., Randomized, placebo-controlled trial of nefazodone maintenance treatment in preventing recurrence in chronic depression. Biol. Psychiatry 54 (8), Henggeler, S.W., Decreasing effect sizes for effectiveness studies implications for the transport of evidence-based treatments: comment on Curtis, Ronan, and Borduin (2004). J. Fam. Psychol. 18 (3), Hirschfeld, R.M., Dunner, D.L., Keitner, G., Klein, D.N., Koran, L.M., Kornstein, S.G., et al., Does psychosocial functioning improve independent of depressive symptoms? A comparison of nefazodone, psychotherapy, and their combination. Biol. Psychiatry 51 (2), Imel, Z.E., Malterer, M.B., McKay, K.M., Wampold, B.E., A meta-analysis of psychotherapy and medication in unipolar depression and dysthymia. J. Affect. Disord. 110 (3), Jindal, R.D., Thase, M.E., Integrating psychotherapy and pharmacotherapy to improve outcomes among patients with mood disorders. Psychiatr. Serv. 54 (11), Judd, L.L., The clinical course of unipolar major depressive disorders. Arch. Gen. Psychiatry 54 (11), Keller, M.B., Klein, D.N., Hirschfeld, R.M., Kocsis, J.H., McCullough, J.P., Miller, I., et al., Results of the DSM-IV mood disorders field trial. Am. J. Psychiatry 152 (6), Keller, M.B., McCullough, J.P., Klein, D.N., Arnow, B., Dunner, D.L., Gelenberg, A.J., et al., A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression. N. Engl. J. Med. 342 (20), Kennedy, S.H., Lam, R.W., Cohen, N.L., Ravindran, A.V., Clinical guidelines for the treatment of depressive disorders. IV. Medications and other biological treatments. Can. J. Psychiatry 46 (Suppl 1), 38S 58S. Kessler, R.C., McGonagle, K.A., Zhao, S., Nelson, C.B., Lifetime and 12- month prevalence of DSM-III-R psychiatric disorders in the United States: results from the national comorbidity survey. Arch. Gen. Psychiatry 51, Klein, D.N., Classification of depressive disorders in the DSM-V: proposal for a two-dimension system. J. Abnorm. Psychology 117 (3), Klerman, G.L., Weissman, M.M., Rounsaville, B.J., Chevron, E.S., Interpersonal Psychotherapy for Depression. Basic Books, New York. Kocsis, J.H., Pharmacotherapy for chronic depression. J. Clin. Psychol. 59 (8), Lam, R.W., Choosing the right antidepressant: a matter of therapeutic profiling. Paper presented at the Annual Meeting of the Canadian Psychiatric Association. Lam, R.W., Wan, D.D., Cohen, N.L., Kennedy, S.H., Combining antidepressants for treatment-resistant depression: a review. J. Clin. Psychiatry 63 (8), Manber, R., Kraemer, H.C., Arnow, B.A., Trivedi, M.H., Rush, A.J., Thase, M.E., et al., Faster remission of chronic depression with combined psychotherapy and medication than with each therapy alone. J. Consult. Clin. Psychol. 76 (3), Markowitz, J.C., Psychotherapy of dysthymia. Am. J. Psychiatry 151 (8), Markowitz, J.C., Kocsis, J.H., Bleiberg, K.L., Christos, P.J., Sacks, M., A comparative trial of psychotherapy and pharmacotherapy for "pure" dysthymic patients. J. Affect. Disord. 89 (1 3), McColl, M.A., Paterson, M., Davies, D., Doubt, L., Law, M., Validity and community utility of the Canadian Occupational Performance Measure. Can. J. Occup. Ther. 67 (1), McCullough Jr., J.P., Treatment for chronic depression using Cognitive Behavioral Analysis System of Psychotherapy (CBASP). J. Clin. Psychol. 59 (8), McCullough Jr., J.P., Klein, D.N., Borian, F.E., Howland, R.H., Riso, L.P., Keller, M.B., et al., Group comparisons of DSM-IV subtypes of chronic depression: validity of the distinctions, part 2. J. Abnorm. Psychology 112 (4), Mello, M.F.D., Myczcowisk, L.M., Menezes, P.R., A randomized controlled trial comparing moclobemide and moclobemide plus interpersonal psychotherapy in the treatment of dysthymic disorder. J. Psychother. Pract. Res. 10, Michalak, E.E., Lam, R.W., Breaking the myths: new treatment approaches for chronic depression. Can. J. Psychiatry 47 (7), Michalak, E.E., Murray, G., Young, A.H., Lam, R.W., Burden of bipolar depression: impact of disease and medications on quality of life. CNS Drugs 22 (5). Ravindran, A.V., Anisman, H., Merali, Z., Charbonneau, Y., Telner, J., Bialik, R.J., et al., Treatment of primary dysthymia with group cognitive therapy and pharmacotherapy: clinical symptoms and functional impairments. Am. J. Psychiatry 156 (10), Rowland, N., Goss, S., Evidence-Based Counselling and Psychological Therapies. Routledge, NY. Rush, A.J., Trivedi, M.H., Wisniewski, S.R., Nierenberg, A.A., Stewart, J.W., Warden, D., et al., Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR D report. Am. J. Psychiatry 163 (11), Schramm, E., Schneider, D., Zobel, I., van Calker, D., Dykierek, P., Kech, S., et al., Efficacy of Interpersonal Psychotherapy plus pharmacotherapy in chronically depressed inpatients. J. Affect. Disord. 109 (1 2), Segal, Z.V., Whitney, D.K., Lam, R.W., Clinical guidelines for the treatment of depressive disorders. III. Psychotherapy. Can. J. Psychiatry 46 (Suppl 1), 29S 37S. Sheehan, D.V., Lecrubier, Y., Sheehan, K.H., et al., The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J. Clin. Psychiatry 59 (Suppl. 20), Toomey, M., Nicholson, D., Carswell, A., The clinical utility of the Canadian Occupational Performance Measure. Can. J. Occup. Ther. 62 (5), Trivedi, M.H., Kleiber, B.A., Using treatment algorithms for the effective management of treatment-resistant depression. J. Clin. Psychiatry 62 (Suppl 18), Wilfley, D.E., MacKenzie, K.R., Welch, R.R., Ayres, V., Weissman, M.M., Interpersonal Psychotherapy for Group. Basic Books, New York. Williams, J.B.W., Link, M.J., Rosenthal, N.E., Terman, M., Structured Interview Guide for the Hamilton Depression Rating Scale Seasonal Affective Disorder Version (SIGH-SAD). New York State Psychiatric Institute, NY.