Chronic depression meta analysis cuijpers

Clinical Psychology Review 30 (2010) 51–62 Contents lists available at ScienceDirect Clinical Psychology Review Psychotherapy for chronic major depression and dysthymia: A meta-analysis Pim Cuijpers a,⁎, Annemieke van Straten a, Josien Schuurmans a, Patricia van Oppen b, Steven D. Hollon c, Gerhard Andersson d,e a Department of Clinical Psychology and EMGO+ Institute, VU University Amsterdam, The Netherlands b Department of Psychiatry and EMGO+ Institute, VU University Medical Center, Amsterdam, The Netherlands c Vanderbilt University, Nashville, United States d Department of Behavioural Sciences and Learning, Linköping University, Sweden e Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Stockholm, Sweden a r t i c l e i n f o a b s t r a c t Article history: Although several studies have examined the effects of psychotherapy on chronic depression and dysthymia, Received 22 June 2009 no meta-analysis has been conducted to integrate results of these studies. We conducted a meta-analysis of Received in revised form 2 September 2009 16 randomized trials examining the effects of psychotherapy on chronic depression and dysthymia. We Accepted 4 September 2009 found that psychotherapy had a small but significant effect (d = 0.23) on depression when compared to control groups. Psychotherapy was significantly less effective than pharmacotherapy in direct comparisons Keywords: Chronic depression (d = − 0.31), especially SSRIs, but that this finding was wholly attributable to dysthymic patients (the Dysthymia studies examining dysthymia patients were the same studies that examined SSRIs). Combined treatment Psychological treatment was more effective than pharmacotherapy alone (d = 0.23) but even more so with respect to psychotherapy Psychotherapy alone (d = 0.45), although again this difference may have reflected the greater proportion of dysthymic Meta-analysis samples in the latter. No significant differences were found in drop-out rates between psychotherapy and the other conditions. We found indications that at least 18 treatment sessions are needed to realize optimal effects of psychotherapy. We conclude that psychotherapy is effective in the treatment of chronic depression and dysthymia but probably not as effective as pharmacotherapy (particularly the SSRIs). © 2009 Elsevier Ltd. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 2. Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 2.1. Identification and selection of studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 2.2. Coding of study characteristics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 2.3. Quality assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 2.4. Meta-analyses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 3. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 3.1. Characteristics of included studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 3.2. Quality of included studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 3.3. Psychological treatment versus control groups . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 3.4. Psychological treatment versus pharmacotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 3.5. Pharmacotherapy versus combined treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 3.6. Other comparisons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 3.7. Drop-out rates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 3.8. Improvement from baseline to post-test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 4. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 ⁎ Corresponding author. Department of Clinical Psychology, VU University Amsterdam, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands. Tel.: +31 20 598 8757; fax: +31 20 598 8758. E-mail address: p.cuijpers@psy.vu.nl (P. Cuijpers). 0272-7358/$ – see front matter © 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.cpr.2009.09.003

52 P. Cuijpers et al. / Clinical Psychology Review 30 (2010) 51–62 1. Introduction distinguished (Schramm et al., 2008): 1) dysthymia, 2) chronic major depressive disorder (MDD), 3) double depression (MDD It is well established that psychological interventions are effective superimposed on a dysthymic disorder), and 4) recurrent MDD with in the treatment of depression. In the past three decades, about 200 incomplete recovery between episodes. Although chronic MDD is controlled and comparative studies have examined the effects of more severe than dysthymia, few indications have been found that psychological treatments compared to control conditions and to other these two types of depression differ systematically from each other treatments (Cuijpers, van Straten, Warmerdam, & Andersson, 2008). (Torpey & Klein, 2008; Karlsson, Pelkonen, & Heilä, 2007; McCul- This large number of studies has shown that psychological treatments lough, Klein, & Borian, 2003). Prospective research has shown that have significant effects on depression in adults (Churchill et al., 2001; most patients with dysthymia eventually experience exacerbations Cuijpers, van Straten, Warmerdam, & Smits, 2008). A considerable for longer or shorter periods of time in which they meet criteria for number of studies has shown that psychological treatments are also MDD (Klein, Shankman, & Rose, 2006), which suggests that effective in specific populations, such as older adults (Cuijpers, van dysthymia and double depression may be different phases of the Straten & Smit, 2006), women with postpartum depression (Lumley, same disorder. Austin, & Mitchell, 2004), and patients with both depression and Although several meta-analyses have shown that pharmacother- general medical disorders, including multiple sclerosis (Mohr & apy is effective in the treatment of chronic depressive disorders and Goodkin, 1999), stroke patients (Hackett, Anderson, & House, 2004), dysthymia (De Lima, Hotoph, & Wessely, 1999; Kocsis, 2003), the and cancer patients (Sheard & McGuire, 1999). Furthermore, several status of psychological treatments is less clear and sometimes specific types of psychological treatment have been found to be questioned. While several reviews have described the studies effective. Most research has focused on cognitive behavior therapy, in examining these psychological treatments (Markowitz, 1994; Torpey which restructuring of negative cognitions is the core element & Klein; 2008; Arnow & Constantino, 2003), no meta-analytic study (Gloaguen, Cottraux, Cucherat, & Blackburn, 1998; Churchill et al., has been conducted, mostly because the number of studies has been 2001). However, several other psychological treatments have also considered to be too small for such a study. Some meta-analyses have been found to be effective, including interpersonal psychotherapy (de included small subsamples of studies on dysthymia (Cuijpers, van Mello, De Jesus Mari, Bacaltchuk, Verdeli, & Neugebauer, 2005), Straten, Andersson, & van Oppen, 2008; Cuijpers, van Straten, van problem-solving therapy (Malouff, Thorsteinsson, & Schutte, 2007; Oppen, et al., 2008; Cuijpers, van Straten, Warmerdam, & Andersson, Cuijpers, van Straten, & Warmerdam, 2007a), behavioral activation 2008; Cuijpers, van Straten, Warmerdam, & Smits, 2008; Imel, (Cuijpers, van Straten, & Warmerdam, 2007b; Ekers, Richards, & Malterer, McKay, & Wampold, 2008), suggesting that psychotherapy Gilbody, 2008), and psychodynamic therapies (Leichsenring, 2001; is less effective than pharmacotherapy in the treatment of dysthymia. Leichsenring & Rabung, 2008). These treatments can be delivered in However, the evidence is inconclusive, because of the lack of individual format, group format, or as guided self-help (McDermut, adequately sized samples included in previous meta-analytical Miller, & Brown, 2001). The effects of psychological treatments are research. As will be shown in the present paper, the number of comparable to those of pharmacological treatments (De Maat, Dekker, studies examining psychotherapy for chronic depression and dysthy- Schoevers, & de Jonghe, 2006; Cuijpers, van Straten, van Oppen, & mia has grown considerably in the past few years, opening up the Andersson, 2008), and combined treatments are more effective than possibility to conduct such a meta-analysis that will provide more psychological treatment alone (De Maat, Dekker, Schoevers, & de definite answers. Jonghe, 2007; Cuijpers, van Straten, Warmerdam, & Andersson, 2009) In light of the increased number of controlled studies we decided and than pharmacotherapy alone (Friedman et al., 2004; Pampanolla, to conduct a new meta-analysis in which we collected all studies of Bollini, Tibaldi, Kupelnick, & Munizza, 2004; Cuijpers, Dekker, Hollon, psychotherapy for patients with chronic depressive disorders or & Andersson, 2009). dysthymia, in which psychotherapy was compared to control Despite this large body of research, however, very few of the conditions, pharmacotherapy and combined treatments of psycho- studies on psychological treatments have focused on more chronic therapy and pharmacotherapy. We expected effect sizes of psy- forms of depression. It is estimated, however, that 20% of all chotherapies for chronic depression to be smaller than those of depressed individuals and up to 47% of the patients treated in mental psychotherapies for adult depression in general, because chronic health care, suffer from a chronic depression (Torpey & Klein, 2008; depression is more persistent and a history of previous treatment Arnow & Constantino, 2003). This implies that about 3% of the adult failure is more common in patients suffering from chronic depression. population in Western countries suffers from a chronic depression Furthermore, in concordance with clinical practice for those who are (Kessler et al., 1994). All depressive disorders have a large impact on chronically depressed, we expected a combined treatment of quality of life of patients (Ustun, Ayuso-Mateos, Chatterji, Mathers, & psychotherapy and pharmacotherapy to be more effective than either Murray, 2004; Saarni et al., 2007), and are associated with high psychotherapy or pharmacotherapy alone. levels of service use and enormous economic costs (Berto, D'Ilario, Ruffo, & Di Virgilio, 2000; Greenberg & Birnbaum, 2005; Smit et al., 2. Methods 2006). Chronic depressive disorders have, however, considerably more adverse impact on quality of life (Wells, Burnam, Rogers, Hays, 2.1. Identification and selection of studies & Camp, 1992), service use (Howland, 1993), and economic costs (Smit et al., 2006), and more often result in suicide attempts and A database covering 1036 papers on the psychological treatment of hospitalization than acute depressive disorders (Torpey & Klein, depression was used for the present meta-analysis. This database 2008; Arnow & Constantino, 2003), because they begin early in life includes studies on combined treatments and comparisons with in many cases (Keller, McCullough, Klein, Arnow, Dunner, Gelenberg pharmacotherapies, and it has been described in detail elsewhere et al., 2000; Cassano, Akiskal, Perugi, Musetti, & Savino, 1992). (Cuijpers, van Straten, Andersson, et al., 2008). The database has been Moreover, chronic depressive disorders are often lifelong, and are used in a series of earlier meta-analyses and more information is responsible for a considerable proportion of the enormous disease available on the Internet (www.evidencebasedpsychotherapies.org). burden associated with depression (Greenberg & Birnbaum, 2005; It was developed through a comprehensive literature search (from Keller et al., 2000). 1966 to January 2009) in which we examined 9011 abstracts from Although the terminology has varied over the years, depressive Pubmed (1629 abstracts), Psycinfo (2439), Embase (2,606), and the disorders are considered to be chronic when they last for two years Cochrane Central Register of Controlled Trials (2337). These abstracts or longer. In the DSM-IV four types of chronic depression are were identified by combining terms indicative of psychological

P. Cuijpers et al. / Clinical Psychology Review 30 (2010) 51–62 53 treatment and depression (both MeSH-terms and text words). For this 2.4. Meta-analyses database, we also collected the primary studies from 42 meta- analyses of psychological treatment for depression (www.evidence- For each comparison between a psychological treatment and a basedpsychotherapies.org). For the current study, we examined the control group (or another active treatment), we calculated the effect full texts of these 1036 papers. We also examined the reference lists of size indicating the difference between the two groups at post-test earlier reviews of psychotherapies for chronic depression and (Cohen's d or standardized mean difference). Effect sizes were dysthymia (Arnow & Constantino, 2003; Torpey & Klein, 2008; calculated by subtracting (at post-test) the average score of the Markowitz, 1994) and we checked the references of the included psychological treatment group from the average score of the primary studies. comparison group, and dividing the result by the pooled standard We included (a) randomized trials (b) in which the effects of a deviations of the two groups. Effect sizes of 0.8 can be assumed to be psychological treatment (c) was compared to the effects of a control large, while effect sizes of 0.5 are moderate, and effect sizes of 0.2 are group, another active treatment, or a combined psychological and small (Cohen, 1988). pharmacological treatment (d) in adults (e) with a chronic major In the calculations of effect sizes we only used those instruments depressive disorder or dysthymia, and which was established with a that explicitly measured symptoms of depression. If more than one diagnostic interview (such as the SCID, or the CIDI). We also included depression measure was used, the mean of the effect sizes was studies which examined psychological treatment of broader catego- calculated, so that each study only provided one effect size. If means ries of depressive disorders, but which presented separate data for and standard deviations were not reported, we used the procedures of patients meeting criteria for chronic depression or dysthymia. We the Comprehensive Meta-Analysis software (see below) to calculate excluded studies on adolescents or children (below 18 years of age). the effect size using dichotomous outcomes. If insufficient data were Comorbid general medical or psychiatric disorders were not used as reported to calculate an effect size, the study was excluded (which an exclusion criterion. No language restrictions were applied. was the case in one study, which reported no data or tests for the 4 conditions to which the subjects were randomized) (Waring et al., 1988). 2.2. Coding of study characteristics We only used the effect sizes indicating the differences between the psychotherapy and the alternative condition at post-test. We We coded major characteristics of the included studies, including decided not to examine the effects at follow-up, because the number characteristic of the target group (age, percentage women, percentage of effect sizes was small. In addition, the follow-up period differed married), the definition of chronic depression, recruitment method, considerably among these studies, and in several studies some exclusion criteria (anxiety disorders, substance-related disorders, treatments were continued and others discontinued. Because only personality disorders), type of psychotherapy, number of sessions, few of the included studies reported outcomes on anxiety and treatment format, country where the study was conducted, and quality of life, we decided not to examine these outcomes in a meta- whether the study was conducted in a subsample of a larger study or analysis. not. Type of psychotherapy was defined according to definitions To calculate pooled mean effect sizes, we used the computer developed for a recent comparative meta-analysis (Cuijpers, van program Comprehensive Meta-Analysis (version 2.2.021). As we Straten, Andersson, et al., 2008). In these definitions a psychotherapy expected considerable heterogeneity among the studies, we decided is considered to be cognitive behavior therapy if cognitive restructur- to calculate mean effect sizes using a random effects model. In the ing is the core element of the treatment; problem-solving therapy is a random effects model it is assumed that the included studies are treatment in which personal problems are systematically solved using drawn from ‘populations’ of studies that differ from each other specific steps; and interpersonal psychotherapy is a brief and highly systematically (heterogeneity). In this model, the effect sizes resulting structured psychotherapy that addresses interpersonal issues in from included studies not only differ because of the random error depression to the exclusion of all other foci of clinical attention within studies (as in the fixed effects model), but also because of true (Cuijpers, van Straten, Andersson, & van Oppen, 2008). The majority variation in effect size from one study to the next. of therapies examined in the current meta-analyses used one of these The standardized mean difference is not easy to interpret from a three types of psychotherapy. clinical point of view. Therefore, we transformed the standardized mean differences into the numbers-needed-to-be-treated (NNT), 2.3. Quality assessment using the formulae provided by Kraemer and Kupfer (2006). The NNT indicates the number of patients that have to be treated in order We assessed validity of included studies using a number of basic to generate an additional positive outcome in one of them (Sackett, criteria, as suggested in the Cochrane Handbook (Higgins & Green, Strauss, Richardson, Rosenberg, & Haynes, 2000). 2005): allocation to conditions conducted by an independent (third) As a test of homogeneity of effect sizes, we calculated the I2- party; blinding of assessors of outcomes; and completeness of follow- statistic which is an indicator of heterogeneity in percentages. A value up data. We did not check for the fourth criterion for validity of 0% indicates no observed heterogeneity, and larger values show (adequacy of random allocation concealment to respondents), increasing heterogeneity, with 25% as low, 50% as moderate, and 75% because it was not possible in these studies to conceal the as high heterogeneity (Higgins, Thompson, & Deeks, 2003). We also randomization to patients. calculated the Q-statistic, but only report whether this was significant We also rated the quality of the treatment implementation using or not. three criteria which were based on an authoritative review of Subgroup analyses were conducted according to the mixed effect empirically supported psychotherapies (Chambless & Hollon, 1998): model. In this model, studies within subgroups are pooled with the (1) the study referred to the use of a treatment manual (either a random effects model, while tests for significant differences between published manual, or a manual specifically designed for the study); subgroups are conducted with the fixed effects model. For contin- (2) the therapists who conducted the therapy were trained for the uous variables, we used meta-regression analyses to test whether specific therapy, either specifically for this study or as a general there was a significant relationship between the continuous variable training; (3) treatment integrity was checked during the study (by and the effect size, as indicated with a Z-value and an associated p- supervision of the therapists during treatment or by recording of value. treatment sessions or by systematic screening of protocol adherence Publication bias was tested by inspecting the funnel plot on by a standardized measurement instrument). primary outcome measures, and by Duval and Tweedie's trim and fill

54 P. Cuijpers et al. / Clinical Psychology Review 30 (2010) 51–62 procedure (Duval & Tweedie, 2000) which yields an estimate of the Apart from the outcomes on depression, we also calculated the effect size after the publication bias has been taken into account (as relative risk (RR) of dropping out from the treatments. Again, we implemented in Comprehensive Meta-analysis, version 2.2.021). conducted all meta-analyses with the random effects model and we Table 1 Selected characteristics of studies examining psychological treatments of chronic depression in adults. 1st author Population Age (Mn) %♀ %M Recr Definition of Excluded Conditions N Nse Frm TQ Measuresb C SubS [range] depression disordersa Agosti and Adults 31.3 NR NR Clin Chronic MDD SUB/PAN/ 1. CBT 16 16 Ind M/ HRSD US S Ocepek- with early [18–65] (≥ 2 years) ASPD 2. IPT 14 16 Ind T/I Welikson onset (SADS/RDC) + 3. Imipramine 20 (1997) chronic HRSD > 14 4. Placebo 15 MDD Barker, Adult 49.3 63.6 NR Clin Chronic MDD – 1. Pharmacotherapy 10 15 Ind NR HRSD UK N Scott, and inpatients [<65] (≥ 2 years) 2. Pharmacotherapy + CBT 10 Eccleston (RDC) AND (1987) treatment refractory Barrett et al. Adults 44.1 63.9 90.0 Clin DYST + – 1. PST 43 6 Ind M/ HSCL-D US S (2001) [18–59] HRSD > 10 2. Paroxetine 42 T/I 3. Placebo 42 Browne Adults 42.1 68 NR Com DYST (DSM-IV/ – 1. IPT 178 10 Ind M/ MADRS CA N et al. [18–74] UM-CIDI); 15% 2. IPT + Sertraline 212 T/I (2002) had current MDD 3. Sertraline 196 de Mello, Adults NR 80.0 NR Clin DYST (ICD-10 SUB 1. IPT + Moclobemide 16 16 Ind T HDRS, BR N Myczcowisk, [18–60] symptom 2. Moclobemide 19 MADRS and Menezes checklist); 91% (2001) had current MDD de Jong et al. Adult 36.6 70.0 NR Clin MDD + – 1. BA + SST + CT 10 33 Mixed M/ HDRS, GE N (1986) inpatients [NR] dysthymia 2. CT 10 47 T/I BDI, D- (DSM-III) + 3. Non-specific control 10 scale BDI ≥ 20 Dunner et al. Adults 35.7 45.8 NR NR DYST (DSM-III-R/ – 1. CBT 13 16 Ind M/ HDRS, BDI US N (1996) [18–60] SCID); no current 2. Fluoxetine 18 T/I MDD Harpin, Adults 42.0 41.7 NR Clin Chronic MDD – 1. CBT 6 20 Ind T/I HDRS, US N Liberman, [21–58] (≥ 2 years) 2. Waiting list 6 Wakefield Marks, Stern, (psychiatrist) + scale and Bohannon HDRS ≥ 20 + (1982) Wakefield ≥ 20 Hellerstein et al. Adults 45.1 50.0 87.5 Clin DYST (DSM-III-R; SUB/PAN/ 1. CIGP + Fluoxetine 20 16 Grp M/ HDRS, US N (2001) [21–65] SCID) + GAD/OCD/ 2. Fluoxetine 20 T/I BDI, CDRS HDRS ≥ 14; no PTSD/BPD current MDD Keller et al. Adults 43.0 65.3 90.5 Clin Chronic OR SUB/OCD/ 1. CBASP 228 18 Ind M/ HRSD US N (2000) [18–75] MDD + dysth OR PAN/GAD, 2. CBASP + Nefazodone 227 T/I recurrent MDD SOCPHOB/ 3. Nefazodone 226 with incomplete PTSD/ASPD/ inter-episode STPD/BPD recovery (DSM- IV/SCID) + HRSD ≥ 20 Markowitz, Adults 42.3 63.0 63.0 Com DYST (SCID) with SUB/ASPD/ 1. IPT 23 17 Ind M/ HRSD, US N Kocsis, [18–60] early onset BPD/Cluster 2. Brief supportive therapy 26 17 T/I BDI, CDRS Bleiberg, (< 21 years); no A PD 3. IPT + sertraline 21 Christos, and MDD in past 4. Sertraline 24 Sacks (2005) 6 months Markowitz, Adults 38.4 31 69.2 Com DYST (SCID-II) ASPD/BPD/ 1. IPT 14 17 Ind M/ HRSD, US N Kocsis, with [18–60] with onset before Cluster A 2. Supportive therapy 12 17 T/I BDI, CDRS Christos, alcohol age ≤ 21; 54% had Bleiberg, and abuse/dep. current MDD Carlin (2008) Miller, Norman, Adult 37.4 80.7 NR Clin MDD + DYST SUB/ASPD 1. CBT + pharmacotherapy 6 40 Ind M/ M-HDRS, US S and Keitner inpatients [18–65] (DIS) 2. Social skills tr + pharm. 8 40 T BDI (1999) 3. Pharmacotherapy 5 Ravindran et al. Adults NR 57.7 NR Com DYST (DSM/ Current Axis- 1. CBT + sertraline 24 12 Grp M/ HRSD CA N (1999) [21–54] MINI); no current I disorder/ 2. CBT + placebo 24 12 T MDD Any PD 3. Sertraline 22 4. Placebo 24 Schramm et al. Adult 42.8 73.2 Clin Chronic MDD Axis-I 1. IPT + pharmacotherapy 24 11 Mixed M/ BDI, HDRS GE S (2008) inpatients [18–65] (SCID) + disorder/ 2. Pharmacotherapy 21 T/I HDRS ≥ 16 SUB/BPD/ ASPD Williams et al. Adults 71.0 41.5 77.8 Clin DYST + SUB/BPD/ 1. PST 72 6 Ind M/ HSCL-D US S (2000) [> 60] HDRS ≥ 10 ASPD 2. Paroxetine 69 T/I 3. Placebo 70

P. Cuijpers et al. / Clinical Psychology Review 30 (2010) 51–62 55 calculated the Q-statistic and the I2-statistic to estimate heterogeneity one of the studies the therapists were trained for this specific therapy, between study outcomes. and 12 of the 16 studies reported that the integrity of the treatment was checked during the study. 3. Results 3.3. Psychological treatment versus control groups 3.1. Characteristics of included studies We could compare a psychological treatment with a control group Sixteen studies with a total of 2116 patients met our inclusion criteria (placebo, care-as-usual, non-specific control, or waiting list) in (689 in the psychological treatment conditions; 167 in the control 8 comparisons. The mean effect size was d = 0.23 (95% CI: 0.06– conditions; 692 in the pharmacotherapy conditions; and 568 in the 0.41), which corresponds with an NNT of 7.69. Heterogeneity was combined psychological and pharmacological treatment conditions). zero (I2 = 0). The results of these analyses are summarized in Table 2. Selected characteristics of the included studies are presented in Table 1. The effect sizes and 95% confidence intervals of the individual contrast Seven studies were aimed at patients with dysthymia (and no groups are plotted in Fig. 1. major depression; one study in which 15% of the patients also had When we limited the analyses to the effect sizes found for the 17- MDD was categorized in this group of studies); four studies were item version of the HAM-D (the most frequently used instrument), a aimed at patients with chronic major depression; three at patients comparable effect size was found (d = 0.33; 95% CI: 0.01–0.64; with double depression (both MDD and dysthymia); and the NNT = 5.43), and again heterogeneity was found to be zero. remaining two studies were focused on patients with other categories In our analyses, we included two studies in which two separate of chronic depression and/or dysthymia. Most studies were aimed at psychological treatments were compared to a control group. This adult outpatients in general, while two focused on inpatients, and two means that multiple comparisons from these two studies were others were aimed at more specific target groups (adults with early included in the same analysis. These multiple comparisons, however, onset chronic MDD, and adults with secondary alcohol abuse/ are not independent of each other, which may have resulted in an dependence). In most studies the majority of patients was female artificial reduction of heterogeneity and a distortion of the mean effect and married, and had a mean age between 30 and 50. size. Therefore, we conducted another meta-analysis, in which we A total of 21 psychological treatments were examined, seven of included only one comparison per study (Table 2). From the two which were cognitive behavior therapy, six were interpersonal studies with multiple comparisons we first included only the psychotherapy, and eight were other therapies (problem-solving comparison with the largest effect size. Then we conducted another therapy; cognitive–interpersonal group psychotherapy for chronic meta-analysis in which we included only the smallest effect size from depression; cognitive behavioral-analysis system of psychotherapy; the two studies. As can be seen in Table 2, these analyses did not and supportive therapy). Number of treatment sessions ranged from 6 indicate that the mean effect size changed considerably, nor did we to 47. Most therapies used an individual treatment format (sixteen), find indications that heterogeneity was affected by these two studies while two used a group format and the remaining three a mixed (I2 = 0 in both meta-analyses). individual and group format. In order to examine the influence of each of the individual studies, In seven studies only one measurement instrument was used to we conducted a series of analyses in which each of the studies was calculate effect sizes, six studies used two instruments, and the removed, and the mean effect size of the remaining studies was remaining three studies used three instruments. The Hamilton calculated. This allowed us to examine the influence of each individual Depression Rating Scale (HDRS) was used in 13 studies, seven studies study on the overall outcomes. Removal of the study by de Jong, the Beck Depression Inventory (BDI), and three used the Cornell Treiber, and Henrich (1986) resulted in the largest decrease of the Dysthymia Rating Scale (CDRS). mean effect size (the resulting effect size was d = 0.21); and removal Five studies used subsamples of a larger trial in which broader of the study by Williams et al. (2000) resulted in the largest increase categories of depressed patients were examined. Ten of the sixteen of the effect size (d = 0.30). studies were conducted in the United States, two in Canada, three in Neither the funnel plot nor Duval and Tweedie's trim and fill Europe (UK, Germany, the Netherlands), and one in Brazil. procedure pointed to a significant publication bias. The mean effect size did not change considerably after adjustment for possible 3.2. Quality of included studies publication bias (observed d = 0.23; adjusted d = 0.20; number of imputed studies: 2). The quality of the included studies varied. Four of the 16 studies Because of the small number of comparisons we conducted only the reported that allocation to conditions was conducted by an indepen- most basic subgroup analyses. We found no indications for a significant dent party, while 6 studies reported that a computerized randomi- difference between studies examining chronic MDD and those zation schedule was used, and the remaining studies did not report examining double depression or dysthymia, nor between CBT and the randomization methods. Blinding of assessors was reported in 11 other psychological treatments, although there was a trend (p < 0.1) studies. Intention-to-treat analyses were conducted in six studies (the indicating a possible difference between pill placebo control groups and other studies were limited to completers-only analyses). other control groups (Table 2). These results should be considered with The quality of the treatment implementation of the included caution, however, since the statistical power to detect such differences is studies was good. Thirteen studies used a treatment manual, in all but very low because of the small number of studies in the subgroups. Notes to Table 1: Abbreviations (for abbreviations of the measurement instruments the reader is referred to the original studies): %♀; percentage women; %M: percentage married; ASPD: antisocial personality disorder; BA: behavioral activation; BPD: borderline personality disorder; BR: Brazil; C: country; CA: Canada; CBASP: Cognitive behavioral-analysis system of psychotherapy; CBT: cognitive behavior therapy; CIGP: Cognitive–interpersonal group psychotherapy for chronic depression; Clin: recruitment from clinical samples; Com: recruitment from the community; CT: cognitive therapy; Dep: dependence; DYST: dysthymia; Frm: format; GAD: generalized anxiety disorder; GE: Germany; Grp: group format; I: check of integrity; Ind: individual format; IPT: interpersonal psychotherapy; M: manual; Mn: mean; MDD: major depressive disorder; N: no subsample of larger study; NL: Netherlands; NR: not reported; Nse: number of sessions; OCD: obsessive compulsive disorder; PAN: panic disorder; PD: personality disorder; Pharm.: pharmacotherapy; PST: problem-solving therapy; PTSD: posttraumatic stress disorder; Recr: recruitment method; S: subsample of larger study; SOCPHOB: social phobia; SST: social skills training; STPD: schizotypical personality disorder; SUB: substance-related disorder; SubS: subsample of larger study; T: training of therapists; TQ: treatment quality; UK: United Kingdom; US: United States. a We report only excluded anxiety disorders, substance-related disorders, and personality disorders. b In this column we only report the instruments that measure depression and that were used to calculate effect sizes.

56 P. Cuijpers et al. / Clinical Psychology Review 30 (2010) 51–62 Table 2 Meta-analyses of studies comparing the effects of psychological treatments on chronic depression at post-test. Study Ncomp d 95% CI Z I2a pb NNT Psychological treatment versus control groups ▪ All studies 8 0.23 0.06–0.41 2.66 ⁎⁎ 0 n.s. 7.69 ▪ One ES per study (highest) 6 0.24 0.05–0.42 2.55 ⁎ 0 n.s. 7.46 ▪ One ES per study (lowest) 6 0.23 0.05–0.41 2.44 ⁎ 0 n.s. 7.69 ▪ Only HAM-Dc 6 0.33 0.01–0.64 2.03 ⁎ 0 n.s. 5.43 Subgroup analyses ▪ Diagnosisd – Chronic MDD 3 0.06 − 0.41–0.52 0.25 n.s. 0 n.s. 0.179 29.41 – Double depr 2 0.79 0.15–1.44 2.40 ⁎ 0 n.s. 2.36 – Dysthymia 3 0.21 0.02–0.41 2.17 ⁎ 0 n.s. 8.47 ▪ Psychological treatment – CBT 5 0.43 0.08–0.78 2.40 ⁎ 0 n.s. 0.212 4.20 – Other 3 0.17 − 0.03–0.37 1.69 o 0 n.s. 10.42 ▪ Control group – Placebo 5 0.18 − 0.00–0.36 1.95 o 0 ns 0.056 9.80 – Other 3 0.76 0.19–1.32 2.63 ⁎⁎ 0 ns 2.44 Psychological treatment versus pharmacotherapy ▪ All studies 10 − 0.31 − 0.53 to − 0.09 − 2.73 ⁎⁎ 59.03 ⁎⁎ 5.75 ▪ One ES per study (highest) 8 − 0.31 − 0.56 to − 0.07 − 2.51 ⁎ 62.41 ⁎⁎ 5.75 ▪ One ES per study (lowest) 8 − 0.30 − 0 .54 to − 0.05 − 2.39 ⁎ 62.38 ⁎ 5.95 ▪ Only HAM-Dc 7 − 0.42 − 0.77 to − 0.06 − 2.30 ⁎ 67.23 ⁎⁎ 4.27 Subgroup analyses ▪ Diagnosise – Chronic MDD 2 0.06 − 0.42–0.53 0.24 0 0.036 29.41 – Dysthymia 7 − 0.47 − 0.75 to − 0.18 − 3.17 ⁎⁎ 58.82 ⁎ 3.85 – Mixed 1 − 0.04 − 0.23–0.15 − 0.42 0 45.45 ▪ Psychological treatment – CBT 3 − 0.50 − 1.16–0.16 − 1.48 ns 62.69 o 0.800 3.62 – IPT 3 − 0.30 − 0.58 to − 0.01 − 2.05 ⁎ 15.81 ns 5.95 – Other 4 − 0.25 − 0.59–0.10 − 1.40 ns 71.04 ⁎ 7.14 ▪ Pharmacotherapy – SSRI 7 − 0.47 − 0.75 to − 0.18 − 3.17 ⁎⁎ 58.82 ⁎ 0.011 3.85 – TCA/other 3 − 0.03 − 0.20–0.15 − 0.30 ns 0 ns 62.50 Pharmacotherapy versus combined treatment ▪ All studiesf 9 0.23 − 0.01–0.47 1.90 o 53.71 ⁎ 7.69 ▪ Only HAM-Dc 6 0.42 0.27–0.58 5.30 ⁎⁎⁎ 0 ns 4.27 Subgroup analyses ▪ Diagnosisg − Chronic MDD 2 0.27 − 0.22–0.76 1.07 n.s. 0 0.001 6.58 − Double depr 2 0.68 0.10–1.25 2.32 ⁎ 0 2.70 − Dysthymia 4 − 0.04 − 0.24–0.17 − 0.33 n.s. 0 45.45 – Mixed 1 0.50 0.31–0.69 5.20 ⁎⁎⁎ 0 3.62 ▪ Psychological treatment – CBT 3 0.25 − 0.28–0.79 0.92 ns 36.74 ns 0.318 7.14 – IPT 4 0.06 − 0.18–0.30 0.51 ns 8.86 ns 29.41 – Other 2 0.39 0.02–0.76 2.08 ⁎ 39.32 ns 4.59 ▪ Pharmacotherapy – SSRI 4 − 0.04 − 0.24–0.17 − 0.33 ns 0 0.000 45.45 – TCA/other 5 0.49 0.32–0.66 5.69 ⁎⁎⁎ 0 3.68 Psychological treatment versus combined treatmenth ▪ All studiesf 4 0.45 0.20–0.70 3.49 ⁎⁎⁎ 50.90 ns 4.00 ▪ Only HAM-Dc 3 0.55 0.38–0.73 6.27 ⁎⁎⁎ 0 3.31 Psychological treatment versus other psychological treatment ▪ IPT versus other psychological treatments 3 0.15 − 0.25–0.55 0.75 ns 5.79 ns 11.90 ▪ Only HAM-Dc 3 0.14 − 0.25–0.52 0.70 ns 0 12.82 All italicized entries represent exact p-values. o: p < 0.10; ⁎: p < 0.05; ⁎⁎: p < 0.01; ⁎⁎⁎: p < 0.001. Abbreviations: CBT: cognitive behavior therapy; CI: confidence interval; DYST: dysthymia; IPT: interpersonal psychotherapy; MDD: major depressive disorder; Ncomp: Number of comparisons; NNT: numbers-needed-to-be-treated. a The p-values in this column indicate whether the Q-statistic is significant (the I2 statistics does not include a test of significance). b The p-values in this column indicate whether the difference between the effect sizes in the subgroups is significant. c These analyses were limited to those studies that reported the severity of the HAM-D at pretest. d We also conducted this subgroup analysis after removing the one study with mixed diagnoses. This did not result in a significant difference between the subgroups. e We also conducted this subgroup analysis after removing the one study with mixed diagnoses. This resulted in a trend (p = 0.065) indicating a difference between the two remaining subgroups. f In these analyses only one comparison from each study was used. g We also conducted this subgroup analysis after removing the one study with mixed diagnoses. This resulted in a trend (p = 0.051) indicating a difference between the two remaining subgroups. h There were not enough studies available to conduct subgroup analyses. 3.4. Psychological treatment versus pharmacotherapy superior effect of pharmacotherapy (p < 0.01), and which corresponds with an NNT of 5.75. Heterogeneity was moderate to high (I2 = 59.03). The effects of psychological treatments were directly compared Again, we found no indication that multiple comparisons from one with those of pharmacotherapy in ten comparisons. The mean effect study influenced the effect size or heterogeneity, and the effect size size was d = −0.31 (95% CI: − 0.53 to −0.09), which indicates a based on the HAM-D was comparable to the overall effect size.

P. Cuijpers et al. / Clinical Psychology Review 30 (2010) 51–62 Fig. 1. Standardized effect sizes of psychological treatments of chronic depression and dysthymia at post-test. 57

58 P. Cuijpers et al. / Clinical Psychology Review 30 (2010) 51–62 In the subgroup analyses we found a significant difference Removal of each of the individual studies from the analyses between studies in which SSRIs were used, compared to those in indicated that the study by Keller et al. (2000) had a considerable which TCAs were used (p < 0.01), suggesting that especially SSRIs may impact on the mean effect size. Removal of this study resulted in a be more effective than psychotherapy in chronic depression and considerable reduction of the mean effect size (to 0.08). Removal of dysthymia. However, the seven studies in which SSRIs were examined the study by Browne and colleagues resulted in an increased mean were the same seven studies that were aimed at patients with effect size (d = 0.37). Results of the subgroup analyses are, therefore, dysthymia. We found that the seven studies aimed at patients with probably affected considerably by these two studies. dysthymia differed significantly from the studies which were aimed at Again, no indication for publication bias was found. chronic or mixed samples. We did not find that type of psychotherapy was significantly associated with the effect size. 3.6. Other comparisons Removal of each of the individual studies from the analyses did not indicate that one of the studies had a large impact on the mean We could examine only four comparisons in which psychother- effect size (removal of the study by Ravindran and colleagues apy was compared to the combination of pharmacotherapy and resulted in the largest decrease of the effect size with d = 0.24; and psychotherapy. These four comparisons resulted in an effect size of removal of the study by Williams resulted in the largest increase of d = 0.45 (95% CI: 0.20–0.70; p < 0.001), in favor of the combined the effect size, with d = 0.37). Neither the funnel plot nor Duval and treatment. This corresponds to an NNT of 4.00. Heterogeneity was Tweedie's trim and fill procedure pointed at a significant publication moderate (I2 = 50.90). The effect size based on the HAM-D was bias (the unadjusted and adjusted effect sizes were exactly the comparable, although heterogeneity was zero. Because of the small same). number of comparisons, we did not conduct further analyses. In four studies, two different types of psychotherapy were 3.5. Pharmacotherapy versus combined treatment compared directly with each other. In three of these studies, interpersonal psychotherapy (IPT) was compared with another In nine comparisons pharmacotherapy was compared to the therapy. The mean effect size indicating the difference between IPT combination of pharmacotherapy and psychotherapy. The mean and other psychotherapies was small (d = 0.15, n.s.). effect size indicating the difference between these two types of treatment was d = 0.23 (95% CI: −0.01–0.47, p < 0.1) in favor of the combined treatment, which corresponds with an NNT of 7.69. 3.7. Drop-out rates Heterogeneity was moderate (I2 = 53.71). All comparisons originated from different studies and there were no studies with two or more We examined whether the relative risk of dropping out from an comparisons. The effect size based on the HAM-D was somewhat active treatment was different in the psychological conditions larger than the overall effect size (d = 0.42; 95% CI: 0.27–0.58; compared to the other conditions. However, we did not find that p < 0.001). the drop-out rate in the psychological treatments differed signifi- Subgroup analyses indicated a significant difference between the cantly from the drop-out rate in the pharmacotherapy conditions effect sizes of studies examining different diagnostic populations, (RR = 0.97; 95% CI: 0.73–1.28; N = 5; I2 = 0.50), nor did we find that ranging from a negligible effect size for dysthymic patients to a large the drop-out rate was significantly different in the psychological effect size for double depression (p < 0.01). We also found a significant conditions compared to the combined treatments (RR = 1.10; 95% CI: difference between SSRIs and other pharmacotherapies (TCAs, or other) 0.79–1.52; N = 3; I2 = 0), or when the pharmacotherapies were (p < 0.001). However, the studies examining dysthymia patients were compared to the combined treatments (RR = 0.82; 95% CI: 0.62– again the same studies that examined SSRIs. No significant differences 1.08; N = 7; I2 = 0). However, because the number of comparisons between types of psychotherapy were found. was small, the non-significant results can very well be related to a lack Table 3 Meta-analyses of studies examining the effects of psychological treatments on chronic depression: improvement from baseline to post-test. Study Ncomp d 95% CI Z I2a pb ▪ All studies 14 1.16 0.86–1.45 7.77 ⁎⁎⁎ 72.96 ⁎⁎⁎ ▪ One ES per study (highest) 10 1.23 0.87–1.60 6.60 ⁎⁎⁎ 80.02 ⁎⁎⁎ ▪ One ES per study (lowest) 10 1.09 0.74–1.45 5.99 ⁎⁎⁎ 79.54 ⁎⁎⁎ ▪ Only HAM-D 6 1.68 1.48–1.88 16.36 ⁎⁎⁎ 0 Subgroup analyses ▪ Diagnosis – Chronic MDD 3 1.30 0.79–1.81 4.99 ⁎⁎⁎ 0 0.340 – Double depression 2 1.49 0.73–2.25 3.84 ⁎⁎⁎ 13.77 – Dysthymia 6 0.93 0.65–1.21 6.53 ⁎⁎⁎ 49.88 – Mixed 3 1.30 0.65–1.95 3.90 ⁎⁎⁎ 70.62 ⁎ ▪ Psychological – CBT 6 1.44 1.09–1.80 7.92 ⁎⁎⁎ 0 0.120 treatment – IPT 4 1.01 0.78–1.23 8.63 ⁎⁎⁎ 0 – Other 4 0.98 0.24–1.71 2.59 ⁎⁎ 92.53 ⁎⁎⁎ ▪ Target group – Adults 10 1.15 0.80–1.50 6.44 ⁎⁎⁎ 79.95 ⁎⁎⁎ 0.781 – Specific target group 4 1.17 0.71–1.63 4.97 ⁎⁎⁎ 5.58 ns ▪ Number of – ≤12 sessions 3 0.93 0.48–1.37 4.09 ⁎⁎⁎ 76.13 ⁎ 0.045 sessions – 13–17 sessions 7 1.07 0.79–1.34 7.55 ⁎⁎⁎ 0 – ≥18 session 4 1.58 1.20–1.96 8.15 ⁎⁎⁎ 21.73 ns ▪ Analyses – Intention-to-treat 7 1.02 0.74–1.30 7.09 ⁎⁎⁎ 0 0.355 – No intention-to-treat 7 1.27 0.81–1.73 5.45 ⁎⁎⁎ 85.78 ⁎⁎⁎ ▪ Format – Individual 11 1.09 0.75–1.42 6.36 ⁎⁎⁎ 78.03 ⁎⁎⁎ 0.199 – Group/mixed 3 1.47 0.99–1.94 6.09 ⁎⁎⁎ 0 o: p < 0.10; ⁎: p < 0.05; ⁎⁎: p < 0.01; ⁎⁎⁎: p < 0.001. a The p-values in this column indicate whether the Q-statistic is significant (the I2 statistics does not include a test of significance). b The p-values in this column indicate whether the difference between the effect sizes in the subgroups is significant.

P. Cuijpers et al. / Clinical Psychology Review 30 (2010) 51–62 59 of statistical power and therefore these results have to be interpreted et al. 6 sessions were used, while the study of de Jong et al. used more with caution. than 30 sessions in both psychological treatment groups). Therefore we repeated this analysis, while we included only the studies with 12 3.8. Improvement from baseline to post-test to 20 sessions. However, this still resulted in a strong association between effect size and number of sessions (slope: 0.060; 95% CI: We also calculated the effect sizes based on the improvement from 0.019–0.102; p < 0.01). Removing the possible outlier (Keller et al., baseline to post-test in the groups in which the participants received a 2000) reduced the strength of the association, but it was still psychological treatment (combined treatments were not examined in significant (slope: 0.022; 95% CI: 0.002–0.042; p < 0.05). these analyses). These effect sizes indicate the difference between the We examine the influence of each of the individual studies, and depression score at baseline and the score at post-test in those who found that removal of the study by Keller et al. (2000) resulted in a received psychotherapy. These analyses allowed us to get an decreased mean effect size of 1.03, and removal of the study by Barrett impression of the improvement of patients from baseline to post- and colleagues resulted in an increased effect size of 1.23. test. Furthermore, we could calculate these improvement rates for all studies in which a psychotherapy condition was used (regardless of 4. Discussion the comparison group). This resulted in a larger group of effect sizes than we get from each of the more specific comparisons (psycho- In this meta-analysis we found that psychotherapy for chronic therapy versus control group, psychotherapy versus pharmacother- major depression and dysthymia has a small but significant effect apy, psychotherapy versus combined treatment). This larger number (d = 0.23) on depression when compared to control groups. When of comparisons allows us to conduct more subgroup analyses, and to psychotherapy was directly compared with pharmacotherapy, it was explore possible sources of heterogeneity better. found that pharmacotherapy was significantly more effective (d = We could calculate these effect sizes in 14 comparisons (Table 3). −0.31). We also found an indication that especially SSRIs were more The mean effect size was 1.16 (95% CI: 0.86–1.45). Heterogeneity was effective than psychotherapy. However, the studies in which SSRIs high (I2 = 72.96). Including only one comparison from each study did were examined were precisely the same studies that examined not affect the effect size very much, nor did it result in a considerable dysthymia patients. In the direct comparisons between psychother- decrease of heterogeneity (Table 3). apy and pharmacotherapy, the studies in dysthymia patients found We conducted a series of subgroup analyses (Table 3). As can be also smaller effect sizes than studies in other groups of patients. This seen in Table 3, we found no indication for a significant difference implies that either SSRIs are indeed more effective or that psycho- between studies using different diagnostic categories, between therapy (as it was implemented in these studies) is less effective in studies among adults in general and more specific target groups, dysthymia patients. Unfortunately, it is not possible in the current between studies in which different types of psychological treatment study, to establish which of these possibilities is responsible for our were used, between an individual or group treatment format, nor findings. However, in the studies in which pharmacotherapy was between studies in which the effect size was based on the intention- compared to the combination of pharmacotherapy and psychother- to-treat sample and studies in which no intention-to-treat analyses apy, we also found few indications that the combined treatment was were conducted. However, we did find that studies reporting a larger more effective than pharmacotherapy alone in dysthymia patients number of treatment sessions resulted in larger effect sizes. (while the combined treatment was more effective in other diagnostic We decided to explore the association between the effect size and groups). This supports the hypothesis that psychotherapy is less the number of sessions in a meta-regression analysis. We found that effective in dysthymia patients, or that the psychotherapies were not this association was highly significant (slope: 0.038; 95% CI: 0.019– implemented well enough in these studies. More research is needed 0.056; p < 0.001), suggesting that each treatment session increased to examine this issue. the effect size with 0.038 point. We have presented this association We did find clear evidence from the comparisons between graphically in Fig. 2. pharmacotherapy and combined treatments, that combined treat- In most studies, the therapies consisted of 12 to 20 sessions. Only ments resulted in a higher effect size than pharmacotherapy alone two studies had a different number of sessions (in the study by Barrett (d = 0.23). Combined treatments were also found to be superior to Fig. 2. Relation of effect size to number of treatment sessions in psychological treatments of chronic depression and dysthymia.

60 P. Cuijpers et al. / Clinical Psychology Review 30 (2010) 51–62 psychotherapy alone (d = 0.45). We found no indications that psychotherapies examined, but also in terms of excluded and included psychotherapy reduced drop-out rates relative to pharmacotherapy comorbidity, demographic and other characteristics of the samples. either alone or in combination. These differences may limit the generalizability of our findings to all Although the overall effect of psychotherapy for chronic depres- patient groups. A third important limitation was that it was not clear in sion and dysthymia were small, we did find indications that the effect most studies whether the patients included had been treated size was associated with the number of treatment sessions. These unsuccessfully before they entered the study. A fourth limitation is results suggested that each extra session increased the effect size with that in our analyses, SSRI treatment was confounded by diagnosis (the 0.04. The results suggest that at least 18 sessions are needed for studies using SSRIs were exactly the same as the studies examining psychotherapy to have an optimal effect. dysthymia). Consequences of this have been described above. A final How this relates to the literature on sudden gains during limitation is that the quality of several included studies was not optimal. psychotherapy is not clear. This literature has found indications that As indicated earlier, the study by Keller et al. (2000) is the largest and most gains of psychotherapy for depression are realised during the most influential study in this field. This study met all our quality criteria first eight to ten sessions (Ilardi & Craighead, 1994; Tang, Derubeis, and found a relative high improvement rate compared to several other Hollon, Amsterdam, & Shelton, 2007) and in some cases as few as studies. Because of the large sample size, this study had also a three (Hopko, Robertson, & Carvalho, 2009). It could be possible that considerable impact on the mean effect sizes in several comparisons. in people with chronic depression this improvement is not realized These results suggest that the study by Keller et al. may be more during the first sessions, but only gradually during the therapy. This exemplary of the possible effects of psychotherapy than we found in our could be related to the smaller effect sizes found for patients with meta-analysis, and that psychotherapy may potentially have higher chronic depression or dysthymia. effect sizes than we found. Our results suggest that psychotherapy may be less effective in Despite limitations of this meta-analysis, evidence is convincing chronic depression and especially in dysthymia than it is in non- that psychotherapy has a significant effect on chronic depression and chronic depressive disorders. Meta-analyses of psychotherapies for dysthymia. Furthermore, combined treatments of psychotherapy and non-chronic depression typically find large effects relative to wait list pharmacotherapy are more effective than each of the treatments and minimal treatment controls (effect sizes ranging from 0.70 to alone. Given the chronic nature of the disorders, treatment guidelines 0.90) (Churchill et al., 2001; Cuijpers, van Straten, Andersson, et al., should recommend that combined treatments for chronic major 2008; Cuijpers, van Straten, van Oppen, et al., 2008; Cuijpers, van depression should be used (Fochtmann & Gelenberg, 2005; NICE, Straten, Warmerdam, & Andersson, 2008; Cuijpers, van Straten, 2007; RANZCP, 2004). However, the added value of psychotherapy for Warmerdam, & Smits, 2008), with pill placebo control groups dysthymia has not been convincingly shown, and it may currently not resulting in smaller effect sizes (d = 0.36). be advised on the available evidence to use psychotherapy as a It may be possible that this smaller overall effect size was a standalone treatment in this group of patients. consequence of psychotherapy not being implemented well in these More research in the area of psychotherapy for chronic depression studies as it was in the non-chronic depression literature. This also and dysthymia is certainly needed. Quality of the studies included in could explain the rather puzzling difference between studies on this meta-analysis was not optimal, and more high-quality studies are dysthymia and other types of chronic depression. However, there is needed. Such studies should give specific attention to important no particular reason to assume that psychotherapy was poorly quality criteria, such as adequate randomization procedures, blinding implemented in these trials and most of the relevant studies adhered of assessors, and the inclusion of all randomized respondents in the to the criteria for quality implementation laid out by Chambless and final analyses. More research is needed to examine how the contents Hollon (1998). Most studies used a treatment manual, in almost all of psychotherapies should be adapted for this group of patients. studies the therapists were trained, and in most studies the integrity Although some treatments for chronic depression are available, it is of the treatment was checked. Still, it is not clear that adhering to not clear what specific components are especially important for this these criteria will necessarily ensure that treatment is adequately group of patients. It is also important to examine why research seems implemented and few of the studies were conducted by groups with to indicate that psychotherapy is less effective in dysthymia. It seems recognized expertise in the implementation of the treatments that unlikely that dysthymia is very different from other types of chronic they tested. major depression (Klein et al., 2006), and more research is needed to We found no indication that the drop-out rates were lower in examine whether psychotherapy for dysthymia and other forms of psychotherapy than in pharmacotherapy. This is in contrast with the chronic depression should indeed be different. results of earlier meta-analyses (Cuijpers, van Straten, Andersson, This meta-analysis has made it clear that psychotherapy has a et al., 2008; Cuijpers, van Straten, van Oppen, et al., 2008; Cuijpers, significant effect on chronic depression and dysthymia, and although van Straten, Warmerdam, & Andersson, 2008; Cuijpers, van Straten, these effects are small, any help in improving chronic depression is Warmerdam, & Smits, 2008; Cuijpers et al., 2009), in which we found relevant from a clinical perspective. clear indications that the drop-out rate in psychotherapy was significantly lower than in pharmacotherapy. However, these earlier meta-analyses examined studies on all types of depressive disorders. References It is very well possible that patients with chronic types of depression Agosti, V., & Ocepek-Welikson, K. (1997). 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