Clinical Psychology Review 30 (2010) 51–62

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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 Netherlandsb Department of Psychiatry and EMGO+ Institute, VU University Medical Center, Amsterdam, The Netherlandsc Vanderbilt University, Nashville, United Statesd Department of Behavioural Sciences and Learning, Linköping University, Swedene Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Stockholm, Sweden

⁎ Corresponding author. Department of Clinical Psychfax: +31 20 598 8758.

E-mail address: p.cuijpers@psy.vu.nl (P. Cuijpers).

0272-7358/$ – see front matter © 2009 Elsevier Ltd. Aldoi:10.1016/j.cpr.2009.09.003

a b s t r a c t

a r t i c l e i n f o

Article history:Received 22 June 2009Received in revised form 2 September 2009Accepted 4 September 2009

Keywords:Chronic depressionDysthymiaPsychological treatmentPsychotherapyMeta-analysis

Although several studies have examined the effects of psychotherapy on chronic depression and dysthymia,no meta-analysis has been conducted to integrate results of these studies. We conducted a meta-analysis of16 randomized trials examining the effects of psychotherapy on chronic depression and dysthymia. Wefound that psychotherapy had a small but significant effect (d=0.23) on depression when compared tocontrol groups. Psychotherapy was significantly less effective than pharmacotherapy in direct comparisons(d=−0.31), especially SSRIs, but that this finding was wholly attributable to dysthymic patients (thestudies examining dysthymia patients were the same studies that examined SSRIs). Combined treatmentwas more effective than pharmacotherapy alone (d=0.23) but even more so with respect to psychotherapyalone (d=0.45), although again this difference may have reflected the greater proportion of dysthymicsamples in the latter. No significant differences were found in drop-out rates between psychotherapy and theother conditions. We found indications that at least 18 treatment sessions are needed to realize optimaleffects of psychotherapy. We conclude that psychotherapy is effective in the treatment of chronic depressionand dysthymia but probably not as effective as pharmacotherapy (particularly the SSRIs).

ology, VU University Amsterdam, Van der Boechorststraa

l rights reserved.

© 2009 Elsevier Ltd. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 522. Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52

2.1. Identification and selection of studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 522.2. Coding of study characteristics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 532.3. Quality assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 532.4. Meta-analyses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53

3. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 553.1. Characteristics of included studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 553.2. Quality of included studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 553.3. Psychological treatment versus control groups . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 553.4. Psychological treatment versus pharmacotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 563.5. Pharmacotherapy versus combined treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 583.6. Other comparisons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 583.7. Drop-out rates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 583.8. Improvement from baseline to post-test . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59

4. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60

t 1, 1081 BT Amsterdam, The Netherlands. Tel.: +31 20 598 8757;

52 P. Cuijpers et al. / Clinical Psychology Review 30 (2010) 51–62

1. Introduction

It is well established that psychological interventions are effectivein the treatment of depression. In the past three decades, about 200controlled and comparative studies have examined the effects ofpsychological treatments compared to control conditions and to othertreatments (Cuijpers, van Straten, Warmerdam, & Andersson, 2008).This large number of studies has shown that psychological treatmentshave significant effects on depression in adults (Churchill et al., 2001;Cuijpers, van Straten, Warmerdam, & Smits, 2008). A considerablenumber of studies has shown that psychological treatments are alsoeffective in specific populations, such as older adults (Cuijpers, vanStraten & Smit, 2006), women with postpartum depression (Lumley,Austin, & Mitchell, 2004), and patients with both depression andgeneral medical disorders, including multiple sclerosis (Mohr &Goodkin, 1999), stroke patients (Hackett, Anderson, & House, 2004),and cancer patients (Sheard & McGuire, 1999). Furthermore, severalspecific types of psychological treatment have been found to beeffective. Most research has focused on cognitive behavior therapy, inwhich restructuring of negative cognitions is the core element(Gloaguen, Cottraux, Cucherat, & Blackburn, 1998; Churchill et al.,2001). However, several other psychological treatments have alsobeen found to be effective, including interpersonal psychotherapy (deMello, De Jesus Mari, Bacaltchuk, Verdeli, & Neugebauer, 2005),problem-solving therapy (Malouff, Thorsteinsson, & Schutte, 2007;Cuijpers, van Straten, & Warmerdam, 2007a), behavioral activation(Cuijpers, van Straten, & Warmerdam, 2007b; Ekers, Richards, &Gilbody, 2008), and psychodynamic therapies (Leichsenring, 2001;Leichsenring & Rabung, 2008). These treatments can be delivered inindividual format, group format, or as guided self-help (McDermut,Miller, & Brown, 2001). The effects of psychological treatments arecomparable to those of pharmacological treatments (DeMaat, Dekker,Schoevers, & de Jonghe, 2006; Cuijpers, van Straten, van Oppen, &Andersson, 2008), and combined treatments are more effective thanpsychological treatment alone (De Maat, Dekker, Schoevers, & deJonghe, 2007; Cuijpers, van Straten, Warmerdam, & Andersson, 2009)and than pharmacotherapy alone (Friedman et al., 2004; Pampanolla,Bollini, Tibaldi, Kupelnick, & Munizza, 2004; Cuijpers, Dekker, Hollon,& Andersson, 2009).

Despite this large body of research, however, very few of thestudies on psychological treatments have focused on more chronicforms of depression. It is estimated, however, that 20% of alldepressed individuals and up to 47% of the patients treated inmentalhealth care, suffer from a chronic depression (Torpey & Klein, 2008;Arnow & Constantino, 2003). This implies that about 3% of the adultpopulation in Western countries suffers from a chronic depression(Kessler et al., 1994). All depressive disorders have a large impact onquality of life of patients (Ustun, Ayuso-Mateos, Chatterji, Mathers, &Murray, 2004; Saarni et al., 2007), and are associated with highlevels of service use and enormous economic costs (Berto, D'Ilario,Ruffo, & Di Virgilio, 2000; Greenberg & Birnbaum, 2005; Smit et al.,2006). Chronic depressive disorders have, however, considerablymore adverse impact on quality of life (Wells, Burnam, Rogers, Hays,& Camp, 1992), service use (Howland, 1993), and economic costs(Smit et al., 2006), and more often result in suicide attempts andhospitalization than acute depressive disorders (Torpey & Klein,2008; Arnow & Constantino, 2003), because they begin early in lifein many cases (Keller, McCullough, Klein, Arnow, Dunner, Gelenberget al., 2000; Cassano, Akiskal, Perugi, Musetti, & Savino, 1992).Moreover, chronic depressive disorders are often lifelong, and areresponsible for a considerable proportion of the enormous diseaseburden associated with depression (Greenberg & Birnbaum, 2005;Keller et al., 2000).

Although the terminology has varied over the years, depressivedisorders are considered to be chronic when they last for two yearsor longer. In the DSM-IV four types of chronic depression are

distinguished (Schramm et al., 2008): 1) dysthymia, 2) chronicmajor depressive disorder (MDD), 3) double depression (MDDsuperimposed on a dysthymic disorder), and 4) recurrent MDD withincomplete recovery between episodes. Although chronic MDD ismore severe than dysthymia, few indications have been found thatthese two types of depression differ systematically from each other(Torpey & Klein, 2008; Karlsson, Pelkonen, & Heilä, 2007; McCul-lough, Klein, & Borian, 2003). Prospective research has shown thatmost patients with dysthymia eventually experience exacerbationsfor longer or shorter periods of time in which they meet criteria forMDD (Klein, Shankman, & Rose, 2006), which suggests thatdysthymia and double depression may be different phases of thesame disorder.

Although several meta-analyses have shown that pharmacother-apy is effective in the treatment of chronic depressive disorders anddysthymia (De Lima, Hotoph, & Wessely, 1999; Kocsis, 2003), thestatus of psychological treatments is less clear and sometimesquestioned. While several reviews have described the studiesexamining these psychological treatments (Markowitz, 1994; Torpey& Klein; 2008; Arnow & Constantino, 2003), no meta-analytic studyhas been conducted, mostly because the number of studies has beenconsidered to be too small for such a study. Some meta-analyses haveincluded small subsamples of studies on dysthymia (Cuijpers, vanStraten, Andersson, & van Oppen, 2008; Cuijpers, van Straten, vanOppen, et al., 2008; Cuijpers, van Straten, Warmerdam, & Andersson,2008; Cuijpers, van Straten, Warmerdam, & Smits, 2008; Imel,Malterer, McKay, & Wampold, 2008), suggesting that psychotherapyis less effective than pharmacotherapy in the treatment of dysthymia.However, the evidence is inconclusive, because of the lack ofadequately sized samples included in previous meta-analyticalresearch. As will be shown in the present paper, the number ofstudies examining psychotherapy for chronic depression and dysthy-mia has grown considerably in the past few years, opening up thepossibility to conduct such a meta-analysis that will provide moredefinite answers.

In light of the increased number of controlled studies we decidedto conduct a new meta-analysis in which we collected all studies ofpsychotherapy for patients with chronic depressive disorders ordysthymia, in which psychotherapy was compared to controlconditions, pharmacotherapy and combined treatments of psycho-therapy and pharmacotherapy. We expected effect sizes of psy-chotherapies for chronic depression to be smaller than those ofpsychotherapies for adult depression in general, because chronicdepression is more persistent and a history of previous treatmentfailure is more common in patients suffering from chronic depression.Furthermore, in concordance with clinical practice for those who arechronically depressed, we expected a combined treatment ofpsychotherapy and pharmacotherapy to be more effective than eitherpsychotherapy or pharmacotherapy alone.

2. Methods

2.1. Identification and selection of studies

A database covering 1036 papers on the psychological treatment ofdepression was used for the present meta-analysis. This databaseincludes studies on combined treatments and comparisons withpharmacotherapies, and it has been described in detail elsewhere(Cuijpers, van Straten, Andersson, et al., 2008). The database has beenused in a series of earlier meta-analyses and more information isavailable on the Internet (www.evidencebasedpsychotherapies.org).It was developed through a comprehensive literature search (from1966 to January 2009) in which we examined 9011 abstracts fromPubmed (1629 abstracts), Psycinfo (2439), Embase (2,606), and theCochrane Central Register of Controlled Trials (2337). These abstractswere identified by combining terms indicative of psychological

53P. Cuijpers et al. / Clinical Psychology Review 30 (2010) 51–62

treatment and depression (bothMeSH-terms and text words). For thisdatabase, we also collected the primary studies from 42 meta-analyses of psychological treatment for depression (www.evidence-basedpsychotherapies.org). For the current study, we examined thefull texts of these 1036 papers.We also examined the reference lists ofearlier reviews of psychotherapies for chronic depression anddysthymia (Arnow & Constantino, 2003; Torpey & Klein, 2008;Markowitz, 1994) and we checked the references of the includedprimary studies.

We included (a) randomized trials (b) in which the effects of apsychological treatment (c) was compared to the effects of a controlgroup, another active treatment, or a combined psychological andpharmacological treatment (d) in adults (e) with a chronic majordepressive disorder or dysthymia, and which was established with adiagnostic interview (such as the SCID, or the CIDI). We also includedstudies which examined psychological treatment of broader catego-ries of depressive disorders, but which presented separate data forpatients meeting criteria for chronic depression or dysthymia. Weexcluded studies on adolescents or children (below 18 years of age).Comorbid general medical or psychiatric disorders were not used asan exclusion criterion. No language restrictions were applied.

2.2. Coding of study characteristics

We coded major characteristics of the included studies, includingcharacteristic of the target group (age, percentage women, percentagemarried), the definition of chronic depression, recruitment method,exclusion criteria (anxiety disorders, substance-related disorders,personality disorders), type of psychotherapy, number of sessions,treatment format, country where the study was conducted, andwhether the study was conducted in a subsample of a larger study ornot. Type of psychotherapy was defined according to definitionsdeveloped for a recent comparative meta-analysis (Cuijpers, vanStraten, Andersson, et al., 2008). In these definitions a psychotherapyis considered to be cognitive behavior therapy if cognitive restructur-ing is the core element of the treatment; problem-solving therapy is atreatment in which personal problems are systematically solved usingspecific steps; and interpersonal psychotherapy is a brief and highlystructured psychotherapy that addresses interpersonal issues indepression to the exclusion of all other foci of clinical attention(Cuijpers, van Straten, Andersson, & van Oppen, 2008). The majorityof therapies examined in the current meta-analyses used one of thesethree types of psychotherapy.

2.3. Quality assessment

We assessed validity of included studies using a number of basiccriteria, as suggested in the Cochrane Handbook (Higgins & Green,2005): allocation to conditions conducted by an independent (third)party; blinding of assessors of outcomes; and completeness of follow-up data. We did not check for the fourth criterion for validity(adequacy of random allocation concealment to respondents),because it was not possible in these studies to conceal therandomization to patients.

We also rated the quality of the treatment implementation usingthree criteria which were based on an authoritative review ofempirically supported psychotherapies (Chambless & Hollon, 1998):(1) the study referred to the use of a treatment manual (either apublished manual, or a manual specifically designed for the study);(2) the therapists who conducted the therapy were trained for thespecific therapy, either specifically for this study or as a generaltraining; (3) treatment integrity was checked during the study (bysupervision of the therapists during treatment or by recording oftreatment sessions or by systematic screening of protocol adherenceby a standardized measurement instrument).

2.4. Meta-analyses

For each comparison between a psychological treatment and acontrol group (or another active treatment), we calculated the effectsize indicating the difference between the two groups at post-test(Cohen's d or standardized mean difference). Effect sizes werecalculated by subtracting (at post-test) the average score of thepsychological treatment group from the average score of thecomparison group, and dividing the result by the pooled standarddeviations of the two groups. Effect sizes of 0.8 can be assumed to belarge, while effect sizes of 0.5 are moderate, and effect sizes of 0.2 aresmall (Cohen, 1988).

In the calculations of effect sizes we only used those instrumentsthat explicitly measured symptoms of depression. If more than onedepression measure was used, the mean of the effect sizes wascalculated, so that each study only provided one effect size. If meansand standard deviations were not reported, we used the procedures ofthe Comprehensive Meta-Analysis software (see below) to calculatethe effect size using dichotomous outcomes. If insufficient data werereported to calculate an effect size, the study was excluded (whichwas the case in one study, which reported no data or tests for the 4conditions to which the subjects were randomized) (Waring et al.,1988).

We only used the effect sizes indicating the differences betweenthe psychotherapy and the alternative condition at post-test. Wedecided not to examine the effects at follow-up, because the numberof effect sizes was small. In addition, the follow-up period differedconsiderably among these studies, and in several studies sometreatments were continued and others discontinued. Because onlyfew of the included studies reported outcomes on anxiety andquality of life, we decided not to examine these outcomes in a meta-analysis.

To calculate pooled mean effect sizes, we used the computerprogram Comprehensive Meta-Analysis (version 2.2.021). As weexpected considerable heterogeneity among the studies, we decidedto calculate mean effect sizes using a random effects model. In therandom effects model it is assumed that the included studies aredrawn from ‘populations’ of studies that differ from each othersystematically (heterogeneity). In this model, the effect sizes resultingfrom included studies not only differ because of the random errorwithin studies (as in the fixed effects model), but also because of truevariation in effect size from one study to the next.

The standardized mean difference is not easy to interpret from aclinical point of view. Therefore, we transformed the standardizedmean differences into the numbers-needed-to-be-treated (NNT),using the formulae provided by Kraemer and Kupfer (2006). TheNNT indicates the number of patients that have to be treated in orderto generate an additional positive outcome in one of them (Sackett,Strauss, Richardson, Rosenberg, & Haynes, 2000).

As a test of homogeneity of effect sizes, we calculated the I2-statistic which is an indicator of heterogeneity in percentages. A valueof 0% indicates no observed heterogeneity, and larger values showincreasing heterogeneity, with 25% as low, 50% as moderate, and 75%as high heterogeneity (Higgins, Thompson, & Deeks, 2003). We alsocalculated the Q-statistic, but only report whether this was significantor not.

Subgroup analyses were conducted according to the mixed effectmodel. In this model, studies within subgroups are pooled with therandom effects model, while tests for significant differences betweensubgroups are conducted with the fixed effects model. For contin-uous variables, we used meta-regression analyses to test whetherthere was a significant relationship between the continuous variableand the effect size, as indicated with a Z-value and an associated p-value.

Publication bias was tested by inspecting the funnel plot onprimary 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 theeffect size after the publication bias has been taken into account (asimplemented in Comprehensive Meta-analysis, version 2.2.021).

Table 1Selected characteristics of studies examining psychological treatments of chronic depressio

1st author Population Age (Mn)[range]

%♀ %M Recr Definition ofdepression

Excluddisorde

Agosti andOcepek-Welikson(1997)

Adultswith earlyonsetchronicMDD

31.3[18–65]

NR NR Clin Chronic MDD(≥2 years)(SADS/RDC)+HRSD>14

SUB/PAASPD

Barker,Scott, andEccleston(1987)

Adultinpatients

49.3[<65]

63.6 NR Clin Chronic MDD(≥2 years)(RDC) ANDtreatmentrefractory

–

Barrett et al.(2001)

Adults 44.1[18–59]

63.9 90.0 Clin DYST+HRSD>10

–

Browneet al.(2002)

Adults 42.1[18–74]

68 NR Com DYST (DSM-IV/UM-CIDI); 15%had current MDD

–

de Mello,Myczcowisk,and Menezes(2001)

Adults NR[18–60]

80.0 NR Clin DYST (ICD-10symptomchecklist); 91%had current MDD

SUB

de Jong et al.(1986)

Adultinpatients

36.6[NR]

70.0 NR Clin MDD+dysthymia(DSM-III)+BDI≥20

–

Dunner et al.(1996)

Adults 35.7[18–60]

45.8 NR NR DYST (DSM-III-R/SCID); no currentMDD

–

Harpin,Liberman,Marks, Stern,and Bohannon(1982)

Adults 42.0[21–58]

41.7 NR Clin Chronic MDD(≥2 years)(psychiatrist)+HDRS≥20+Wakefield≥20

–

Hellerstein et al.(2001)

Adults 45.1[21–65]

50.0 87.5 Clin DYST (DSM-III-R;SCID)+HDRS≥14; nocurrent MDD

SUB/PAGAD/OPTSD/B

Keller et al.(2000)

Adults 43.0[18–75]

65.3 90.5 Clin Chronic ORMDD+dysth ORrecurrent MDDwith incompleteinter-episoderecovery (DSM-IV/SCID)+HRSD≥20

SUB/OCPAN/GSOCPHPTSD/ASTPD/B

Markowitz,Kocsis,Bleiberg,Christos, andSacks (2005)

Adults 42.3[18–60]

63.0 63.0 Com DYST (SCID) withearly onset(<21 years); noMDD in past6 months

SUB/ASBPD/ClA PD

Markowitz,Kocsis,Christos,Bleiberg, andCarlin (2008)

Adultswithalcoholabuse/dep.

38.4[18–60]

31 69.2 Com DYST (SCID-II)with onset beforeage≤21; 54% hadcurrent MDD

ASPD/BCluster

Miller, Norman,and Keitner(1999)

Adultinpatients

37.4[18–65]

80.7 NR Clin MDD+DYST(DIS)

SUB/AS

Ravindran et al.(1999)

Adults NR[21–54]

57.7 NR Com DYST (DSM/MINI); no currentMDD

CurrenI disordAny PD

Schramm et al.(2008)

Adultinpatients

42.8[18–65]

73.2 Clin Chronic MDD(SCID)+HDRS≥16

Axis-IdisordeSUB/BPASPD

Williams et al.(2000)

Adults 71.0[> 60]

41.5 77.8 Clin DYST+HDRS≥10

SUB/BPASPD

Apart from the outcomes on depression, we also calculated therelative risk (RR) of dropping out from the treatments. Again, weconducted all meta-analyses with the random effects model and we

n in adults.

edrsa

Conditions N Nse Frm TQ Measuresb C SubS

N/ 1. CBT2. IPT3. Imipramine4. Placebo

16142015

1616

IndInd

M/T/I

HRSD US S

1. Pharmacotherapy2. Pharmacotherapy+CBT

1010

15 Ind NR HRSD UK N

1. PST2. Paroxetine3. Placebo

434242

6 Ind M/T/I

HSCL-D US S

1. IPT2. IPT+Sertraline3. Sertraline

178212196

10 Ind M/T/I

MADRS CA N

1. IPT+Moclobemide2. Moclobemide

1619

16 Ind T HDRS,MADRS

BR N

1. BA+SST+CT2. CT3. Non-specific control

101010

3347

Mixed M/T/I

HDRS,BDI, D-scale

GE N

1. CBT2. Fluoxetine

1318

16 Ind M/T/I

HDRS, BDI US N

1. CBT2. Waiting list

66

20 Ind T/I HDRS,Wakefieldscale

US N

N/CD/PD

1. CIGP+Fluoxetine2. Fluoxetine

2020

16 Grp M/T/I

HDRS,BDI, CDRS

US N

D/AD,OB/SPD/PD

1. CBASP2. CBASP+Nefazodone3. Nefazodone

228227226

18 Ind M/T/I

HRSD US N

PD/uster

1. IPT2. Brief supportive therapy3. IPT+sertraline4. Sertraline

23262124

1717

Ind M/T/I

HRSD,BDI, CDRS

US N

PD/A

1. IPT2. Supportive therapy

1412

1717

Ind M/T/I

HRSD,BDI, CDRS

US N

PD 1. CBT+pharmacotherapy2. Social skills tr+pharm.3. Pharmacotherapy

685

4040

Ind M/T

M-HDRS,BDI

US S

t Axis-er/

1. CBT+sertraline2. CBT+placebo3. Sertraline4. Placebo

24242224

1212

Grp M/T

HRSD CA N

r/D/

1. IPT+pharmacotherapy2. Pharmacotherapy

2421

11 Mixed M/T/I

BDI, HDRS GE S

D/ 1. PST2. Paroxetine3. Placebo

726970

6 Ind M/T/I

HSCL-D US S

55P. Cuijpers et al. / Clinical Psychology Review 30 (2010) 51–62

calculated the Q-statistic and the I2-statistic to estimate heterogeneitybetween study outcomes.

3. Results

3.1. Characteristics of included studies

Sixteen studieswith a total of 2116patientsmet our inclusion criteria(689 in the psychological treatment conditions; 167 in the controlconditions; 692 in the pharmacotherapy conditions; and 568 in thecombined psychological and pharmacological treatment conditions).Selected characteristics of the included studies are presented in Table 1.

Seven studies were aimed at patients with dysthymia (and nomajor depression; one study in which 15% of the patients also hadMDD was categorized in this group of studies); four studies wereaimed at patients with chronic major depression; three at patientswith double depression (both MDD and dysthymia); and theremaining two studies were focused on patients with other categoriesof chronic depression and/or dysthymia. Most studies were aimed atadult outpatients in general, while two focused on inpatients, and twoothers were aimed at more specific target groups (adults with earlyonset chronic MDD, and adults with secondary alcohol abuse/dependence). In most studies the majority of patients was femaleand married, and had a mean age between 30 and 50.

A total of 21 psychological treatments were examined, seven ofwhich were cognitive behavior therapy, six were interpersonalpsychotherapy, and eight were other therapies (problem-solvingtherapy; cognitive–interpersonal group psychotherapy for chronicdepression; cognitive behavioral-analysis system of psychotherapy;and supportive therapy). Number of treatment sessions ranged from 6to 47. Most therapies used an individual treatment format (sixteen),while two used a group format and the remaining three a mixedindividual and group format.

In seven studies only one measurement instrument was used tocalculate effect sizes, six studies used two instruments, and theremaining three studies used three instruments. The HamiltonDepression Rating Scale (HDRS) was used in 13 studies, seven studiesthe Beck Depression Inventory (BDI), and three used the CornellDysthymia Rating Scale (CDRS).

Five studies used subsamples of a larger trial in which broadercategories of depressed patients were examined. Ten of the sixteenstudies were conducted in the United States, two in Canada, three inEurope (UK, Germany, the Netherlands), and one in Brazil.

3.2. Quality of included studies

The quality of the included studies varied. Four of the 16 studiesreported that allocation to conditions was conducted by an indepen-dent party, while 6 studies reported that a computerized randomi-zation schedule was used, and the remaining studies did not reportthe randomization methods. Blinding of assessors was reported in 11studies. Intention-to-treat analyses were conducted in six studies (theother studies were limited to completers-only analyses).

The quality of the treatment implementation of the includedstudies was good. Thirteen studies used a treatment manual, in all but

Notes to Table 1:Abbreviations (for abbreviations of the measurement instruments the reader is referred to thpersonality disorder; BA: behavioral activation; BPD: borderline personality disorder; Bpsychotherapy; CBT: cognitive behavior therapy; CIGP: Cognitive–interpersonal group precruitment from the community; CT: cognitive therapy; Dep: dependence; DYST: dysthymicheck of integrity; Ind: individual format; IPT: interpersonal psychotherapy; M: manual;Netherlands; NR: not reported; Nse: number of sessions; OCD: obsessive compulsive disoproblem-solving therapy; PTSD: posttraumatic stress disorder; Recr: recruitment method; Sschizotypical personality disorder; SUB: substance-related disorder; SubS: subsample of laUnited States.a We report only excluded anxiety disorders, substance-related disorders, and personalityb In this column we only report the instruments that measure depression and that were u

one of the studies the therapists were trained for this specific therapy,and 12 of the 16 studies reported that the integrity of the treatmentwas checked during the study.

3.3. Psychological treatment versus control groups

We could compare a psychological treatment with a control group(placebo, care-as-usual, non-specific control, or waiting list) in8 comparisons. The mean effect size was d=0.23 (95% CI: 0.06–0.41), which corresponds with an NNT of 7.69. Heterogeneity waszero (I2=0). The results of these analyses are summarized in Table 2.The effect sizes and 95% confidence intervals of the individual contrastgroups are plotted in Fig. 1.

When we limited the analyses to the effect sizes found for the 17-item version of the HAM-D (the most frequently used instrument), acomparable effect size was found (d=0.33; 95% CI: 0.01–0.64;NNT=5.43), and again heterogeneity was found to be zero.

In our analyses, we included two studies in which two separatepsychological treatments were compared to a control group. Thismeans that multiple comparisons from these two studies wereincluded in the same analysis. These multiple comparisons, however,are not independent of each other, which may have resulted in anartificial reduction of heterogeneity and a distortion of themean effectsize. Therefore, we conducted another meta-analysis, in which weincluded only one comparison per study (Table 2). From the twostudies with multiple comparisons we first included only thecomparison with the largest effect size. Then we conducted anothermeta-analysis in which we included only the smallest effect size fromthe two studies. As can be seen in Table 2, these analyses did notindicate that the mean effect size changed considerably, nor did wefind indications that heterogeneity was affected by these two studies(I2=0 in both meta-analyses).

In order to examine the influence of each of the individual studies,we conducted a series of analyses in which each of the studies wasremoved, and the mean effect size of the remaining studies wascalculated. This allowed us to examine the influence of each individualstudy on the overall outcomes. Removal of the study by de Jong,Treiber, and Henrich (1986) resulted in the largest decrease of themean effect size (the resulting effect size was d=0.21); and removalof the study by Williams et al. (2000) resulted in the largest increaseof the effect size (d=0.30).

Neither the funnel plot nor Duval and Tweedie's trim and fillprocedure pointed to a significant publication bias. The mean effectsize did not change considerably after adjustment for possiblepublication bias (observed d=0.23; adjusted d=0.20; number ofimputed studies: 2).

Because of the small number of comparisons we conducted only themost basic subgroup analyses. We found no indications for a significantdifference between studies examining chronic MDD and thoseexamining double depression or dysthymia, nor between CBT andother psychological treatments, although there was a trend (p<0.1)indicating a possible difference between pill placebo control groups andother control groups (Table 2). These results should be considered withcaution, however, since the statistical power todetect suchdifferences isvery low because of the small number of studies in the subgroups.

e original studies): %♀; percentage women; %M: percentage married; ASPD: antisocialR: Brazil; C: country; CA: Canada; CBASP: Cognitive behavioral-analysis system ofsychotherapy for chronic depression; Clin: recruitment from clinical samples; Com:a; Frm: format; GAD: generalized anxiety disorder; GE: Germany; Grp: group format; I:Mn: mean; MDD: major depressive disorder; N: no subsample of larger study; NL:rder; PAN: panic disorder; PD: personality disorder; Pharm.: pharmacotherapy; PST:: subsample of larger study; SOCPHOB: social phobia; SST: social skills training; STPD:rger study; T: training of therapists; TQ: treatment quality; UK: United Kingdom; US:

disorders.sed to calculate effect sizes.

Table 2Meta-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 ofcomparisons; 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.

56 P. Cuijpers et al. / Clinical Psychology Review 30 (2010) 51–62

3.4. Psychological treatment versus pharmacotherapy

The effects of psychological treatments were directly comparedwith those of pharmacotherapy in ten comparisons. The mean effectsize was d=−0.31 (95% CI: −0.53 to −0.09), which indicates a

superior effect of pharmacotherapy (p<0.01), andwhich correspondswith an NNT of 5.75. Heterogeneitywasmoderate to high (I2=59.03).Again, we found no indication that multiple comparisons from onestudy influenced the effect size or heterogeneity, and the effect sizebased on the HAM-D was comparable to the overall effect size.

Fig. 1. Standardized effect sizes of psychological treatments of chronic depression and dysthymia at post-test.

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In the subgroup analyses we found a significant differencebetween studies in which SSRIs were used, compared to those inwhich TCAswere used (p<0.01), suggesting that especially SSRIs maybe more effective than psychotherapy in chronic depression anddysthymia. However, the seven studies in which SSRIs were examinedwere the same seven studies that were aimed at patients withdysthymia. We found that the seven studies aimed at patients withdysthymia differed significantly from the studies whichwere aimed atchronic or mixed samples. We did not find that type of psychotherapywas significantly associated with the effect size.

Removal of each of the individual studies from the analyses didnot indicate that one of the studies had a large impact on the meaneffect size (removal of the study by Ravindran and colleaguesresulted in the largest decrease of the effect size with d=0.24; andremoval of the study by Williams resulted in the largest increase ofthe effect size, with d=0.37). Neither the funnel plot nor Duval andTweedie's trim and fill procedure pointed at a significant publicationbias (the unadjusted and adjusted effect sizes were exactly thesame).

3.5. Pharmacotherapy versus combined treatment

In nine comparisons pharmacotherapy was compared to thecombination of pharmacotherapy and psychotherapy. The meaneffect size indicating the difference between these two types oftreatment was d=0.23 (95% CI: −0.01–0.47, p<0.1) in favor of thecombined treatment, which corresponds with an NNT of 7.69.Heterogeneity was moderate (I2=53.71). All comparisons originatedfrom different studies and there were no studies with two or morecomparisons. The effect size based on the HAM-D was somewhatlarger than the overall effect size (d=0.42; 95% CI: 0.27–0.58;p<0.001).

Subgroup analyses indicated a significant difference between theeffect sizes of studies examining different diagnostic populations,ranging from a negligible effect size for dysthymic patients to a largeeffect size for double depression (p<0.01). We also found a significantdifference between SSRIs and other pharmacotherapies (TCAs, or other)(p<0.001). However, the studies examining dysthymia patients wereagain the same studies that examined SSRIs. No significant differencesbetween types of psychotherapy were found.

Table 3Meta-analyses of studies examining the effects of psychological treatments on chronic dep

Study Ncomp d

▪ All studies 14 1.16▪ One ES per study (highest) 10 1.23▪ One ES per study (lowest) 10 1.09▪ Only HAM-D 6 1.68

Subgroup analyses▪ Diagnosis – Chronic MDD 3 1.30

– Double depression 2 1.49– Dysthymia 6 0.93– Mixed 3 1.30

▪ Psychologicaltreatment

– CBT 6 1.44– IPT 4 1.01– Other 4 0.98

▪ Target group – Adults 10 1.15– Specific target group 4 1.17

▪ Number ofsessions

– ≤12 sessions 3 0.93– 13–17 sessions 7 1.07– ≥18 session 4 1.58

▪ Analyses – Intention-to-treat 7 1.02– No intention-to-treat 7 1.27

▪ Format – Individual 11 1.09– Group/mixed 3 1.47

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 statistb The p-values in this column indicate whether the difference between the effect sizes in

Removal of each of the individual studies from the analysesindicated that the study by Keller et al. (2000) had a considerableimpact on the mean effect size. Removal of this study resulted in aconsiderable reduction of the mean effect size (to 0.08). Removal ofthe study by Browne and colleagues resulted in an increased meaneffect size (d=0.37). Results of the subgroup analyses are, therefore,probably affected considerably by these two studies.

Again, no indication for publication bias was found.

3.6. Other comparisons

We could examine only four comparisons in which psychother-apy was compared to the combination of pharmacotherapy andpsychotherapy. These four comparisons resulted in an effect size ofd=0.45 (95% CI: 0.20–0.70; p<0.001), in favor of the combinedtreatment. This corresponds to an NNT of 4.00. Heterogeneity wasmoderate (I2=50.90). The effect size based on the HAM-D wascomparable, although heterogeneity was zero. Because of the smallnumber of comparisons, we did not conduct further analyses.

In four studies, two different types of psychotherapy werecompared directly with each other. In three of these studies,interpersonal psychotherapy (IPT) was compared with anothertherapy. The mean effect size indicating the difference between IPTand other psychotherapies was small (d=0.15, n.s.).

3.7. Drop-out rates

We examined whether the relative risk of dropping out from anactive treatment was different in the psychological conditionscompared to the other conditions. However, we did not find thatthe drop-out rate in the psychological treatments differed signifi-cantly from the drop-out rate in the pharmacotherapy conditions(RR=0.97; 95% CI: 0.73–1.28; N=5; I2=0.50), nor did we find thatthe drop-out rate was significantly different in the psychologicalconditions compared to the combined treatments (RR=1.10; 95% CI:0.79–1.52; N=3; I2=0), or when the pharmacotherapies werecompared to the combined treatments (RR=0.82; 95% CI: 0.62–1.08; N=7; I2=0). However, because the number of comparisonswas small, the non-significant results can very well be related to a lack

ression: improvement from baseline to post-test.

95% CI Z I2a pb

0.86–1.45 7.77 ⁎⁎⁎ 72.96 ⁎⁎⁎

0.87–1.60 6.60 ⁎⁎⁎ 80.02 ⁎⁎⁎

0.74–1.45 5.99 ⁎⁎⁎ 79.54 ⁎⁎⁎

1.48–1.88 16.36 ⁎⁎⁎ 0

0.79–1.81 4.99 ⁎⁎⁎ 0 0.3400.73–2.25 3.84 ⁎⁎⁎ 13.770.65–1.21 6.53 ⁎⁎⁎ 49.880.65–1.95 3.90 ⁎⁎⁎ 70.62 ⁎

1.09–1.80 7.92 ⁎⁎⁎ 0 0.1200.78–1.23 8.63 ⁎⁎⁎ 00.24–1.71 2.59 ⁎⁎ 92.53 ⁎⁎⁎

0.80–1.50 6.44 ⁎⁎⁎ 79.95 ⁎⁎⁎ 0.7810.71–1.63 4.97 ⁎⁎⁎ 5.58 ns0.48–1.37 4.09 ⁎⁎⁎ 76.13 ⁎ 0.0450.79–1.34 7.55 ⁎⁎⁎ 01.20–1.96 8.15 ⁎⁎⁎ 21.73 ns0.74–1.30 7.09 ⁎⁎⁎ 0 0.3550.81–1.73 5.45 ⁎⁎⁎ 85.78 ⁎⁎⁎

0.75–1.42 6.36 ⁎⁎⁎ 78.03 ⁎⁎⁎ 0.1990.99–1.94 6.09 ⁎⁎⁎ 0

ics does not include a test of significance).the subgroups is significant.

59P. Cuijpers et al. / Clinical Psychology Review 30 (2010) 51–62

of statistical power and therefore these results have to be interpretedwith caution.

3.8. Improvement from baseline to post-test

We also calculated the effect sizes based on the improvement frombaseline to post-test in the groups in which the participants received apsychological treatment (combined treatments were not examined inthese analyses). These effect sizes indicate the difference between thedepression score at baseline and the score at post-test in those whoreceived psychotherapy. These analyses allowed us to get animpression of the improvement of patients from baseline to post-test. Furthermore, we could calculate these improvement rates for allstudies in which a psychotherapy condition was used (regardless ofthe comparison group). This resulted in a larger group of effect sizesthan we get from each of the more specific comparisons (psycho-therapy versus control group, psychotherapy versus pharmacother-apy, psychotherapy versus combined treatment). This larger numberof comparisons allows us to conduct more subgroup analyses, and toexplore possible sources of heterogeneity better.

We could calculate these effect sizes in 14 comparisons (Table 3).The mean effect size was 1.16 (95% CI: 0.86–1.45). Heterogeneity washigh (I2=72.96). Including only one comparison from each study didnot affect the effect size very much, nor did it result in a considerabledecrease of heterogeneity (Table 3).

We conducted a series of subgroup analyses (Table 3). As can beseen in Table 3, we found no indication for a significant differencebetween studies using different diagnostic categories, betweenstudies among adults in general and more specific target groups,between studies in which different types of psychological treatmentwere used, between an individual or group treatment format, norbetween studies in which the effect size was based on the intention-to-treat sample and studies in which no intention-to-treat analyseswere conducted. However, we did find that studies reporting a largernumber of treatment sessions resulted in larger effect sizes.

We decided to explore the association between the effect size andthe number of sessions in a meta-regression analysis. We found thatthis association was highly significant (slope: 0.038; 95% CI: 0.019–0.056; p<0.001), suggesting that each treatment session increasedthe effect size with 0.038 point. We have presented this associationgraphically in Fig. 2.

In most studies, the therapies consisted of 12 to 20 sessions. Onlytwo studies had a different number of sessions (in the study by Barrett

Fig. 2. Relation of effect size to number of treatment sessions in ps

et al. 6 sessions were used, while the study of de Jong et al. used morethan 30 sessions in both psychological treatment groups). Thereforewe repeated this analysis, while we included only the studies with 12to 20 sessions. However, this still resulted in a strong associationbetween effect size and number of sessions (slope: 0.060; 95% CI:0.019–0.102; p<0.01). Removing the possible outlier (Keller et al.,2000) reduced the strength of the association, but it was stillsignificant (slope: 0.022; 95% CI: 0.002–0.042; p<0.05).

We examine the influence of each of the individual studies, andfound that removal of the study by Keller et al. (2000) resulted in adecreasedmean effect size of 1.03, and removal of the study by Barrettand colleagues resulted in an increased effect size of 1.23.

4. Discussion

In this meta-analysis we found that psychotherapy for chronicmajor depression and dysthymia has a small but significant effect(d=0.23) on depression when compared to control groups. Whenpsychotherapy was directly compared with pharmacotherapy, it wasfound that pharmacotherapy was significantly more effective (d=−0.31). We also found an indication that especially SSRIs were moreeffective than psychotherapy. However, the studies in which SSRIswere examined were precisely the same studies that examineddysthymia patients. In the direct comparisons between psychother-apy and pharmacotherapy, the studies in dysthymia patients foundalso smaller effect sizes than studies in other groups of patients. Thisimplies that either SSRIs are indeed more effective or that psycho-therapy (as it was implemented in these studies) is less effective indysthymia patients. Unfortunately, it is not possible in the currentstudy, to establish which of these possibilities is responsible for ourfindings. However, in the studies in which pharmacotherapy wascompared to the combination of pharmacotherapy and psychother-apy, we also found few indications that the combined treatment wasmore effective than pharmacotherapy alone in dysthymia patients(while the combined treatmentwasmore effective in other diagnosticgroups). This supports the hypothesis that psychotherapy is lesseffective in dysthymia patients, or that the psychotherapies were notimplemented well enough in these studies. More research is neededto examine this issue.

We did find clear evidence from the comparisons betweenpharmacotherapy and combined treatments, that combined treat-ments resulted in a higher effect size than pharmacotherapy alone(d=0.23). Combined treatments were also found to be superior to

ychological 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 thatpsychotherapy reduced drop-out rates relative to pharmacotherapyeither alone or in combination.

Although the overall effect of psychotherapy for chronic depres-sion and dysthymia were small, we did find indications that the effectsize was associated with the number of treatment sessions. Theseresults suggested that each extra session increased the effect size with0.04. The results suggest that at least 18 sessions are needed forpsychotherapy to have an optimal effect.

How this relates to the literature on sudden gains duringpsychotherapy is not clear. This literature has found indications thatmost gains of psychotherapy for depression are realised during thefirst eight to ten sessions (Ilardi & Craighead, 1994; Tang, Derubeis,Hollon, Amsterdam, & Shelton, 2007) and in some cases as few asthree (Hopko, Robertson, & Carvalho, 2009). It could be possible thatin people with chronic depression this improvement is not realizedduring the first sessions, but only gradually during the therapy. Thiscould be related to the smaller effect sizes found for patients withchronic depression or dysthymia.

Our results suggest that psychotherapy may be less effective inchronic depression and especially in dysthymia than it is in non-chronic depressive disorders. Meta-analyses of psychotherapies fornon-chronic depression typically find large effects relative to wait listand minimal treatment controls (effect sizes ranging from 0.70 to0.90) (Churchill et al., 2001; Cuijpers, van Straten, Andersson, et al.,2008; Cuijpers, van Straten, van Oppen, et al., 2008; Cuijpers, vanStraten, Warmerdam, & Andersson, 2008; Cuijpers, van Straten,Warmerdam, & Smits, 2008), with pill placebo control groupsresulting in smaller effect sizes (d=0.36).

It may be possible that this smaller overall effect size was aconsequence of psychotherapy not being implemented well in thesestudies as it was in the non-chronic depression literature. This alsocould explain the rather puzzling difference between studies ondysthymia and other types of chronic depression. However, there isno particular reason to assume that psychotherapy was poorlyimplemented in these trials and most of the relevant studies adheredto the criteria for quality implementation laid out by Chambless andHollon (1998). Most studies used a treatment manual, in almost allstudies the therapists were trained, and in most studies the integrityof the treatment was checked. Still, it is not clear that adhering tothese criteria will necessarily ensure that treatment is adequatelyimplemented and few of the studies were conducted by groups withrecognized expertise in the implementation of the treatments thatthey tested.

We found no indication that the drop-out rates were lower inpsychotherapy than in pharmacotherapy. This is in contrast with theresults of earlier meta-analyses (Cuijpers, van Straten, Andersson,et al., 2008; Cuijpers, van Straten, van Oppen, et al., 2008; Cuijpers,van Straten, Warmerdam, & Andersson, 2008; Cuijpers, van Straten,Warmerdam, & Smits, 2008; Cuijpers et al., 2009), in which we foundclear indications that the drop-out rate in psychotherapy wassignificantly lower than in pharmacotherapy. However, these earliermeta-analyses examined studies on all types of depressive disorders.It is very well possible that patients with chronic types of depressionhave had several types of treatment and are now willing to try andcomplete any new type of treatment, as long as there is a chance ofimprovement. However, it is also known that some individuals withchronic depression and dysthymia first seek treatment after severalyears (Kessler, Merikangas, & Wang, 2007), and may not have ahistory of any completed treatment.

This study has several limitations. First, the number of studies inmost comparisonswas small, andwewerenot able to conduct elaboratesubgroup analyses to examine possible differences between subgroupsand the causes of heterogeneity. Furthermore, there were considerabledifferences between the included studies, which may have causedheterogeneity. Not only did the studies differ in terms of the

psychotherapies examined, but also in terms of excluded and includedcomorbidity, demographic and other characteristics of the samples.These differences may limit the generalizability of our findings to allpatient groups. A third important limitation was that it was not clear inmost studies whether the patients included had been treatedunsuccessfully before they entered the study. A fourth limitation isthat in our analyses, SSRI treatment was confounded by diagnosis (thestudies using SSRIs were exactly the same as the studies examiningdysthymia). Consequences of this have been described above. A finallimitation is that the quality of several included studieswas not optimal.As indicated earlier, the study by Keller et al. (2000) is the largest andmost influential study in this field. This studymet all our quality criteriaand found a relative high improvement rate compared to several otherstudies. Because of the large sample size, this study had also aconsiderable impact on the mean effect sizes in several comparisons.These results suggest that the study by Keller et al. may be moreexemplary of the possible effects of psychotherapy thanwe found in ourmeta-analysis, and that psychotherapy may potentially have highereffect sizes than we found.

Despite limitations of this meta-analysis, evidence is convincingthat psychotherapy has a significant effect on chronic depression anddysthymia. Furthermore, combined treatments of psychotherapy andpharmacotherapy are more effective than each of the treatmentsalone. Given the chronic nature of the disorders, treatment guidelinesshould recommend that combined treatments for chronic majordepression should be used (Fochtmann & Gelenberg, 2005; NICE,2007; RANZCP, 2004). However, the added value of psychotherapy fordysthymia has not been convincingly shown, and it may currently notbe advised on the available evidence to use psychotherapy as astandalone treatment in this group of patients.

More research in the area of psychotherapy for chronic depressionand dysthymia is certainly needed. Quality of the studies included inthis meta-analysis was not optimal, and more high-quality studies areneeded. Such studies should give specific attention to importantquality criteria, such as adequate randomization procedures, blindingof assessors, and the inclusion of all randomized respondents in thefinal analyses. More research is needed to examine how the contentsof psychotherapies should be adapted for this group of patients.Although some treatments for chronic depression are available, it isnot clear what specific components are especially important for thisgroup of patients. It is also important to examine why research seemsto indicate that psychotherapy is less effective in dysthymia. It seemsunlikely that dysthymia is very different from other types of chronicmajor depression (Klein et al., 2006), and more research is needed toexamine whether psychotherapy for dysthymia and other forms ofchronic depression should indeed be different.

This meta-analysis has made it clear that psychotherapy has asignificant effect on chronic depression and dysthymia, and althoughthese effects are small, any help in improving chronic depression isrelevant from a clinical perspective.

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