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The Efficacy of Cognitive-Behavioral Therapy and Psychodynamic Therapy in the Outpatient Treatment of Major Depression: A Randomized Clinical Trial
Ellen Driessen, Ph.D.; Henricus L. Van, M.D., Ph.D.; Frank J. Don, M.Sc.; Jaap Peen, Ph.D.; Simone Kool, M.D., Ph.D.; Dieuwertje Westra, M.Sc.; Mariëlle Hendriksen, M.Sc.; Robert A. Schoevers, M.D., Ph.D.; Pim Cuijpers, Ph.D.; Jos W.R. Twisk, Ph.D.; Jack J.M. Dekker, Ph.D.
Am J Psychiatry 2013;170:1041-1050. doi:10.1176/appi.ajp.2013.12070899
View Author and Article Information

Preliminary results presented at the annual meeting of the Dutch Association of Psychiatry, Amsterdam, March 31, 2011, and the annual meeting of the Society for Psychotherapy Research, Bern, Switzerland, June 30, 2011.

Dr. Van and Ms. Hendriksen have received training fees from RINO, Amsterdam, and VU University, Amsterdam, and Dr. Van is president of the Dutch Association of Psychoanalytic Psychotherapy. Mr. Don has served on the board of the mood disorders section of the Dutch Association of Cognitive and Behavior Therapy, and he receives royalties from Springer Media. Dr. Dekker receives royalties from Springer Media. All other authors report no financial relationships with commercial interests.

Supported by an unrestricted research grant from Wyeth Pharmaceuticals, the Netherlands; by research logistics grants and other research grants from Arkin Mental Health Care, Amsterdam (to Drs. Driessen, Van, Peen, Kool, Schoevers, and Dekker and Mr. Don, Ms. Westra, and Ms. Hendriksen); by a research grant from ProPersona Mental Health Care (to Mr. Don); and by research grants from the Faculty of Psychology and Education, Department of Clinical Psychology, VU University, Amsterdam (to Drs. Driessen and Cuijpers). The authors thank all of the patients, therapists, supervisors, and research assistants who participated in this study. The authors also thank W. van den Brink, M.D., Ph.D. (Amsterdam Institute for Addiction Research, Academic Medical Center, University of Amsterdam) and S.D. Hollon, Ph.D. (Vanderbilt University, Nashville) for their editorial assistance.

Current Controlled Trials identifier: ISRCTN31263312 (http://www.controlled-trials.com).

From Arkin Mental Health Care, Amsterdam; the Departments of Clinical Psychology and Health Sciences, VU University, Amsterdam; EMGO Institute for Health and Care Research, VU University and VU University Medical Center, Amsterdam; ProPersona Mental Health, Ede, the Netherlands; Department of Psychiatry, University Medical Center Groningen, the Netherlands; and the Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam.

Address correspondence to Dr. Driessen (e.driessen@vu.nl).

Copyright © 2013 by the American Psychiatric Association

Received July 11, 2012; Revised October 24, 2012; Revised March 21, 2013; Accepted April 15, 2013.

Abstract

Objective  The efficacy of psychodynamic therapies for depression remains open to debate because of a paucity of high-quality studies. The authors compared the efficacy of psychodynamic therapy with that of cognitive-behavioral therapy (CBT), hypothesizing nonsignificant differences and the noninferiority of psychodynamic therapy relative to CBT.

Method  A total of 341 adults who met DSM-IV criteria for a major depressive episode and had Hamilton Depression Rating Scale (HAM-D) scores ≥14 were randomly assigned to 16 sessions of individual manualized CBT or short-term psychodynamic supportive therapy. Severely depressed patients (HAM-D score >24) also received antidepressant medication according to protocol. The primary outcome measure was posttreatment remission rate (HAM-D score ≤7). Secondary outcome measures included mean posttreatment HAM-D score and patient-rated depression score and 1-year follow-up outcomes. Data were analyzed with generalized estimating equations and mixed-model analyses using intent-to-treat samples. Noninferiority margins were prespecified as an odds ratio of 0.49 for remission rates and a Cohen’s d value of 0.30 for continuous outcome measures.

Results  No statistically significant treatment differences were found for any of the outcome measures. The average posttreatment remission rate was 22.7%. Noninferiority was shown for posttreatment HAM-D and patient-rated depression scores but could not be demonstrated for posttreatment remission rates or any of the follow-up measures.

Conclusions  The findings extend the evidence base of psychodynamic therapy for depression but also indicate that time-limited treatment is insufficient for a substantial number of patients encountered in psychiatric outpatient clinics.

Abstract Teaser
Figures in this Article

Major depressive disorder is a highly prevalent mental disorder, substantially debilitating patients and imposing a tremendous financial burden on society (1, 2). Patients seeking treatment for depression typically are offered antidepressant medication or psychotherapy alone or in combination (3). Given that antidepressants may not be as specifically efficacious as was previously believed (46), treatment guidelines increasingly advocate the option of psychotherapy for mild to moderate depression (7, 8).

However, efficacy research with respect to psychotherapy for depression needs to be broadened for two reasons. First, the efficacy of psychodynamic therapy remains controversial because of a lack of adequately conducted trials (710). Second, while different psychotherapeutic approaches for depression are considered equally efficacious by many (11), high-quality studies directly comparing psychotherapies for depression are rare (12), and the literature is dominated by superiority trials designed to show significant differences between conditions, which cannot demonstrate equal efficacy (13).

We report the results of a randomized clinical trial comparing psychodynamic therapy with cognitive-behavioral therapy (CBT) in patients seeking treatment for a major depressive episode in psychiatric outpatient clinics (the study protocol was described previously [14]). We first examined whether treatment outcomes differed significantly, and in case of nonsignificant differences, we examined whether psychodynamic therapy was noninferior to CBT. We hypothesized that there would be 1) no significant differences between the modalities at the posttreatment assessment and 1-year follow-up and 2) noninferiority of psychodynamic therapy relative to CBT at the posttreatment assessment and 1-year follow-up.

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Design

This study was a randomized clinical trial with an allocation ratio of 1:1 for CBT and psychodynamic therapy. The study design was approved by the Dutch Union of Medical Ethics Trial Committees for mental health organizations.

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Participants

Participants were referred by their general practitioner to one of three psychiatric outpatient clinics in Amsterdam. Inclusion criteria were presence of a major depressive episode according to DSM-IV criteria, as assessed with the Mini-International Neuropsychiatric Interview–Plus (15); a Hamilton Depression Rating Scale (HAM-D [16]) score ≥14; age 18–65 years; and written informed consent after receiving a complete description of the study.

Exclusion criteria included presence of psychotic symptoms or bipolar disorder, severe suicidality warranting immediate intensive treatment or hospitalization, substance misuse or abuse in the past 6 months, pregnancy, inability to meet trial demands, and use of psychotropic or other medications that might influence mental functions. Patients on an antidepressant regimen were included only if the medication they were currently taking was judged to be inefficacious by both the patient and the intake psychiatrist. If so, the medication was tapered off under medical supervision, and baseline assessment took place after a washout period of at least 1 week after the medication was completely stopped (16/25 of these patients subsequently restarted medication during the study).

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Interventions

Both psychotherapies comprised 16 individual sessions within 22 weeks and were conducted according to published treatment manuals (17, 18). Additionally, both were suitable for application in a broad group of patients, including those of a non-Northwest European (immigrant) cultural background. CBT was based on the principles described by Beck (19) and included behavioral activation and cognitive restructuring according to a session-by-session protocol with homework assignments. Short-term psychodynamic supportive psychotherapy (18, 2024) was used to represent the psychodynamic intervention. This modality involved an open patient-therapist dialogue that used supportive and insight-facilitating techniques to address the emotional background of the depressive symptoms by discussing current relationships, internalized past relationships, and intrapersonal patterns.

Psychotherapists in both treatment conditions were psychiatrists or psychologists with at least a master’s degree who completed either a 3-day course in short-term psychodynamic supportive psychotherapy or a 100-hour basic CBT training course accredited by the Dutch Association for Behavioral and Cognitive Therapy. Moreover, all therapists adequately conducted at least one intensively supervised therapy case in accordance with the relevant treatment manual as judged by a study supervisor. Although no formal assessments were conducted, manual fidelity was checked by means of biweekly supervision sessions, chaired by a study supervisor, in which audiotaped material was discussed. All study supervisors were registered supervisors with either the Dutch Association of Psychoanalytic Psychotherapy (one supervisor was in training) or the Dutch Association for Behavioral and Cognitive Therapy. Differences in the mean number of years that the supervisors had been conducting their respective modalities were minimal (CBT, 10.9 years [SD=11.0]; psychodynamic therapy, 9.7 years [SD=2.9]) but somewhat larger with respect to mean years conducting supervision (CBT, 14.6 years [SD=10.3]; psychodynamic therapy, 6.3 years [SD=3.2]), although neither difference was significant.

Thirty-seven CBT therapists and 56 psychodynamic therapists treated, on average, 4.2 patients (range, 1–16) and 3.0 patients (range, 1–12), respectively. No differences between treatment conditions were found with regard to the average number of times a patient was discussed in supervision (CBT, 4.3; psychodynamic therapy, 4.6) or the mean number of therapy sessions patients received (CBT, 10.6; psychodynamic therapy, 10.9; mean numbers are lower than the maximum of 16 because of premature termination, dropout, and patients missing sessions). Regarding therapist protocol adherence, CBT therapists reported a mean score of 7.1 (scale range, 0–10) over 1,218 CBT sessions. Conditions did not differ regarding the mean number of years of clinical experience therapists had after completing their master’s degree or medical degree (CBT, 7.5 years [SD=7.3]; psychodynamic therapy, 7.4 years [SD=6.7]), but CBT was more often conducted by psychologists, and psychodynamic therapy was more often conducted by psychiatrists (χ2=109.80, df=1, p<0.001). Furthermore, CBT was conducted more often by a female therapist than was psychodynamic therapy (χ2=15.91, df=1, p<0.001). We therefore conducted a sensitivity analysis controlling for therapist gender and profession (psychologist, psychiatrist).

Patients with severe depression (HAM-D score >24) at baseline (N=129) and those with moderate depression at baseline who developed severe symptoms during psychotherapy monotherapy (N=21) were offered additional antidepressant medication administrated by a psychiatrist (who was not the patient’s psychotherapist) according to a protocol starting with extended-release venlafaxine at 75 mg/day, which could be increased to a maximum dosage of 225 mg/day. In case of intolerance or nonresponse, venlafaxine was switched to either citalopram or nortriptyline. Pharmacotherapy consultations addressed symptom evaluation, side effects, and adherence. Three research psychiatrists supervised pharmacotherapy.

Eight patients (6.2%) did not start the recommended pharmacotherapy, and 14 (10.8%) switched medication during treatment. The number of patients not starting pharmacotherapy, the pharmacotherapy dosages used, and patient-reported medication adherence did not differ significantly between treatment conditions.

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Outcome Measures

The primary outcome measure was posttreatment remission rate (HAM-D score ≤7). Secondary outcome measures included 1-year follow-up remission rates and posttreatment and follow-up observer-rated (HAM-D) and patient-rated mean depression scores (Inventory of Depressive Symptomatology–Self-Report [IDS-SR] [25]).

Trained research assistants (master’s-level graduate students in clinical psychology) assessed the HAM-D according to the Dutch scoring manual (26). Assessors participated in biweekly 1-hour peer supervision sessions, in which audiotaped interviews were discussed. The average intraclass correlation coefficient over 46 audiotaped assessments scored by multiple assessors was 0.97. Both observer- and patient-rated depression measures showed good reliability at baseline assessment (Cronbach’s alpha: observer-rated, 0.75; patient-rated, 0.78). HAM-D assessors were not blind to treatment condition. We therefore requested the assessors’ hypotheses regarding treatment effects at the posttreatment and follow-up assessments and conducted a sensitivity analysis controlling for these variables.

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Randomization

Separate random allocation sequences were generated for each of the three clinics by one of the authors (J.P.) using the SPSS random number generator (SPSS, Chicago). Randomization was stratified by gender and age (<32.5 years and >32.5 years). Research assistants, aware of the allocation sequence, enrolled participants and assigned them to interventions.

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Statistical Methods

Analyses were based on an intent-to-treat sample, including all patients randomly assigned. Patients were considered dropouts if they completed less than eight psychotherapy sessions. Response was defined as a reduction in HAM-D scores ≥50% at posttreatment.

Given the hierarchical data structure, linear mixed-model analyses were used for continuous outcomes, and logistic generalized estimating equation analyses were used for dichotomous outcomes. These analyses were preferred over logistic mixed-model analyses because of the instability of the latter (27). In examining pre- to posttreatment outcomes, we excluded follow-up data (for which additional help-seeking could not be controlled) from the analyses. Mixed-model analyses were conducted according to a three-level structure (therapist, patient, and repeated measures). Location (clinic) was included as a covariate in a sensitivity analysis, rather than as a level because of the small number of categories (N=3). Mixed-model analyses were performed with MLwiN, version 2.22 (http://www.bristol.ac.uk/cmm/software/mlwin). All other analyses were performed with SPSS, version 16.0.

We started with a basic model including main effects for treatment and time and a time-by-treatment interaction. Time was treated as a categorical variable to assess treatment effects at the different time points. To control for possible confounders, we next added the following sets of covariates: 1) clinic and number of patients with a baseline HAM-D score >24; 2) demographic characteristics (as listed in Table 1); 3) depression characteristics (as listed in Table 1); 4) therapist gender and profession; 5) the HAM-D assessors’ treatment outcome hypotheses; and 6) help-seeking during the follow-up period (as reported in Table S1 in the data supplement that accompanies the online edition of this article). The estimated main effects for treatment at different assessment points under these different models are reported as odds ratios with 95% confidence intervals for remission rates and differences in means for continuous outcomes. For the latter, we also calculated effect sizes (Cohen’s d) and 95% confidence intervals using Comprehensive Meta-Analysis, version 2.2.046 (Biostat, Englewood, N.J.).

 
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TABLE 1.Baseline Demographic and Clinical Characteristics of Participants in a Study of the Efficacy of Psychodynamic Therapy Relative to Cognitive-Behavioral Therapya
Table Footer Note

a CBT=cognitive-behavioral therapy; HAM-D=Hamilton Depression Rating Scale.

Table Footer Note

b Comorbid axis I disorders were assessed by the psychotherapists during treatment without the use of a structured interview, and comorbidity rates may therefore be underestimated.

We then used a two-step strategy for the interpretation of outcomes. First, we examined whether treatment outcomes differed significantly. We considered treatment differences to be nonsignificant if the 95% confidence interval included 1.00 or 0.00 for odds ratios and effect sizes, respectively. This constituted our primary research question. Second, when differences were nonsignificant, we next examined whether psychodynamic therapy was noninferior to CBT by comparing outcomes to prespecified noninferiority margins. These margins were determined based on the expert opinion of 10 experienced depression research clinicians (unaware of preliminary trial results) who rated a difference of 10% for remission rates and 2.6 HAM-D points (equivalent to a Cohen’s d value of 0.30) as the maximum difference allowable to conclude noninferiority. Based on a maximum difference of 10% (remission rates of 12% and 22%), noninferiority margins for remission were set at an odds ratio of 0.49. For all continuous outcome measures, noninferiority margins were prespecified at a Cohen’s d value of 0.30. We compared the 95% confidence intervals of the effect sizes and odds ratios with the above-mentioned prespecified noninferiority margins and considered psychodynamic therapy noninferior to CBT on a given outcome measure if the 95% confidence interval limit did not exceed the prespecified noninferiority margin for that measure. This constituted our secondary research question. We repeated the main analyses in the subgroup of moderately depressed patients (HAM-D score ≤24) receiving psychotherapy only and in the subgroup of severely depressed patients (HAM-D score >24) receiving combined psychotherapy and pharmacotherapy in order to investigate whether pooling these subgroups may have obscured differential patterns of results.

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Power Analysis

An a priori power analysis (14) indicated that 300 participants were required (alpha=0.05, 1−β=0.80) to answer our primary research question. To detect the 10% difference in remission rates between conditions that constituted the noninferiority margin (alpha=0.05, 1−β=0.80), 344 participants were needed (using SPSS SamplePower for equivalence studies, one-tailed). Power to detect an outcome difference of a Cohen’s d value of 0.30 for continuous outcome measures was 0.87.

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Participants

The CONSORT diagram for the study is presented in Figure 1. From April 2006 to December 2009, 4,866 patients were assessed for eligibility during a standard intake procedure; 570 (11.7%) were found to be potentially eligible and invited for baseline assessment. Of these patients, 229 (40.2%) did not meet inclusion criteria or were not willing to participate. Therefore, 341 patients were randomly assigned to CBT (N=164) or psychodynamic therapy (N=177). Demographic and clinical characteristics of the sample are summarized in Table 1. No significant differences were found between the two treatment conditions.

 
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FIGURE 1.CONSORT Diagram of Participants in a Study of the Efficacy of Psychodynamic Therapy Relative to Cognitive-Behavioral Therapya

a CBT=cognitive-behavioral therapy; HAM-D=Hamilton Depression Rating Scale; MINI-Plus=Mini-International Neuropsychiatric Interview–Plus.

No significant differences were found between treatment conditions regarding the proportion of patients who did not complete treatment (CBT, 31.1%; psychodynamic therapy, 25.9%). The majority of patients who dropped out were those who missed treatment appointments without specifying a reason (53.9%). Recruitment was discontinued when the intended number of participants was reached. One-year follow-up assessments were conducted from April 2007 to January 2011.

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Posttreatment Outcomes

Based on observed data, 24.3% (N=27/111) of the patients in the CBT condition and 21.3% (N=26/122) in the psychodynamic therapy condition met the remission criterion at the posttreatment assessment. Observed response rates were 38.7% (N=43/111) for CBT and 36.9% (N=45/122) for psychodynamic therapy. Estimated odds ratios for remission at different assessment points are listed in Table 2. At the posttreatment assessment, the odds ratio was 0.82 (95% CI=0.45–1.50), indicating that remission rates did not differ significantly. The lower limit of the odds ratio’s 95% confidence interval exceeded the prespecified noninferiority margin of 0.49. This pattern of results did not change when different sets of covariates were added (Table 2).

 
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TABLE 2.Treatment Effects at Different Assessment Points According to the Basic Model of Analysis and When Corrected for Different Sets of Covariatesa
Table Footer Note

a HAM-D=Hamilton Depression Rating Scale; IDS-SR=Inventory of Depressive Symptomatology–Self Report. Model 1 is the basic model including a main effect for treatment and time and a time-by-treatment interaction; model 2 is the basic model with clinic and number of patients with baseline HAM-D scores >24 added as covariates; model 3 is the basic model with demographic characteristics (as listed in Table 1) added as covariates; model 4 is the basic model with depression characteristics (as listed in Table 1) added as covariates; model 5 is the basic model with therapist gender and profession added as covariates; and model 6 is the basic model with HAM-D assessors' hypotheses regarding treatment outcomes added as a covariate.

Mean observer- and patient-rated depression scores during treatment for both groups are presented in Figure 2; depressive symptom scores in both conditions improved over time. Estimated observer- and patient-rated mean differences at different assessment points are presented in Table 2, along with effect sizes of the posttreatment differences between conditions. At week 22, the estimated observer-rated difference between treatment conditions was 0.24 points (SE=0.90) on the HAM-D, corresponding with an effect size (Cohen’s d) of 0.02 (95% CI=−0.24 to 0.27), indicating that treatment differences were nonsignificant. The estimated patient-rated difference between treatment conditions was 1.94 points (SE=1.92) on the IDS-SR, corresponding with an effect size of −0.08 (95% CI=−0.38 to 0.22), also indicating that differences were not significant. The upper limits of the 95% confidence intervals for both effect sizes did not exceed the prespecified noninferiority margin of 0.30. This pattern of results did not change when controlling for different covariates, although the noninferiority margin was slightly exceeded when controlling for clinic and number of patients with baseline HAM-D scores >24 (HAM-D estimated mean difference=0.64 [SE=0.81]; Cohen’s d=0.05, 95% CI=−0.21 to 0.31).

 
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FIGURE 2.Observer-Rated and Patient-Rated Mean Depression Scores During Treatmenta

a CBT=cognitive-behavioral therapy; HAM-D=Hamilton Depression Rating Scale; IDS-SR=Inventory of Depressive Symptomatology–Self Report.

In the moderately depressed subgroup, observed remission rates for CBT and psychodynamic therapy were 26.5% (N=18/68) and 27.7% (N=23/83), respectively, with estimated odds ratios (1.02, 95% CI=0.50–2.06), observer ratings (Cohen’s d=–0.05, 95% CI=–0.37 to 0.27), and patient ratings (Cohen’s d=–0.24, 95% CI=–0.61 to 0.13) all indicating that psychodynamic therapy was noninferior to CBT. In the severely depressed subgroup receiving additional pharmacotherapy, observed remission rates for CBT and psychodynamic therapy were 20.9% (N=9/43) and 7.7% (N=3/39), respectively, with estimated odds ratios (0.31, 95% CI=0.08–1.26), observer ratings (Cohen’s d=0.21, 95% CI=–0.23 to 0.64), and patient ratings (Cohen’s d=0.17, 95% CI=–0.35 to 0.69) all indicating no significant differences, without demonstrating noninferiority of psychodynamic therapy relative to CBT.

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Follow-Up Outcomes

Follow-up assessments were conducted with 192 (56.3%) participants (Figure 1). More patients reported having received additional treatment during the follow-up period in the CBT condition (N=41 [44.6%]) than in the psychodynamic therapy condition (N=32 [33.0%]), but this difference did not reach significance (χ2=2.67, df=1, p=0.10) (see Table S1 in the online data supplement).

Based on observed data, 34.7% (N=33/95) of patients in the CBT condition and 26.8% (N=26/97) of those in the psychodynamic therapy condition met the remission criterion. The estimated odds ratio of remission rates at follow-up was 0.74 (95% CI=0.41–1.34) (Table 3), indicating that remission rates did not differ significantly. The lower limit of the odds ratio’s 95% confidence interval exceeded the prespecified noninferiority margin of 0.49. This pattern of results did not change when different sets of covariates were added.

 
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TABLE 3.Follow-Up Outcomes According to the Basic Model of Analysis and When Corrected for Different Sets of Covariatesa
Table Footer Note

a HAM-D=Hamilton Depression Rating Scale; IDS-SR=Inventory of Depressive Symptomatology–Self Report. Model 1 is the basic model including a treatment and time main effect and a time-by-treatment interaction; model 2 is the basic model with clinic and number of patients with baseline HAM-D scores >24 added as covariates; model 3 is the basic model with demographic characteristics (as listed in Table 1) added as covariates; model 4 is the basic model with depression characteristics (as listed in Table 1) added as covariates; model 5 is the basic model with therapist gender and profession added as covariates; model 6 is the basic model with HAM-D assessors' hypotheses regarding treatment outcomes added as a covariate; and model 7 is the basic model with patient-reported treatments in the follow-up period added as a covariate.

Estimated observer- and patient-rated mean differences at follow-up and corresponding effect sizes are presented in Table 3. The estimated observer-rated difference between treatment conditions was 1.94 points (SE=1.01) on the HAM-D (Cohen’s d=0.14, 95% CI=−0.14 to 0.42), and the estimated patient-rated difference was 2.99 points (SE=2.22) on the IDS-SR (Cohen’s d=0.12, 95% CI=−0.23 to 0.48), both indicating that treatment differences were not significant. The upper limits of the 95% confidence intervals for both effect sizes exceeded the prespecified noninferiority margin of 0.30. This pattern of results did not change when controlling for different covariates.

In the moderately depressed subgroup, observed remission rates were 40.0% (N=22/55) in the CBT condition and 35.4% (N=23/65) in the psychodynamic therapy condition (odds ratio=0.84, 95% CI=0.41–1.73; observer rated: Cohen’s d=0.08, 95% CI=−0.28 to 0.44; patient rated: Cohen’s d=0.02, 95% CI=−0.40 to 0.45). In the severely depressed subgroup receiving additional pharmacotherapy, observed remission rates were 27.5% (N=11/40) for CBT and 9.4% (N=3/32) for psychodynamic therapy (odds ratio=0.27, 95% CI=0.07–1.08; observer rated: Cohen’s d=0.32, 95% CI=−0.15 to 0.79; patient rated: Cohen’s d=0.40, 95% CI=−0.27 to 1.07). All these differences were nonsignificant, but noninferiority could not be demonstrated for any of them.

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Adverse Events

Serious adverse events during treatment and follow-up were mostly increases in depressive symptoms or suicidality for which additional treatment was needed (see Table S2 in the online data supplement). No differences were found between the treatment conditions with regard to the proportion of patients reporting serious adverse events during treatment (CBT, 6.1%; psychodynamic therapy, 6.2%) or follow-up (CBT, 1.8%; psychodynamic therapy, 2.3%).

We used a randomized clinical design and noninferiority margins to compare the efficacy of CBT and psychodynamic therapy for major depression in a large sample of patients treated in psychiatric outpatient clinics. Primary analyses indicated no significant differences between treatment conditions at the posttreatment assessment. In secondary analyses, noninferiority could not be demonstrated for posttreatment remission rates but was demonstrated for posttreatment patient- and observer-rated depression scores. Follow-up findings again showed no significant differences between treatments, but noninferiority could not be demonstrated for any of the three outcome measures. However, the follow-up findings must be interpreted with caution because of a nonsignificant result suggesting that patients in the CBT condition received more additional treatment during the follow-up period. Our findings are in line with previous meta-analyses (9, 11, 28) that reported no significant differences between individual CBT and psychodynamic therapy at posttreatment assessments.

Post hoc analyses revealed no significant differences between treatment conditions in the subgroup of moderately depressed patients receiving psychotherapy only, and noninferiority of psychodynamic therapy relative to CBT was shown for all posttreatment outcome measures in this group of patients. These findings add to the evidence base of psychodynamic therapy for depression. No significant differences between treatments were found in the subgroup of severely depressed patients receiving combined treatment, but differences were large enough to be significant if replicated in a larger sample, and noninferiority could not be concluded in this group.

One notable finding was that only 22.7% of the patients achieved remission at posttreatment, with 40% seeking additional treatment afterward. These remission rates are lower than those found in previous trials examining either short-term psychodynamic supportive psychotherapy (22) or CBT (29, 30). This difference may be related to the relatively low socioeconomic status and income levels in our sample, which in naturalistic studies have been identified as predictors for less favorable treatment response (31, 32), or to the relatively high rate of comorbid axis I disorders. Our findings indicate that a substantial proportion of patients in specialized second-line outpatient clinics require more than time-limited treatment to achieve remission. These results are in line with findings regarding psychotherapy in real-world clinical practice (33) and show that depression as it is encountered in secondary care can be characterized as a difficult-to-treat disorder. Since residual depressive symptoms have been found to be the main predictor of future relapse (34), our findings also indicate that psychotherapeutic treatment needs to be improved. The findings suggest that clinicians and policymakers should be realistic about the expected outcome of time-limited depression treatments and should bear in mind that mandated limits on treatment duration may lead to undertreatment of depression.

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Strengths and Limitations

This study has a number of strengths. First, several elements contribute to the generalizability of the study’s findings. Treatment was provided in regular psychiatric outpatient clinics by a large number of therapists with different experience levels. Patients were not recruited by advertisement but instead were referred by general practitioners, and no selection criteria with regard to previous treatment or suitability for psychotherapy were applied. Patients with relatively low socioeconomic status were included, and almost one-half of the patient sample reported a non-Northwest European (immigrant) cultural background. Second, we included severely depressed patients who were additionally treated with pharmacotherapy prescribed according to a protocol. Third, this is, to our knowledge, the largest randomized controlled trial to date comparing CBT and psychodynamic therapy in the treatment of depression (N=341). By comparison, a meta-analysis of psychodynamic therapy for depression included a total of 421 patients across six CBT-psychodynamic randomized controlled trials (9). Finally, this was the first study to test whether psychodynamic therapy can be demonstrated to be noninferior to CBT in the treatment of depression.

This study also has a number of limitations. First, a substantial number of patients did not complete treatment or were lost to assessment. Second, treatment fidelity was not systematically assessed but was instead checked by means of intensive supervision by experienced supervisors and subjective therapist ratings. These ratings suggested adequate adherence to the CBT manual, but no such measure was available for psychodynamic treatment. Third, HAM-D assessors were not blind to treatment condition, and therefore we cannot rule out observer bias. However, controlling for assessor-rated treatment expectations did not alter the pattern of results, and results were similar for observer- and patient-rated outcomes. Fourth, research assistants enrolling participants were aware of the allocation sequence, which may have introduced selection bias. However, no significant differences were found with regard to any of the sample baseline characteristics. Fifth, although noninferiority margins were carefully thought through and based on clinical expert opinion, they were still set in an arbitrary fashion. Sixth, we could not prevent patients from seeking additional treatment during the follow-up period, and a nonsignificant finding suggested that patients in the CBT group may have returned to treatment more than those in the psychodynamic therapy group. However, controlling for additional treatment in the follow-up period did not change the general pattern of results. Finally, the study did not include a control condition.

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Conclusions

No statistically significant differences were found between psychodynamic therapy and CBT in a large sample of patients treated for a major depressive episode, and less than one-fourth of the patients reached remission within 22 weeks of treatment. Noninferiority of psychodynamic therapy relative to CBT was demonstrated for posttreatment mean depression scores but could not be demonstrated for remission rates and follow-up measures. Our findings extend the evidence base of psychodynamic therapy for depression but also indicate that time-limited psychotherapy is not sufficient for a substantial number of patients encountered in psychiatric outpatient clinics.

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Kirsch  I;  Deacon  BJ;  Huedo-Medina  TB;  Scoboria  A;  Moore  TJ;  Johnson  BT:  Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration.  PLoS Med 2008; 5:e45
[CrossRef] | [PubMed]
 
American Psychiatric Association:  Practice Guideline for the Treatment of Major Depressive Disorder, 3rd ed .  Washington, DC,  American Psychiatric Publishing, 2010
 
National Institute for Health and Care Excellence (NICE): Clinical Guideline 91–Depression: The Treatment and Management of Depression in Adults (update). London, NICE, 2010. http://guidance.nice.org.uk/CG90/
 
Driessen  E;  Cuijpers  P;  de Maat  SCM;  Abbass  AA;  de Jonghe  F;  Dekker  JJM:  The efficacy of short-term psychodynamic psychotherapy for depression: a meta-analysis.  Clin Psychol Rev 2010; 30:25–36
[CrossRef] | [PubMed]
 
Gerber  AJ;  Kocsis  JH;  Milrod  BL;  Roose  SP;  Barber  JP;  Thase  ME;  Perkins  P;  Leon  AC:  A quality-based review of randomized controlled trials of psychodynamic psychotherapy.  Am J Psychiatry 2011; 168:19–28
[CrossRef] | [PubMed]
 
Cuijpers  P;  van Straten  A;  Andersson  G;  van Oppen  P:  Psychotherapy for depression in adults: a meta-analysis of comparative outcome studies.  J Consult Clin Psychol 2008; 76:909–922
[CrossRef] | [PubMed]
 
Weissman  MM:  Cognitive therapy and interpersonal psychotherapy: 30 years later.  Am J Psychiatry 2007; 164:693–696
[CrossRef] | [PubMed]
 
Piaggio  G;  Elbourne  DR;  Altman  DG;  Pocock  SJ;  Evans  SJCONSORT Group:  Reporting of noninferiority and equivalence randomized trials: an extension of the CONSORT statement.  JAMA 2006; 295:1152–1160
[CrossRef] | [PubMed]
 
Driessen  E;  Van  HL;  Schoevers  RA;  Cuijpers  P;  van Aalst  G;  Don  FJ;  Hendriksen  M;  Kool  S;  Molenaar  PJ;  Peen  J;  Dekker  JJM:  Cognitive behavioral therapy versus short psychodynamic supportive psychotherapy in the outpatient treatment of depression: a randomized controlled trial.  BMC Psychiatry 2007; 7:58
[CrossRef] | [PubMed]
 
Sheehan  DV;  Lecrubier  Y;  Sheehan  KH;  Amorim  P;  Janavs  J;  Weiller  E;  Hergueta  T;  Baker  R;  Dunbar  GC:  The Mini-International Neuropsychiatric Interview (MINI): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10.  J Clin Psychiatry 1998; 59(suppl 20):22–33
[PubMed]
 
Hamilton  M:  A rating scale for depression.  J Neurol Neurosurg Psychiatry 1960; 23:56–62
[CrossRef] | [PubMed]
 
Molenaar  PJ;  Don  F;  van den Bout  J;  Sterk  F;  Dekker  J:  Cognitieve gedragstherapie bij depressie .  Houten, the Netherlands,  Bohn Stafleu van Loghum, 2009
 
de Jonghe  F:  Kort en Krachtig: Kortdurende Psychoanalytische Steungevende Psychotherapie .  Amsterdam,  Benecke NI, 2005
 
Beck  AT:  Cognitive Therapy and the Emotional Disorders .  New York,  International Universities Press, 1976
 
de Jonghe  F;  de Maat  S;  Van  R;  Hendriksen  M;  Kool  S;  van Aalst  G;  Schoevers  R;  Dekker  J:  Short-term psychoanalytic supportive psychotherapy for depressed patients.  Psychoanal Inq  (in press)
 
de Jonghe  F;  Kool  S;  van Aalst  G;  Dekker  J;  Peen  J:  Combining psychotherapy and antidepressants in the treatment of depression.  J Affect Disord 2001; 64:217–229
[CrossRef] | [PubMed]
 
de Jonghe  F;  Hendricksen  M;  van Aalst  G;  Kool  S;  Peen  V;  Van  R;  van den Eijnden  E;  Dekker  J:  Psychotherapy alone and combined with pharmacotherapy in the treatment of depression.  Br J Psychiatry 2004; 185:37–45
[CrossRef] | [PubMed]
 
Dekker  J;  Molenaar  PJ;  Kool  S;  Van Aalst  G;  Peen  J;  de Jonghe  F:  Dose-effect relations in time-limited combined psycho-pharmacological treatment for depression.  Psychol Med 2005; 35:47–58
[CrossRef] | [PubMed]
 
Dekker  JJ;  Koelen  JA;  Van  HL;  Schoevers  RA;  Peen  J;  Hendriksen  M;  Kool  S;  Van Aalst  G;  De Jonghe  F:  Speed of action: the relative efficacy of short psychodynamic supportive psychotherapy and pharmacotherapy in the first 8 weeks of a treatment algorithm for depression.  J Affect Disord 2008; 109:183–188
[CrossRef] | [PubMed]
 
Rush  AJ;  Giles  DE;  Schlesser  MA;  Fulton  CL;  Weissenburger  J;  Burns  C:  The Inventory for Depressive Symptomatology (IDS): preliminary findings.  Psychiatry Res 1986; 18:65–87
[CrossRef] | [PubMed]
 
de Jonghe  F:  Leidraad voor het scoren van de Hamilton Depression Rating Scale .  Amsterdam,  Benecke, 1994.
 
Twisk  JWR:  Applied Multilevel Analysis: A Practical Guide.   Cambridge, United Kingdom,  Cambridge University Press, 2006
 
Leichsenring  F:  Comparative effects of short-term psychodynamic psychotherapy and cognitive-behavioral therapy in depression: a meta-analytic approach.  Clin Psychol Rev 2001; 21:401–419
[CrossRef] | [PubMed]
 
Elkin  I;  Shea  MT;  Watkins  JT;  Imber  SD;  Sotsky  SM;  Collins  JF;  Glass  DR;  Pilkonis  PA;  Leber  WR;  Docherty  JP;  Fiester  SJ;  Parloff  MB:  National Institute of Mental Health Treatment of Depression Collaborative Research Program: general effectiveness of treatments.  Arch Gen Psychiatry 1989; 46:971–982, discussion 983
[CrossRef] | [PubMed]
 
Dimidjian  S;  Hollon  SD;  Dobson  KS;  Schmaling  KB;  Kohlenberg  RJ;  Addis  ME;  Gallop  R;  McGlinchey  JB;  Markley  DK;  Gollan  JK;  Atkins  DC;  Dunner  DL;  Jacobson  NS:  Randomized trial of behavioral activation, cognitive therapy, and antidepressant medication in the acute treatment of adults with major depression.  J Consult Clin Psychol 2006; 74:658–670
[CrossRef] | [PubMed]
 
Löwe  B;  Schenkel  I;  Bair  MJ;  Göbel  C:  Efficacy, predictors of therapy response, and safety of sertraline in routine clinical practice: prospective, open-label, non-interventional postmarketing surveillance study in 1,878 patients.  J Affect Disord 2005; 87:271–279
[CrossRef] | [PubMed]
 
Ostler  K;  Thompson  C;  Kinmonth  AL;  Peveler  RC;  Stevens  L;  Stevens  A:  Influence of socio-economic deprivation on the prevalence and outcome of depression in primary care: the Hampshire Depression Project.  Br J Psychiatry 2001; 178:12–17
[CrossRef] | [PubMed]
 
Morrison  KH;  Bradley  R;  Westen  D:  The external validity of controlled clinical trials of psychotherapy for depression and anxiety: a naturalistic study.  Psychol Psychother 2003; 76:109–132
[CrossRef] | [PubMed]
 
Paykel  ES:  Remission and residual symptomatology in major depression.  Psychopathology 1998; 31:5–14
[CrossRef] | [PubMed]
 
References Container

FIGURE 1. CONSORT Diagram of Participants in a Study of the Efficacy of Psychodynamic Therapy Relative to Cognitive-Behavioral Therapya

a CBT=cognitive-behavioral therapy; HAM-D=Hamilton Depression Rating Scale; MINI-Plus=Mini-International Neuropsychiatric Interview–Plus.

FIGURE 2. Observer-Rated and Patient-Rated Mean Depression Scores During Treatmenta

a CBT=cognitive-behavioral therapy; HAM-D=Hamilton Depression Rating Scale; IDS-SR=Inventory of Depressive Symptomatology–Self Report.

Anchor for Jump
TABLE 1.Baseline Demographic and Clinical Characteristics of Participants in a Study of the Efficacy of Psychodynamic Therapy Relative to Cognitive-Behavioral Therapya
Table Footer Note

a CBT=cognitive-behavioral therapy; HAM-D=Hamilton Depression Rating Scale.

Table Footer Note

b Comorbid axis I disorders were assessed by the psychotherapists during treatment without the use of a structured interview, and comorbidity rates may therefore be underestimated.

Anchor for Jump
TABLE 2.Treatment Effects at Different Assessment Points According to the Basic Model of Analysis and When Corrected for Different Sets of Covariatesa
Table Footer Note

a HAM-D=Hamilton Depression Rating Scale; IDS-SR=Inventory of Depressive Symptomatology–Self Report. Model 1 is the basic model including a main effect for treatment and time and a time-by-treatment interaction; model 2 is the basic model with clinic and number of patients with baseline HAM-D scores >24 added as covariates; model 3 is the basic model with demographic characteristics (as listed in Table 1) added as covariates; model 4 is the basic model with depression characteristics (as listed in Table 1) added as covariates; model 5 is the basic model with therapist gender and profession added as covariates; and model 6 is the basic model with HAM-D assessors' hypotheses regarding treatment outcomes added as a covariate.

Anchor for Jump
TABLE 3.Follow-Up Outcomes According to the Basic Model of Analysis and When Corrected for Different Sets of Covariatesa
Table Footer Note

a HAM-D=Hamilton Depression Rating Scale; IDS-SR=Inventory of Depressive Symptomatology–Self Report. Model 1 is the basic model including a treatment and time main effect and a time-by-treatment interaction; model 2 is the basic model with clinic and number of patients with baseline HAM-D scores >24 added as covariates; model 3 is the basic model with demographic characteristics (as listed in Table 1) added as covariates; model 4 is the basic model with depression characteristics (as listed in Table 1) added as covariates; model 5 is the basic model with therapist gender and profession added as covariates; model 6 is the basic model with HAM-D assessors' hypotheses regarding treatment outcomes added as a covariate; and model 7 is the basic model with patient-reported treatments in the follow-up period added as a covariate.

+

References

Kessler  RC;  Berglund  P;  Demler  O;  Jin  R;  Koretz  D;  Merikangas  KR;  Rush  AJ;  Walters  EE;  Wang  PSNational Comorbidity Survey Replication:  The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R).  JAMA 2003; 289:3095–3105
[CrossRef] | [PubMed]
 
World Health Organization:  The World Health Report 2001–Mental Health: New Understanding, New Hope .  Geneva,  World Health Organization, 2001. http://www.who.int/whr/2001/en/index.html
 
Marcus  SC;  Olfson  M:  National trends in the treatment for depression from 1998 to 2007.  Arch Gen Psychiatry 2010; 67:1265–1273
[CrossRef] | [PubMed]
 
Turner  EH;  Matthews  AM;  Linardatos  E;  Tell  RA;  Rosenthal  R:  Selective publication of antidepressant trials and its influence on apparent efficacy.  N Engl J Med 2008; 358:252–260
[CrossRef] | [PubMed]
 
Fournier  JC;  DeRubeis  RJ;  Hollon  SD;  Dimidjian  S;  Amsterdam  JD;  Shelton  RC;  Fawcett  J:  Antidepressant drug effects and depression severity: a patient-level meta-analysis.  JAMA 2010; 303:47–53
[CrossRef] | [PubMed]
 
Kirsch  I;  Deacon  BJ;  Huedo-Medina  TB;  Scoboria  A;  Moore  TJ;  Johnson  BT:  Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration.  PLoS Med 2008; 5:e45
[CrossRef] | [PubMed]
 
American Psychiatric Association:  Practice Guideline for the Treatment of Major Depressive Disorder, 3rd ed .  Washington, DC,  American Psychiatric Publishing, 2010
 
National Institute for Health and Care Excellence (NICE): Clinical Guideline 91–Depression: The Treatment and Management of Depression in Adults (update). London, NICE, 2010. http://guidance.nice.org.uk/CG90/
 
Driessen  E;  Cuijpers  P;  de Maat  SCM;  Abbass  AA;  de Jonghe  F;  Dekker  JJM:  The efficacy of short-term psychodynamic psychotherapy for depression: a meta-analysis.  Clin Psychol Rev 2010; 30:25–36
[CrossRef] | [PubMed]
 
Gerber  AJ;  Kocsis  JH;  Milrod  BL;  Roose  SP;  Barber  JP;  Thase  ME;  Perkins  P;  Leon  AC:  A quality-based review of randomized controlled trials of psychodynamic psychotherapy.  Am J Psychiatry 2011; 168:19–28
[CrossRef] | [PubMed]
 
Cuijpers  P;  van Straten  A;  Andersson  G;  van Oppen  P:  Psychotherapy for depression in adults: a meta-analysis of comparative outcome studies.  J Consult Clin Psychol 2008; 76:909–922
[CrossRef] | [PubMed]
 
Weissman  MM:  Cognitive therapy and interpersonal psychotherapy: 30 years later.  Am J Psychiatry 2007; 164:693–696
[CrossRef] | [PubMed]
 
Piaggio  G;  Elbourne  DR;  Altman  DG;  Pocock  SJ;  Evans  SJCONSORT Group:  Reporting of noninferiority and equivalence randomized trials: an extension of the CONSORT statement.  JAMA 2006; 295:1152–1160
[CrossRef] | [PubMed]
 
Driessen  E;  Van  HL;  Schoevers  RA;  Cuijpers  P;  van Aalst  G;  Don  FJ;  Hendriksen  M;  Kool  S;  Molenaar  PJ;  Peen  J;  Dekker  JJM:  Cognitive behavioral therapy versus short psychodynamic supportive psychotherapy in the outpatient treatment of depression: a randomized controlled trial.  BMC Psychiatry 2007; 7:58
[CrossRef] | [PubMed]
 
Sheehan  DV;  Lecrubier  Y;  Sheehan  KH;  Amorim  P;  Janavs  J;  Weiller  E;  Hergueta  T;  Baker  R;  Dunbar  GC:  The Mini-International Neuropsychiatric Interview (MINI): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10.  J Clin Psychiatry 1998; 59(suppl 20):22–33
[PubMed]
 
Hamilton  M:  A rating scale for depression.  J Neurol Neurosurg Psychiatry 1960; 23:56–62
[CrossRef] | [PubMed]
 
Molenaar  PJ;  Don  F;  van den Bout  J;  Sterk  F;  Dekker  J:  Cognitieve gedragstherapie bij depressie .  Houten, the Netherlands,  Bohn Stafleu van Loghum, 2009
 
de Jonghe  F:  Kort en Krachtig: Kortdurende Psychoanalytische Steungevende Psychotherapie .  Amsterdam,  Benecke NI, 2005
 
Beck  AT:  Cognitive Therapy and the Emotional Disorders .  New York,  International Universities Press, 1976
 
de Jonghe  F;  de Maat  S;  Van  R;  Hendriksen  M;  Kool  S;  van Aalst  G;  Schoevers  R;  Dekker  J:  Short-term psychoanalytic supportive psychotherapy for depressed patients.  Psychoanal Inq  (in press)
 
de Jonghe  F;  Kool  S;  van Aalst  G;  Dekker  J;  Peen  J:  Combining psychotherapy and antidepressants in the treatment of depression.  J Affect Disord 2001; 64:217–229
[CrossRef] | [PubMed]
 
de Jonghe  F;  Hendricksen  M;  van Aalst  G;  Kool  S;  Peen  V;  Van  R;  van den Eijnden  E;  Dekker  J:  Psychotherapy alone and combined with pharmacotherapy in the treatment of depression.  Br J Psychiatry 2004; 185:37–45
[CrossRef] | [PubMed]
 
Dekker  J;  Molenaar  PJ;  Kool  S;  Van Aalst  G;  Peen  J;  de Jonghe  F:  Dose-effect relations in time-limited combined psycho-pharmacological treatment for depression.  Psychol Med 2005; 35:47–58
[CrossRef] | [PubMed]
 
Dekker  JJ;  Koelen  JA;  Van  HL;  Schoevers  RA;  Peen  J;  Hendriksen  M;  Kool  S;  Van Aalst  G;  De Jonghe  F:  Speed of action: the relative efficacy of short psychodynamic supportive psychotherapy and pharmacotherapy in the first 8 weeks of a treatment algorithm for depression.  J Affect Disord 2008; 109:183–188
[CrossRef] | [PubMed]
 
Rush  AJ;  Giles  DE;  Schlesser  MA;  Fulton  CL;  Weissenburger  J;  Burns  C:  The Inventory for Depressive Symptomatology (IDS): preliminary findings.  Psychiatry Res 1986; 18:65–87
[CrossRef] | [PubMed]
 
de Jonghe  F:  Leidraad voor het scoren van de Hamilton Depression Rating Scale .  Amsterdam,  Benecke, 1994.
 
Twisk  JWR:  Applied Multilevel Analysis: A Practical Guide.   Cambridge, United Kingdom,  Cambridge University Press, 2006
 
Leichsenring  F:  Comparative effects of short-term psychodynamic psychotherapy and cognitive-behavioral therapy in depression: a meta-analytic approach.  Clin Psychol Rev 2001; 21:401–419
[CrossRef] | [PubMed]
 
Elkin  I;  Shea  MT;  Watkins  JT;  Imber  SD;  Sotsky  SM;  Collins  JF;  Glass  DR;  Pilkonis  PA;  Leber  WR;  Docherty  JP;  Fiester  SJ;  Parloff  MB:  National Institute of Mental Health Treatment of Depression Collaborative Research Program: general effectiveness of treatments.  Arch Gen Psychiatry 1989; 46:971–982, discussion 983
[CrossRef] | [PubMed]
 
Dimidjian  S;  Hollon  SD;  Dobson  KS;  Schmaling  KB;  Kohlenberg  RJ;  Addis  ME;  Gallop  R;  McGlinchey  JB;  Markley  DK;  Gollan  JK;  Atkins  DC;  Dunner  DL;  Jacobson  NS:  Randomized trial of behavioral activation, cognitive therapy, and antidepressant medication in the acute treatment of adults with major depression.  J Consult Clin Psychol 2006; 74:658–670
[CrossRef] | [PubMed]
 
Löwe  B;  Schenkel  I;  Bair  MJ;  Göbel  C:  Efficacy, predictors of therapy response, and safety of sertraline in routine clinical practice: prospective, open-label, non-interventional postmarketing surveillance study in 1,878 patients.  J Affect Disord 2005; 87:271–279
[CrossRef] | [PubMed]
 
Ostler  K;  Thompson  C;  Kinmonth  AL;  Peveler  RC;  Stevens  L;  Stevens  A:  Influence of socio-economic deprivation on the prevalence and outcome of depression in primary care: the Hampshire Depression Project.  Br J Psychiatry 2001; 178:12–17
[CrossRef] | [PubMed]
 
Morrison  KH;  Bradley  R;  Westen  D:  The external validity of controlled clinical trials of psychotherapy for depression and anxiety: a naturalistic study.  Psychol Psychother 2003; 76:109–132
[CrossRef] | [PubMed]
 
Paykel  ES:  Remission and residual symptomatology in major depression.  Psychopathology 1998; 31:5–14
[CrossRef] | [PubMed]
 
References Container
+
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