|Psychotherapy versus the combination of psychotherapy and pharmacotherapy in the treatment of depression: a meta-analysis
|Cuijpers P, van Straten A, Warmerdam L, Andersson G
This meta-analysis compared combined pharmacological and psychological therapy with psychological therapy alone for depression and concluded that the combined treatment was superior in the short-term. The authors' conclusions seem to be appropriate, but should be treated with caution, given the quality of the evidence and the lack of detail in the review methods.
To evaluate the addition of pharmacotherapy to psychotherapy for depression.
A specialist database of studies of the psychological treatment of depression was searched without language restrictions. This database was developed from searches between 1966 and December 2007 of PubMed, PsycINFO, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL), plus articles from meta-analyses. References of identified papers and previous reviews were also searched and the search terms were reported.
Randomised controlled trials (RCTs) that compared a psychological intervention with the same intervention plus an antidepressant in patients of any age with depression (diagnosed through a clinical interview or by self report) were eligible for inclusion. Verbal communication with a therapist was the core element of psychological interventions, which were based on theory. Trials of maintenance treatments and those that used a placebo antidepressant were excluded.
The included trials were of adults and one was of older adults (over 60 years). Two were of people with human immunodeficiency virus (HIV), one was of people with chronic depression, and one was of people with multiple sclerosis. Psychological treatments varied, but included cognitive-behavioural therapy (CBT), group behavioural therapy, interpersonal psychotherapy, and group therapy. The additional antidepressants were amitriptyline, sertraline, imipramine, fluoxetine, and others. The most commonly used outcome measures were the Beck Depression Inventory (BDI) and the Hamilton Rating Scale for Depression (HRSD). Outcomes were measured before and after treatment and for up to two years later.
The authors did not state how many reviewers selected trials.
Assessment of study quality
Trial validity was assessed based on the recommendations of the Cochrane Handbook and these covered independent randomisation, allocation concealment, outcome assessor blinding, and missing follow-up data.
The authors did not report how many reviewers assessed validity.
Standardised effect sizes were calculated from the means of the treatment and control groups at the assessments after treatment, using the difference in means divided by the pooled standard deviation. If more than one depression outcome was reported in a trial, the mean of all effect sizes was calculated. The relative risk of recovery was also calculated.
The authors did not state how many reviewers extracted the data.
Methods of synthesis
Trials were pooled in meta-analyses, using both fixed-effect and random-effects models. Cochran's Q statistic and the I2 statistic were used to assess heterogeneity. Subgroup analyses were performed on clinical samples versus other ways of recruiting participants, all adults versus specific populations, CBT versus other psychological therapy, and tricyclic versus selective serotonin re-uptake inhibitors versus other antidepressants. Further subgroup analyses compared dropout rates (less than 20% versus 20% or more), type of analysis (intention-to-treat versus complete data only), and trial publication year (before 1995 versus 1995 or later). Funnel plots, the fail safe N, and the trim-and-fill method were used to assess publication bias.
Results of the review
Nineteen trials (1,838 patients) were included. Their quality varied and only four reported independent randomisation, none reported adequate allocation concealment, 11 reported outcome assessor blinding, and dropouts ranged from six to 55% of participants. There was no evidence of publication bias for any outcome.
Continuous outcomes: Combined therapy was more effective than psychotherapy alone with a pooled effect size of 0.35 (95% CI 0.24 to 0.45; 19 comparisons, 17 RCTs). The results were similar for analyses only using the BDI (ES 0.28, 95% CI 0.12 to 0.43; 15 comparisons) and the HRSD (ES 0.35, 95% CI 0.24 to 0.46; 17 comparisons). Statistical heterogeneity was low (I2=0 or 18.9). Sensitivity analyses excluding an outlying trial and multiple comparisons from the same trial produced similar results.
Analyses of later follow-up assessments showed no evidence of benefit with combined treatment for three-to-six months, nor up to one year, but these were based on three and five comparisons, respectively. Subgroup analyses found a significantly smaller effect size for trials that used CBT (ES 0.15, 95% CI -0.06 to 0.37; eight comparisons) compared with other psychological therapies (ES 0.40, 95% CI 0.29 to 0.52; 11 comparisons). No other subgroup comparisons showed statistical differences at a 5% significance level.
Dichotomous outcomes: For recovery, combination therapy was more effective than psychotherapy alone (RR 0.78, 95% CI 0.71 to 0.86; I2=0; 17 comparisons). None of the subgroup analyses showed a significant difference between groups.
A combined psychological and pharmacological treatment was superior to a psychological treatment alone in the short-term for depression.
This meta-analysis specified the inclusion and exclusion criteria and had good search methods, without language restrictions. Publication bias was assessed using three methods and no reason to suspect it was found. Duplication of the study selection, quality assessment, and data extraction was not reported, so the potential for error and bias cannot be ruled out. The authors stated that the trials were generally of poor quality, but did not report the full details for each one. The meta-analysis used both fixed-effect and random-effects models, with sensitivity and subgroup analyses, which seems to have been appropriate.
The conclusions were supported by the evidence presented, but should be treated with caution, given the quality of the evidence and the lack of detail in the review methods.
Implications of the review for practice and research
Practice: The authors stated that combined treatment should be offered to patients before psychological treatment alone.
Research: The authors stated that meta-analyses were needed to compare the effects of pharmacotherapy and combined treatment. Further research was also needed to assess whether the relative treatment effects were related to the severity or chronicity of the condition or to comorbid psychiatric or general medical disorders, and to explore the combination of treatments that was most effective and its mechanisms of action.
Cuijpers P, van Straten A, Warmerdam L, Andersson G. Psychotherapy versus the combination of psychotherapy and pharmacotherapy in the treatment of depression: a meta-analysis. Depression and Anxiety 2009; 26(3): 279-288
Subject indexing assigned by NLM
Cognitive Therapy /methods; Combined Modality Therapy; Depressive Disorder, Major /drug therapy /psychology /therapy; Drug Therapy /methods; Humans; Psychotherapy /methods
Database entry date
This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.