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, 7 (7), e41778

A Systematic Review of Comparative Efficacy of Treatments and Controls for Depression


A Systematic Review of Comparative Efficacy of Treatments and Controls for Depression

Arif Khan et al. PLoS One.


Background: Although previous meta-analyses have examined effects of antidepressants, psychotherapy, and alternative therapies for depression, the efficacy of these treatments alone and in combination has not been systematically compared. We hypothesized that the differences between approved depression treatments and controls would be small.

Methods and findings: The authors first reviewed data from Food and Drug Administration Summary Basis of Approval reports of 62 pivotal antidepressant trials consisting of data from 13,802 depressed patients. This was followed by a systematic review of data from 115 published trials evaluating efficacy of psychotherapies and alternative therapies for depression. The published depression trials consisted of 10,310 depressed patients. We assessed the percentage symptom reduction experienced by the patients based on treatment assignment. Overall, antidepressants led to greater symptom reduction compared to placebo among both unpublished FDA data and published trials (F = 38.5, df = 239, p<0.001). In the published trials we noted that the magnitude of symptom reduction with active depression treatments compared to controls was significantly larger when raters evaluating treatment effects were un-blinded compared to the trials with blinded raters (F = 2.17, df = 313, p<0.05). In the blinded trials, the combination of antidepressants and psychotherapy provided a slight advantage over antidepressants (p = 0.027) and psychotherapy (p = 0.022) alone. The magnitude of symptom reduction was greater with psychotherapies compared to placebo (p = 0.019), treatment-as-usual (p = 0.012) and waiting-list (p<0.001). Differences were not seen with psychotherapy compared to antidepressants, alternative therapies or active intervention controls.

Conclusions: In conclusion, the combination of psychotherapy and antidepressants for depression may provide a slight advantage whereas antidepressants alone and psychotherapy alone are not significantly different from alternative therapies or active intervention controls. These data suggest that type of treatment offered is less important than getting depressed patients involved in an active therapeutic program. Future research should consider whether certain patient profiles might justify a specific treatment modality.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.


Figure 1
Figure 1. Process of Exclusion of Trials Identified During Search of Depression Treatment Reviews and Analyses, and the Website by Cuijpers and Colleagues.
Figure 2
Figure 2. Mean Percentage Symptom Reduction from Un-blinded and Blinded Treatment Arms from Published Depression Trials Compared to Data from Pivotal Registration Depression Trials as Reported by the FDA.
Red Bars Represent Un-Blinded Trial Arms Blue Bars Represent Blinded Trial Arms Yellow Represents Placebo Control Arms from Published Non-Registration trials Green Bars Represent Data from Pivotal Registration Trials The mean percentage symptom reduction was weighted by the number of assigned patients. Error Bars Represent 95% Confidence Intervals. Active treatment arms consist of combination antidepressant + therapy, antidepressants, psychotherapy, antidepressant therapy and alternative therapy. Control treatment arms consisted of placebo control, active intervention control, treatment-as-usual and waiting-list control. Blinded trials were operationally defined as those that utilized depression symptom raters that were blinded to treatment assignment of the patients.
Figure 3
Figure 3. Mean Weighted Percentage Symptom Reduction of Psychotherapy Trial Arms from Published Depression Trials based on Type of Therapy Administered.
The number of treatment arms for each therapy type was 24 for Cognitive Behavioral Therapy (16 un-blinded, 8 blinded), 39 for Cognitive Therapy (22 un-blinded, 17 blinded), 9 for Behavioral Therapy (7 un-blinded, 2 blinded), 14 for Interpersonal Therapy (7 un-blinded, 7 blinded) and 43 for therapies with other titles (26 un-blinded, 17 blinded).

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The authors have no support or funding to report.