Combination Treatment for Acute Depression Is Superior Only when Psychotherapy Is Added to Medication

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Abstract
Although several forms of effective therapy exist for outpatients suffering from major depressive disorder, many patients do not profit from treatment. Combining psychotherapy and medication may be an effective strategy. However, earlier studies have rarely found a clear advantage for the combination. Where an advantage was found, a possible placebo effect of adding 2 types of treatment could not be ruled out as cause for the superior effect of the combination. A total of 353 patients were screened, of whom 193 were randomized over 4 conditions: nefazodone plus clinical management, interpersonal psychotherapy (IPT), the combination of the two or the combination of IPT and pill-placebo. All patients suffered from major depressive disorder and had a score of at least 14 on the 17-item Hamilton Rating Scale (HAMD). The patients were treated for 12-16 weeks. At baseline, at 6 weeks and on completion of treatment, ratings were performed by independent raters. The primary outcome measure was the HAMD, and the Montgomery-Asberg Depression Rating Scale (MADRS) the secondary outcome measure. Of the 193 patients included, 138 completed the trial. All treatments were effective. Using a random regression model, no differences between treatments were found on the HAMD. On the MADRS, however, the combination of medication with psychotherapy was more effective in reducing depressive symptoms compared to medication alone, but not to psychotherapy alone or IPT with pill-placebo. The results of this study yield support for the use of combining medication with psychotherapy instead of using medication only in the treatment of depressed outpatients. Combination treatment does not have an advantage over psychotherapy alone in the present study.

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