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Combination of Antidepressant Medications From Treatment Initiation for Major Depressive Disorder: A Double-Blind Randomized Study

Objective: Various classes of antidepressant medications generally induce remission of major depressive disorder in only about one-third of patients. In a previous study using mirtazapine or paroxetine alone or in combination from treatment initiation, the rate of patients who remitted within a 6-week period was twice that of patients using either drug alone. In this double-blind study, the authors sought to produce evidence for the superiority of different combinations of antidepressant drugs from treatment initiation.

Method: Patients (N=105) meeting DSM-IV criteria for major depressive disorder were randomly assigned to receive, from treatment initiation, either fluoxetine monotherapy (20 mg/day) or mirtazapine (30 mg/day) in combination with fluoxetine (20 mg/day), venlafaxine (225 mg/day titrated in 14 days), or bupropion (150 mg/day) for 6 weeks. The primary outcome measure was the Hamilton Depression Rating Scale (HAM-D) score.

Results: The overall dropout rate was 15%, without notable differences among the four groups. Compared with fluoxetine monotherapy, all three combination groups had significantly greater improvements on the HAM-D. Remission rates (defined as a HAM-D score of 7 or less) were 25% for fluoxetine, 52% for mirtazapine plus fluoxetine, 58% for mirtazapine plus venlafaxine, and 46% for mirtazapine plus bupropion. Among patients who had a marked response, double-blind discontinuation of one agent produced a relapse in about 40% of cases.

Conclusions: The combination treatments were as well tolerated as fluoxetine monotherapy and more clinically effective. The study results, which add to a growing body of evidence, suggest that use of antidepressant combinations from treatment initiation may double the likelihood of remission compared with use of a single medication.

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Combining Antidepressant Medications: A Good Idea?

A. John Rush
Am J Psychiatry 2010 167: 241-243. [Full Text] [PDF]

This article has been cited by other articles:

				L. Tarsitani and M. Pasquini Compared with fluoxetine monotherapy, mirtazapine plus venlafaxine or fluoxetine increase remission but not response in patients with major depressive disorder Evid. Based Ment. Health, July 22, 2010; (2010) ebmh1061v1. [Full Text] [PDF]

				A. J. Rush Combining Antidepressant Medications: A Good Idea? Am J Psychiatry, March 1, 2010; 167(3): 241 - 243. [Full Text] [PDF]

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