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

University of Ottawa Institute of Mental Health Research, University of Ottawa, Ottawa, Ontario, Canada K1Z 7K4.
American Journal of Psychiatry (Impact Factor: 12.3). 12/2009; 167(3):281-8. DOI: 10.1176/appi.ajp.2009.09020186
Source: PubMed


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.
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.
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.
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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Available from: Pierre Blier, Oct 13, 2015
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    • "Downloaded from in combination with fluoxetine, venlafaxine or bupropion compared with fluoxetine monotherapy found that the three combination therapies were associated with approximately double the remission rate of fluoxetine monotherapy (46–58% versus 25%) (Blier et al., 2010). However, consideration of combination regimens should also take into account the single-blind, prospective study by Rush et al. (2011), which showed no difference in response or remission between treatment with escitalopram plus placebo, sustained-release bupropion plus escitalopram, or extended-release venlafaxine plus mirtazapine. "
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    • "Despite the prevalence of depression and its broad consequences , our understanding of the pathophysiology of this disorder and its treatment is still somewhat limited in several respects. To be sure, antidepressant treatments have been effective for many patients, although the efficacy of drug treatments can be further improved through the judicious use of combination therapies (Blier et al., 2010; Millan, 2006). There is room for antidepressant treatments to be improved with respect to the success rate for given agents, reducing the time lag for treatment effects to appear, diminishing side effects, and limiting the recurrence of illness. "
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