Antidepressant Combination Therapy in Initial Depression Management
Blier P, Ward HE, Tremblay P, Laberge L, H??bert C, Bergeron R
Am J Psychiatry. 2010;167:281-288
In this double-blind study, 105 participants initiating treatment for major depressive disorder were randomly assigned to receive 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. Compared with fluoxetine monotherapy, all 3 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 1 agent produced a relapse in about 40% of cases. The combination treatments were as well tolerated as fluoxetine monotherapy.
The study authors note that the use of mirtazapine in combination with another antidepressant may double the likelihood of remission compared with use of a single medication. Remission is the holy grail of treatment because it greatly decreases the risk for relapse. Therefore, the use of antidepressant medication combinations from day 1 may represent a significant advance in the treatment of major depressive disorder. There are several caveats, however. Although the number needed to treat to encounter 1 additional remitted patient was as strong as 3 for the comparison of fluoxetine vs mirtazapine plus venlafaxine, time to response and time to remission was the same for monotherapy as it was for combination treatment. In addition, fluoxetine monotherapy was at a fixed dose of 20 mg/day, with no provision for adjustment upwards. A remaining unknown factor is the potential utility of combination treatment for patients in their first major depressive episode vs those who have experienced multiple episodes and varying histories of therapeutic response. A practical obstacle is the need to prescribe 2 medications. The development of a combination pill would be a possible solution.