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Combination of Antidepressant Medications From Treatment Initiation for Major Depressive Disorder: A Double-Blind Randomized Study.
Am J Psychiatry. 2009 Dec 15;
Authors: Blier P, Ward HE, Tremblay P, Laberge L, Hébert C, Bergeron R
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.
PMID: 20008946 [PubMed – as supplied by publisher]
(Via Am J Psychiatry – Medline.)
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Interesting evidence to support polypharmacy in the treatment of depression.
Depression, itself, has a complex pathophysiology that includes not only pathology in the nervous system, but also in the immune system and endocrine system, coupled often with metabolic and nutritional problems.
Thus, antidepressant medication treatment often is not enough to address the pathophysiology involved – and certainly not the psychological problems involved.
This is why weasel words have to be used for “Remission”. Remission is defined in the study as a HAM-D score of 7 or less. This means a person can still be significantly ill and be defined as being in remission. Remission should instead be defined as a HAM-D score of ZERO. But then, the antidepressants, which are only partial treatments, would not pass.
Notably, the best score for “remission” is in 58% of patients – again supporting a complex pathophysiology plus-or-minus significant psychological pathology underlying depression.