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Tuesday, November 27, 2007

Dual Action not Better Than Mono Action Antidepressants


24 patients would need to be treated with a dual-action antidepressant drug instead of SSRIs in order to obtain one additional responder. This is called a Number Needed to Treat (NNT) of 24. A number of 10 or lower is considered relevant, so 24 is way above it and not relevant although the authors of this review do their out most to let us believe otherwise.

This is the conclusion of a large meta-analysis published in Biological Psychiatry. The assumption is that antidepressants that simultaniously enhance noradrenergic and serotonergic neurotransmission might benefit depressed patients more than antidepressants working on just one neurotransmittor: serotonin.

They indcluded as much data as possible. The did not only search medline/pubmed and EMBase but also clinical trial registries, program syllabi from major psychiatric meetings held since 1995, and documents from relevant pharmaceutical companies. These last options means also including non peer reviewed work in their search and analysis.

They included 93 trials (n= 17036 patients)for analysis. All comparing a SSRI and a dual action antidepressant: venlafaxine, duloxetine, milnacipran, mirtazepine, mianserin, or moclobemide. Even these so called dual action antidepressant vary much in mechanism of action, their action is not solely based on the inhibition of reuptake of serotonin and noradrenalin.

Duloxetine was apparently less efficacious compared to the others and SSRIs.

Especially important in a meta-analysis is a test for heterogeneity of trials. From the article it is not clear which test they used for heterogeneity, their conclusion was that there existed no heterogeneity. All trials were comparable.

Heterogeneity:
Trials studying the same question are unlikely to have the same outcomes on the basis of sampling error. A difference between trials may be due to chance. It is important to know whether discrepancies between trials are greater than we would expect by chance. With heterogeneity the results of various trials are more different than one would expect by chance alone. In short the trials are different.


Article Discussed
Biol Psychiatry. 2007 Dec 1;62(11):1217-27. Epub 2007 Jun 22.

Are Antidepressant Drugs That Combine Serotonergic and Noradrenergic Mechanisms
of Action More Effective Than the Selective Serotonin Reuptake Inhibitors in
Treating Major Depressive Disorder? A Meta-analysis of Studies of Newer Agents.
Blogging on Peer-Reviewed Research

Papakostas GI, Thase ME, Fava M, Nelson JC, Shelton RC.
PMID: 17588546



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