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Letter to the Editor
Published Online: 1 August 2010

Placebo Group Needed for Interpretation of Combination Trial

To the Editor: In the study conducted by Pierre Blier, M.D., Ph.D., et al. (1) and the accompanying editorial by A. John Rush, M.D., (2), it was suggested that two antidepressant medications are therapeutically more effective than single agents. This conclusion was based on research in which depressed patients were randomly assigned to one of four treatment arms: fluoxetine plus placebo, fluoxetine plus mirtazapine, bupropion plus mirtazapine, and venlafaxine plus mirtazapine. Subjects receiving two drug treatments reportedly did better than those receiving monotherapy.
The research design does not support the conclusion that combined treatment is better than mirtazapine monotherapy. There was no mirtazapine plus placebo study group. This comparison arm is necessary in order to be confident that the observed effect by the three combined treatments could not have been accomplished by mirtazapine as a single drug. The observation that mirtazapine alone was equivalent to fluoxetine or paroxetine alone in a previous study (3) does not negate the need for a control in the Blier et al. study. Without such a control, one cannot assume that two antidepressant medications are more effective than mirtazapine alone.
While there are many issues that can confound an investigation, it would have been important for the research article (1) and the accompanying editorial (2) to note this design flaw. Without such a disclaimer, conclusive evidence for these combination pharmacotherapies as being superior to mirtazapine alone is not present.

References

1.
Blier P, Ward HE, Tremblay P, Laberge L, Hébert C, Bergeron R: Combination of antidepressant medications from treatment initiation for major depressive disorder: a double-blind randomized study. Am J Psychiatry 2010; 167:281–288
2.
Rush AJ: Combining antidepressant medications: A good idea? Am J Psychiatry 2010; 167:241–243
3.
Blier P, Gobbi G, Turcotte JE, de Montgny C, Boucher N, Hébert C, Debonnel G: Mirtazapine and paroxetine in major depression: a comparison of monotherapy versus their combination. Eur Neuropsychopharmacol 2009; 19:457–465

Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 996
PubMed: 20693473

History

Accepted: May 2010
Published online: 1 August 2010
Published in print: August 2010

Authors

Details

Rif S. El-Mallakh, M.D.
Steven Lippman, M.D.

Competing Interests

Dr. El-Mallakh has received research funding from Forest and Shire; he also serves on the speaker's bureaus of AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Merck, Novartis, and Pfizer. Drs. Kaur and Lippmann report no financial relationships with commercial interests.

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