Landmark STAR*D Depression Study Offers 'Sobering' Third-Round Results

New results of the nation's largest depression study show that patients who have already failed on two prior antidepressants and then switch to a different class of antidepressants have only a minimal chance at remission by making the switch. The finding is part of the third wave of reports from the "Sequenced Treatment Alternatives to Relieve Depression" (STAR*D) study and is being released in the July 2006 issue of The American Journal of Psychiatry (AJP), the official journal of the American Psychiatric Association (APA).


The AJP article is entitled "A Comparison of Mirtazapine and Nortriptyline Following Two Consecutive Failed Medication Treatments for Depressed Outpatients: A STAR*D Report" and is by Maurizio Fava, M.D., of Massachusetts General Hospital.


In this trial, the 235 patients who opted for a switch in their medications were randomly assigned to nortriptyline or mirtazapine, antidepressants they had not taken in Level 1 or 2. The rates of remission after 14 weeks were 20 percent for nortriptyline and 12 percent for mirtazapine, but the difference was not considered statistically significant. The frequencies of adverse side effects were also similar.



"The results of STAR*D continue to be sobering. By the third wave of the study, the rate of remission continues to be quite low, which underscores the persistence of depression and its resistance to current treatments," states Robert Freedman, M.D., AJP editor-in-chief.


STAR*D was designed to parallel real-world practice. After the failure of the first one or two medications, often the clinician tries an antidepressant from a different pharmacological class. The antidepressants in Level 3 had pharmacological actions different from those in the previous levels and from each other.


"This finding is particularly relevant to clinical practice because it is based on typical patients," said Darrel A. Regier, M.D., M.P.H., director of the APA's Division of Research. "The scope and design of this large National Institute of Mental Health study makes it a welcome addition to evidence-based treatment in an effort to guide clinical practice."


"STAR*D is a laudable endeavor," comments Matthew Menza, M.D., of the Robert Wood Johnson Medical School in an accompanying editorial. "The study is the largest randomized clinical trial in depression ever conducted, and it is very well designed. The enrollment was efficient and included a large number of minorities, which is a rarity in clinical trials."


This study was funded by the National Institute of Mental Health. Medications for the STAR*D trials were provided at no cost by Bristol-Myers Squibb, Forest Pharmaceuticals, GlaxoSmithKline, King Pharmaceuticals, Organon, Pfizer, and Wyeth-Ayerst Laboratories.



(Am J Psychiatry. 2006; 163: 1161-1172).




Results from STAR*D Level 3 Augmentation Treatment Step to be reported in an upcoming American Journal of Psychiatry issue.



Earlier STAR*D results were reported in the following:


American Journal of Psychiatry 2006; 163:28-40, January 2006

New England Journal of Medicine 2006; 354:1231-1242, March 23, 2006

New England Journal of Medicine 2006; 354:1243-1252, March 23, 2006


About The American Journal of Psychiatry


The American Journal of Psychiatry, the official journal of the American Psychiatric Association, publishes a monthly issue with scientific articles submitted by psychiatrists and other scientists worldwide. The peer review and editing process is conducted independently of any other American Psychiatric Association components. Therefore, statements in this press release or the articles in the Journal are not official policy statements of the American Psychiatric Association. The Journal's editorial policies conform to the Uniform Requirements of the International Committee of Medical Journal Editors, of which it is a member.

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