New, third-round results for the U.S. STAR*D study show that patients who fail two trials of an antidepressant have only a minimal chance for remission with a third type of medication, according to an article in the July issue of the American Journal of Psychiatry.

The article is entitled “A Comparison of Mirtazapine and Nortriptyline Following Two Consecutive Failed Medication Treatments for Depressed Outpatients: A STAR*D Report,” with Maurizio Fava, MD, of Massachusetts General Hospital the lead author.

In this phase of the trial, the 235 patients who opted for a switch in medication were randomized 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,” said Robert Freedman, MD, journal editor-in-chief.

STAR*D was designed to parallel real-world practice. After failure of one or two medications, clinicians often try an antidepressant from a different 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, MD, MPH., 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,” commented Matthew Menza, MD, 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.