Depression That Doesn’t Respond To One Drug May Respond To Another, According To Two Studies In NEJM

PITTSBURGH, March 23, 2006 — One in four people with treatment resistant depression will do better by switching to a different antidepressant and one in three will benefit from adding an additional drug to their current antidepressant therapy, according to research results published in two studies in today’s edition of the New England Journal of Medicine. The results come from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study.

STAR*D is the largest and longest trial to-date of clinical depression in the United States to determine what treatments for depression work for patients in “the real world.” The study had four levels of participation. Results of the two studies published today come from the second level of the study.

The multi-site study was led by researchers from the University of Texas Southwestern Medical Center and involved 14 regional centers, including one at the University of Pittsburgh School of Medicine, led by Michael E. Thase, M.D., professor of psychiatry, Edward S. Friedman, M.D., associate professor of psychiatry, and Robert H. Howland, M.D., associate professor of psychiatry. Each of the regional centers had two to four clinical sites, for a total of 41 sites. Additionally, the Data Coordinating Center for the study was located at the University of Pittsburgh’s Epidemiology Data Center (EDC), and directed by Stephen R. Wisniewski, Ph.D., deputy director of the EDC and an associate dean for research at the university’s Graduate School of Public Health.

In the first level of the study, researchers enrolled 4041 participants who were treated for depression with the selective serotonin reuptake inhibitor (SSRI) citalopram. One-third of those participants reached remission, which meant that they were symptom-free. The remaining two-thirds were eligible to enroll in Level 2 of the study. Of those, 1,439 chose to participate in

Level 2. Level 2 participants were then asked if they would prefer to be switched to a different treatment, receive an additional treatment to add to the citalopram they were currently taking, or if they had no preference. Interestingly, only 21 participants out of the 1,439 said that any of the treatment options would be acceptable, while the remainder stated having a preference.

In the medication switch study, 727 participants stopped taking citalopram and were treated with sertaline, bupropion-SR or venlafaxine-XR, all drugs commonly prescribed for depression, for up to 14 weeks. Twenty-five percent of the participants became symptom-free. While the three drugs represented three different classes of antidepressants, the differences in remission rates among the three drugs were small and unlikely to be clinically significant.

In the medication addition study, 565 participants continued taking citalopram and also were given either bupropion-SR or buspirone for up to 14 weeks. The two drugs are thought to enhance the efficacy of SSRIs in different ways: bupropion-SR acts on the serotonin neurotransmitter, while buspirone blocks other neurotransmitters. Overall, 30 percent of the participants became symptom-free. Bupropion-SR provided a slightly better outcome than buspirone in terms of symptom reduction and severity and tolerability of side effects, though these differences were not clinically significant.

“Most clinicians have a favorite drug or two for treatment of their depressed patients. With this study we tried to find out if one of the common first choice antidepressants didn’t help, is there one ‘best’ or even one ‘better&


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