Navigate Up

UPMC/University of Pittsburgh Schools of the Health Sciences
Patients and medical professionals may call 1-800-533-UPMC (8762) for more information.

Michael E. Thase, M.D.

Michael E. Thase, M.D.

University of Pittsburgh Schools of the Health Sciences

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’ treatment. What we are seeing is that different treatments work for different people,” said Dr. Thase. “It’s critical for doctors and their patients to realize that while the first treatment they use may not work, they should not give up. There still may be an available treatment that will.”

Researchers note that the study was conducted under relatively normal clinical conditions where patients and their doctors were able to exercise some choice over the options they might receive.

“By further analyzing the data from STAR*D we hope to one day put even more meaning behind these findings,” said Dr. Wisniewski. “By using information on the characteristics of the participants, we may be able to determine who would benefit from specific treatments.”

The study was funded by the National Institute of Mental Health (NIMH). Study medications for Levels 1 and 2 were provided by Forest Laboratories, Pfizer, GlaxoSmithKline, Wyeth and Bristol-Myers-Squibb.

Level 1 results were published in the January 2006 issue of the American Journal of Psychiatry.

UPMC | Affiliated with the University of Pittsburgh Schools of the Health Sciences Supplemental content provided by Healthwise, Incorporated. To learn more, visit

For help in finding a doctor or health service that suits your needs, call the UPMC Referral Service at 412-647-UPMC (8762) or 1-800-533-UPMC (8762). Select option 1.

UPMC is an equal opportunity employer. UPMC policy prohibits discrimination or harassment on the basis of race, color, religion, ancestry, national origin, age, sex, genetics, sexual orientation, gender identity, marital status, familial status, disability, veteran status, or any other legally protected group status. Further, UPMC will continue to support and promote equal employment opportunity, human dignity, and racial, ethnic, and cultural diversity. This policy applies to admissions, employment, and access to and treatment in UPMC programs and activities. This commitment is made by UPMC in accordance with federal, state, and/or local laws and regulations.

Medical information made available on is not intended to be used as a substitute for professional medical advice, diagnosis, or treatment. You should not rely entirely on this information for your health care needs. Ask your own doctor or health care provider any specific medical questions that you have. Further, is not a tool to be used in the case of an emergency. If an emergency arises, you should seek appropriate emergency medical services.

Pittsburgh, PA, USA |