"Clinicians should not rush to prescribe combinations of antidepressant medications as first-line treatment for patients with major depressive disorder," said Dr. Madhukar H. Trivedi, professor of psychiatry and chief of the division of mood disorders at UT Southwestern and principal investigator of the study, which is available online today and is scheduled for publication in an upcoming issue of the American Journal of Psychiatry.
"The clinical implications are very clear - the extra cost and burden of two medications is not worthwhile as a first treatment step," he said.
In the Combining Medication to Enhance Depression Outcomes, or CO-MED, study, researchers at 15 sites across the country studied 665 patients ages 18 to 75 with major depressive disorder. Three treatment groups were formed and prescribed antidepressant medications already approved by the Food and Drug Administration. One group received escitalopram (a selective serotonin reuptake inhibitor, or SSRI) and a placebo; the second group received the same SSRI paired with bupropion (a non-tricyclic antidepressant); and a third group took different antidepressants: venlafaxine (a tetracyclic antidepressant) and mirtazapine (a serotonin norepinephrine reuptake inhibitor). The study was conducted from March 2008 through February 2009.
After 12 weeks of treatment, remission and response rates were similar across the three groups: 39 percent, 39 percent and 38 percent, respectively, for remission, and about 52 percent in all three groups for response. After seven months of treatment, remission and response rates across the three groups remained similar, but side effects were more frequent in the third group.
Only about 33 percent of depressed patients go into remission in the first 12 weeks of treatment with antidepressant medication, as Dr. Trivedi and colleagues previously reported from the Sequenced Treatment Alternatives to Relieve Depression, or STAR*D, study. STAR*D was the largest study ever undertaken on the treatment of major depressive disorder and is considered a benchmark in the field of depression research. That six-year, $33 million study initially included more than 4,000 patients from sites across the country. Dr. Trivedi was a co-principal investigator of STAR*D.
The next step, Dr. Trivedi said, is to study biological markers of depression to see if researchers can predict response to antidepressant medication and, thus, improve overall outcomes.
Other UT Southwestern researchers involved in the study were Drs. Benji Kurian and David Morris, assistant professors of psychiatry; Dr. Diane Warden, associate professor of psychiatry; and Dr. Mustafa Husain, professor of psychiatry, internal medicine, and neurology and neurotherapeutics. Former UT Southwestern professor Dr. A. John Rush, now with the Duke-NUS Graduate Medical School in Singapore, and researchers from the University of Pittsburgh; Massachusetts General Hospital; Columbia University College of Physicians and Surgeons; the University of California, Los Angeles; Vanderbilt University; Harbor-UCLA Medical Center; Virginia Commonwealth University; and Columbia University Medical Center also contributed.
The study was funded by the National Institute of Mental Health. Forest Pharmaceuticals, GlaxoSmithKline, Organon and Wyeth Pharmaceuticals provided the medications.
Source: UT Southwestern