Published: March 27, 2007

UCDHSC news release

Psychiatric researchers at both the University of Colorado at Denver and Health Sciences Center and the University of Colorado at Boulder took part in a $26.8 million, 22-center study across the United States between 1998 and 2005 that looked at medication effectiveness in patients with bipolar disorder.

The study found that treatment of bipolar patients with a mood stabilizer in conjunction with an antidepressant did not provide any benefit and had similar outcomes to treatment with just a mood stabilizer and a placebo sugar pill. Results are published March 28 in the online edition of the New England Journal of Medicine.

Bipolar disorder is also known as manic-depressive illness and affects 5.7 million American adults, or approximately 2.6 percent of the population age 18 and older (data from the National Institute of Mental Health). Those with bipolar disorder suffer from unusual or extreme shifts in mood, energy, and ability to function, often with periods of normal mood in between. Bipolar disorder typically develops in the teen years or young adulthood.

"A significant portion of depressed individuals are depressed because of bipolar disorder, and often misdiagnosed as suffering from major depression," said Dr. Michael Allen, principal investigator of the study at UCDHSC, associate professor of psychiatry, director of Emergency and Consultation Psychiatry, and co-director of the Mood Disorders Program at the UCDHSC School of Medicine. "Bipolar depressed patients have been systematically excluded from studies of antidepressants up to this point, so there has been little information about the benefits. On the other hand, there is evidence that antidepressants can destabilize bipolar patients. This study was done to test whether there was any benefit or risk associated with adding antidepressants to mood stabilizers in bipolar depressed patients. We found that there was no advantage to using antidepressants."

The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study was funded by the National Institutes of Health's National Institute of Mental Health (NIMH) and is the largest federally funded research program ever conducted for bipolar disorder. Over the course of the seven years of the study, 22 research centers around the United States enrolled and treated participants. Thirteen centers, including UCDHSC, participated for the majority of the project, and participants from these centers comprise 90 percent of the total number enrolled.

More than 4,000 subjects in the study were diagnosed with bipolar I or bipolar II disorder. In Colorado, 200 bipolar patients participated. Of the 2,689 individuals who experienced an acute depressive episode while in the study, 366 were eligible and agreed to enter the randomized trial.

Each of the 366 participants in the trial was taking a mood stabilizer and was randomized to receive either an antidepressant - bupropion (Wellbutrin) or paroxetine (Paxil) - or a placebo sugar pill. After 26 weeks, 24 percent of those taking the antidepressants recovered from their episode of bipolar depression (they had minimal or no symptoms for at least eight consecutive weeks), whereas 27 percent of those assigned to placebo also stayed for well for the same time period. Ten percent of each group (the antidepressant groups and the placebo group) experienced mania symptoms, indicating the antidepressants were no more likely to trigger a manic episode than placebo.

According to the authors, episodes of depression are the most frequent cause of disability among patients with bipolar disorder, which is the sixth-leading cause of disability worldwide. Annual health care costs associated with bipolar disorder exceed those of diabetes and recurrent major depressive disorder.

"Bipolar depression is notoriously difficult to treat, and finding the right treatment balance for people with bipolar disorder is a challenge," said David Miklowitz, professor of psychology and psychiatry at CU-Boulder and co-principal investigator of the study. "This seven-year study helps us identify what does and does not work. Antidepressants may not be required as an addition to mood stabilizers in the initial treatment of bipolar depression."

For more information about the multi-center study, visit .

The School of Medicine faculty work to advance science and improve care as the physicians, educators and scientists at University of Colorado Hospital, The Children's Hospital, Denver Health, National Jewish Medical and Research Center and the Veterans Administration Medical Center. The School is part of the University of Colorado at Denver and Health Sciences Center, one of three universities in the University of Colorado system. For more information, visit the Web site at or the UCDHSC Newsroom at .