Antidepressants May Not Help Fight Bipolar Disorder

Stick to mood stabilizer alone, major new study suggests

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HealthDay Reporter

WEDNESDAY, March 28, 2007 (HealthDay News) -- Patients with bipolar disorder will gain no treatment benefit by adding an antidepressant to a standard mood stabilizer such as lithium, a new study finds.

The results suggest that treating with a mood stabilizer alone is preferable, a recommendation that goes against common practice.

"We really think that at the beginning of your treatment, it is very reasonable to have this 'mood-stabilizer-optimized' kind of approach, and what we've learned from this study is it makes sense to give that some time to work," said Dr. Gary Sachs, lead author of the study, director of the bipolar clinic and research program at Massachusetts General Hospital and associate professor of psychiatry at Harvard Medical School in Boston.

"The patient loses nothing from that," Sachs added. "We did not show that any group benefited from having antidepressants added."

On the other hand, doubling up the medications did not confer any risk, Sachs's team reported in the March 29 issue of the New England Journal of Medicine.

Treating bipolar disorder is never a one-size-fits-all proposition, however.

"It's hard to judge at the individual level because of individual variation," said Dr. Christopher Colenda, dean of the Texas A&M Health Science Center College of Medicine in College Station. "As a treating clinician, you may try single therapy for a while and, if it doesn't work, add the antidepressant. This study gives us a rational place to start and to make clinically relevant decisions."

Bipolar disorder is characterized by alternating swings of very high and very low -- or depressed -- moods, along with changes in energy and the ability to function. About 5.7 million American adults, or about 2.6 percent of the population 18 and older, may have bipolar disorder, according to the National Institute of Mental Health.

The standard of care for bipolar disorder is treatment with a mood stabilizer such as lithium, valproate, carbamazepine or other medications that reduce mania.

Although antidepressants have never been approved to treat bipolar disorder, and although there is limited evidence as to their safety and efficacy, such medications are commonly prescribed in addition to a mood stabilizer.

However, many researchers worry that antidepressants may even trigger a manic episode in bipolar patients.

"This practice is extremely prevalent," Sachs said. "The investigators agreed that the number one priority was resolving this issue, because there are two competing expert recommendations: a stabilizer plus an antidepressant or a stabilizer alone. We asked the question, 'Would two be better than one?' "

This trial, a collaboration with the U.S. National Institutes of Mental Health, randomly assigned 336 individuals with bipolar disorder from "real world," clinical settings to take a mood stabilizer plus either an antidepressant (bupropion/Wellbutrin or paroxetine/Paxil) or a placebo.

After about 26 weeks, 23.5 percent of patients taking antidepressants had stayed well for at least eight weeks in a row vs. 27.3 percent of those taking a placebo. The difference was not statistically significant.

"In this study, we do not show a benefit nor a problem due to antidepressants," Sachs said. "We didn't show anything to gain. We also didn't show any harm, and there may well be individual patients who might respond to antidepressants and individual antidepressants that actually work better."

Also, about 10 percent of each group -- with or without antidepressants -- experienced the onset of mania.

Sachs was surprised by the finding. "I had firmly believed that antidepressants triggered mania," he said. "This is an important finding of the study. That's a real thing I have to take to heart."

Another expert said the study could change doctors' thinking.

"Treatment needs to be individualized, but, for the vast majority of patients, antidepressants don't offer critical benefit and may carry significant risk," said Dr. Richard Weisler, adjunct professor of psychiatry at the University of North Carolina at Chapel Hill and adjunct associate professor of psychiatry at Duke University Medical Center in Durham, N.C.

Other studies have suggested that antidepressants do come with their own dangers, and, "if you've got those risks and little benefit, then we need to be rethinking how most clinicians are actually treating bipolar in this country," Weisler said.

As early as next week, results regarding the effects of psychosocial treatments used in the trial will be released. And there will likely be many more papers from this set of data, Sachs said.

More information

For more on bipolar illness, head to the National Institute of Mental Health.

SOURCES: Gary S. Sachs, M.D., director, bipolar clinic and research program, Massachusetts General Hospital, and associate professor, psychiatry, Harvard Medical School, Boston; Christopher Colenda, M.D., dean, Texas A&M Health Science Center College of Medicine, College Station; Richard Weisler, M.D., adjunct professor, psychiatry, University of North Carolina at Chapel Hill, and adjunct associate professor, psychiatry, Duke University Medical Center, Durham, N.C.; March 29, 2007, New England Journal of Medicine

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