Giving patients with bipolar disorder antidepressants on top of their mood stabilizer medications does not relieve their depression any better than an inactive pill called a placebo, said researchers who reported on this large, multi-center study that appears online today in the New England Journal of Medicine.
“If you are on mood stabilizer treatment, which is the best first-line treatment for most people with bipolar disorder, adding an antidepressant usually does not help you out of your depression,” said Dr. Lauren Marangell, the Brown Foundation Chair of the Psychopharmacology of Mood Disorders in the Menninger Department of Psychiatry at Baylor College of Medicine and one of the lead investigators in the study. “As first line treatment for depression in bipolar disorder, we do not recommend antidepressants.”
These results “indicate that careful management of mood stabilizer medications is a reasonable alternative to adding an antidepressant medication for treating bipolar depression,” said Dr. Gary D. Sachs of Massachusetts General Hospital in Boston, the lead author in this study.
A second finding was that if patients are taking a mood stabilizer, the antidepressant was no more likely to trigger a manic episode than a placebo. That was another critical question answered by this study.
Bipolar disorder is marked by episodes of depression and mania. Mood stabilizers such as lithium, valproate, lamotrignine, carbamazepine or other medications are usually used in treatment to reduce mood swings, or episodes of mania and depression. However, antidepressants are often prescribed sometimes for the depressed phase of the illness. Depression is more common than mania in bipolar disorder and causes the most difficulty for most people with bipolar disorder. One concern about adding antidepressants is that they might trigger a manic episode. This study puts that concern to rest for most patients, as long as they are taking a mood stabilizer.
The study was part of the work of the Systematic Treatment Enhancement Program for Bipolar Disorder, a collaboration sponsored by the National Institute of Mental Health to foster large “real world” studies to evaluate the effectiveness of treatments.
In this study, 366 patients at 22 sites across the nation were randomly assigned to receive a mood stabilizer plus placebo (an inactive sugar pill) or a mood stabilizer plus one of two antidepressants – buproprion ( Wellbutrin) or paroxetine (Paxil). Neither the patient nor the doctor knew who was in which groups. Forty-two of the 179 who receive the mood stabilizer plus antidepressant therapy had a positive effect called a durable recovery and 51 of the 187 who received the mood stabilizer plus placebo had a positive effect. (Before the study began, physicians adjusted the dose of mood stabilizer to an optimal level.) There was no statistically significant difference between the two groups.
All these patients were drawn from real world populations, and many of them had other disorders such as anxiety, substance abuse or psychosis. Typical studies of drugs exclude patients who have other problems. That is one of the factors that makes this study more valuable, Marangell said.
Marangell said there might be individual patients, particularly those who also have other problems, where antidepressants might be helpful. However, she said, that decision should be made individually by that person’s physician.
The large study group that put together this study and a series of others is poised to significantly help the understanding of bipolar disorder, which the World Health Organization ranks as one of the top 10 causes of disability in the world.
“This is a lifelong disorder that is disabling to millions of Americans”, Marangell said.
Marangell is now the national co-director of the new NIMH Bipolar Trials Network, designed to identify the best treatments for the disorder in real-world settings. One project of this group is a registry in which people with bipolar disorder can enroll. If they become part of the registry, researchers will contact them when a new study becomes available.
Funding for this study came from the NIMH.
Laura Madden-Fuentes
713-798-4710
maddenfu@bcm.tmc.edu
