Studies nix use of antidepressants for bipolar disorder, advocate psychotherapy
By Laura Madden-Fuentes
Two recent studies – one that challenges using antidepressants with mood stabilizers as first-line therapy and another that backs the effectiveness of intensive psychotherapy -- will have a major effect on how people with bipolar disorder are treated, said Laura Marangell, M.D., associate professor of psychiatry and behavioral sciences and director of mood disorders research at Baylor College of Medicine.
Both studies were part of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), a collaboration sponsored by the National Institute of Mental Health to foster large, real-world studies to evaluate the effectiveness of treatment.
Mood stabilizers seen as best treatment
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 Marangell, who along with a consortium of researchers reported on this large, multi-center study that appeared in a recent issue of 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 Marangell, professor of psychiatry and behavioral medicine at BCM and one of the lead investigators in the study. "As first-line treatment for depression in bipolar disorder, we do not recommend antidepressants."
Antidepressants don't trigger manic episodes
The study also determined that adding an antidepressant to a mood stabilizer was unlikely to trigger a manic episode.
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 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 the disorder.
In this study, 366 patients at 22 sites across the nation were randomly assigned to receive a mood stabilizer plus placebo 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. 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.
Specialized psychotherapy helpful
Intensive psychotherapy treatments that involve problem-solving and other coping strategies were more effective as an adjunct treatment for patients receiving mood stabilizers for their bipolar disorder than standard, brief interventions, said a consortium of researchers including Marangell. The study appeared in a recent issue of the Archives of General Psychiatry.
"These treatments were not what most people think of as psychotherapy," Marangell said. "They deal much more with the here-and-now issues such as current problem-solving strategies."
"It is important to remember that this was not psychotherapy alone," Marangell said. "This was in addition to standard medications that are needed to treat bipolar disorder."
This study was one of several carried out by STEP-BD. Across 15 study sites, 293 patients were randomly assigned to receive either intensive, specialized psychosocial treatment or a minimal psychosocial intervention, in addition to mood-stabilizing drugs.
If assigned to receive intensive psychosocial treatment, the patient received one of three forms of therapy including: cognitive behavior therapy, which focuses on changing thoughts and behaviors; interpersonal and social rhythm therapy, which addresses disruptions to social routines and interpersonal problems; or family-focused therapy, which involves patients and their families educational sessions that teach them to work together to solve problems related to the illness. These therapies were provided in up to 30 sessions in nine months.
The minimal psychosocial intervention consisted of three sessions in six weeks and focused on patient education about the illness through video and workbooks.
Quicker recovery through therapy
While the study found no significant difference between the three intensive psychosocial therapies, it did find that the intensive psychosocial treatment resulted in quicker recovery from a depressive episode than the minimal standard treatment. Also, the intensive therapy increased the likelihood that a patient would remain well for 12 months.
"These therapies are not ‘counseling,' or the type of therapy that involves talking about childhood feelings," said Marangell. "A good analogy is with a person that has a heart attack: you treat it medically but also don't advise that the person goes back to an unhealthy lifestyle that they may have had before. There is a rehabilitation and adaptation component to recovery.
"Psychotherapy is rehabilitation for the circuitry in the brain. It helps people learn how to regulate their moods as much as they can and to identify and understand the effects of lack of sleep and other triggers so that they can take control of their illness."
"Bipolar disorder is one of the top 10 causes of morbidity worldwide," said Marangell. "It's a lifelong disorder, typically starting in early life, and it can be truly disabling."
The large study group that put together this research and a series of other studies is poised to help the understanding of bipolar disorder, which the World Health Organization ranks as one of the top 10 causes of disability in the world.
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.
Houston area residents wishing to enroll in the registry can call 713-798-MOOD. Additional information is available on the national web site at www.bipolartrials.org.
Future findings from studies in the new Bipolar Trials Network (http://www.bipolartrials.org) will attempt to answer questions on how best to treat the many facets of bipolar disorder.
Marangell is the Brown Foundation Chair of the Psychopharmacology of Mood Disorders in the Menninger Department of Psychiatry and Behavioral Sciences at Baylor College of Medicine
Abstracts of the articles can be found at http://content.nejm.org/cgi/content/abstract/356/17/1711 and
http://archpsyc.ama-assn.org/cgi/content/abstract/64/4/419.
