Antidepressants may not help fight bipolar disorder

Times Staff Writer

Antidepressants, which are widely prescribed with mood stabilizers to treat patients with bipolar disorder, do not work in relieving the depressive symptoms of the illness, a large federal study reported Wednesday.

The study in the New England Journal of Medicine narrows the already limited number of treatments for bipolar disorder, which affects 5.7 million adults in the U.S., experts said.

“A new generation of drugs is needed,” said Dr. Thomas R. Insel, director of the National Institute of Mental Health. “It is clear from this data that antidepressants are not the answer.”


Still, some doctors said antidepressants would continue to have a role because there were so few options, and the drugs seemed to alleviate other symptoms that often accompanied the complex disorder.

“Many people we see are refractory to a mood stabilizer alone, and adding an antidepressant markedly improves them,” said Dr. Lori Altshuler, professor of psychiatry at UCLA, who was not involved in the study.

But Altshuler, who has consulted for companies that market drugs for psychological disorders, said the study clearly demonstrated that patients should first try a mood stabilizer, which could also have antidepressant effects.

People with bipolar disorder experience severe mood swings between depression and mania, a state marked by an excess of energy and restlessness. For most patients, depressive episodes are three times more common and longer-lasting than those of mania. Symptoms of the disorder can interfere with daily activities, and severe cases carry a risk of suicide.

Standard treatment consists of mood stabilizers such as lithium, valproate and carbamazepine. Antidepressants are often added to control severe depressive swings, despite concerns the drugs may trigger a switch to a manic episode.

Researchers estimated that 50% to 70% of people with bipolar disorder take antidepressants, although the Food and Drug Administration has approved none of the drugs as a treatment for the disorder.


The study, part of the institute’s $27-million Systematic Treatment Enhancement Program for Bipolar Disorder, set out to determine whether the common antidepressants Wellbutrin and Paxil would enhance the benefits of mood-stabilizer drugs. The study was also designed to find out whether the antidepressants would trigger mania.

Previous studies provided mixed results on effectiveness. Wellbutrin and Paxil were chosen because earlier studies indicated they were less likely to trigger mania than other antidepressants.

In the study, 366 patients at 22 academic centers in the U.S. were randomly assigned to receive one of the two antidepressants or a placebo for 26 weeks, in addition to their mood stabilizers. Patients also received psychological and social therapy.

The study, designed to mimic real-world conditions, differed from a typical clinical trial in that many patients had complicating disorders, including anxiety, substance abuse or psychosis.

Of the 179 participants who received an antidepressant in addition to a mood stabilizer, 23.5% achieved a durable recovery, defined as an eight-week period marked by no more than two depressive or two manic symptoms.

In the placebo group, 27.3% of patients achieved a durable recovery.

The difference between the groups was not statistically significant, researchers said.

The criteria of durable recovery were stricter than in other trials, which used rating systems to measure overall improvements in patients’ moods.

Researchers reported there was no sign that Wellbutrin or Paxil could trigger a manic episode. They said 10.1% of patients on antidepressants and 10.7% of those on placebo exhibited manic symptoms.

Lead author Dr. Gary Sachs, director of the bipolar clinic at Massachusetts General Hospital, said the study should guide the way new patients were treated, but there was no need for patients doing well on antidepressants to quit taking them.

“There is no benefit from standard antidepressant medication,” he said. “But there is no risk to adding it, either.”

In an editorial accompanying the report, Dr. Robert H. Belmaker of Ben Gurion University in Beersheba, Israel, said the study would not settle debates about the safety and efficacy of antidepressants in treatment of bipolar disorder.

Patients who had become manic in response to antidepressants in the past would not have enrolled in the trial, he said, casting doubt on whether the drugs are safe for all bipolar patients.

Belmaker noted that two European reviews of published studies found antidepressants to be effective, and that in his own practice he prescribed antidepressants to patients with severe depression but mild mania.

He said that bipolar disorder showed wide variability in symptoms, which argued for flexibility in treatment.