With the Food and Drug Administration’s approval in March of olanzapine (Zyprexa) for the treatment of mania in bipolar disorder, psychiatry gains a much needed tool in the difficult management of the disorder. Studies have shown that olanzapine not only controls mania, but also acts as a mood stabilizer, therefore significantly reducing the danger of precipitating a depressive event following an acute manic episode.

Researchers believe that olanzapine may be effective as the primary pharmacological agent in bipolar I disorder, without the use of other antipsychotic or antidepressant medications.

Frederick K. Goodwin, M.D., a professor of psychiatry and director of the Center on Neuroscience, Medical Progress, and Society at George Washington University Medical Center, and Paul E. Keck, M.D., a professor of psychiatry and pharmacology and vice chair for research in the department of psychiatry at the University of Cincinnati College of Medicine, participated in a teleconference press briefing last month on mania in bipolar disorder and its treatment. Joining them was Mauricio Tohen, M.D., Dr. P.H., an associate clinical professor of psychiatry at Harvard Medical School and a medical advisor at Eli Lilly and Co., the maker of Zyprexa.

Goodwin detailed evidence that bipolar disorder may be significantly underdiagnosed. He cited a study that followed patients who had been initially diagnosed with bipolar disorder while hospitalized. Five to seven years after discharge, roughly half the patients either denied or forgot about their bipolar diagnosis. In addition, Goodwin presented data from a study he conducted in Boston in which he looked at a group of patients who were diagnosed with bipolar disorder, again during a hospitalization. Only 59 percent of patients were diagnosed prior to their admission to the hospital for an acute manic episode.

"Most of them were diagnosed as having major depression," Goodwin said, "and had been treated as having major depression. Of course, we know that using antidepressant medications in these patients in the absence of a mood stabilizer can increase the likelihood of manic switches."

According to Goodwin, the best estimates of prevalence for bipolar disorder in the U.S. are in the range of 3 million to 5 million postadolescent patients.

Goodwin also discussed the significantly increased morbidity and mortality associated with untreated bipolar disorder. People with bipolar disorder will spend as much as one quarter of their adult lives in the hospital, and they will live one quarter of their adult lives disabled. This results in as much as 14 years of cumulative lost productivity. Bipolar disorder results in a 9.2 year reduction in expected life span, and as many as one in five patients with bipolar disorder commits suicide.

Keck and Tohen followed Goodwin’s presentation with a review of treatment options available prior to olanzapine’s approval. Only two other medications have been approved for the indication of bipolar disorder: lithium and, more recently, divalproex. They have been used in combination with off-label prescribing of antidepressants, neuroleptics, anticonvulsants, and some of the newer, atypical antipsychotics, including off-label use of olanzapine in bipolar disorder.

According to Keck and Tohen, the approval of olanzapine is a significant step in treatment protocols for bipolar disorder. Olanzapine acts both as an antimanic and an antidepressant, and therefore it may be used as a primary mood stabilizer in bipolar disorder. In addition, olanzapine appears to be more effective in bipolar patients who exhibit "mixed states," a benefit not inherent with either lithium or divalproex. An added feature is its ability to control psychotic manifestations in those patients who are prone to them.

The FDA looked at two studies in its approval of olanzapine for mania. In the two studies, involving a total of 254 patients hospitalized for an active manic episode, 58 percent experienced a clinical response defined as a 50 percent reduction in their symptoms. The patient groups in both studies included subjects with psychotic features and without psychotic features, as well as patients displaying mixed states.

The potential for drug interactions and adverse reactions has been significant with these combinations of medications used in bipolar disorder. With olanzapine, no blood monitoring is necessary, and the side-effect profile and drug interactions appear to be less significant. The most significant side effects associated with olanzapine are dizziness (due to hypotension), dry mouth, and drowsiness. The only significant drug interaction observed so far with olanzapine occurs when administered together with carbamazepine (Tegretol). Carbamazepine therapy significantly increases the clearance of olanzapine (by as much as 50 percent).