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FDA approves Zyprexa in combination with lithium or valproate for bipolar I acute manic episodes

INDIANAPOLIS, IND., July 15, 2003 -- Eli Lilly and Company announced that the FDA has approved Zyprexa (olanzapine) for use in combination with lithium or valproate (Depakote, Abbott) for the treatment of acute manic episodes associated with bipolar I disorder. Zyprexa is the first agent to be approved for use in combination with other mood stabilizers to treat acute bipolar mania. Zyprexa was approved by the FDA in 2000 as a monotherapy for the short-term treatment of acute manic episodes associated with bipolar disorder and is the only atypical antipsychotic approved by the FDA to treat this patient population.

"Since bipolar mania is often challenging to treat and many patients do not respond rapidly or completely to a single agent, they are frequently treated with a combination of therapies.," said Paul Keck, M.D., professor of psychiatry, pharmacology and neuroscience, vice chairman for research, Department of Psychiatry, University of Cincinnati College of Medicine.

The FDA approval is based on data from two double-blind, randomized, placebo-controlled trials which showed that bipolar patients in manic or mixed episodes, treated with Zyprexa in combination therapy, demonstrated improved manic and depressive symptoms when compared to patients treated only with lithium or valproate alone.(1)

"Patients in manic episodes often have simultaneous depressive symptoms which can be very difficult to treat," said Dr. Keck. "Clinicians should welcome an FDA-approved combination therapy that helps them help these patients," he added.

"This new Zyprexa indication strengthens the substantial body of evidence showing that Zyprexa is a solid foundation for clinicians to use in their treatment of patients with acute bipolar mania," said Mauricio Tohen, M.D., Dr. PH., Lilly Clinical Research Fellow, Lilly Research Laboratories. "At Lilly, we are committed to the continued study of Zyprexa to help provide answers that matter to clinicians in the treatment of this devastating condition."

In addition to its approval more than three years ago for short-term treatment of acute bipolar mania, Zyprexa is currently under FDA review for long-term maintenance of response in the treatment of bipolar disorder. Additionally, Symbyax, an agent that combines Zyprexa with Prozac (fluoxetine), is under FDA review for the treatment of bipolar depression. There is currently no FDA-approved treatment for bipolar depression.

In addition to the newly approved indication, Zyprexa is indicated in the United States for the treatment of schizophrenia, the short-term treatment of acute manic episodes associated with bipolar disorder and for the long-term therapy and maintenance of treatment response of schizophrenia. Zyprexa was the first atypical antipsychotic to prove its long-term effectiveness in patients with schizophrenia. Since Zyprexa was introduced in 1996, it has been prescribed to 12 million people worldwide.

The most common treatment-emergent adverse event associated with Zyprexa in placebo-controlled, short-term schizophrenia and bipolar mania trials was somnolence. Other common events were dizziness, weight gain, personality disorder (COSTART term for nonaggressive objectionable behavior), constipation, akathisia, postural hypotension, dry mouth, asthenia, dyspepsia, increased appetite, and tremor. A small number of patients experienced asymptomatic elevations of hepatic transaminase; none of these patients experienced jaundice.

Prescribing should be consistent with the need to minimize the risk of neuroleptic malignant syndrome, tardive dyskinesia, seizures and orthostatic hypotension.

In short-term (six-week) acute bipolar mania trials in combination with lithium or valproate, the most common treatment emergent adverse event associated with Zyprexa and lithium or valproate was dry mouth. Other common events were weight gain, increased appetite, dizziness, back pain, constipation, speech disorder, increased salivation, amnesia and paresthesia.

Full prescribing information is available at


1. Tohen, M et al. "Efficacy of Olanzapine in Combination With Valproate or Lithium in the Treatment of Mania in Patients Partially Nonresponsive to Valproate or Lithium Monotherapy." Arch Gen Psych 2002; 59:62-69

Source: Eli Lilly

Posted: July 2003