Zyprexa Superior to Lithium for Bipolar Disorder

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Title: New Data Suggest Zyprexa (Olanzapine) Superior To Standard Of Care (Lithium) For Preventing Mania Relapse In Bipolar Disorder

"New Data Suggest Zyprexa (Olanzapine) Superior To Standard Of Care (Lithium) For Preventing Mania Relapse In Bipolar Disorder"

INDIANAPOLIS, IN -- September 16, 2002 -- Zyprexa (olanzapine) was found to be more effective than lithium in helping patients with bipolar disorder remain in remission and prevent relapse into mania, according to new data presented at the Third European Stanley Foundation Conference on Bipolar Disorder. The year-long study showed that in the maintenance treatment of bipolar disorder, patients taking Zyprexa relapsed into mania only half as often as patients taking lithium, which has long been considered a standard of care for stabilizing mood in bipolar disorder. The two treatments were comparable with regard to preventing relapse into depression. In addition, significantly more Zyprexa-treated patients completed the study and significantly fewer were hospitalized. "While both drugs performed well, Zyprexa was found to be superior to lithium. This is especially impressive from a clinical standpoint given that lithium has been the gold standard for decades for the prevention of mania," said Frederick Goodwin, M.D., Director, Center on Neuroscience, Medical Progress, and Society, Washington University Medical Center, Washington, DC. "This advance is very encouraging for the long-term treatment of the disease, meanwhile, we must continue our efforts to improve outcomes for bipolar depression." Devastation of Bipolar Disorder An estimated three million Americans have bipolar disorder, a chronic condition consisting of cycles of mania and depression interspersed with periods of normal mood. People with the disorder also may experience mixed episodes, marked by symptoms of mania and clinical depression occurring simultaneously. Without proper treatment, patients with bipolar disorder often participate in harmful activities such as abusing drugs and spending excessively. They are also more likely to attempt and commit suicide than individuals with other psychiatric conditions or in the general population. In fact, an estimated 25 percent of people with bipolar disorder will attempt suicide at least once and between 10 to 20 percent will succeed. Effective treatment is available for many but not all patients. However, patients with bipolar disorder often take multiple medications or suffer unmanageable side effects that can interfere with compliance. Lithium, for example, requires blood monitoring for potential adverse reactions. Study Design Remission was defined as a score of less than or equal to 12 on the Young Mania Rating Scale (YMRS), an 11-item scale used to assess severity of mania, and less than or equal to 8 on the Hamilton Depression Rating Scale (HAMD-21), a 21-item scale used to assess severity of depression. 543 patients with bipolar I disorder (manic or mixed episode), a history of at least two manic or mixed episodes within six years, and YMRS greater than or equal to 20 received open label Zyprexa and lithium combination therapy for six to 12 weeks. 431 patients met remission criteria and were randomized to 52 weeks of double-blind monotherapy treatment with Zyprexa (n=217; 5-20 mg/d) or lithium (n=214; 0.6-1.2 mEq/L blood level in a dose range of 300-1800 mg/d). Key Results The study found that Zyprexa was superior to lithium for the maintenance treatment of bipolar disorder: -- Zyprexa-treated patients had lower rates of relapse into mania or depression compared to lithium-treated patients (30.0% vs. 38.8%, p=.055). -- Rates of relapse into mania were significantly less with Zyprexa than with lithium (14.3% vs. 28.0%, p<.001). Rates of relapse into a depressive episode were similar between treatment groups (16.1% vs. 15.4% respectively, p=.895). -- Patients taking lithium experienced a mania relapse significantly sooner than those taking Zyprexa (estimated time for 25% of patients on each treatment to relapse was 212 days for lithium vs. 380 days for Zyprexa; p<.001). -- Zyprexa-treated patients had a lower rate of hospital admissions than lithium-treated patients (14.3% vs. 22.9%, p=.026). -- Significantly more Zyprexa-treated patients completed the trial than those taking lithium (46.5% vs. 32.7%, p=.004). The Zyprexa group experienced lower discontinuation rates due to adverse events compared to the lithium group (18.9% vs. 25.7%, p=.105). -- Lithium patients had a significantly faster time to discontinuation (p=0.017). Median time to discontinuation was 303 days for Zyprexa and 207 days for lithium. "What we have are two solid treatment options," said Mauricio Tohen, MD, Ph.D., Lilly Clinical Research Fellow, Lilly Research Laboratories. "This study provides further evidence that Zyprexa as a foundational treatment can help patients maintain dependable control in all phases of bipolar disorder, ultimately helping them to move their lives forward." The most common self-reported treatment-emergent adverse event for patients treated with Zyprexa was depression. The most common adverse events with lithium were insomnia and mania. Other common events were insomnia, mania, drowsiness and nausea for the Zyprexa-group and depression and nausea for the lithium group. Mean weight gain during the stabilization of the index manic episode (lithium + olanzapine) was 2.74 kg. During the double blind phase weight gain was significantly greater in the Zyprexa group than in the lithium group (1.79 kg vs. -1.38 kg, P<.001). The Stanley Medical Research Institute is the largest private provider of research on schizophrenia and bipolar disorder in the United States and is a major provider of research on these diseases in England, Ireland, Germany, Sweden, Denmark, Israel, and Australia. The Third European Stanley Foundation Conference on Bipolar Disorder was held in Freiburg, Germany, on September 12th and 13th. Zyprexa Background Zyprexa is currently indicated 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 is 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 10 million people worldwide. In the original schizophrenia registration trials, Zyprexa was generally well tolerated. However, as with all medications, Zyprexa was associated with some side effects. In the original six-week, acute-phase schizophrenia trials, the most common treatment-emergent adverse event associated with Zyprexa was somnolence. Other common events were dizziness, weight gain, constipation, akathisia (restlessness) and postural hypotension. Modest elevations of prolactin were also seen, although mean changes from baseline to endpoint were not statistically significantly different between Zyprexa and placebo. A small number of patients experienced asymptomatic elevations of hepatic transaminase; none of these patients developed jaundice or drug-induced hepatitis. In short-term (3- and 4-week) acute bipolar mania trials, the most common treatment-emergent adverse event associated with Zyprexa was somnolence. Other common events were dry mouth, dizziness, asthenia, constipation, dyspepsia, increased appetite and tremor. For safety information regarding lithium, see the product's full prescribing information. Lilly, a leading innovation-driven corporation, is developing a growing portfolio of best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers -- through medicines and information - for some of the world's most urgent medical needs. Additional information about Lilly is available at http://www.lilly.com. SOURCE: Eli Lilly & Co.