Zyprexa + Prozac Combo Pill For Bipolar Depression
Data Suggest Olanzapine and Olanzapine/Fluoxetine Combination May Provide Rapid Antidepressant Action Without Inducing Mania in Patients With Bipolar Depression

May 22, 2003

New data presented today at the American Psychiatric Association's 156th annual meeting in San Francisco, showed that both olanzapine (Zyprexa) and olanzapine combined with fluoxetine (Prozac) (olanzapine/fluoxetine combination or OFC) provided a rapid onset of action in treating patients with bipolar depression. Furthermore, data showed that Lilly's investigational compound OFC demonstrated a robust and sustained antidepressant action and further improvement in the symptoms of bipolar depression.

Data from a second analysis presented today at the APA demonstrated that patients with bipolar depression treated with OFC were no more likely to develop treatment-emergent mania than patients receiving placebo or olanzapine alone. In patients with bipolar depression, a manic episode is a potential consequence of treatment with an antidepressant medication.

"Rapid onset of action and avoiding mania are both key elements in effectively treating patients with bipolar depression because these individuals are at a high risk of suicide," said Dr. Paul Keck, Professor of Psychiatry, Pharmacology and Neuroscience, Vice Chairman for Research, Department of Psychiatry, University of Cincinnati College of Medicine. "These studies add to the growing body of scientific evidence suggesting that using olanzapine as the foundation of treatment for bipolar disorder may speed the antidepressant effect of fluoxetine while stabilizing patients' mood," he added.

Key Findings

Onset of Action Study

• Both olanzapine and OFC demonstrated a statistically significant faster onset of action compared to placebo. Both olanzapine and OFC separated from placebo within the first week of treatment.
• The estimated median time to a partial response was eight days with OFC, 14 days with olanzapine, and 35 days with placebo. A partial response is defined as at least a 20 percent reduction in depressive symptom scores for two consecutive weeks that is maintained for the remainder of treatment.
• The rapid and robust effect of OFC in patients with bipolar depression was sustained, and it separated from both placebo and olanzapine by the end of the study.

Treatment-Emergent Mania Study

• Neither OFC nor olanzapine had a greater risk of treatment-emergent mania than placebo.
• During the acute phase of the study, mania symptom scores in OFC and olanzapine-treated patients decreased, separating from placebo at weeks one, six, and eight.
• Rates of treatment-emergent mania for OFC and olanzapine during the open-label extension phase were also low, and were lower than those seen for placebo during the acute phase.

"While olanzapine is well-recognized as an effective treatment for mania, these studies demonstrate that both OFC and olanzapine may be useful in filling the need for new treatment choices for people who suffer from bipolar depression," added Dr. Keck.

"When physicians can offer their patients medications that work quickly, effectively and dependably, this strengthens the doctor-patient relationship, allowing physicians to help their patients achieve their full potential," said Mauricio Tohen, MD, Dr. PH, Lilly Clinical Research Fellow, Lilly Research Laboratories. "We hope, through our continued work , to provide answers to help guide clinicians through the challenges they face in treating bipolar depression," he added.

Olanzapine/fluoxetine combination is currently under U.S. Food and Drug Administration (FDA) review for the treatment of bipolar depression. There is currently no FDA-approved treatment for acute bipolar depression. Olanzapine is currently indicated for the short-term treatment of acute manic episodes associated with bipolar disorder and is under review by the FDA for long-term maintenance of response in the treatment of bipolar disorder.

Study Design

Both analyses were conducted of an eight-week, double-blind, placebo-controlled study of 833 patients, age 18 and older with a diagnosis of bipolar 1 disorder. Patients were randomly assigned to one of three treatment groups: OFC, olanzapine alone, or placebo. Researchers employed the Montgomery-Asberg Depression Rating Scale (MADRS), a commonly-used depression rating scale, to measure improvements in symptoms throughout the study period for those in the first study. In the second study, treatment-emergent mania was evaluated by using two scales the Young Mania Rating Scale (YMRS) and the Clinical Global Impression-Improvement Scale (CGI) to identify a potential switch to a manic episode and the severity. This study included an optional six-month open label extension phase in which patients started on olanzapine alone and subsequently switched to OFC.

The most common treatment-emergent adverse event for patients treated with both olanzapine and OFC in the study was drowsiness. Other common events for olanzapine-treated patients included weight gain, increased appetite, headache and dry mouth. For patients treated with OFC, other common treatment-emergent adverse events included diarrhea, weight gain, dry mouth, headache, increased appetite, asthenia (muscle weakness) and nausea.

SOURCE: Eli Lilly and Company press release

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