Data Show Olanzapine/Fluoxetine Combination Resulted in Higher Remission Rates in Treatment-Resistant Depression.

Business Editors/Health & Medical Writers

PHILADELPHIA--(BW HealthWire)--May 21, 2002

(NYSE:LLY)

In Studies, Combination Also Maintained Effect Longer Than

Monotherapy Treatment

The combination of olanzapine and fluoxetine significantly reduced depressive symptoms and resulted in significantly higher remission rates in the management of treatment-resistant depression (TRD) when compared with the use of olanzapine or fluoxetine alone, according to new data from two studies presented today at the American Psychiatric Association's 155th annual meeting.(1)

Eli Lilly and Company (NYSE:LLY) is currently developing a new medicine that is an olanzapine/fluoxetine combination (OFC) for the treatment of difficult-to-treat mood disorders, such as TRD, bipolar depression and psychotic depression. Lilly plans to submit a New Drug Application in the second half of this year to the U.S. Food and Drug Administration for its use of OFC as a treatment for bipolar depression.

In the studies, TRD, a subset of major depressive disorder, is defined as the failure of a patient to respond to at least two antidepressants. Up to 30 percent of patients with major depression may be resistant to conventional antidepressant treatment.(2) More than 50 percent of suicides are associated with a major depressive disorder.(3) Currently, there is no standard, clinically accepted treatment algorithm for patients who fail to respond to adequate antidepressant therapy and there is no approved medication for TRD.

Study Results

A meta-analysis of data from two studies presented today showed that patients taking OFC had a significant decrease from baseline Montgomery-Asberg Depression Rating Scale (MADRS) depression scores within one week of treatment (-7.31) compared with patients taking olanzapine (-5.18 p=0.013) or fluoxetine (-5.26 p=0.004) alone.

This effect was maintained throughout the eight weeks of treatment (-11.60; -7.55, p= less than 0.001; -8.73, p less than 0.001) and OFC had a significantly greater response rate than olanzapine (37.3 percent, 21.1 percent) and significantly greater remission rates than olanzapine or fluoxetine (24.9 percent, 13.1 percent and 15.2 percent).(1)

Study Design

Patients included in the two studies were those that had historic failure to respond to a 4-week trial of a selective serotonin reuptake inhibitor (SSRI) antidepressant and had a prospective failure to respond to a trial taking a non-SSRI. Patients with TRD (N=797) without psychotic features were randomized to receive either OFC, olanzapine or fluoxetine. MADRS was the primary efficacy measure.

"The data show OFC may be a promising new treatment strategy for patients with TRD," said Sanjay Dube, M.D., lead author of the study and medical director for Lilly's OFC team. "The combination demonstrated impressive response and remission rates, which began at the outset of the trial and were sustained throughout the eight-week duration, suggesting that OFC may provide a superior approach for the management of TRD."

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 www.lilly.com.

References

1. Dube, Andersen SW, Paul S, Corya SA, Van Campen LE, Sanger TM,

Tollefson GD. Metanalysis of olanzapine/fluoxetine use in

treatment-resistant depression. Poster presentation at the

annual meeting of the American Psychiatric Association,

Philadelphia, Pennsylvania, May 2002.

2. Cadieux RJ. (1998). Practical management of

treatment-resistant depression. American Family Physician.

58(9):2059-2062

3. Janicak PG, et al. Clinical Cornerstone: Depression. Vol

1;(4):58-70