Ateeq Ahmad
Jina Pharmaceuticals, Inc., USA
Title: The calming down of emotional ferris wheel, Bipolar disease: Demonstration of anti-manic efficacy of endoxifen in Bipolar I disorder patients
Biography
Biography: Ateeq Ahmad
Abstract
Protein kinase C (PKC) activity is increased in frontal cortex of subjects with bipolar affective disorder. Endoxifen, an active metabolite of tamoxifen, was recently demonstrated to inhibit PKC1. We report for the first time the anti-manic effect of endoxifen in patients with bipolar I disorder (BPD I) with current manic or mixed episode. The efficacy was evidenced by change from baseline on total scores of mania [e.g., Young Mania Rating Scale (YMRS)] measures. In a double-blind, active-controlled study, 84 subjects with BPD I were randomly assigned to receive endoxifen (4 mg/day or 8 mg/day) or divalproex (1000 mg/day) in a 2:1 ratio. Patients orally administered at 4 or 8 mg/day endoxifen showed significant improvement in mania assessed by the YMRS as early as 4 days. The effect remained significant throughout the 21-day period. At study end point, YMRS scores showed the response rates were 44.44% and 64.29% at 4 and 8 mg/day of endoxifen treatment respectively. The Exposure-Response (PK-PD) analysis shows dose proportionality of endoxifen2. Thus, endoxifen has been shown as a promising anti-manic or mood stabilizing agent.