Princeton N.J. & Tokyo — Bristol-Myers Squibb Company and Otsuka Pharmaceutical Co., Ltd., announced today that the U.S. Food and Drug Administration (FDA) has approved Abilify (aripiprazole) as an adjunct to the mood stabilizers lithium or valproate for the maintenance treatment of Bipolar I Disorder.
Abilify was approved as an adjunct to lithium or valproate for the acute treatment of manic or mixed episodes associated with Bipolar I Disorder in May 2008. Abilify is also approved as monotherapy for the acute treatment of manic or mixed episodes associated with Bipolar I Disorder and for the maintenance treatment of Bipolar I Disorder.
Abilify has a boxed warning regarding increased mortality in elderly patients with dementia-related psychosis. Elderly patients treated with antipsychotic drugs are at an increased risk of death. Abilify is not approved for the treatment of patients with dementia-related psychosis.
“Patients with Bipolar I Disorder often experience cycles of severe mood swings rather than a single episode1,” said John Tsai, MD, vice president, U.S. Medical, Bristol-Myers Squibb.
“Because Bipolar Disorder is a lifelong and recurrent illness, this labeling update provides physicians with the option to prescribe Abilify as an add-on to either lithium or valproate as a long-term treatment to help manage symptoms of Bipolar I Disorder. Patients should be periodically reassessed by their physician to determine the continued need for maintenance treatment.”
“Otsuka remains committed to developing products that are able to meet their fullest potential while helping physicians provide effective care for their patients,” said William H. Carson, MD, President and CEO, Otsuka Pharmaceutical Development and Commercialization, Inc.
“By updating the label to include maintenance treatment with Abilify as an add-on to lithium or valproate for patients with Bipolar I Disorder, we are helping to provide more options to physicians.”
The new indication is based on results from a 52-week maintenance trial of Abilify (aripiprazole) and lithium or valproate in patients meeting DSM-IV criteria for Bipolar I Disorder. In this study, adjunctive Abilify was superior to adjunctive placebo on the primary study endpoint of time from randomization to relapse to any mood event.
Mood events were defined as hospitalization for a manic, mixed or depressive episode, study discontinuation due to lack of efficacy (accompanied by Y-MRS and/or MADRS score >16)*, or a serious adverse event of worsening disease (accompanied by Y-MRS and/or MADRS score >16).
Through 52 weeks, the most commonly observed treatment-emergent adverse event associated with adjunctive Abilify and lithium or valproate (incidence ≥5% and at least twice that of adjunctive placebo) in patients with Bipolar I Disorder was tremor (adjunctive Abilify: 6.0%; adjunctive placebo: 2.4%).
This randomized, double-blind, placebo-controlled study enrolled adult patients meeting DSM-IV criteria for Bipolar I Disorder, who experienced a recent manic or mixed episode and who had a history of one or more manic or mixed episodes of sufficient severity to require hospitalization and/or treatment with a mood stabilizer or antipsychotic.
In this study, patients were initiated on open-label lithium (0.6 mEq/L to 1.0 mEq/L) or valproate (50 μg/mL to 125 μg/mL) at therapeutic serum levels, and remained on stable doses for two weeks.
After two weeks, patients who demonstrated an inadequate response (Y-MRS total score ≥16 and ≤35% improvement on the Y-MRS total score) to lithium or valproate alone received Abilify as adjunctive therapy with a starting dose of 15 mg/day, and the option to increase to 30 mg/day or reduce to 10 mg/day as early as day four.
After 12 consecutive weeks of stability (Y-MRS and MADRS total scores ≤12) on adjunctive Abilify and lithium or valproate, 337 patients were randomized in a double-blind fashion to receive either the same dose of Abilify and lithium or valproate as they received at the end of the stabilization period or placebo and lithium or valproate.
Patients were then monitored for manic, mixed or depressive relapse for a maximum of 52 weeks. A total of 68 mood events were observed during the double-blind treatment phase. Twenty-five were from the Abilify group and 43 were from the placebo group.
The number of observed manic episodes in the Abilify (aripiprazole) group (7) were fewer than that in the placebo group (19), while the number of depressive episodes in the Abilify group (14) was similar to that in the placebo group (18).
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