The FDA ( Food and Drug Administration ) 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 disorder type 1 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.

The new indication is based on results from a 52-week maintenance trial of Aripiprazole and Lithium or Valproate in patients meeting DSM-IV criteria for bipolar disorder type 1. In this study, adjunctive Aripiprazole 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 greater than 16 ), or a serious adverse event of worsening disease ( accompanied by Y-MRS and/or MADRS score greater than 16 ).

Through 52 weeks, the most commonly observed treatment-emergent adverse event associated with adjunctive Aripiprazole and Lithium or Valproate ( incidence greater than or equal to 5% and at least twice that of adjunctive placebo ) in patients with bipolar disorder type 1 was tremor ( adjunctive Aripiprazole: 6%; adjunctive placebo: 2.4% ).

The randomized, double-blind, placebo-controlled study enrolled adult patients meeting DSM-IV criteria for bipolar disorder type 1, 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.
Patients were initiated on open-label Lithium ( 0.6 mEq/L to 1.0 mEq/L ) or Valproate ( 50 mcg/mL to 125 mcg/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 greater than or equal to16 and less than or equal to 35% improvement on the Y-MRS total score ) to Lithium or Valproate alone received Aripiprazole 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 less than or equal to 12 ) on adjunctive Ariprazole and Lithium or Valproate, 337 patients were randomized in a double-blind fashion to receive either the same dose of Aripiprazole 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 Aripiprazole group and 43 were from the placebo group. The number of observed manic episodes in the Aripiprazole group ( 7 ) were fewer than that in the placebo group ( 19 ), while the number of depressive episodes in the Aripiprazole group ( 14 ) was similar to that in the placebo group ( 18 ).

Source: BMS, 2011

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