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Aripiprazole Shows Efficacy as Long-Term Maintenance Therapy in Adults With Bipolar I Disorder

PRINCETON, N.J., and TOKYO, Dec. 7 /PRNewswire-FirstCall/ -- Maintenance therapy with the Bristol-Myers Squibb Company (NYSE: BMY - News) and Otsuka Pharmaceutical Co., Ltd. atypical antipsychotic Abilify® (aripiprazole) for nearly two years significantly delayed time to relapse in adults with Bipolar I Disorder who had a recent manic or mixed episode and were then stabilized with the medication for at least six weeks, according to findings published in a supplement to Neuropsychopharmacology. The results - from the longest double-blind, randomized, placebo-controlled study reported to date investigating the treatment of Bipolar I Disorder with Abilify - were based on rigorous criteria used to define stability for Bipolar I Disorder.

"Bipolar I Disorder is a lifelong episodic illness. These findings are important because they support existing Abilify data for delaying the recurrence of mood symptoms," said Roger S. McIntyre, MD, Head, Mood Disorders Psychopharmacology Unit, University Health Network, Associate Professor of Psychiatry and Pharmacology, University of Toronto. "In fact, a recent study showed that nearly 50 percent of individuals who responded to initial treatment had relapses within two years, underscoring the importance of long- term maintenance treatment." Bipolar I Disorder can be treated with antipsychotic medications. Abilify is indicated for the treatment of acute manic and mixed episodes associated with Bipolar I Disorder, and for maintaining efficacy in adults with Bipolar I Disorder with a recent manic or mixed episode who had been stabilized and then maintained for at least six weeks. Abilify is one of only two atypical antipsychotics indicated for maintenance therapy in Bipolar I Disorder. Physicians who elect to use Abilify® (aripiprazole) for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.

Study Design and Findings
In this double-blind, randomized, placebo-controlled long-term study, adults with Bipolar I Disorder who had recently been hospitalized and treated for a manic or mixed episode were initially stabilized with Abilify monotherapy (15 or 30 mg/day for 6-18 weeks). In the open-label stabilization phase, the adults in the study were required to maintain a total score of 10 or less on the Young Mania Rating Scale (Y-MRS) and 13 or less on the Montgomery-Asberg Depression Rating Scale (MADRS) for six consecutive weeks prior to randomization into the double-blind phase. One hundred and sixty one adults were randomly assigned to Abilify (n=78) or placebo (n=83) in a double- blind fashion and monitored for relapse. The primary endpoint was time to relapse for a manic, mixed, or depressive episode up to and including Week 26. Relapse was defined by a discontinuation from the study attributed to a lack of efficacy (indicated by hospital admission for a mood episode, or addition to or increase in psychotropic medication other than Abilify to treat affective symptoms). Adults who completed the 26-week phase of the trial were allowed to continue in a double-blind fashion with aripiprazole or placebo for an additional 74 weeks (for a maximum of 100 weeks). This study was terminated when a pre-determined number of subjects had relapsed for the primary endpoint.

Of the 161 adults who entered the trial, 67 completed the 26-week phase (Abilify n=39, placebo n=28). Sixty-six adults entered the 74-week phase (Abilify n=39, placebo n=27). Of these adults, 30 discontinued due to various reasons (Abilify n=18, placebo n=12), 24 discontinued prematurely due to study termination (Abilify n=14, placebo n=10), and 12 completed the additional 74 weeks of treatment (Abilify n=7, placebo n=5). Such drop-out rates are common in long-term studies of people with Bipolar I Disorder.

The study showed in adults with up to 100 weeks of treatment, Abilify continued to delay the time to relapse (manic, depressive, or mixed) compared to placebo (hazard ratio=0.53, p-value equals 0.011). The majority of the relapses were due to manic rather than depressive symptoms. There is insufficient data to know whether Abilify is effective in delaying the time to occurrence of depression in adults with Bipolar I Disorder.

These results were consistent with those previously reported in the 26- week findings, which showed that Abilify delayed the time to relapse (manic, depressive, or mixed) compared to placebo (hazard ratio=0.52, p-value equals 0.02). In addition, compared to adults treated with placebo, those treated with Abilify® (aripiprazole) experienced significantly fewer relapses (25% vs 43%, p-value equals 0.013) and fewer manic relapses (8% vs 23%, p-value equals 0.009).

In this study (up to and including 100 weeks of treatment), adverse events reported at an incidence of 5% or more with Abilify and at least twice the rate of placebo were the following: flu syndrome (5.2% vs 0%), pharyngitis (5.2% vs 2.4%), abnormal thinking (5.2% vs 2.4%), vaginitis (6.4% vs 0%), weight gain (6.5% vs 0%), hypertension (7.8% vs 3.6%), dry mouth (7.8% vs 1.2%), akathisia (7.8% vs 1.2%), and tremor (9.1% vs 1.2%). The safety profile was generally consistent with data reported in other long-term placebo controlled trials of Abilify including changes in weight, prolactin, QTc, and extrapyramidal symptoms.

About Bipolar Disorder
Bipolar disorder, formerly called manic-depressive illness, is a condition that affects more than two million Americans. People who have this illness tend to experience extreme mood swings, along with other specific symptoms and behaviors. These mood swings or "episodes" can take three forms: manic episodes, depressive episodes, or "mixed" episodes. The symptoms of bipolar disorder are thought to be caused by an imbalance of key chemicals in the brain. Although there is no cure for bipolar disorder, medicine can play a key role in helping to manage symptoms and extreme mood swings.

About Abilify
The first and only available dopamine partial agonist, Abilify is indicated for the treatment of schizophrenia including maintaining stability in adults who had been symptomatically stable on other antipsychotic medications for periods of three months or longer and observed for relapse during a period of up to 26 weeks. Abilify is also indicated for the treatment of acute manic and mixed episodes associated with Bipolar I Disorder, and for maintaining efficacy in adults with Bipolar I Disorder with a recent manic or mixed episode who had been stabilized and then maintained for at least six (6) weeks. Physicians who elect to use Abilify for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual. Initially approved in November 2002, Abilify is the fastest-growing atypical antipsychotic in the United States with over nine million prescriptions written through May 2006.

Abilify (aripiprazole) is available by prescription only. The effective dose range for adults living with schizophrenia is 10-30 mg/day and 15 or 30 mg/day for adults living with Bipolar I Disorder. Abilify tablets are available in 2-, 5-, 10-, 15-, 20- and 30-mg strengths. Abilify DISCMELT(TM) Orally Disintegrating Tablets are available in 10 mg and 15 mg strengths. Abilify is also available in a 1 mg/mL nonrefrigerated oral solution. The FDA recently approved Abilify Injection, an injectable form of Abilify, for intramuscular use. The safety of doses of Abilify above 30 mg/day has not been evaluated in clinical trials. Abilify is taken once daily with or without food. It is important to talk to a healthcare professional for more information about Abilify.

Source: Bristol-Myers Squibb Company and Otsuka Pharmaceutical Co.,

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