FDA Approves Long-acting Injectable for Bipolar Disorder

Pauline Anderson

July 31, 2017

The extended-release formulation of aripiprazole (Abilify Maintena, Otsuka Pharmaceutical Co, Ltd, and H. Lundbeck A/S) has been approved by the US Food and Drug Administration (FDA) for use as an injectable suspension for maintenance monotherapy of bipolar I disorder (BP-I) in adults, the companies have announced.

Abilify Maintena, an atypical antipsychotic, is a sterile lyophilized powder that, when reconstituted with sterile water, forms a suspension that can be administered by injection. It was created by Otsuka in Japan and has been jointly developed and commercialized by Otsuka and Lundbeck.

"Abilify Maintena provides healthcare professionals a new treatment option for their patients who have established tolerability with oral aripiprazole," Joseph Calabrese, MD, director, Mood Disorders Program, University Hospitals Cleveland Medical Center, and professor of psychiatry, Case Western Reserve University School of Medicine, Cleveland, Ohio, said in a press release.

"Receiving Abilify Maintena each month as prescribed and administered by a healthcare professional provides patients an opportunity to be free from taking their daily antipsychotic for bipolar I disorder."

He stressed that concomitant oral antipsychotic medication must be administered for 14 days after the first injection.

Chronic Illness

BP-I is a chronic mental illness. The 12-month prevalence is 1.5%, and the lifetime prevalence is 2.1%, according to information provided by the company. Patients with BP-I experience one or more episodes of mania and may have episodes of both mania and depression.

The phase 3, double-blind, placebo-controlled, randomized withdrawal trial that supported regulatory approval demonstrated the efficacy and safety of Abilify Maintena in the maintenance monotherapy of BP-I. The study included patients aged 18 to 65 years who were experiencing a manic episode and who met DSM-IV-TR criteria for bipolar I disorder.

The patients had a history of at least one previous manic or mixed episode with manic symptoms severe enough to require hospitalization and/or treatment with a mood stabilizer, and/or treatment with an antipsychotic agent.

Study participants' conditions had been stabilized with Abilify Maintena prior to randomization.

The study found that the drug significantly delayed time to recurrence of any mood episode during a 52-week treatment period compared with placebo. There were significant differences between treatment groups in delaying time to recurrence of both manic and mixed episodes, but there was no substantial difference in depressive mood episodes.

The mechanism of this drug's efficacy is unknown, but it is reported that the drug may act through a combination of partial agonist activity at dopamine D2 and serotonin 5-HT1A receptors and antagonist activity at 5-HT2A receptors.

Adverse Events

Abilify Maintena was approved in the United States in 2013 for the treatment of adults with schizophrenia. The most common adverse reactions with the drug in patients with schizophrenia are an increase in weight, akathisia, injection site pain, and sedation.

According to background information in the company's release, elderly patients with dementia-related psychosis who are treated with antipsychotic drugs are at increased risk for death. Abilify Maintena is not approved for the treatment of patients with dementia-related psychosis. The drug is contraindicated in patients who are known to have hypersensitivity reactions to aripiprazole

The press release listed additional possible adverse events and noted an increase in the incidence of cerebrovascular adverse events (eg, stroke and transient ischemic attack) in elderly patients with dementia-related psychosis who undergo treatment with oral aripiprazole.

Neuroleptic malignant syndrome is a potentially fatal symptom complex reported in association with the use of Abilify Maintena and other antipsychotic drugs. The risk for tardive dyskinesia is believed to increase with duration of treatment and total cumulative dose of antipsychotic drugs, the companies noted.

Atypical antipsychotic drugs have also been linked to metabolic changes, including hyperglycemia and diabetes. Intense urges, particularly for gambling, and the inability to control these urges have been reported in patients who are taking aripiprazole.

The press release warned that Abilify Maintena may cause orthostatic hypotension and should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, or conditions that would predispose them to hypotension.

Other potential adverse events may be found in the drug's prescribing information, which includes a boxed warning.

To report suspected adverse reactions, contact Otsuka America Pharmaceutical, Inc. at 1-800-438-9927 or FDA at 1-800-FDA-1088 (www.fda.gov/medwatch).


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