The U.S. FDA ( Food and Drug Administration ) approved Aripiprazole ( Abilify ) for maintaining efficacy in patients with bipolar I disorder with a recent manic or mixed episode who had been stabilized and then maintained for at least six weeks.
This new, expanded, indication is based on the positive results of a trial designed to compare the maintenance of efficacy of Aripiprazole versus placebo, measured by time to relapse.
In this study, patients who had recently experienced a manic or mixed episode were first stabilized with Aripiprazole for at least six consecutive weeks, and subsequently 161 patients were treated with Aripiprazolo or placebo in the double-blind, randomization phase.
The primary endpoint was time to relapse of manic and depressive symptoms.
Of those patients who experienced a relapse, patients treated with Aripiprazolo relapsed significantly later than placebo-treated patients.
In addition, the total number of relapses was significantly fewer in patients treated with Aripiprazole than with placebo ( 25 percent versus 43 percent, respectively ).
Aripiprazole has already been approved for the treatment of schizophrenia and acute manic and mixed episodes associated with bipolar disorder.
Aripiprazole is an antipsychotic with partial dopamine antagonism and agonism, showing effects on serotonin 5-HT2A and 5-HT1A receptors.
A potentially fatal symptom complex, sometimes referred to as neuroleptic malignant syndrome ha been reported in association with administration of antipsychotic drugs, including Aripiprazole.
A syndrome of potentially irreversibile, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs.
It is unknown whether antipsychotic drugs differ in their potential to cause tardive dyskinesia.
Cerebrovascular adverse events ( e.g., stroke, transient ischemic attack ), including fatalities, have been reported at an increased incidence in clinical trials of elderly patients with dementia-related psychosis treated with Aripiprazole.
Aripiprazole is not approved for the treatment of patients with dementia-related psychosis.
Hyperglycemia, including some serious cases ( ketoacidosis, hyperosmolar coma, or death ) has been reported in patients treated with atypical antipsychotics.
There have been few reports of hyperglycemia in patients treated with Aripiprazole.
It is unknown if the paucity of such reports is due to limited experience with this drug.
Patients should be appropriately tested before and monitored during treatment.
Aripiprazole may be associated with orthostatic hypotension and should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, or conditions which would predispose them to hypotension.
As with other antipsychotic drugs, Aripiprazole should be used with caution in patients with a history of seizures or with conditions that lower the seizure threshold.
Like other antipsychotics, Aripiprazole may have the potential to impair judgment, thinking or motor skills. Patients should not drive or operate hazardous machinery until they are certain Aripiprazole does not affect them adversely.
Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotics.
The patients, who exercise strenuously, are exposed to extreme heat, receive concomitant medications with anticholinergic activity, or are subject to dehydration, are at risk.
As antipsychotics have been associated with esophageal dysmotility and aspiration, Aripiprazole should be used cautiously in patients at risk for aspiration pneumonia.
As the possibility of a suicide attempt is inherent in psychotic illness and bipolar disorder, close supervision of high-risk patients should accompany drug therapy.
Elimination of Aripiprazole is mainly through hepatic metabolism involving two P450 isozymes CYP3A4 and CYP2D6.
Agents that induce CYP3A4 ( e.g., Carbamazepine ) could cause an increase in Aripiprazole clearance and lower blood levels.
Inhibitors of CYP3A4 ( e.g., Ketoconazole ) or CYP2D6 ( e.g., Quinidine, Fluoxetine, or Paroxetine ) can inhibit Aripiprazole elimination and cause increased blood levels.
Commonly observed adverse events reported with Aripiprazole in 3-week bipolar mania trials at >5 percent incidence for Aripiprazole and at a rate at least twice the rate of placebo include, respectively, akathisia ( 15 percent vs 4 percent ), constipation ( 13 percent vs 6 percent ), and accidental injury ( 6 percent vs 3 percent ).
Treatment-emergent adverse events reported with Aripiprazole in short-term trials at an incidence > 10 percent and greater than placebo, respectively, include headache ( 31 percent vs 26 percent ), agitation ( 25 percent vs 24 percent ), anxiety ( 20 percent vs 17 percent ), insomnia ( 20 percent vs 15 percent ), nausea ( 16 percent vs 12 percent ), dyspepsia ( 15 percent vs 13 percent ), somnolence (12 percent vs 8 percent ), akathisia ( 12 percent vs 5 percent ), lightheadedness ( 11 percent vs 8 percent ), vomiting ( 11 percent vs 6 percent ), and constipation ( 11 percent vs 7 percent ).
Abilify is taken once daily with or without food.
Source: BMS, 2005