The Food and Drug Administration's approval of aripiprazole for the acute treatment of bipolar I disorder in children and adolescents is helpful for physicians and parents, according to an investigator in the study that led to the approval.
The agency approved the atypical antipsychotic aripiprazole (Abilify) for the treatment of manic and mixed episodes associated with bipolar I disorder in children and adolescents.
“When parents have questions now, they can look to the indication and the labeling to know what the common side effects are, how long it takes for the medicine to work, and what they can expect,” Dr. Adelaide Robb, medical director of inpatient psychiatry at Children's National Medical Center, Washington, said in an interview.
The 4-week, multicenter U.S. study compared two fixed doses of aripiprazole to placebo in 296 outpatients, aged 10–17 years, who met DSM-IV criteria for bipolar I disorder manic or mixed episodes with or without psychotic features, and who had a Young Mania Rating Scale (YMRS) score of 20 or more at baseline.
After 4 weeks, improvements from baseline in the mean YMRS total score were significantly greater in patients titrated to a target dose of 10 mg or 30 mg, compared with those on placebo.
Both doses were effective in reducing manic symptoms, compared with placebo, as early as 1 week after treatment started, Dr. Robb said.
Aripiprazole, which was first approved for schizophrenia in 2002, is marketed by Bristol-Myers Squibb Co. and is manufactured by the Otsuka Pharmaceutical Co.
“What is exciting is that this is another labeled indication for pediatric bipolar disorder for ages 10 and up,” said Dr. Robb, who is a speaker for BMS and a consultant to Otsuka.
In the antipsychotic category, the only other drug approved for a pediatric bipolar indication is risperidone (Risperdal), and lithium is in the nonantipsychotic category, she pointed out. Neither divalproex sodium (Depakote) nor oxcarbazepine (Trileptal)—both anticonvulsants that have been approved for bipolar disorder in adults—has been approved for pediatric bipolar treatment because of negative trials, she added.
Risperidone was approved in August 2007 for the short-term treatment of bipolar mania associated with manic or mixed episodes of bipolar I disorder in children and adolescents aged 10–17 years. (It was also approved for treating schizophrenia in adolescents aged 13–17 years at that time.)
Olanzapine (Zyprexa) remains under review at the agency for the treatment of schizophrenia and bipolar disorder in adolescents aged 13–17 years, and the drug is considered “approvable” for those two indications.
In the 4-week aripiprazole study, the most common adverse effects that were observed in at least 5% of those who were in the two aripiprazole-treated groups combined and that were at least twice the rate observed in those on placebo were somnolence (23% vs. 3%), extrapyramidal disorder (20% vs. 3%), fatigue (11% vs. 4%), nausea (11% vs. 4%), akathisia (10% vs. 2%), blurred vision (8% vs. 0%), salivary hypersecretion (6% vs. 0%), and dizziness (5% vs. 1%).
Four of these side effects—extrapyramidal disorder, somnolence, akathisia, and salivary hypersecretion—were possibly related to the dose, as they were more common after 4 weeks of treatment among those on the 30-mg dose and were lowest among those on placebo, according to BMS and Otsuka.
Over the 4 weeks, 9.4% of those on the 30-mg dose gained at least 7% of their baseline weight, compared with 3.2% of those on the 10-mg dose and 3.3% of those on placebo.
Dr. Robb said that now that aripiprazole is approved for bipolar disorder and schizophrenia, a lot more safety data are available than when it was used off label for pediatric patients, based on experience in adults.
The pediatric bipolar indication does not include maintenance treatment. However, Dr. Robb said that the maintenance phase of the treatment trial has been completed, which showed that people continued to experience resolution of manic symptoms.
Dr. Robb said that the reauthorization of the Best Pharmaceuticals for Children Act by Congress will allow the continued expansion of knowledge about medications used in children and adolescents for psychiatric reasons.
Without this legislation—which provides incentives to pharmaceutical companies to study drugs in children and adolescents—these trials would not have been conducted, and providers would still be using adult experience to guide treatment in pediatric patients, Dr. Robb said.