The U.S. Food and Drug Administration (FDA) has approved a second atypical antipsychotic, aripiprazole (Abilify), for the treatment of schizophrenia in adolescents aged 13 to 17, according to an announcement in November by Otsuka Pharmaceutical Co. and Bristol-Myers Squibb Co., which developed and market the drug.
Another atypical antipsychotic, risperidone (Risperdal, manufactured by Johnson and Johnson), was approved in August for treating schizophrenia in 13- to 17-year-olds and for short-term treatment of manic or mixed episodes of bipolar I disorder in 10- to 17-year-olds (Psychiatric News, September 21). Both aripiprazole and risperidone as well as other atypical antipsychotics have been known to be prescribed off-label for pediatric patients in recent years despite the lack of clinical trial data on the safety and efficacy in this population.
The drug companies conducted a six-week, randomized, double-blind, placebo-controlled study of 302 adolescent patients aged 13 to 17 with a DSM-IV diagnosis of schizophrenia. Robert Findling, M.D., director of the Division of Child and Adolescent Psychiatry at University Hospitals Case Medical Center and a professor of psychiatry and pediatrics at Case Western Reserve University, and other investigators presented the study findings as a poster at the American Academy of Child and Adolescent Psychiatry's annual meeting in Boston in October. Patients were enrolled during hospitalization for an acute episode of schizophrenia. Participants were randomized to receive aripiprazole 10 mg/day, 30 mg/day, or placebo in equal ratio. At the end of six weeks, 258 (85 percent) of patients remained in the study.
Both aripiprazole groups had a statistically significant reduction in Positive and Negative Syndrome Scale (PANSS) total scores compared with the placebo group. Both groups also had a statistically significant reduction in PANSS positive symptom scores at the end of the study, but only the 10 mg group achieved a significant reduction in the PANSS negative symptom score. The adverse events of extrapyramidal symptoms, somnolence, and tremor seemed to be dose related, with higher rates in the 30 mg group. Weight gain of more than 7 percent occurred in 1 percent of the placebo group, compared with 4 percent and 5.2 percent in the the 10 mg group and 30 mg group, respectively.
In the current prescribing information, the recommended dosage of aripiprazole in adolescent is 10 mg/day. “The 30 mg/day dose was not shown to be more efficacious than the 10 mg/day dose,” according to the approved wording.
Aripiprazole carries the indications for the treatment of schizophrenia and acute manic or mixed episodes associated with bipolar I disorder in adults.
The prescribing information on aripiprazole is posted at<packageinserts.bms.com/pi/pi_abilify.pdf>.▪
