Risperdal: Psychotropic agent recently approved by FDA for the treatment of schizophrenia in adolescent patients and for the short-term treatment of bipolar I disorder in pediatric and adolescent patients

October 1, 2007

FDA has approved a new indication for risperdal. The drug is now indicated for the treatment of schizophrenia in adolescents aged 13 to 17 years and for the short-term treatment of acute manic or mixed episodes associated with bipolar I disorder in children and adolescents aged 10 to 17 years.

Key Points

JANSSEN

Risperidone is a selective monoaminergic antagonist with high affinity for the serotonin type 2 (5-HT2), dopamine type 2 (D2), alpha1 and alpha2 adrenergic, and H1 histaminergic receptors. Although the precise mechanism of action of risperidone is unknown, it has been proposed that the agent's activity is mediated through D2 and 5-HT2 receptor antagonism. This agent, already approved for the treatment of schizophrenia and bipolar I disorder in adults, was approved on August 22, 2007, for the treatment of schizophrenia in adolescents aged 13 to 17 years and for the short-term treatment of acute manic or mixed episodes associated with bipolar I disorder in children and adolescents aged 10 to 17 years.

Efficacy. The efficacy of risperidone for the treatment of schizophrenia in adolescent patients was evaluated in 2 short-term, double-blind, controlled trials. All patients met the Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria for schizophrenia and were experiencing an acute episode at the time of enrollment. In the first study, patients were randomized to treatment with risperidone 1 to 3 mg/d (n=55; mean modal dose, 2.6 mg), risperidone 4 to 6 mg/d (n=51; mean modal dose, 5.3 mg), or placebo (n=54). In the second study, patients were randomized to risperidone 0.15 to 0.6 mg/d (n=132; mean modal dose, 0.5 mg) or risperidone 1.5 to 6 mg/d (n=125; mean modal dose, 4 mg). In both trials, risperidone treatment was initiated at 0.5 mg/d (excluding the patients treated with 0.15–0.6 mg/d, in whom treatment was initiated at 0.05 mg/d) and was titrated to the target range by ~Day 7. Dosages were then increased to the maximum tolerated dose within the dosing range by Day 14. The primary efficacy end point was the mean change from baseline in total Positive and Negative Syndrome Scale (PANSS) score. All patients treated with risperidone 1 to 6 mg/d experienced a significant reduction in total PANSS score compared with placebo-treated patients. Doses >3 mg/d did not demonstrate a trend towards greater efficacy. The efficacy of risperidone for the treatment of mania in pediatric and adolescent patients with bipolar I disorder was demonstrated in a 3-week, randomized, double-blind, placebo-controlled, multicenter trial in patients aged 10 to 17 years who were experiencing a manic or mixed episode of bipolar I disorder at the time of enrollment. Patients were randomized to treatment with risperidone 0.5 to 2.5 mg/d (n=50; mean modal dose, 1.9 mg), risperidone 3 to 6 mg/d (n=61; mean modal dose, 4.7 mg), or placebo (n=58). Treatment was initiated at 0.5 mg/d and titrated to the target range by Day 7. Dosages were then increased to the maximum tolerated dose within the dosing range by Day 10. The primary efficacy end point was the mean change from baseline in total Young Mania Rating Scale (YMRS) score. Patients in the risperidone-treated groups experienced a significant reduction in total YMRS score compared with placebo-treated patients. Doses >2.5 mg/d did not demonstrate a trend towards greater efficacy.

Dosing. For the treatment of schizophrenia in adolescent patients, risperidone should be initiated at a dose of 0.5 mg QD (administered as a single daily dose). Dosage adjustments should occur at intervals ≥24 hours in increments of 0.5 or 1 mg/d, as tolerated, to the recommended dose of 3 mg/d. For the treatment of acute manic or mixed episodes associated with bipolar I disorder in pediatric and adolescent patients, a similar dosing titration schedule should be used to reach the recommended dose of 2.5 mg/d.