Out Of The Pipeline

Risperidone’s 2 new pediatric indications

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Approval supports antipsychotic use in children with schizophrenia or bipolar disorder.



Risperidone is the first second-generation antipsychotic (SGA) to receive FDA approval for treating children and adolescents with bipolar mania or schizophrenia. Specifically, the SGA is indicated for treating schizophrenia in patients age 13 to 17 and as monotherapy in short-term treatment of manic or mixed episodes of bipolar I disorder in patients age 10 to 17 (Table 1).

Risperidone also is approved for:

  • schizophrenia in adults
  • acute mania or mixed episodes associated with bipolar I disorder in adults, alone or in combination with lithium or valproate
  • irritability associated with autistic disorder in patients age 5 to 16.

Table 1

Risperidone: Fast facts

Brand name: Risperdal
Class: Second-generation antipsychotic
New indications: Schizophrenia in adolescents age 13 to 17 and monotherapy in short-term treatment of manic or mixed episodes of bipolar I disorder in children and adolescents age 10 to 17. (Risperidone had been approved for schizophrenia and short-term treatment of acute manic or mixed episodes associated with bipolar I disorder in adults and treatment of irritability associated with autistic disorder in children and adolescents.)
Approval date: August 22, 2007 for pediatric schizophrenia and mania indications
Manufacturer: Janssen, L.P.
Dosing forms: 0.25-, 0.5-, 1-, 2-, 3-, and 4-mg tablets; 0.5-, 1-, 2-, 3-, and 4-mg orally disintegrating tablets; 1 mg/mL oral solution
Recommended target dosage: 3 mg/d (pediatric schizophrenia) or 2.5 mg/d (pediatric bipolar mania). See Table 2 for initial dosages and titration

Clinical implications

Risperidone is widely used off-label to treat irritability in children with pervasive developmental disorders,1,2 aggressive behaviors associated with conduct disorder,3 psychotic disorders,4 and bipolar disorder.5 It also has been used off-label to treat pediatric schizophrenia and bipolar disorder for many years.

These 2 new indications give clinicians additional support for using SGAs in children and adolescents with these serious psychiatric disorders.

How it works

Risperidone’s therapeutic activity in schizophrenia seems to be mediated through a combination of dopamine type 2 (D2) and serotonin type 2 (5HT2) receptor antagonism. Antagonism at receptors other than D2 and 5HT2 may explain some of risperidone’s other therapeutic effects.


In children, the half-lives of risperidone and its major active metabolite 9-hydroxyrisperidone are 3±2.3 hours and 22±46 hours, respectively.6 The pharmacologic activity of 9-hydroxyrisperidone is similar to that of risperidone.

Risperidone is extensively metabolized in the liver by the cytochrome P-450 (CYP) 2D6 enzyme system. The main metabolic pathway is through hydroxylation of risperidone to 9-hydroxyrisperidone by CYP 2D6. Food does not affect the rate or extent of the drug’s absorption.6

Efficacy studies

In schizophrenia. Approval of the indication for pediatric schizophrenia was based on data from 2 short-term (6 and 8 weeks) randomized, double-blind, controlled trials involving a total of 416 patients age 13 to 17 who met DSM-IV-TR criteria for schizophrenia and were experiencing an acute episode at enrollment.7 In one study, patients received risperidone, 1 to 3 mg/d, 4 to 6 mg/d, or placebo. In the other study, dosages were 0.15 to 0.6 mg/d or 1.5 to 6 mg/d. Except for patients in the 0.15 to 0.6 mg group (who initially received 0.05 mg/d), most patients started risperidone at 0.5 mg/d. In both trials, starting dosages were titrated to the target range in approximately 7 days.

Outcomes were measured as changes in total Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance (PSP) scale scores. The multi-item PANSS inventory measures positive and negative schizophrenia symptoms, disorganized thoughts, uncontrolled hostility/excitement, and anxiety/depression. The PSP gauges personal and social functioning in socially useful activities (work and study), personal and social relationships, self-care, and disturbing/ aggressive behaviors.

Risperidone, 1 to 6 mg/d, improved schizophrenia symptoms significantly more than placebo, as measured by PANSS scores. Doses >3 mg/d did not show greater efficacy than lower doses, as evaluated by PANSS and PSP scores.

Adverse reactions experienced by >5% of patients treated with risperidone included somnolence, parkinsonism, tremor, dystonia, dizziness, akathisia, increased salivation, and anxiety.7

In bipolar I disorder. Risperidone’s efficacy for short-term treatment of mania in children and adolescents was demonstrated in a 3-week, randomized, double-blind, placebo-controlled, multi-center study of 169 patients age 10 to 17 who were experiencing a manic or mixed episode of bipolar I disorder.7 Patients were randomly assigned to risperidone, 0.5 to 2.5 mg/d or 3 to 6 mg/d, or placebo. All patients were started at 0.5 mg/d and this dose was titrated to the target dosage range in 7 days.

Risperidone, 0.5 to 6 mg/d, significantly decreased the total Young Mania Rating Scale score—a measure of the severity of elevated mood, increased motor activity energy, sexual interest, sleep, irritability, speech (rate/amount), language (thought disorder, content, disruptive), aggressive behavior, appearance, and insight. No evidence of increased efficacy was observed at doses >2.5 mg/d. In this trial, symptoms reported by >5% of patients included fatigue, dizziness, dystonia, parkinsonism, akathisia, abdominal pain, dyspepsia, nausea, vomiting, and diarrhea.7

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