Risperidone’s 2 new pediatric indications

Pediatric dosing. Based on these studies, the recommended starting dose for children and adolescents is 0.5 mg/d, with titration in 0.5-to 1-mg increments to targets of:

• 3 mg/d for schizophrenia
• 2.5 mg/d for bipolar mania (Table 2).⁷

Table 2

Recommended dosing of risperidone
for pediatric schizophrenia and bipolar mania

Tolerability studies

In long-term studies, the most commonly reported adverse events associated with risperidone in children and adolescents have been rhinitis, abdominal pain, increased saliva, body pain, gynecomastia, and weight increase.⁸ Specific adverse effects that pose long-term concerns are:

• tardive dyskinesia (TD)
• weight gain
• increased prolactin levels

Tardive dyskinesia. In clinical trials that included 1,885 children and adolescents with autistic disorder or other psychiatric disorders treated with risperidone, 2 patients (0.1%) were reported to have TD, which resolved when risperidone was discontinued.⁷ To monitor for TD, administer the Abnormal Involuntary Movement Scale at baseline and every 6 months while using risperidone in pediatric patients.

Weight gain. In long-term, open-label trials, patients with autistic or other psychiatric disorders gained an average 7.5
kg after 12 months of risperidone treatment. Most of the weight gain occurred in the first 6 months.⁹ Expected normal weight gain in children is 3 to 3.5 kg/year adjusted for age, based on Centers for Disease Control and Prevention normative data.

Follow the American Diabetes Association guidelines¹⁰ for monitoring metabolic parameters during antipsychotic
treatment, and intervene if clinically significant weight gain occurs.

In a 16-week, placebo-controlled study,¹¹ metformin reversed weight gain associated with SGAs in children and adolescents. Metformin’s potential side effects include hypoglycemia, diarrhea, nausea/vomiting, and (rarely) lactic acidosis, but no adverse events were attributed to metformin.

Increased prolactin. As in adults, risperidone elevates serum prolactin in children and adolescents. All pediatric risperidone trials—of autism,² disruptive behavior disorders in children with subaverage intelligence,⁹ schizophrenia,⁷ and bipolar mania—have shown increased serum prolactin. Risperidone’s long-term effects on growth and sexual maturation have not been fully evaluated, but hyperprolactinemia may inhibit reproductive function.

Findling et al¹² analyzed data from 5 clinical trials (total 700 patients) in which children and adolescents age 5 to 15 years with subaverage IQs and conduct or other disruptive behavior disorders received risperidone for up to 55 weeks. Mean prolactin levels rose from 7.8 ng/mL
at baseline to 29.4 ng/mL at weeks 4 to 7, then progressively decreased to 16.1 ng/mL at weeks 40 to 48 (n=358) and 13.0 ng/mL at weeks 52 to 55 (n=42). Girls returned to a mean value within the normal range (≤30 ng/mL) by weeks 8 to 12, and boys were close to normal values (≤18 ng/mL) by weeks 16 to 24.

The researchers concluded that serum prolactin levels in children tend to rise and peak within the first 1 to 2 months of risperidone treatment and then steadily decline to values within or very close to normal range by 3 to 5 months.

The biological significance of chronic, mild prolactin elevations is unknown.¹³ Children entering puberty appear to be at highest risk for elevated prolactin and clinical symptoms while treated with risperidone.¹⁴ Therefore, ask all adolescents treated with risperidone about increases in breast size and galactorrhea. Switch those who develop these symptoms to an SGA that does not increase serum prolactin.

Contraindications. Risperidone is contraindicated in patients with a known hypersensitivity to the drug.

Related resources

• Risperdal prescribing information. www.risperdal.com/risperdal/shared/pi/risperdal.pdf.

Drug brand names

• Lithium • Eskalith, Lithobid
• Risperidone • Risperdal
• Metformin • Glucophage, Fortamet
• Valproate • Depakote

Disclosures

Dr. Kowatch receives research support from Bristol-Meyers Squibb, Stanley Research Foundation, National Institute of Mental Health, and National Institute of Child Health and Human Development. He is a consultant for Creative Educational Concepts, Child and Adolescent Bipolar Foundation, Abbott Laboratories, and sanofi-aventis, and a speaker for Abbott Laboratories and AstraZeneca.