Use of Risperidone in Children With Autism, Bipolar Disease, or Schizophrenia

Marcia L. Buck, Pharm.D., FCCP

Pediatr Pharm. 2008;14(1) 

In This Article

Adverse Effects

In pediatric clinical trials, the most common adverse effects associated with risperidone were somnolence (in 67% of patients), fatigue (42%), increased appetite (49%), upper respiratory tract infection (34%), increased salivation (22%), constipation (21%), dry mouth (13%), dystonia, tremor, and Parkinsonian/extrapyramidal symptoms (8-12% each), dizziness (9%), tachycardia and dyskinesia (7% each), confusion and weight gain (5% each).[2]

Weight gain is a relatively common adverse effect with atypical antipsychotics. This effect may limit the utility of therapy in some patients, as effective symptom control may only be achieved at the cost of obesity and limited mobility. Weight gain was reported in 7.4% of 391 children receiving risperidone who were monitored as part of an observational cohort study in New Zealand.[9]

In 2002, Ratzoni and colleagues compared weight changes in 50 adolescents treated for 12 weeks with olanzapine, risperidone, or haloperidol.[10] They reported an average weight gain of 3.9±4.8 kg in the teens given risperidone and an increase of 7.2±6.3 kg in the patients given olanzapine. In contrast, the haloperidol group had only a 1.1±3.3 kg increase. Extreme weight gain, defined by the authors as an increase of 7% body weight or greater, occurred in 19 of the olanzapine patients (90%), 9 of the risperidone patients (43%), and only one of the haloperidol patients (12%).

In a similar study, Fleischhaker and colleagues reported a relatively small increase in weight with clozapine and risperidone, compared to olanzapine.[11] A total of 45 hospitalized children were placed into one of the three treatment groups for 6 weeks. At the end of the study, the average change in weight was 2.5±2.9 kg in the clozapine group, 2.8±1.3 kg in the risperidone group, and 4.6±1.9 kg in the olanzapine group.

Endocrinologic adverse effects are a known complication of the atypical antipsychotics. Hyperglycemia has been reported with all the agents in this class, and in some cases has resulted in ketoacidosis, hyperosmolar coma, and death. Children receiving risperidone should be routinely monitored for symptoms of polydipsia, polyuria, polyphagia, or weakness. In those with additional risk factors for diabetes, such as obesity or a positive family history, periodic fasting blood glucose measurements are recommended.[2,3]

Risperidone can also increase serum prolactin levels, leading to suppression of hypothalamic gonadotropin-releasing hormone. As a result, patients may develop galactorrhea, amenorrhea, gynecomastia, or impotence. Long-standing increases in prolactin release can also lead to decreased bone density and could potentially affect growth. Utilizing data from the RUPP study, Anderson and colleagues compared serum prolactin levels in 42 children given risperidone and 36 controls at 8 weeks, 6 months, and 22 months.[12] At 8 weeks, the prolactin level was 39.0±19.2 ng/mL in the risperidone group, compared to 10.1±8.8 ng/mL for controls (p<0.0001). Prolactin levels remained significantly higher in the risperidone-treated patients at 6 and 22 months. Despite the increase, none of the patients developed adverse effects. Based on combined data from premarketing studies, the manufacturer reports only a 0.8% incidence of galactorrhea and a 2.3% incidence of gynecomastia in pediatric patients given risperidone.[2,3]

Prolactin production also appears to be correlated with the rate of risperidone metabolism.[13] In a recent study of 25 children (5 to 15 years of age) receiving risperidone who were genotyped for CYP2D6 polymorphisms, those with the ultrarapid metabolizer phenotype had the highest concentrations of 9-hydroxyrisperidone and the highest prolactin levels. There was no relationship between prolactin level and patient age. Despite the elevated prolactin levels in these patients, none experienced adverse effects.

Although less common than with traditional antipsychotics, there have been reports of neuroleptic malignant syndrome (NMS) and tardive dyskinesia with risperidone use. The risk for these reactions increases as the dose of risperidone is increased and receptor-site specificity is lost. Neuroleptic malignant syndrome typically manifests as hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability. Some patients may develop rhabdomyolysis leading to myoglobinuria and acute renal failure.[2,3] Patients and family members should understand the presenting symptoms of NMS and be aware of the need to seek immediate medical attention.

Tardive dyskinesia (TD) is associated with longterm use of antipsychotics. Involuntary movements associated with TD may not fully reverse with drug discontinuation. Although rare with the atypical antipsychotics, TD has been reported with their use. In a meta-analysis of 10 long-term pediatric studies, Correll and Kane found only 3 cases of TD reported with atypical antipsychotics, resulting an annualized rate of 0.42% (95% CI 0.087-1.24).[14] Other rare, but serious, adverse effects associated with risperidone include orthostatic hypotension, seizures, depression, arrhythmias, and hypersensitivity reactions.[2,3]


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