An open-label extension study of the safety and efficacy of risperidone in children and adolescents with autistic disorder

Abstract

Objective: The purpose of this study was to evaluate the long-term safety and efficacy of risperidone in treating irritability and related behaviors in children and adolescents with autistic disorders.

Methods: In this 6 month (26 week) open-label extension (OLE) study, patients (5-17 years of age, who completed the previous fixed-dose, 6 week, double-blind [DB] phase) were flexibly dosed with risperidone based on body weight. The maximum allowed dose was 1.25 mg/day for those weighing 20 to <45 kg, and 1.75 mg/day for those weighing ≥ 45 kg. The study primarily assessed risperidone's safety; efficacy was assessed as a secondary end-point.

Results: Fifty-six (71%) out of 79 enrolled patients completed the OLE; the most common discontinuations were for insufficient response (7 [9%]) or adverse events (AE) (5 [6%]). The most common (≥ 5% frequency in the total group) AEs were increased appetite (11% [n=9]); increased weight and vomiting (9% [n=7] each); sedation, pyrexia, and upper respiratory tract infection (8% [n=6] each); nasopharyngitis (6% [n=5]); and somnolence and fatigue (5% [n=4] each). Extrapyramidal AEs were reported in 6 (8%) patients. Increase in mean weight (11-15%) and body mass index (5-10%) occurred; one patient discontinued because of weight increase. One potentially prolactin-related AE (irregular menstruation) was reported. The risperidone high-dose group had the greatest mean improvement in sleep visual analog scale (24.6). All groups showed additional improvement in efficacy scale scores during the OLE.

Conclusions: During this OLE, safety findings with risperidone treatment (maximum weight-based dose of 1.25 mg/day or 1.75 mg/day) were consistent with those observed in the DB phase, and with the current safety information for risperidone in autistic, psychiatric, and behavioral disorders. Patients experienced some additional improvement in irritability and related behaviors.

Clinical trials registry: This phase-4 study is registered at ClinicalTrials.gov (NCT00576732).

Figures

FIG. 1.

Study design and patient disposition. a0.125 mg/day (patients weighing 20 kg to <45 kg). b0.175 mg/day (patients weighing≥45 kg). cPatients randomly assigned to placebo during double-blind (DB) phase who continued into open-label extension (OLE) and received risperidone. dPatients randomly assigned to risperidone low dose in DB phase and receiving risperidone (as per weight class) in OLE phase. ePatients randomly assigned to risperidone high dose in DB phase and receiving risperidone (as per weight class) in OLE phase.

FIG. 2.

Mean change in weight and body mass index (BMI) Z-scores over time (open-label safety analysis set). (A) Mean change in weight. (B) Mean change in BMI Z-scores. RIS, risperidone; placebo/RIS, patients randomly assigned to placebo during double-blind (DB) phase who continued into open-label extension (OLE) and received risperidone; RIS low dose/RIS, patients randomly assigned to risperidone low dose during DB phase who continued into OLE and received risperidone; RIS high dose/RIS, patients randomly assigned to risperidone high dose during DB phase who continued into OLE and received risperidone.

FIG. 3.

Mean (±standard error [SE]) Aberrant Behavior Checklist - Irritability Subscale over time (open label analysis set). Placebo/RIS, patients randomly assigned to placebo during double-blind (DB) phase who continued into open-label extension (OLE) and received risperidone; RIS low dose/RIS, patients randomly assigned to risperidone low dose during DB phase who continued into OLE and received risperidone; RIS high dose/RIS, patients randomly assigned to risperidone high dose during DB phase who continued into OLE and received risperidone.