Tolerability, Safety, and Benefits of Risperidone in Children and Adolescents with Autism: 21-Month Follow-up After 8-Week Placebo-Controlled Trial.

Abstract

OBJECTIVE:

Risperidone has demonstrated efficacy for acute (8 week) and intermediate length (6 month) management of severe irritability and aggression in children and adolescents with autism. Less is known about the long-term effects of risperidone exposure in this population. We examined the tolerability, safety, and therapeutic benefit of risperidone exposure over a 1-2 year follow-up period.

METHODS:

In a naturalistic study, 84 children and adolescents 5-17 years of age (from an original sample of 101) were assessed an average of 21.4 months after initial entry into a placebo-controlled 8 week trial of risperidone for children and adolescents with autism and severe irritability. They were assessed at baseline and at follow-up on safety and tolerability measures (blood, urinalysis, electrocardiogram [ECG], medical history, vital signs, neurological symptoms, other adverse events), developmental measures (adaptive behavior, intelligence quotient [IQ]), and standardized rating instruments. Treatment over the follow-up period, after completion of protocol participation, was uncontrolled. Statistical analyses assessed outcome over time with or without prolonged risperidone therapy.

RESULTS:

Two-thirds of the 84 subjects continued to receive risperidone (mean 2.47 mg/day, S.D. 1.29 mg). At follow-up, risperidone was associated with more enuresis, more excessive appetite, and more weight gain, but not more adverse neurological effects. No clinically significant events were noted on blood counts, chemistries, urinalysis, ECG, or interim medical history. Regardless of drug condition at follow-up, there was considerable improvement in maladaptive behavior compared with baseline, including core symptoms associated with autism. Height and weight gains were elevated with risperidone. Social skills on Vineland Adaptive Behavior Scale (VABS) improved with risperidone. Parent-rated Aberrant Behavior Checklist (ABC) Irritability subscale scores were reduced in those taking risperidone at follow-up. Several other measures of maladaptive behavior (some related to socialization) also showed improved functioning in association with risperidone on the ABC or on the Modified Real Life Rating Scale.

CONCLUSIONS:

Increased appetite, weight gain, and enuresis are risks associated with long-term risperidone. Our data suggest that these risks were balanced by longer-term behavioral and social benefits for many children over 1.8 years of ongoing treatment.

• Authors: Michael Aman, Mallikarjuna Rettiganti, Haikady N Nagaraja, Jill A Hollway, James McCracken, Christopher J McDougle, Elaine Tierney, Lawrence Scahill, L Eugene Arnold, Jessica Hellings, David J Posey, Naomi B Swiezy, Jaswinder Ghuman, Marco Grados, Bhavik Shah, Benedetto Vitiello
• Journal: Journal of child and adolescent psychopharmacology (J Child Adolesc Psychopharmacol) Vol. 25 Issue 6 Pg. 482-93 (Aug 2015) ISSN: 1557-8992 [Electronic] United States
• PMID: 26262903 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

• Antipsychotic Agents
• Risperidone

Topics

• Adolescent
• Aggression (drug effects)
• Antipsychotic Agents (administration & dosage, adverse effects, therapeutic use)
• Autistic Disorder (drug therapy)
• Child
• Child, Preschool
• Double-Blind Method
• Enuresis (chemically induced)
• Female
• Follow-Up Studies
• Humans
• Irritable Mood (drug effects)
• Male
• Risperidone (administration & dosage, adverse effects, therapeutic use)
• Time Factors
• Treatment Outcome
• Weight Gain (drug effects)