Tolerability, Safety, and Benefits of Risperidone in Children and Adolescents with Autism: 21-Month Follow-up After 8-Week Placebo-Controlled Trial.
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.
1 Nisonger Center, Ohio State University , Columbus, Ohio.
Michael
M
Aman
2 Biostatistics Program, Department of Pediatrics, University of Arkansas for Medical Sciences , Little Rock, Arkansas.
Mallikarjuna
M
Rettiganti
3 Biostatistics, College of Public Health, Ohio State University , Columbus, Ohio.
Haikady N
HN
Nagaraja
1 Nisonger Center, Ohio State University , Columbus, Ohio.
Jill A
JA
Hollway
4 Department of Psychiatry and Behavioral Sciences, David Geffen School of Medicine UCLA - Semel Institute, University of California , Los Angeles, California.
James
J
McCracken
5 Department of Psychiatry, Indiana University School of Medicine , Indianapolis, Indiana.
Christopher J
CJ
McDougle
6 Kennedy Krieger Institute , Baltimore Maryland.
Elaine
E
Tierney
7 Marcus Autism Center, Atlanta, Georgia .
Lawrence
L
Scahill
1 Nisonger Center, Ohio State University , Columbus, Ohio.
L Eugene
LE
Arnold
1 Nisonger Center, Ohio State University , Columbus, Ohio.
Jessica
J
Hellings
5 Department of Psychiatry, Indiana University School of Medicine , Indianapolis, Indiana.
David J
DJ
Posey
5 Department of Psychiatry, Indiana University School of Medicine , Indianapolis, Indiana.
Naomi B
NB
Swiezy
6 Kennedy Krieger Institute , Baltimore Maryland.
Jaswinder
J
Ghuman
6 Kennedy Krieger Institute , Baltimore Maryland.
Marco
M
Grados
4 Department of Psychiatry and Behavioral Sciences, David Geffen School of Medicine UCLA - Semel Institute, University of California , Los Angeles, California.
Bhavik
B
Shah
8 National Institute of Mental Health , Bethesda, Maryland.
Benedetto
B
Vitiello
D000293:Adolescent; D000374:Aggression / Q000187:drug effects; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001321:Autistic Disorder / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004775:Enuresis / Q000139:chemically induced; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007508:Irritable Mood / Q000187:drug effects*; D008297:Male; D018967:Risperidone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D015430:Weight Gain / Q000187:drug effects
D014150:Antipsychotic Agents; D018967:Risperidone