Risperidone in children with autism and serious behavioral problems.
BACKGROUND
Atypical antipsychotic agents, which block postsynaptic dopamine and serotonin receptors, have advantages over traditional antipsychotic medications in the treatment of adults with schizophrenia and may be beneficial in children with autistic disorder who have serious behavioral disturbances. However, data on the safety and efficacy of atypical antipsychotic agents in children are limited.


METHODS
We conducted a multisite, randomized, double-blind trial of risperidone as compared with placebo for the treatment of autistic disorder accompanied by severe tantrums, aggression, or self-injurious behavior in children 5 to 17 years old. The primary outcome measures were the score on the Irritability subscale of the Aberrant Behavior Checklist and the rating on the Clinical Global Impressions - Improvement (CGI-I) scale at eight weeks.


RESULTS
A total of 101 children (82 boys and 19 girls; mean [+/-SD] age, 8.8+/-2.7 years) were randomly assigned to receive risperidone (49 children) or placebo (52). Treatment with risperidone for eight weeks (dose range, 0.5 to 3.5 mg per day) resulted in a 56.9 percent reduction in the Irritability score, as compared with a 14.1 percent decrease in the placebo group (P<0.001). The rate of a positive response, defined as at least a 25 percent decrease in the Irritability score and a rating of much improved or very much improved on the CGI-I scale, was 69 percent in the risperidone group (34 of 49 children had a positive response) and 12 percent in the placebo group (6 of 52, P<0.001). Risperidone therapy was associated with an average weight gain of 2.7+/-2.9 kg, as compared with 0.8+/-2.2 kg with placebo (P<0.001). Increased appetite, fatigue, drowsiness, dizziness, and drooling were more common in the risperidone group than in the placebo group (P<0.05 for each comparison). In two thirds of the children with a positive response to risperidone at eight weeks (23 of 34), the benefit was maintained at six months.


CONCLUSIONS
Risperidone was effective and well tolerated for the treatment of tantrums, aggression, or self-injurious behavior in children with autistic disorder. The short period of this trial limits inferences about adverse effects such as tardive dyskinesia.
McCracken
James T
JT
University of California, Los Angeles, USA.
McGough
James
J
Shah
Bhavik
B
Cronin
Pegeen
P
Hong
Daniel
D
Aman
Michael G
MG
Arnold
L Eugene
LE
Lindsay
Ronald
R
Nash
Patricia
P
Hollway
Jill
J
McDougle
Christopher J
CJ
Posey
David
D
Swiezy
Naomi
N
Kohn
Arlene
A
Scahill
Lawrence
L
Martin
Andres
A
Koenig
Kathleen
K
Volkmar
Fred
F
Carroll
Deirdre
D
Lancor
Allison
A
Tierney
Elaine
E
Ghuman
Jaswinder
J
Gonzalez
Nilda M
NM
Grados
Marco
M
Vitiello
Benedetto
B
Ritz
Louise
L
Davies
Mark
M
Robinson
James
J
McMahon
Don
D
D000293:Adolescent; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001321:Autistic Disorder / Q000188:drug therapy* / Q000523:psychology; D002648:Child; D002652:Child Behavior / Q000187:drug effects; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D018967:Risperidone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D018967:Risperidone