title: Retrospective review of clozapine in the treatment of patients with autism spectrum disorder and severe disruptive behaviors.
abstract: Autism spectrum disorder (ASD) is a serious childhood-onset disorder in which social and language development are primarily affected, with associated repetitive behavior and, in some patients, behavioral symptoms including aggression and self-injury. In ASD, risperidone and aripiprazole are the only second-generation antipsychotic drugs that have shown to decrease disruptive behaviors in large-scale, controlled, double-blind studies. However, in some patients, these medications are not effective. Clozapine, a second-generation antipsychotic drug known to be effective in the treatment of aggression associated with schizophrenia, has received little attention in ASD.We conducted a retrospective analysis of the changes in disruptive behaviors for all patients with ASD treated with clozapine from 2002 to 2010. Disruptive behaviors were monitored during the 4 to 6 months before and after the initiation of clozapine. Long-term tolerance (10 months to 7 years) was also assessed. The relationship between disruptive behaviors and period of treatment (before and after clozapine) was studied with a generalized linear marginal model. Clozapine resulted in a significant 2-fold decrease in the number of the days with aggression, a decrease in the number of psychotropic drugs, and a decrease in the dose of the antipsychotic drugs. The long-term tolerance of clozapine (white blood cell count and extrapyramidal effects) was good, with the exception of significant weight gain (14.3 ± 10.9 kg), the occurrence of metabolic syndrome in 1 patient, and tachycardia in another patient.These results suggest that clozapine should be considered for the management of disruptive behaviors in patients with ASD not improved by first-line antipsychotic drugs.
authors.affiliation: Department of Psychiatry 3, Centre Hospitalier du Rouvray, Centre Hospitalier du Rouvray, Sotteville-lé s-Rouen, France.
authors.forename: Laurène
authors.initials: L
authors.lastname: Beherec
authors.forename: Simon
authors.initials: S
authors.lastname: Lambrey
authors.forename: Gwendoline
authors.initials: G
authors.lastname: Quilici
authors.forename: Antoine
authors.initials: A
authors.lastname: Rosier
authors.forename: Bruno
authors.initials: B
authors.lastname: Falissard
authors.forename: Olivier
authors.initials: O
authors.lastname: Guillin
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019958:Attention Deficit and Disruptive Behavior Disorders / Q000150:complications / Q000188:drug therapy*; D002659:Child Development Disorders, Pervasive / Q000150:complications / Q000188:drug therapy*; D002675:Child, Preschool; D003024:Clozapine / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine