Autism spectrum disorder (ASD) is a serious childhood-onset disorder that affects all areas of development and is associated with disruptive symptoms including aggression and self injury. In ASD, risperidone and aripiprazole are the only second generation antipsychotic drugs (SGA) that have shown to decrease disruptive behaviours in controlled double-blind studies. However, some patients are not improved by these drugs. Clozapine, a SGA known to be effective to treat aggressiveness in schizophrenia, has received little attention in ASD. We conducted a retrospective analysis of the changes in disruptive for all patients with ASD who were treated with clozapine from 2002 to 2010. Disruptive behaviours were monitored during the 4 to 6 months before and after the initiation of clozapine, and long term tolerance (10 months to 7 years) was also assessed. The relationship between disruptive behaviours and periods of treatment 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 of the number of psychotropic drugs and the dose of the antipsychotic drugs. The long term tolerance (white blood cell count, extrapyramidal effects) was good with the exception for a significant weight gain (of 22.3% +/- 18,2%), the occurence of metabolic syndrome in one patient and tachycardia in another patient.

These results suggest that clozapine should be considered for the management of disruptive behaviours in patients with ASD not improved by first line antipsychotic drugs.