Abstract | Summary | Original Article

A systematic review of the use of atypical antipsychotics in autism.

Barnard L, Young AH, Pearson J, Geddes J, O'Brien G.

Journal of Psychopharmacology 16(1): 93-101. 2002.

Question: Do atypical antipsychotics improve the behaviour, cognition, and physical well-being of people with autistic disorders?

Background: Many children with autism spectrum disorders exhibit challenging behaviours that may include aggression towards others, self-harm, and stereotypies (repetitive movements such as hand flapping). Antipsychotic medications have been used with success in this population, but despite their effectiveness, medications such as haloperidol or pimozide can have serious side effects. Newer, atypical antipsychotic drugs have also shown some success and are said to have fewer side effects. This is a review of the efficacy of atypical antipsychotics in autism spectrum disorders.

Data Sources: The authors searched MEDLINE for the years 1966 to June 2000 and Web of Science from 1981 to June 2000. They used the terms, "atypical/novel/new generation antipsychotic," "antipsychotic," "amisulpride," "benzamide," "clozapine," "iloperidone," "olanzapine," "pipamperone," "quetiapine," "risperidone," "sertindole," "ziprasidone," "zotepine," "autism," and "autistic". They also hand searched journals for relevant articles.

Study Selection: The authors placed no restrictions on the types of studies to be assessed for the review because the literature on the subject is sparse.

Data Extraction: No information was provided.

Main Results: Nineteen studies were found: 13 studies of risperidone, 3 of olanzapine, 1 of clozapine, 1 of amisulpride and 1 of quetiapine.

Risperidone: Risperidone has been found useful in uncontrolled clinical trials for aggression, hyperactivity, and repetitive behaviours in children with ASD. It was also found useful, but less so, for treating mood disorders. There were reports of weight gain, short term sedation, liver problems, the possibility of seizures, and endocrine problems in both males and females.

Olanzapine: There is emerging evidence that olanzapine is useful in autism. Small studies suggest that the drug improves social functioning and language, and reduces aggression and hyperactivity. The side effects were limited to weight gain and short term sedation.

Clozapine: It is possible that clozapine may be useful in children with autism, but the evidence is slight. The side effects include the potential risk of a blood disorder which requires weekly monitoring. Although there were no serious side effects reported in the three study participants, clozapine should be used only when nothing else works.

Amisulpride: This drug did not affect overall functioning, but was reported to have improved symptoms of inhibition and withdrawal in one study. There were more than the usual the number of adverse effects reported, but none were serious.

Quetiapine: Only one third of trial participants could remain on the drug due to its high incidence of side effects and there was little evidence of a positive effect on children with autism.

Conclusions: The studies reviewed did not find any drug that had a specific effect on cognition. However, the atypical antipsychotic drugs were shown to have an effect on aggression, obsessions, and interfering behaviours (e.g., self-stimulation), to a degree that they might improve the ability to pay attention and thus to learn.

The studies reviewed were not methodologically sound (only two employed used randomized, double-blind, cross-over design) and thus their findings cannot be accepted as conclusive at this time. Since the publication of this review, the results of a randomized controlled trial of risperidone that demonstrated the effectiveness of the drug in children with autism have been reported in the New England Journal of Medicine. However, there need to be randomized controlled trials of each of the atypical antipsychotics noted here to determine their effectiveness and safety.