Objective: Second generation antipsychotics (SGA) have gained increased evidence for the treatment of
irritability and aggression in children and adolescents with lower functioning autistic disorder. Individuals with
Asperger’s Disorder (AD) and High Functioning Autism (HFA) experience significant emotional and behavioral problems
and psychiatric comorbidity. There is a need to review the published literature on SGA treatment efficacy in the AD and
HFA populations to provide more effective treatment choices for these subgroups.
Methods: We conducted a systematic review and meta-analysis of the recent English literature on SGA use in children and
adolescents (ages 0-24 years) with AD and HFA using the Medline/PubMed and PsychINFO computerized databases.
Key search words were ‘Asperger’, ‘high functioning autism’, ‘autism spectrum disorders (ASD)’, and ‘pervasive
developmental disorder (PDD)’ in combination with ‘second generation antipsychotics’, ‘aripiprazole; ‘olanzapine’,
‘quetiapine’, ‘risperidone’, or ‘ziprasidone’.
Results: Our search yielded 214 citations, however only open-label or randomized-controlled trials (RCT) with ≥25% of
their subjects having an IQ≥71 were included in our review. Eleven original studies met our inclusion parameters for
review; eight studies for the meta-analysis. These studies, although limited in methodological rigor, and the meta-analytic
results suggest that SGAs provide improvement in behavioral symptoms associated with AD and HFA. The majority of
the studies reported weight gain as a potentially concerning adverse effect.
Conclusion: There is a lack of robustly conducted trials on the use of SGAs in the management of AD and HFA. More
research in pharmacological and psychosocial treatments is warranted. Clinicians are cautioned to approach
pharmacological treatment prudently balancing benefit with potential cardiometabolic risk.