Pharmacotherapy for Autism Spectrum Disorder

Evidence-Based Medications

The American Academy of Child and Adolescent Psychiatry recommends risperidone and aripiprazole as first-line atypical antipsychotics for managing irritability, aggression, and severe disruptive behaviors in children with Autism Spectrum Disorder, with robust evidence supporting their use 1, 2.
Risperidone may reduce irritability symptoms compared to placebo in children with Autism Spectrum Disorder in the short term, with a mean difference of -7.89 (95% CI -9.37 to -6.42) 2.
Aripiprazole may also reduce irritability compared to placebo, with a mean difference of -6.26 (95% CI -7.62 to -4.91) 2.

The American Academy of Child and Adolescent Psychiatry suggests that pharmacotherapy should only be considered after identifying a specific target symptom or comorbid psychiatric disorder, attempting behavioral interventions first, and ruling out medical contributors 1, 3.
For irritability and severe aggression, risperidone (0.5-3.5 mg/d) or aripiprazole (5-15 mg/d) are recommended as first-line treatments, with monitoring for weight gain, sedation, and elevated prolactin (risperidone) 2, 4, 5.
Effects of risperidone and aripiprazole typically begin within 2 weeks 5, 6.

Children with Autism Spectrum Disorder may be more sensitive to medication side effects than typically developing children, and conservative dosing is recommended 6.
Common pitfalls to avoid include prescribing for behavioral problems without identifying underlying psychiatric diagnosis, using benzodiazepines chronically, and ignoring metabolic monitoring with atypical antipsychotics 3, 4, 5.
Risperidone and aripiprazole side effects include weight gain, sedation, somnolence, extrapyramidal symptoms, and elevated prolactin (risperidone) 2, 4, 5, 6.

The American Academy of Child and Adolescent Psychiatry recommends starting aripiprazole with a dose of 2 mg/day, then gradually increasing to a target dose of 5-15 mg/day based on clinical response and tolerability in children with autism and irritability 7
Aripiprazole has been shown to be effective at doses of 5 mg/day, 10 mg/day, and 15 mg/day in controlled studies, with all three doses resulting in significant improvement compared to placebo by week 8 7
Flexible dosing of 5-15 mg/day has also been found to be effective in separate studies 7

Aripiprazole has been found to be effective in reducing irritability in children with autism, with significant improvement seen as early as week 1 and continuing through week 8 7
Common side effects include weight gain, sedation, and extrapyramidal symptoms, with sedation being the most common reason for discontinuation 7