No medications directly treat the core symptoms of AS. Although research into the efficacy of pharmaceutical intervention for AS is limited, it is essential to diagnose and treat comorbid conditions. Deficits in self-identifying emotions or in observing effects of one's behavior on others can make it difficult for individuals with AS to see why medication may be appropriate. Medication can be effective in combination with behavioral interventions and environmental accommodations in treating comorbid symptoms such as anxiety disorder, major depressive disorder, inattention and aggression. The atypical antipsychotic medications risperidone and olanzapine have been shown to reduce the associated symptoms of AS; risperidone can reduce repetitive and self-injurious behaviors, aggressive outbursts and impulsivity, and improve stereotypical patterns of behavior and social relatedness. The selective serotonin reuptake inhibitors (SSRIs) fluoxetine, fluvoxamine, and sertraline have been effective in treating restricted and repetitive interests and behaviors.
Care must be taken with medications, as side effects may be more common and harder to evaluate in individuals with AS, and tests of drugs' effectiveness against comorbid conditions routinely exclude individuals from the autism spectrum. Abnormalities in metabolism, cardiac conduction times, and an increased risk of type 2 diabetes have been raised as concerns with these medications, along with serious long-term neurological side effects. SSRIs can lead to manifestations of behavioral activation such as increased impulsivity, aggression, and sleep disturbance. Weight gain and fatigue are commonly reported side effects of risperidone, which may also lead to increased risk for extrapyramidal symptoms such as restlessness and dystonia and increased serum prolactin levels. Sedation and weight gain are more common with olanzapine, which has also been linked with diabetes. Sedative side-effects in school-age children have ramifications for classroom learning. Individuals with AS may be unable to identify and communicate their internal moods and emotions or to tolerate side effects that for most people would not be problematic.