Background: Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition which presents in childhood. In the UK, risperidone is the only antipsychotic drug approved for the management of behavioural disturbance in children and adolescents with ASD. Aim: To explore the safety of antipsychotic medication use in people with ASD. Method: Four observational studies using a UK primary care database as a data source. The first study was a descriptive study to provide up-to-date information on the prevalence of ASD and psychotropic medication prescribing. Next, two analytical studies, of different designs, to investigate the risk of incident seizure associated with antipsychotic use, were conducted. A cohort study comparing the risk of incident seizure in people using antipsychotics with the users of other psychotropics; followed by a selfcontrolled case series analysis on the risk of incident seizure associated with antipsychotic use. Lastly, a cohort study to investigate the relationship between the risk of cardiac events and antipsychotic exposure, compared to other psychotropics, was conducted. Results: There has been a noticeable increase (3.3-fold) in the prevalence of ASD over the period from 2009 to 2016. Over this period, 12.4% of the treated ASD patients had been prescribed antipsychotics; 50.7% of antipsychotic prescriptions was for risperidone and 49.3% was for other antipsychotics. The hazard ratios of the risk of incident seizure and cardiac events associated with antipsychotic use were 1.28 (95% CI: 0.74-2.19) and 1.27 (95% CI: 0.62-2.62), respectively. During the first month of other psychotropic medication treatment, the incidence rate ratio of seizure was 1.57, 95% CI:1.03-2.38. Conclusion: This research found no evidence of an increased risk of incident seizure or cardiac outcomes associated with antipsychotic use compared to other psychotropics ASD patients. A short term increase in the risk of incident seizure was noted with the use of psychotropics other than antipsychotics
