Safety and tolerability of antipsychotic agents in neurodevelopmental disorders: a systematic review

Neurodevelopmental disorders (NDDs) are a group of complex and heterogeneous disorders, caused by the disruption of normal brain development. Antipsychotic agents are frequently used in these disorders to treat maladaptive conduct. However, a systematic evaluation of their safety/tolerability in NDDs is still lacking. Given the unique neurobiology of NDDs, antipsychotics may be expected to elicit distinctive side effects. PubMed was systematically searched for all published studies from 1980 until 2020 investigating antipsychotic use in autism spectrum disorders (ASD), intellectual disability (ID), genetic syndromes (GS), attention-deficit/hyperactivity disorder (ADHD), Tourette’s Syndrome and Tic disorders (TS). All ages and study designs were included. Antipsychotics were found to mainly cause the following side effects: metabolic disturbances; sedation; prolactin increases and sexual dysfunctions; neurological and behavioral disorders; cardiological and hematological side effects. The most studied antipsychotics were aripiprazole and risperidone. Risk of side effects varied across the different NDDs. However, evidence was strongly affected by serious methodological drawbacks and lack of studies. Notably, reports on adult patients are underrepresented, mostly for ASD and ADHD.