Antipsychotic Medication for Behaviours that Challenge in Individuals with Intellectual Disabilities: a Clinically Informed Review

Alessandro Pascucci^1,2*Fabienne Gerber²Marie Besson^1,2,3,4Markus Kosel^1,2

• ¹Psychiatry Department, University of Geneva, Geneva, Switzerland
• ²Psychiatry Department, Hôpitaux universitaires de Genève (HUG), Genève, Geneva, Switzerland
• ³Division of clinical pharmacology and toxicology, Geneva University Hospital, Geneva, Switzerland
• ⁴Department of Anesthesiology, pharmacology, Intensive care and Emergency Medicine, University of Geneva, Geneva, Switzerland

Individuals with intellectual disabilities (ID) frequently exhibit behaviours that challenge (BC), such as aggression and self-injury, which significantly impact their quality of life. Pharmacological interventions, particularly antipsy-chotics, are regularly employed to manage these behaviours. However, these medications are frequently prescribed off-label, increasing the risks of polypharmacy, drug-drug interactions, and potential adverse effects. We conducted a comprehensive literature search to identify studies on antipsychotic interventions for BC in individuals with ID. Eligible studies included observational (cross-sectional and longitudinal) studies and randomized controlled trials (RCTs). Findings from RCTs were mixed: while some trials reported reductions in aggression and irritability with antipsy-chotics such as risperidone and olanzapine, others showed no advantage over placebo or supported deprescription strategies. Observational studies generally supported the short-term effectiveness of risperidone, olanzapine, and zuclopenthixol in reducing aggressive behaviours, although evidence for their impact on self-injurious behaviours (SIBs) was inconsistent. Across both study types, the use of antipsychotics was consistently associated with adverse effects, including sedation, weight gain, and metabolic changes. Preliminary open-label evidence suggested that aripiprazole may reduce BC in individuals with Fragile X Syndrome (FXS), while causing fewer metabolic side ef-fects. These findings highlight key limitations of the current literature, including the scarcity of studies focusing specifically on ID populations, small sample sizes, the limited number of RCTs, and often controversial or incon-sistent results. Despite these limitations, the review indicates potential benefits from reducing dosages and discon-tinuing long-term antipsychotic use, particularly when guided by personalised treatment plans and regular reas-sessment. Overall, the results support cautious and individualised prescribing, with close monitoring of adverse effects and attention to deprescribing when appropriate. Further longitudinal and naturalistic studies are warranted, along with the development of structured tools to assist clinicians in optimising pharmacological care for this vulner-able population.