The prevalence of antipsychotic drug use in people with intellectual disability (id) is high and largely off-label for challenging behaviour (cb), while evidence for their efficacy lacks. Side-effects frequently occur. Guidelines recommend appropriate psychotropic drug use by monitoring of effects and side-effects and discontinuing off-label use for cb. However, they are insufficiently adhered to. Discontinuation often fails due to behavioural worsening by largely unknown causes.<br/> AIM: To offer an overview of results of off-label antipsychotic drug discontinuation and determinants for success or failure.<br/> METHOD: Literature search in Medline, embase and Psycinfo.<br/> RESULTS: Prospective open-label studies show that discontinuation in selected populations is possible in 33-40% and in placebo-controlled studies in 55-82%. Challenging behaviours, as measured with a standardized scale, mostly remained similar in those who succeeded as well as in those who failed to discontinue. Health problems, extrapyramidal symptoms, higher antipsychotic drug dosage, more severe cb, autism and male gender in participants, negative emotions towards cb, less knowledge on psychotropic drugs and male gender of support professional were related to less chance of successful discontinuation.<br/> CONCLUSION: To improve results of antipsychotic drug discontinuation, proper diagnostics of underlying causes for cb, involvement of all stakeholders and enhancement of treatment opportunities for psychopathology in people with id are needed. Integrative care and knowledge development of id- and mental health care may be helpful.