Worsening stimulant use disorder outcomes coinciding with off-label antipsychotic prescribing: a commonly unrecognised side effect?

Antipsychotic medications exert their effects via dopamine antagonism and are widely used off-label among persons with substance use disorders (SUD). While dopamine antagonists are recognised to stimulate food craving and weight gain, outside of possibly increasing nicotine craving and use, their impact on other SUD outcomes is poorly recognised. In this context, research has demonstrated that antipsychotic therapy can produce 'supersensitivity' to dopamine, enhancing the motivational effects of addictive drugs. Worsened drug craving and higher rates of substance use have also been observed in double-blind placebo-controlled trials. Nevertheless, widespread off-label antipsychotic prescribing among persons with SUD implies that the risks of worsening SUD outcomes are overall poorly recognised in both primary care and among specialists. We present a typical case of worsening stimulant use disorder in a patient prescribed antipsychotic medication for low mood and insomnia, highlighting that this is likely a widely under-recognised adverse effect of off-label antipsychotic therapy.