The Effect of Dopaminergic Medication on Impulse Control and Compulsive Behaviour: A Translational Perspective

Dopaminergic medication used in disorders like Parkinson's disease (PD) and restless legs syndrome can cause impulsive-compulsive behaviour (ICB), often with strong negative effects on patients' quality of life. This narrative review presents translational evidence on iatrogenic ICB, taking findings from epidemiological, clinical, neuroimaging and preclinical studies into consideration. Epidemiological and clinical studies find dopamine agonists with high D2/3-selectivity to be most strongly linked to ICB. Their effect on ICB has often been shown to be dose-dependent, but the impact of combining different dopaminergic drugs or applying extended-release formulations is less clear. Intervention studies support tapering or replacing dopamine agonists for ICB reduction, whereas no efficacious pharmacotherapy has been identified for ICB treatment specifically. Adequate animal models for mimicking different types of ICB are available, and point, in line with human neuroimaging studies, towards an involvement of striatum and prefrontal cortex in iatrogenic ICB. Overall, complementary research designs have led to profound evidence regarding the occurrence of ICB in PD and establishing methods transferable to other, less-studied patient populations. A combined approach integrating insights from human studies and animal models could contribute to developing dopaminergic drugs with lower ICB risk but also specific pharmacotherapies for impulsivity or compulsivity in the future.