The effect of dopaminergic medication on gambling disorder and impulse control: Epidemiological, clinical, and animal studies

Background: Dopaminergic medication is classically used in neurological disorders like Parkinson’s disease (PD) and restless legs syndrome (RLS), but also in psychotic disorders. As a common side effect of dopaminergic medication, patients can develop impulsive-compulsive disorders (ICDs) such as gambling disorder (GD) or compulsive sexuality. Many aspects of ICDs during dopaminergic therapy remain to be characterised, including least risky treatment strategies and vulnerable patient groups.Methods: As a translational approach, this thesis was based on a broad variety of methods. Cross-sectional risk factors and longitudinal predictors for ICDs during dopaminergic therapy were analysed in two nationwide register studies. ICD recognition and management in clinical PD care were examined through patient questionnaires and medical records screening. In addition, the effect of different dopaminergic treatments on ICD-like behaviour was assessed in a large rat experiment including an immunohistochemical mapping of striatal neuroactivity.Results: Findings throughout the different studies confirmed D2/3 agonists, especially ropinirole, as disadvantageous for developing ICDs, though even MAOB inhibitor treatment was a predictor for GD. ICD-like behaviour under dopaminergic treatment in rats was independent of the PD phenotype, and the majority of ICD patients were being treated for RLS, not PD. In clinical PD care, only half of the patients reported their ICD, and involvement of psychiatric care was limited to a few, severe cases. Ex vivo tissue analysis showed reduced and shifted neuroactivity in the striatum under ropinirole treatment.Conclusions: Our findings suggest that PD therapy for ICD risk patients should not include dopamine agonists or MAO-B inhibitors, but that levodopa, even added to other drugs, seems safe. The attention to ICDs in RLS and other non-PD patients with dopaminergic treatment needs to be increased substantially in clinical care and research. Actively screening for ICDs and routine collaboration with psychiatric care could improve clinical PD care.