Anxiety Change After Dopamine Therapy in Parkinson Disease is Independent of Motor Improvement

Background: Several anxiety syndromes have been associated with Parkinson disease (PD), but their interactions with dopamine replacement therapy (DRT) and motor function dynamics are not completely understood. We sought to delineate how DRT impacts anxiety phenomenology in PD and whether these changes are dissociable from improved motoric function. Methods: We compared anxiety responses to DRT in two cohorts: 1) a study of 200 PD participants who completed neuropsychiatric assessments before and after taking their dopaminergic medications (“On-Off”); 2) participants in the Parkinson's Progression Markers Initiative (PPMI) de novo PD cohort who completed the State-Trait Anxiety Inventory (STAI) at the time of DRT initiation and a subsequent study visit (n = 113, mean 8-month interval). Results: Among On-Off participants transitioning acutely to the On-state, scores on the Hamilton anxiety rating scale decreased by 37% (t = 14.8, df = 199, p <0.0001). Among PPMI participants, STAI-state scores decreased by 10.4% following DRT initiation (t = 4.5, df = 112, p <0.0001). Item-level anxiety changes exhibited weak and nonsignificant correlations (Spearman ρ: −0.24 to 0.33) with objective MDS-UPDRS motor improvements in both immediate and sustained dopamine replacement contexts. Conclusion: Dopamine repletion effected immediate relief of anxiety in an On-Off state comparison. A similar benefit was observed in the longitudinal PPMI cohort by comparing anxiety before and after DRT initiation, suggesting DRT confers sustained anxiolytic effects in early PD. The weak correlations between improvements to anxiety and motor function on both timescales support the view that these changes are not mediated by improved motor function.