Drug-induced Parkinsonism: A strong predictor of idiopathic Parkinson's disease

Abstract

BACKGROUND: Although Idiopathic Parkinson's disease (IPD) develops in considerable patients with drug-induced Parkinsonism (DIP), the association hasn't been well defined. We aimed to evaluate the underlying association and risk factors of DIP and IPD. METHODS: A retrospective cohort study using National Health Insurance Claims data in 2011-2016 was conducted. New-onset DIP patients in 2012 were selected and matched with active controls having diabetes mellitus at a 1:4 ratio by age, sex, and Charlson's Comorbidity Index score. Comorbidity, causative drugs, and prescription days were evaluated as covariates. RESULTS: A total of 441 DIP were selected. During the 4-year follow up, 14 IPD events in the DM group but 62 events in the DIP group were observed (adjusted hazard ratio, HR: 18.88, 95% CI, 9.09-39.22, adjusting for comorbidities and causative drugs). IPD diagnosis in DIP was observed high in males compared to females (15.58/13.24%). The event was the most within the 1st year follow-up, mean days 453 (SD 413.36). Subgroup analysis in DIP showed calcium channel blocker (verapamil, diltiazem, and flunarizine) was significantly associated with increased IPD risk (HR: 2.24, 95% CI, 1.27-3.93). CONCLUSION: Increased IPD in DIP patients might not be from the causal toxicity of antidopaminergic effects but from a trigger by the causative drugs on the DIP patients who already had subclinical IPD pathology. DIP can serve as a strong proxy for IPD incidence. Subjects who develop DIP should be monitored carefully for potential IPD incidence.