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

PLoS One. 2021 Mar 1;16(3):e0247354. doi: 10.1371/journal.pone.0247354. eCollection 2021.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Calcium Channel Blockers / adverse effects
  • Cohort Studies
  • Comorbidity
  • Diabetes Mellitus / physiopathology
  • Female
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Parkinson Disease / diagnosis*
  • Parkinson Disease / etiology*
  • Parkinson Disease, Secondary / chemically induced
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / diagnosis
  • Parkinsonian Disorders / etiology*
  • Proportional Hazards Models
  • Republic of Korea / epidemiology
  • Retrospective Studies
  • Risk Factors

Substances

  • Calcium Channel Blockers

Grants and funding

HM and SJ were supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI15C1240).The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. KHIDI: https://www.khidi.or.kr/board;jsessionid=SRxVfMwJvhwHwP7nrQTfGJY2dV3bBDLLh6l1Shjh7Vrsh4nN2svL!2129625964?menuId=MENU00770&siteId=SITE00012.