Revisiting the Association Between Calcium Channel Blockers and Parkinson's Disease in the E3N Cohort.

BACKGROUND

Previous studies on calcium channel blockers (CCBs) and Parkinson's disease (PD) risk reached conflicting conclusions.

OBJECTIVES

We examined the relationship between CCBs and PD in the E3N cohort of French women followed for 15 years (2004-2018), while taking into account the potential for reverse causation.

METHODS

New users of CCBs were identified using drug reimbursement databases. We validated incident PD using several data sources. We described trajectories of CCBs use using mixed logistic models within a nested case-control study. We used Cox proportional hazards models for time-varying variables to estimate the association between CCBs (overall, amlodipine, non-amlodipine dihydropyridines [DiCCBs], non-dihydropyridines [non-DiCCBs]) and PD. Main analyses used a 5-year lag; sensitivity analyses without a lag were performed for comparison.

RESULTS

Among 82,605 women, 603 developed PD and 13,022 used CCBs. Women who started non-DiCCBs had higher PD risk than never users (hazard ratio [HR] = 1.56; 95% confidence interval [95% CI] = 0.99-2.46; P-trend ≤ 0.02). Among non-DiCCBs, diltiazem was associated with PD (HR = 2.20 [95% CI = 1.19-4.04]). There were no significant associations for CCBs overall, amlodipine, and non-amlodipine DiCCBs. In analyses without a lag, amlodipine (HR = 1.45 [95% CI = 1.13-1.87]) and diltiazem (HR = 1.63 [95% CI = 1.02-2.60]) were associated with PD. Results are consistent with trajectories of CCBs prescriptions in PD patients and controls.

DISCUSSION: Overall, CCBs were not associated with PD but women who started using diltiazem had higher PD incidence in lagged analyses. Diltiazem and amlodipine were associated with PD in analyses without a lag. These findings are consistent with case reports of parkinsonism induced by specific CCBs and warrant further studies and surveillance. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.