Risk of parkinsonism and related movement disorders with gabapentinoids or tramadol: A case-crossover study

Introduction: A safety signal concerning parkinsonism and related movement disorders with gabapentinoids (gabapentin and pregabalin) or tramadol was detected by reviewing individual case reports and data mining in spontaneous report databases. Well-designed pharmacoepidemiological studies are needed to assess the signal.Objective: This study aimed to investigate the association of exposure to gabapentinoids or tramadol with the risk of parkinsonism and related movement disorders.Methods: We conducted a case-crossover study using a Japanese electronic medical records database. Patients with newly diagnosed parkinsonism or related movement disorders between January 1, 2007, and April 14, 2019, were identified. The diagnosis date of outcomes was defined as the index date. We assessed the exposure of each patient to gabapentinoids or tramadol during a 90 -day hazard period ending 1 day before the index date and in three 90 -day reference periods. Multivariable conditional logistic regression models were employed to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). To confirm the robustness of the primary findings, we also performed sensitivity analyses using a case- case- time-control design, a different time window for hazard and reference periods, a different definition of outcome, and different number of reference periods.Results: A total of 28,972 eligible cases were included in the primary analysis. Exposure to gabapentinoids (aOR, 2.12; 95% CI, 1.73- 2.61) and tramadol (aOR, 2.04; 95% CI, 1.57- 2.64) was associated with increased risk. Results were consistent across sensitivity analyses.Conclusion: Our findings serve as a caution to physicians who prescribe gabapentinoids or tramadol in routine clinical practice.