OBJECTIVES: To assess an increased risk of parkinsonism associated with the use of gastrointestinal (GI) prokinetics

METHODS: This case-crossover study was conducted using nationally representative data, the National Health Insurance Service-National Sample Cohort, that covered approximately one million patients from January 1, 2002 to December 12, 2015. We included patients who were newly diagnosed with parkinsonism (ICD-10 G20, G21.1, G25.1) from January 1, 2007 to December 1, 2015 and the first date of diagnosis was defined as the index date. Patients with extrapyramidal and movement disorders or brain tumor within 5 years before the index date were excluded. The exposure to GI prokinetics was self-compared during the risk period (1-30 days) and control period (61-90 days) before or on the index date. We estimated adjusted odds ratios (aOR) of parkinsonism with conditional logistic regression.

RESULTS: Among 5842 patients with parkinsonism (55.7% women; mean [SD] age, 59.9 [19.8] years), 4632 patients were exposed to GI prokinetics (58.7% women; 61.7 [19.2] years) for the 2 years before or on the index date. 2268 and 1674 patients were exposed to GI prokinetics during the risk period and control period, respectively. The use of GI prokinetics significantly increased the risk of parkinsonism (aOR=2.31; 95% CI, 2.06-2.59). Elderly patients (65 years old) with GI prokinetics were associated with the risk of parkinsonism (aOR=2.69; 95% CI, 2.30-3.14). However, relatively lower risk was observed in younger patients (aOR=1.90; 95% CI, 1.59-2.27). GI prokinetics were prescribed more frequently in internal medicine (32.20% among all medical specialties) and primary care facility (41.31% among all medical institutions) in 1980 patients with GI prokinetics during the risk period.

CONCLUSIONS: The use of GI prokinetics was significantly associated with an elevated risk of parkinsonism. The higher risk of parkinsonism was found in elderly. Deliberate consideration is needed when using GI prokinetics.