Metoclopramide as a prokinetic agent for diabetic gastroparesis: revisiting the risk of Parkinsonism

Abstract

Background: Metoclopramide is used to relieve gastrointestinal symptoms, however, it could cause adverse reactions of motor disorders. The aim of this study was to investigate whether metoclopramide treatment has a duration–response or dose–response effect and to estimate the risk of developing Parkinsonism following different and specific durations of treatment. Methods: A cohort study of newly diagnosed type 2 diabetes mellitus in 45- to 79-year-old patients, between 1999 and 2008, was selected using the Longitudinal Health Insurance Database 2005. A nested case–control study was conducted in the diabetes cohort in which all incident cases of Parkinsonism were identified. We randomly matched each case with up to 10 controls from the risk set. Conditional logistic regression was utilized to estimate odds ratio of Parkinsonism associated with metoclopramide use. Results: A total of 34,685 patients with diabetes were assembled as the cohort, and 541 incident Parkinsonism cases were identified. There were duration–response and dose–response effects on the risk of developing Parkinsonism. Compared with never-use patients, the adjusted odds ratios (ORs) of continuing therapy for 0–1 month, 1–2 months, 2–3 months, 3–5 months, and more than 5 months were 1.17 [95% confidence interval (CI) 0.93–1.45], 1.44 (95% CI 1.04–2.00), 1.74 (95% CI 1.14–2.65), 1.90 (95% CI 1.23–2.93), and 2.17 (95% CI 1.50–3.12), respectively. Conclusions: With metoclopramide treatment, regardless of less or more than 3 months of use, the risk of developing Parkinsonism in patients with newly diagnosed diabetes escalated with the duration of therapy. Therefore, we recommend close monitoring for the development of Parkinsonism in patients treated with metoclopramide, particularly (but not limited to) those with prolonged exposure.

A global bibliometric and visualized analysis of the status and trends of gastroparesis research

“…Nevertheless, the adverse effects of the drug continue to be reported. For example, a study of 34,685 diabetic patients treated with metoclopramide found that the risk of Parkinson’s syndrome increased with the duration of treatment, regardless of whether or not the drug was used for more than 3 months [ 70 ]. In fact, in 2009, the USA Food and Drug Administration (FDA) issued a warning that metoclopramide use may lead to irreversible delayed-onset dyskinesia [ 71 ].…”

In silico screening of potentially bioactive-anti-functional dyspepsia constituents of Magnoliae officinalis Cortex based on molecular docking and network pharmacology

“…Some of these drugs e.g. domperidone, have been banned in the USA, Canada, and other counties [16][17][18][19][20]. Thus, it is crucial to identify novel candidate drugs for treating FD.…”

Neuropatía gastrointestinal diabética. Una revisión de la literatura

“…Debido a que atraviesa la barrera hematoencefálica se deben considerar sus efectos adversos extrapiramidales (18) como el parkinsonismo, así como también tener en cuenta que puede producir discinesia y acatisia (29). Por ello se recomienda un monitoreo cercano para detectar tempranamente el parkinsonismo y otros efectos adversos medicamentosos (30).…”