AUTHOR=Lin Wei , Lin Cheng-Li , Hsu Chung Y. , Wei Cheng-Yu 

TITLE=Flunarizine Induced Parkinsonism in Migraine Group: A Nationwide Population-Based Study

JOURNAL=Frontiers in Pharmacology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.01495

DOI=10.3389/fphar.2019.01495

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Flunarizine (Fz) is a first-line prophylactic medication that is widely used in migraine. However, Fz has been recognized as a potential cause of drug-induced parkinsonism for a long time. However, to our knowledge, there has been no population-based subgroup analyses for Fz-induced parkinsonism (FIP) in migraine patients.</p><p><bold>Methods:</bold> Data were obtained from the Taiwan’s National Health Insurance Research Database. The study comprised 6,470 migraine patients who were divided into two groups, based on their exposure or non-exposure to Fz.</p><p><bold>Results:</bold> During the study period (2000–2012), the incidence rate of parkinsonism was 1.92 and 8.72 per 1,000 person-years in the control and Fz -treated groups, respectively. In the study population, the adjusted hazard ratio was 4.07 (95% confidence interval CI: 2.84–5.85). In 45–64-year old subjects and ≥ 65-year old subjects, the risk of FIP was 3.18 times (95% CI = 1.63–6.20) and 4.89 times (95% CI = 3.09–7.72) more than that in the controls. The Fz-treated subjects with comorbidities also had a higher risk (4.54, 95% CI: 3.14-6.57). An average annual cumulative Fz dose &gt; 445 mg was accompanied by the greatest risk of FIP; Fz use for &gt;60 days is a cut-off point for predicting future FIP.</p><p><bold>Conclusion:</bold> At the population level, this study showed a complete picture of FIP in migraine patients. FIP is associated with older age, history of comorbidities, exposure to high-dose of Fz, and longer duration of exposure to Fz.</p>