Abstract
Background: 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. Methods: 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. Results: 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 > 445 mg was accompanied by the greatest risk of FIP; Fz use for >60 days is a cut-off point for predicting future FIP. Conclusion: 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.
Highlights
Flunarizine (Fz) is a derivative of piperazine and exerts calciumchannel blocking, anti-histaminic, anti-serotoninergic, and antidopaminergic properties
The most recent trial has shown that propulsives, antipsychotics, and Fz are significantly associated with an increased risk of Fz-induced parkinsonism (FIP), depending on drug exposure duration and the cumulative dose amount (Kim et al, 2019)
This cohort study utilized the data from the Longitudinal Health Insurance Database (LHID), one of the data subsets of the National Health Insurance Research Database (NHIRD)
Summary
Flunarizine (Fz) is a derivative of piperazine and exerts calciumchannel blocking, anti-histaminic, anti-serotoninergic, and antidopaminergic properties. Drug-induced parkinsonism (DIP) is a serious adverse effect that has been reported from 1984 until today (De Melo-Souza, 1984; Chouza et al, 1986; Micheli et al, 1987; Benvenuti et al, 1988; Capella et al, 1988; Moretti and Lucantoni, 1988; Micheli et al, 1989; Brucke et al, 1995; Negrotti and Calzetti, 1997; Fabiani et al, 2004). To our knowledge, there has been no population-based subgroup analyses for Fz-induced parkinsonism (FIP) in migraine patients
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