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

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 cutoff 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.

Safety and Efficacy of Fremanezumab for the Prevention of Migraine: A Meta-Analysis From Randomized Controlled Trials

“…The prevention of migraines is not to prevent the illness but to reduce the frequency of migraine attacks (9). The traditional preventive medications on migraines frequently lead to an early suspension of treatment due to their poor efficacy and tolerability in migraine people (10,11).…”

Cinnarizine- and flunarizine-associated movement disorder: a literature review

“…Kim et al [128] showed that the odds ratio of the risk of developing PKN in FNZ users when compared to non-FNZ users is 4.95 (2.71-9.03). In another study, Lin et al [129] revealed that a longer duration of exposure to FNZ and high FNZ doses are significantly associated with the occurrence of PKN.…”

“…The majority of the incidences of abnormal movements associated with CNZ/FNZ were not well described in the literature. Table 3 is a resume of the percentages of MD secondary to CNZ/FNZ; the data was extracted from clinical trials and other populationbased studies [26,34,48,49,55,70,76,77,97,115,119,123,127,129]. The incidences of CNZ/FNZ-induced abnormal movements, in general, vary throughout the literature, but the range is much smaller than other drugs with postmarketing evaluation such as valproic acid [132]; for example, extrapyramidal symptoms were found with the use of CNZ/FNZ in Verspeelt and colleagues in 4.30% of individuals with migraine individuals, but in the vestibular vertigo subgroup it was 0.91% [77].…”

“…Martí-Massó and colleagues reported that 40% of PD patients with short-term CNZ/FNZ use showed a severe worsening of the bradykinesia and gait [26]. Recent Asian population-based studies showed important features of the long-term CNZ/FNZ use and its complications [115,119,122,124,[127][128][129]. Lin et al [115] revealed that age, stroke, and diabetes mellitus are risk factors for the development of CNZ/FNZ-induced PKN.…”

Different Dosage Regimens of Eptinezumab for the Treatment of Migraine: A Meta-Analysis from Randomized Controlled Trials

“…Presently, more than 16% of the global population is affected by the attacks of migraine [2]. Unfortunately, since many drugs are available for the therapy of migraine, such as NSAIDS, triptans, ergots, they all have some contraindications or severe adverse effects in certain aspects [3]. Therefore, further studies are needed on the treatment of the migraine, which ultimately may help patients suffering from it by improving the adverse effects.…”