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Background: Sulpiride is a highly selective dopamine D2 receptor antagonist and is commonly used in psychiatric disorders, Tourette syndrome, peptic ulcer disease (PUD), and gastroesophageal reflux disease (GERD). However, sulpiride has been recognized as a potential cause of drug-induced parkinsonism (DIP) for a long time. In this study, we aimed to focus on analysis of sulpiride-induced parkinsonism (SIP) in PUD and GERD patients based on a nationwide population. Methods: Data were obtained from the Taiwan's National Health Insurance Research Database. The study enrolled 5,275 PUD or GERD patients, of whom were divided into two groups, based on their exposure (1,055 cases) or non-exposure (4,220 cases) to sulpiride. Results: During the study period (2000–2012), the incidence rate of parkinsonism was 261.5 and 762.2 per 100,000 person-years in the control and sulpiride-treated groups, respectively. For patients with at least 14 days of prescription for sulpiride, the adjusted hazard ratio (aHR) was 2.89, 95% confidence interval (CI): 2.04-4.11. Patients with age more than 65 years (aHR = 4.99, 95% CI = 2.58-9.65), hypertension (aHR = 2.39, 95% CI = 1.49-3.82), depression (aHR = 2.00, 95% CI = 1.38-2.91), and anxiety (aHR = 1.45, 95% CI = 1.01-2.09) had significant higher risk of developing parkinsonism. An average annual cumulative sulpiride dose > 1,103 mg was accompanied by the greatest risk of SIP; sulpiride use for ≥ 9 days is a cut-off point for predicting future SIP. Conclusion: At the population level, sulpiride may be frequently prescribed and apparently effective for PUD and GERD. SIP is associated with older age, hypertension, depression or anxiety comorbidities. Physicians should be aware of the neurogenic adverse effects, even when the drug is only used in low-dose or a short duration. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: This retrospective cohort study used a population-based dataset to test the risk for parkinsonism in patients receiving flunarizine and cinnarizine, compared with matched controls. Methods: Data were obtained from the National Health Insurance Research Dataset of Taiwan. Patients receiving flunarizine or cinnarizine for more than 1 month between 2000 and 2005 were enrolled. Exclusion criteria included receiving flunarizine, cinnarizine, or antipsychotics for more than 1 month during 1997-1999, a history of neurodegenerative diseases, and an age of less than 30 years. One matched control for each patient was selected. Each participant was followed for diagnosis of parkinsonism within a 3-year observation period. Stroke, diabetes mellitus, total prescription days, and doses of flunarizine or cinnarizine were recorded. Results: The study and control groups consisted of 9830 subjects. In the study group, 280 patients (2.9 %) were diagnosed with parkinsonism with a median observation period of 1.2 years, and 49 participants (0.5 %) were diagnosed in the control group with a median observation period of 1.9 years. The adjusted hazard ratio for parkinsonism among patients receiving flunarizine and cinnarizine was 5.117 (95 % CI = 3.758-6.967). Age, stroke, and diabetes mellitus were significant risk factors, but female sex and total doses of the study drugs were not. Conclusions: This study demonstrates that flunarizine and cinnarizine significantly increase the risk for parkinsonism. The treatment benefits of these two agents should be balanced with this adverse effect. Physicians must look carefully for early signs of parkinsonism in patients treated with flunarizine and cinnarizine. [ABSTRACT FROM AUTHOR]