Risks of Sulpiride-Induced Parkinsonism in Peptic Ulcer and Gastroesophageal Reflux Disease Patients in Taiwan: A Nationwide Population-Based Study

Abstract

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 cutoff 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,

Research progress on the roles of dopamine and dopamine receptors in digestive system diseases

“…Promotes gastric peristalsis and emptying, in addition to inhibiting reflux of gastric contents after meals; can increase pressure on the lower oesophageal sphincter [41,90,91] Sulpiride DRD2 inhibitor Can reduce the secretion of gastric protein and gastric acid and inhibit the development of gastric ulcers [18,35,42] Cisapride DRD2 antagonist Can increase the release of acetylcholine in the intestinal plexus to stimulate the movement of the lower oesophagus, stomach, and small intestine [19] SKF 38393 DRD1 inhibitor Inhibits the development of gastroduodenal ulcers [35] Metoclopramide DR antagonist Increases gastric emptying while also exerting antiemetic effects [39,40] Domperidone DRD2 antagonist Inhibits intestinal motility, regulates sodium absorption and mucosal blood flow, and has a protective effect against gastroduodenal ulcers [47,48] Calilazine DRD3 antagonist Can inhibit multiple drug resistance and make colon and lung cancer cells sensitive to antitumor drugs [52] Pimozite DRD2 antagonist Inhibits the growth and metastasis of colorectal cancer (CRC) [53] Thioridazine DRD2 antagonist Inhibits the growth of gastric cancer cells to exert antitumor effects; ameliorates hepatocellular carcinoma to possibly reduce the risk of tumour metastasis [54,83] Quinpirol DRD2 agonist Reduces the permeability of blood vessels and prevents excessive leakage of blood vessels, thereby decreasing the severity of UC [56,57,62] Bromocriptine…”

“…Therefore, domperidone is a rational option for the treatment of gastro oesophageal reflux disease 16,17 . Sulpiride is a highly selective DRD2 antagonist mainly used for the treatment of PUD and GERD 18 . Sisapride is a DRD2 antagonist.…”

Recognition and Management of Antipsychotic-Induced Parkinsonism in Older Adults: A Narrative Review

“…A study in Korea found an incidence rate of 8.69/100,000 over a three-year period [28], with incidence increasing with age up until the age bracket 75-79y (higher in women than men), and decreasing slightly from age 80. Finally, in a study from Taiwan using data from the National Health Insurance Research Database over the period 2000-2012, the incidence of DIP was found to be of 762.2/100,000 in patients who had taken sulpiride (a highly selective D2R antagonist) for the management of gastro-oesophageal reflux disorder, compared to those who were not treated with this drug [31]. When looking at age groups, the Olmsted study showed an increasing incidence of DIP from age 60, with the highest incidence in women in the age group 80-89 [14]: 31.8/100,000/year in men and 60.8/100,000 in women.…”

“…Most studies report that increasing age (for both sexes) and female gender are more frequently associated with incidence and prevalence of DIP [8][9][10]14,16,17,23,[25][26][27][28]31,33]. However, the vast majority of these studies include all drug groups associated with DIP, hence it is difficult to ascertain the precise prevalence and incidence of AIP.…”

“…In addition to age over 60 and female gender, a number of studies have suggested that other patient and drug-related factors can be associated with an increased risk of developing AIP (Table 4). Patient-related factors are organic brain damage, learning disability, dementia, IPD, hypertension, organic personality disorder, schizophrenia, mania, depression or anxiety, HIV infection, non-European ancestry, and presence of HLA-B44 [3,31,33,[47][48][49]; whilst drug-related causes are high potency APs, higher dosage of APs, and long-term exposure to APs [3,33]. The diagnosis of DIP has also been reported to triple the lifetime risk of developing IPD [50,51], whilst the relative risk of developing IPD was found in one study to be of 24.3 (CI 95%) [52].…”