Department of Neuroscience, Uppsala University, Uppsala, Sweden; Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
Department of Neuroscience, Uppsala University, Uppsala, Sweden.
Biomed Pharmacother. 2021 Nov;143:112234. doi: 10.1016/j.biopha.2021.112234. Epub 2021 Sep 30.
Proton-pump inhibitors (PPIs) are used to suppress gastric acid secretion in several gastrointestinal conditions. While these drugs are generally well tolerated, their long-term use may be associated with different adverse effects, including migraine. We analyzed the association between treatment with PPIs (omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole) and migraine prevalence in the UK Biobank cohort through a cross-sectional analysis (using baseline data for 468,280 participants, 16,390 of whom had migraine) and a longitudinal analysis (including 145,007 participants with no migraine at baseline, of whom 3786 had probable migraine without aura [MWOA] and 9981 probable migraine with aura [MWA] or both MWOA and MWA at an average follow-up time of 10.06 years). We also evaluated the modulating role of the metabolizer phenotype of CYP2C19, the major enzyme involved in PPI clearance. Treatment with PPIs was associated with higher migraine prevalence at baseline (odds ratio [OR] = 1.25, p < 0.0001). CYP2C19 rapid metabolizer phenotype was associated with lower prevalence of migraine exclusively in participants treated with PPIs (OR = 0.89, p = 0.029). In addition, treatment with PPIs was associated with higher incidence of both probable MWOA (OR = 1.24, p = 0.002) and MWA (OR = 1.43, p < 0.0001) at follow-up. Treatment with PPIs and CYP2C19 poor metabolizer status were associated with higher incidence of probable chronic migraine exclusively in men. Our results suggest a significant association between treatment with PPIs and migraine in this large population-based cohort and support a potential relevant role of gender and CYP2C19 phenotype.
质子泵抑制剂 (PPIs) 用于抑制几种胃肠道疾病中的胃酸分泌。虽然这些药物通常耐受性良好，但长期使用可能会引起不同的不良反应，包括偏头痛。我们通过横断面分析（使用 468280 名参与者的基线数据，其中 16390 名患有偏头痛）和纵向分析（包括 145007 名基线时无偏头痛的参与者，其中 3786 名患有无先兆偏头痛 [MWOA]，9981 名患有有先兆偏头痛 [MWA] 或两者兼有偏头痛，平均随访时间为 10.06 年），在英国生物库队列中分析了 PPI（奥美拉唑、埃索美拉唑、兰索拉唑、泮托拉唑和雷贝拉唑）治疗与偏头痛患病率之间的关联。我们还评估了 CYP2C19 代谢表型（主要参与 PPI 清除的酶）的调节作用。PPIs 治疗与基线时偏头痛患病率较高相关（优势比 [OR] = 1.25，p < 0.0001）。CYP2C19 快速代谢表型与仅在接受 PPI 治疗的参与者中偏头痛患病率较低相关（OR = 0.89，p = 0.029）。此外，PPIs 治疗与随访时两种可能的 MWOA（OR = 1.24，p = 0.002）和 MWA（OR = 1.43，p < 0.0001）的发生率较高相关。PPIs 治疗和 CYP2C19 弱代谢状态与仅在男性中偏头痛的发生率较高相关。我们的研究结果表明，在这个大型基于人群的队列中，PPIs 治疗与偏头痛之间存在显著关联，并支持性别和 CYP2C19 表型的潜在相关作用。
