Naps Michelle S, Leong Shirley H, Hartwell Emily E, Rentsch Christopher T, Kranzler Henry R
Mental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania, USA.
School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Alcohol Clin Exp Res (Hoboken). 2023 Mar;47(3):438-447. doi: 10.1111/acer.15011. Epub 2023 Feb 21.
Topiramate, which is increasingly being used to treat alcohol use disorder (AUD), is commonly associated with reduced serum bicarbonate concentrations. However, estimates of the prevalence and magnitude of this effect are from small samples and do not address whether topiramate's effects on acid-base balance differ in the presence of an AUD or by topiramate dosage.
Veterans Health Administration electronic health record (EHR) data were used to identify patients with a minimum of 180 days of topiramate prescription for any indication and a propensity score-matched control group. We differentiated patients into two subgroups based on the presence of a diagnosis of AUD in the EHR. Baseline alcohol consumption was determined using Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) scores in the EHR. Analysis also included a three-level measure representing mean daily dosage. The topiramate-associated changes in serum bicarbonate concentration were estimated in difference-in-differences linear regression models. A serum bicarbonate concentration <17 mEq/L was considered to represent possible clinically significant metabolic acidosis.
The cohort comprised 4287 topiramate-treated patients and 5992 propensity score-matched controls with a mean follow-up period of 417 days. The mean topiramate-associated reductions in serum bicarbonate concentration were <2 mEq/L in the low (≤88.75), medium (>88.75 and ≤141.70), and high (>141.70) mg/day dosage tertiles, irrespective of AUD history. Concentrations <17 mEq/L occurred in 1.1% of topiramate-treated patients and 0.3% of controls and were not associated with alcohol consumption or an AUD diagnosis.
The excess prevalence of metabolic acidosis associated with topiramate treatment does not differ with dosage, alcohol consumption, or the presence of an AUD. Baseline and periodic serum bicarbonate concentration measurements are recommended during topiramate therapy. Patients prescribed topiramate should be educated about the symptoms of metabolic acidosis and urged to report their occurrence promptly to a healthcare provider.
托吡酯越来越多地用于治疗酒精使用障碍（AUD），它通常与血清碳酸氢盐浓度降低有关。然而，这种效应的患病率和程度的估计来自小样本，且未涉及托吡酯对酸碱平衡的影响在存在AUD或托吡酯剂量不同时是否存在差异。
使用退伍军人健康管理局电子健康记录（EHR）数据来识别至少有180天任何适应症托吡酯处方的患者以及倾向评分匹配的对照组。我们根据EHR中是否存在AUD诊断将患者分为两个亚组。使用EHR中的酒精使用障碍识别测试-消费量（AUDIT-C）评分确定基线酒精消费量。分析还包括一个代表平均每日剂量的三级测量指标。在差异-in-差异线性回归模型中估计托吡酯相关的血清碳酸氢盐浓度变化。血清碳酸氢盐浓度<17 mEq/L被认为代表可能具有临床意义的代谢性酸中毒。
该队列包括4287名接受托吡酯治疗的患者和5992名倾向评分匹配的对照，平均随访期为417天。无论AUD病史如何，在低（≤88.75）、中（>88.75且≤141.70）和高（>141.70）mg/天剂量三分位数中，托吡酯相关的血清碳酸氢盐浓度平均降低<2 mEq/L。<17 mEq/L的浓度在1.1%的托吡酯治疗患者和0.3%的对照中出现，且与酒精消费或AUD诊断无关。
与托吡酯治疗相关的代谢性酸中毒的额外患病率在剂量、酒精消费或AUD存在方面没有差异。建议在托吡酯治疗期间进行基线和定期血清碳酸氢盐浓度测量。应告知开具托吡酯处方的患者有关代谢性酸中毒的症状，并敦促他们及时向医疗保健提供者报告症状的出现。
