Department of Internal Medicine, Center for Global Health, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
J Affect Disord. 2019 Jun 1;252:201-211. doi: 10.1016/j.jad.2019.04.009. Epub 2019 Apr 8.
This study compared the largest set of bipolar disorder pharmacotherapies to date (71 drugs and drug combinations) for risk of kidney disorders (KDs).
This retrospective observational study used the IBM MarketScan® database to analyze data on 591,052 adults with bipolar disorder without prior nephropathy, for onset of KDs (of "moderate" or "high" severity) following psychopharmacotherapy (lithium, mood stabilizing anticonvulsants [MSAs], antipsychotics, antidepressants), or "No drug". Cox regression models included fixed pre-treatment covariates and time-varying drug exposure covariates to estimate the hazard ratio (HR) of each treatment versus "No drug".
Newly observed KD occurred in 14,713 patients. No regimen had significantly lower risk of KDs than "No drug". The HR estimates ranged 0.86-2.66 for "all" KDs and 0.87-5.30 for "severe" KDs. As additional drugs were combined to compare more complex polypharmacies, higher HRs were consistently observed. Most regimens containing lithium, MSAs, or antipsychotics had a higher risk than "No drug" (p < 0.05). The risk for "all" and "severe" KDs was highest respectively on monoamine oxidase inhibitors (MAOIs) (HR = 2.66, p = 5.73 × 10), and a lithium-containing four-class combination (HR = 5.30, p = 2.46 × 10). The HR for lithium monotherapy was 1.82 (p = 4.73 × 10) for "severe" KDs.
The limitations inherent for an observational study were non-randomized assignment of patients to treatment groups, non-standardization of diagnostic decisions, and non-uniform quality of data collection. No correction was made for medication dosage.
The findings support literature concerns about lithium nephrotoxicity and highlight the potential risks of MAOIs, MSAs, antipsychotics and psychotropic polypharmacy.
本研究比较了迄今为止最大的一组双相情感障碍药物治疗方案（71 种药物和药物组合），以评估其发生肾脏疾病（KDs）的风险。
本回顾性观察性研究使用 IBM MarketScan®数据库，分析了 591052 名无既往肾病的双相情感障碍成人的数据，以评估精神药理学治疗（锂、心境稳定型抗惊厥药[MSAs]、抗精神病药、抗抑郁药）或“无药物”治疗后 KDs（“中度”或“重度”）的发病情况。Cox 回归模型包括固定的治疗前协变量和随时间变化的药物暴露协变量，以估计每种治疗方法相对于“无药物”的危险比（HR）。
新观察到的 KD 发生在 14713 名患者中。没有一种方案的 KDs 风险明显低于“无药物”。所有 KDs 的 HR 估计值范围为 0.86-2.66，重度 KDs 的 HR 估计值范围为 0.87-5.30。随着更多药物被组合以比较更复杂的多药治疗方案，观察到的 HR 一直较高。大多数包含锂、MSAs 或抗精神病药的方案与“无药物”相比，风险更高（p<0.05）。单胺氧化酶抑制剂（MAOIs）（HR=2.66，p=5.73×10）和含锂的四类联合治疗（HR=5.30，p=2.46×10）的“所有”和“重度”KDs 风险最高。锂单药治疗的“重度”KDs 的 HR 为 1.82（p=4.73×10）。
观察性研究固有的局限性包括患者治疗组的非随机分配、诊断决策的非标准化以及数据收集的非一致性。未对药物剂量进行校正。
这些发现支持文献中关于锂肾毒性的担忧，并突出了 MAOIs、MSAs、抗精神病药和精神药理学多药治疗的潜在风险。
