Taylor David, Poulou Sofia, Clark Ivana
Pharmacy Department, Maudsley Hospital, South London and Maudsley NHS Foundation Trust, Denmark Hill, London SE5 8AZ, UK.
Institute of Pharmaceutical Sciences, King's College London, London, UK.
Ther Adv Psychopharmacol. 2024 May 30;14:20451253241243297. doi: 10.1177/20451253241243297. eCollection 2024.
Tricyclic antidepressants (TCAs) remain widely prescribed for depression and many other conditions. There may be important differences between individual TCA in regard to their overdose toxicity and their cardiac toxicity in clinical use. We conducted a systematic review to compare the toxicity of individual TCA in overdose and the risk of serious adverse cardiac events occurring with therapeutic doses. We used the fatal toxicity index (FTI) and case fatality ratio as markers of fatality in overdose, and hazard ratios or odds ratios for the risk of cardiovascular adverse events during normal clinical use. In all, 30 reports of mortality in overdose and 14 observational studies assessing the risk of cardiovascular adverse events in clinical use were included. FTI values were of the same order of magnitude (10-10) for all TCAs except lofepramine. Desipramine appears to be somewhat more likely than other TCAs to lead to death in overdose. Amitriptyline, clomipramine, dothiepin/dosulepin, doxepin, trimipramine and imipramine showed broadly similar toxicity and were usually reported to be less toxic than desipramine. Data on nortriptyline were contradictory. Lofepramine had the lowest risk of death in overdose. The rank order of overdose toxicity was broadly consistent between different FTI definitions and between markers used. With respect to the risk of cardiovascular events at clinically relevant exposure, amitriptyline, nortriptyline and lofepramine were associated with a greater risk of in-use cardiotoxicity. All measures of overdose toxicity were subject to external influences and confounding. The continued use of TCAs in depression and other conditions should be minimized when considering their undoubted toxicity in overdose and possible toxicity in normal clinical use.
三环类抗抑郁药（TCAs）仍被广泛用于治疗抑郁症及许多其他病症。在临床应用中，不同的三环类抗抑郁药在过量毒性和心脏毒性方面可能存在重要差异。我们进行了一项系统评价，以比较个体三环类抗抑郁药的过量毒性以及治疗剂量下发生严重心脏不良事件的风险。我们使用致命毒性指数（FTI）和病死率作为过量用药致死的指标，使用风险比或比值比来衡量正常临床使用期间发生心血管不良事件的风险。总共纳入了30篇过量用药死亡率报告和14项评估临床使用中心血管不良事件风险的观察性研究。除洛非帕明外，所有三环类抗抑郁药的FTI值都在同一数量级（10-10）。地昔帕明在过量用药时似乎比其他三环类抗抑郁药更易导致死亡。阿米替林、氯米帕明、多塞平/度硫平、多塞平、曲米帕明和丙咪嗪表现出大致相似的毒性，通常报道其毒性低于地昔帕明。去甲替林的数据存在矛盾。洛非帕明过量用药时的死亡风险最低。不同FTI定义之间以及所使用的指标之间，过量毒性的排序大致一致。就临床相关暴露下的心血管事件风险而言，阿米替林、去甲替林和洛非帕明与使用中发生心脏毒性的风险更高相关。所有过量毒性指标均受到外部影响和混杂因素的影响。考虑到三环类抗抑郁药在过量用药时无疑存在毒性以及在正常临床使用中可能存在的毒性，在抑郁症和其他病症中应尽量减少其持续使用。
