PDF(Pubmed)
Abstract：
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 (101-102) 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.
Older tricyclic antidepressants and their toxicity in overdose and in clinical use Tricyclic antidepressants were first used in the 1950s. Their use for depression has gone down in the past 20 or so years. This is because newer antidepressants are better tolerated and less toxic in overdose. Certain tricyclics - dosulepin and amitriptyline - have been identified as being particularly toxic tricyclics and their use has been restricted. However many other tricyclics remain widely used for depression and many other conditions. We examined all the evidence we could find on tricyclic toxicity. We found that, with one exception, all tricyclics are toxic and dangerous when taken in overdose. The exception is lofepramine - a tricyclic used in the UK and some other countries. When looking at toxicity in clinical use, we found no consistent evidence of difference between individual tricyclics. It is possible that most or all tricyclics do not increase the risk of heart attack or sudden cardiac death when used at normal clinical doses.
Older tricyclic antidepressants and their toxicity in overdose and in clinical use Tricyclic antidepressants were first used in the 1950s. Their use for depression has gone down in the past 20 or so years. This is because newer antidepressants are better tolerated and less toxic in overdose. Certain tricyclics - dosulepin and amitriptyline - have been identified as being particularly toxic tricyclics and their use has been restricted. However many other tricyclics remain widely used for depression and many other conditions. We examined all the evidence we could find on tricyclic toxicity. We found that, with one exception, all tricyclics are toxic and dangerous when taken in overdose. The exception is lofepramine - a tricyclic used in the UK and some other countries. When looking at toxicity in clinical use, we found no consistent evidence of difference between individual tricyclics. It is possible that most or all tricyclics do not increase the risk of heart attack or sudden cardiac death when used at normal clinical doses.
摘要：
三环抗抑郁药（TCA）仍然广泛用于抑郁症和许多其他疾病。在临床使用中，个体TCA在其过量毒性和心脏毒性方面可能存在重要差异。我们进行了系统评价，以比较个体TCA在过量用药中的毒性和治疗剂量下发生严重不良心脏事件的风险。我们使用致命性毒性指数（FTI）和病死率作为过量用药的致死率指标，以及正常临床使用期间心血管不良事件风险的风险比或比值比。总之,纳入30例过量死亡报告和14例评估临床使用心血管不良事件风险的观察性研究。除了洛非帕明以外,所有TCA的FTI值具有相同的数量级(101-102)。地西帕明似乎比其他TCA更有可能导致过量死亡。阿米替林,氯米帕明,Dothiepin/dosulepin,多塞平,曲米帕明和丙咪嗪的毒性大致相似，通常据报道毒性低于地昔帕明。去甲替林的数据是矛盾的。洛非帕明在用药过量时死亡风险最低。在不同的FTI定义之间和使用的标记物之间，过量毒性的等级顺序大致一致。关于临床相关暴露时心血管事件的风险，阿米替林,去甲替林和洛非帕明与使用中心脏毒性的更大风险相关.过量毒性的所有措施都受到外部影响和混淆。当考虑到它们在过量服用中的毫无疑问的毒性和在正常临床使用中可能的毒性时，应尽量减少在抑郁症和其他情况下继续使用TCA。
较老的三环抗抑郁药及其在过量和临床使用中的毒性三环抗抑郁药在1950年代首次使用。在过去20年左右的时间里，他们对抑郁症的使用有所下降。这是因为新的抗抑郁药在过量服用时耐受性更好，毒性更小。某些三环类-多舒乐平和阿米替林-已被确定为特别有毒的三环类，并且其使用受到限制。然而，许多其他三环类药物仍然广泛用于抑郁症和许多其他疾病。我们检查了我们能找到的关于三环毒性的所有证据。我们发现,除了一个例外,服用过量时，所有三环类药物都是有毒和危险的。唯一的例外是洛非帕明-在英国和其他一些国家使用的三环。当观察临床使用中的毒性时，我们没有发现单个三环类之间存在差异的一致证据.在正常临床剂量下使用时，大多数或所有三环类药物可能不会增加心脏病发作或心源性猝死的风险。
较老的三环抗抑郁药及其在过量和临床使用中的毒性三环抗抑郁药在1950年代首次使用。在过去20年左右的时间里，他们对抑郁症的使用有所下降。这是因为新的抗抑郁药在过量服用时耐受性更好，毒性更小。某些三环类-多舒乐平和阿米替林-已被确定为特别有毒的三环类，并且其使用受到限制。然而，许多其他三环类药物仍然广泛用于抑郁症和许多其他疾病。我们检查了我们能找到的关于三环毒性的所有证据。我们发现,除了一个例外,服用过量时，所有三环类药物都是有毒和危险的。唯一的例外是洛非帕明-在英国和其他一些国家使用的三环。当观察临床使用中的毒性时，我们没有发现单个三环类之间存在差异的一致证据.在正常临床剂量下使用时，大多数或所有三环类药物可能不会增加心脏病发作或心源性猝死的风险。
