Mason J, Freemantle N, Eccles M
Centre for Health Economics, University of York.
Br J Gen Pract. 2000 May;50(454):366-70.
New selective serotonin reuptake inhibitors (SSRIs) are perceived to be much safer in use than older tricyclic antidepressants (TCAs). However, previous assessments of association with fatal toxicity were made too soon after the introduction of the new drugs to permit accurate estimation.
To determine the level of association of antidepressant drugs with fatal poisoning in the treatment of depression.
National data for England and Wales for three years (1993 to 1995) for fatal poisonings associated with antidepressants were obtained and, together with national primary care data on prescribing, were used to calculate fatality association by antidepressant drug.
There were substantial variations between drugs in the level of association with fatal poisoning. Assuming an average treatment episode lasted three months, one fatality is associated with 11,800 treatment episodes of antidepressant use (95% CI = 11,120 to 12,580) when only single substance fatalities are considered. For SSRIs as a group the association was one in 411,800 (95% CI = 243,300 to 1.34 million) and for TCAs one in 8130 (95% CI = 7650 to 8670). However, for one of the newer TCAs, lofepramine, the single substance fatality rate associated with its use was one in 233,700 (95% CI = 124,500 to 1.89 million), which is not statistically significantly different from the SSRIs (P = 0.35).
Estimated death rates associated with specific antidepressants should be compared with caution because drugs may be used selectively in patients with differing severity of depression. The proportion of these fatalities that could be prevented by switching to safer antidepressants is unclear when so few deaths are recorded as accidental; when there is intent to do self-harm the potential for switching to other means is unknown. However, this approach to relative toxicity may remain the best available since it is unlikely that a randomised trial will ever be conducted with a large enough sample size to obtain experimental data. Fatalities from antidepressant poisoning are very rare but if safety is paramount then lofepramine or an SSRI are justifiable treatment choices.
新型选择性5-羟色胺再摄取抑制剂（SSRIs）在使用中被认为比老式三环类抗抑郁药（TCAs）安全得多。然而，在新药引入后不久就对其与致命毒性的关联进行了评估，无法进行准确估计。
确定抗抑郁药在治疗抑郁症时与致命中毒的关联程度。
获取了英格兰和威尔士三年（1993年至1995年）与抗抑郁药相关的致命中毒的全国数据，并与全国初级保健处方数据一起用于计算各类抗抑郁药的致死关联度。
不同药物与致命中毒的关联程度存在很大差异。假设平均治疗疗程持续三个月，仅考虑单一物质致死情况时，每11,800次抗抑郁药治疗疗程中有1例死亡（95%置信区间 = 11,120至12,580）。作为一个整体，SSRIs的关联度为每411,800次治疗中有1例死亡（95%置信区间 = 243,300至134万），而TCAs为每8130次治疗中有1例死亡（95%置信区间 = 7650至8670）。然而，对于较新的一种TCAs——洛非帕明，其使用相关的单一物质致死率为每233,700次治疗中有1例死亡（95%置信区间 = 124,500至189万），与SSRIs相比无统计学显著差异（P = 0.35）。
比较特定抗抑郁药的估计死亡率时应谨慎，因为药物可能会被选择性地用于抑郁症严重程度不同的患者。当记录的意外死亡如此之少时，尚不清楚改用更安全的抗抑郁药可预防的死亡比例；当有自我伤害意图时，改用其他方式的可能性未知。然而，这种相对毒性的评估方法可能仍是现有最佳方法，因为不太可能进行样本量足够大的随机试验来获取实验数据。抗抑郁药中毒致死非常罕见，但如果安全性至关重要，那么洛非帕明或SSRIs是合理的治疗选择。
