Buckley N A, Dawson A H, Whyte I M, Henry D A
Department of Clinical Pharmacology & Toxicology, Mater Misericordlae Hospital, Newcastle, NSW, Australia.
Lancet. 1994 Jan 15;343(8890):159-62. doi: 10.1016/s0140-6736(94)90940-7.
Epidemiological studies have implicated dothiepin in a greater number of self-poisoning deaths than would be expected from its use. We have prospectively assessed the clinical toxicity of dothiepin and other tricyclic antidepressants (TCAs) in overdose. We followed-up consecutively admitted patients with TCA poisoning managed by our department between January, 1987, and August, 1992. 75 patients had taken dothiepin, 101 amitriptyline, 83 doxepin, and 61 other TCAs. Death after TCA poisoning is rare nowadays, so we used intermediate outcome measures--general seizures, tachyarrhythmias, sedation, and QRS width on the electrocardiogram. 15 patients had seizures and 7 tachyarrhythmias. When we excluded patients who had taken more than one TCA, general seizures were more likely after dothiepin than after other TCAs (9/67 vs 5/220) as were arrhythmias (4/67 vs 3/220). Rates of other complications were similar. The dothiepin group had ingested a larger dose, attributable to the larger average tablet strength, than patients who took other TCAs. The odds ratio for seizures with dothiepin versus other TCAs was 6.7 (95% Cl 2.2-20.7) unadjusted and 7.1 (2.2-23.2) after adjustment for sex, age, and ingested dose. The corresponding odds ratios for arrhythmias were 4.6 (1.0-21.1) and 3.4 (0.7-16.3). Dothiepin in overdose seems to be proconvulsant. Patients with only minor sedation and normal limb-lead QRS width may still have major complications. Consideration should be given to the use of other antidepressants in patients at risk of seizures or suicide. Regulatory authorities should review the need for a 75 mg strength tablet of any TCA.
流行病学研究表明，因服用多塞平导致的自我中毒死亡人数比预期的要多。我们前瞻性地评估了过量服用多塞平和其他三环类抗抑郁药（TCA）的临床毒性。我们对1987年1月至1992年8月间由我科治疗的连续入院的TCA中毒患者进行了随访。75例患者服用了多塞平，101例服用了阿米替林，83例服用了多塞平，61例服用了其他TCA。如今，TCA中毒后死亡情况罕见，因此我们采用了中间结局指标——全身性癫痫发作、快速性心律失常、镇静以及心电图上的QRS波宽度。15例患者出现癫痫发作，7例出现快速性心律失常。当我们排除服用多种TCA的患者后，服用多塞平后发生全身性癫痫发作的可能性高于其他TCA（9/67对5/220），心律失常也是如此（4/67对3/220）。其他并发症的发生率相似。与服用其他TCA的患者相比，多塞平组摄入的剂量更大，这归因于其平均片剂强度更大。未调整时，多塞平与其他TCA相比癫痫发作的比值比为6.7（95%可信区间2.2 - 20.7），在对性别、年龄和摄入剂量进行调整后为7.1（2.2 - 23.2）。心律失常的相应比值比为4.6（1.0 - 21.1）和3.4（0.7 - 16.3）。过量服用多塞平似乎有促惊厥作用。仅有轻微镇静且肢体导联QRS波宽度正常的患者仍可能有严重并发症。对于有癫痫发作或自杀风险的患者，应考虑使用其他抗抑郁药。监管机构应审查是否需要75毫克强度的任何TCA片剂。
