This study evaluated rates of all-cause mortality and self-harm in association with clozapine treatment in individuals with treatment-resistant schizophrenia.

A population-based cohort of 2,370 individuals with treatment-resistant schizophrenia after Jan. 1, 1996, was followed until death, first episode of self-harm, emigration, or June 1, 2013. Time to all-cause death and time to first episode of self-harm were analyzed in Cox regression models with time-varying treatment, adjusted for clinical and sociodemographic covariates.

The rate of all-cause mortality was higher for patients not receiving clozapine than for those given clozapine (hazard ratio: 1.88, 95% confidence interval [CI]: 1.16–3.05). This was driven mainly by periods of no antipsychotic treatment (hazard ratio: 2.50, 95% CI: 1.50–4.17), with nonsignificantly higher mortality during treatment with other antipsychotics (hazard ratio: 1.45, 95% CI: 0.86–2.45). Excess mortality was observed in the year after clozapine discontinuation (hazard ratio: 2.65, 95% CI: 1.47–4.78). The rate of self-harm was higher for nonclozapine antipsychotics than for clozapine (hazard ratio: 1.36, 95% CI: 1.04–1.78).

The results demonstrate a nearly twofold higher mortality rate among individuals with treatment-resistant schizophrenia not treated with clozapine compared with clozapine-treated individuals. Furthermore, the results suggest a harmful effect of other antipsychotics regarding self-harm compared with clozapine. It remains to be investigated to what extent the observed excess mortality after clozapine discontinuation is confounded by nonadherence and other unobserved factors and to what extent it is mediated by adverse effects from recent clozapine exposure or deterioration in physical or mental health precipitated by clozapine discontinuation.

这项研究评估了在患有难治性精神分裂症患者中与氯氮平治疗相关的全因死亡率和自残率。

在1996年1月1日之后，以人群为基础的队列研究，共2370名患有难治性精神分裂症的患者，直至死亡，第一次自残发作，移徙或2013年6月1日。在时变治疗的Cox回归模型中分析了自残发作，并针对临床和社会人口统计学协变量进行了调整。

未接受氯氮平的患者的全因死亡率高于接受氯氮平的患者（危险比：1.88，95％置信区间[CI]：1.16-3.05）。这主要是由于未接受抗精神病药物治疗的时期（危险比：2.50，95％CI：1.50-1.47），在使用其他抗精神病药物治疗期间的死亡率无明显升高（危险比：1.45，95％CI：0.86-2.45）。停用氯氮平后的一年中观察到过高的死亡率（危险比：2.65，95％CI：1.47–4.78）。非氯氮平抗精神病药的自残率高于氯氮平（危险比：1.36，95％CI：1.04–1.78）。

结果表明，与氯氮平治疗的患者相比，未经氯氮平治疗的具有治疗抵抗力的精神分裂症患者的死亡率高出将近两倍。此外，该结果表明与氯氮平相比，其他抗精神病药物对自身伤害的有害作用。氯氮平停药后观察到的过度死亡率在多大程度上与不依从性和其他未观察到的因素混淆，还有多少程度是由于最近氯氮平暴露或由氯氮平停药导致的身体或精神健康恶化所引起的不良影响所介导。