Mortality and Self-Harm in Association With Clozapine in Treatment-Resistant Schizophrenia

作者：Theresa Wimberley, James H. MacCabe, Thomas Munk Laursen, Holger J. Sørensen, Aske Astrup, Henriette Thisted Horsdal, Christiane Gasse, Henrik Støvring · 发表于：American Journal of Psychiatry · 年份：2017 · DOI：10.1176/appi.ajp.2017.16091097 · 被引用次数：134 · 研究领域：Schizophrenia research and treatment、Suicide and Self-Harm Studies、Psychopathy, Forensic Psychiatry, Sexual Offending

OBJECTIVE: This study evaluated rates of all-cause mortality and self-harm in association with clozapine treatment in individuals with treatment-resistant schizophrenia. METHOD: 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. RESULTS: 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). CONCLUSIONS: 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-ha...