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Researchers in England and Denmark conducted a population-based cohort study of 2,370 individuals born in Denmark, who had been diagnosed with treatment-resistant schizophrenia after January 1, 1996. Patients were followed until death, first episode of self-harm, emigration, or June 1, 2013.
During the follow-up period, 1,372 individuals (58%) with treatment-resistant schizophrenia initiated clozapine treatment. After adjusting for confounding factors, nonclozapine antipsychotic treatment was associated with an elevated rate of self-harm (hazard ratio: 1.36) compared with clozapine. Moreover, the absence of clozapine treatment was associated with an elevated rate of all-cause mortality (hazard ratio: 1.88) compared with clozapine treatment. “This was driven mainly by periods of no antipsychotic treatment (hazard ratio: 2.50), with nonsignificantly higher mortality during treatment with other antipsychotics (hazard ratio: 1.45),” Theresa Wimberley, Ph.D., of Aarhus University in Denmark and colleagues wrote.
“Given that the authors focused their study on patients meeting their criteria for treatment-resistant schizophrenia, it is possible that their results actually underestimate the value of clozapine in reducing the risk of suicidality,” John Kane, M.D., the chair of psychiatry at the Zucker Hillside Hospital in Glen Oaks, N.Y., told Psychiatric News. Kane, who was not involved with the study, added that he believes the study indicates another benefit for a medication that he says is vastly underutilized.
The nonclozapine treatment group included some patients who had started but later discontinued clozapine. The authors found that rates of all-cause mortality were highest after clozapine discontinuation, particularly within the first year after clozapine discontinuation when compared with rates during clozapine treatment.
“The extent to which the observed excess mortality rate after clozapine discontinuation is caused by side effects from recent clozapine exposure, unobserved factors, or clozapine discontinuation remains to be investigated,” Wimberley and colleagues wrote. “This study suggests that clozapine discontinuation needs more attention with thorough evaluation, care, and monitoring of the patient.”
For related information, see the Psychiatric News article “Collaborative Effort Among Stakeholders Can Reduce Barriers to Clozapine Use” and the Psychiatric Services article “The Business Case for Expanded Clozapine Utilization.”
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