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Mortality, self-harm lower with clozapine use in schizophrenia

Clozapine use in treatment-resistant schizophrenia was associated with lower all-cause mortality and self-harm rates, according to recent findings.

“Clozapine is the most effective antipsychotic treatment for treatment-resistant schizophrenia and is recommended for such patients in Danish and several other national guidelines. However, clozapine is underused in most countries, probably because of the fear of severe side effects and the inconvenience of therapeutic blood monitoring,” Theresa Wimberley, PhD, of National Centre for Register-Based Research, Aarhus University, Denmark, and colleagues wrote. “Consequently, alternative treatment strategies, such as switching medications or augmenting clozapine with other antipsychotics, are often applied. Antipsychotic polypharmacy is common, despite the lack of evidence for its efficacy.”

To determine all-cause mortality and self-harm rates associated with clozapine treatment in treatment-resistant schizophrenia, researchers evaluated a population-based cohort of 2,370 individuals with treatment-resistant schizophrenia from January 1996 until death, first episode of self-harm, emigration, or June 2013.

Study participants who did not receive clozapine had higher all-cause mortality rates (HR = 1.88; 95% CI, 1.16-3.05). This was mainly due to periods of no antipsychotic treatment (HR = 2.5; 95% CI, 1.5-4.17), with higher mortality during treatment with other antipsychotics (HR = 1.45; 95% CI, 0.86-2.45), according to researchers.

During the year after clozapine discontinuation, researchers observed excess mortality (HR = 2.65; 95% CI, 1.47-4.78).

Self-harm rates were higher among users of non-clozapine antipsychotics, compared with clozapine users (HR = 1.36; 95% CI, 1.04-1.78).

“The results of the present study indicate that clozapine use is associated with a decreased mortality rate, in line with previous research. This was, however, only significant when clozapine treatment was compared with periods of no antipsychotic treatment, a situation probably largely explained by an excess mortality rate observed after clozapine discontinuation,” the researchers wrote. “It remains unclear whether the protective effect of clozapine on self-harm in treatment-resistant schizophrenia could be partly explained by a potentially harmful effect of alternative treatment strategies with other antipsychotics or confounding by indication.” – by Amanda Oldt

Disclosure: Wemberley reports no relevant financial disclosures. Please see the study for a full list of relevant financial disclosures.