Abstract
ObjectiveTo compare the mortality in people using clozapine to that of people using other antipsychotics.MethodsDanish incidence cohort of 22,110 patients with a first diagnosis of non‐affective psychotic disorder (1995–2013) and a prevalence cohort of 50,881 patients ever diagnosed with such a disorder (1969–2013). Hazard ratios (HR) were calculated for the antipsychotic drug used at the time of death (“current use”: incidence and prevalence cohort) and for the drug used for the longest at that moment (“cumulative use”: incidence cohort), using a Cox model with adjustment for somatic comorbidity. Clozapine was the reference drug.ResultsAs for current drug use, the risk of suicide was higher among users of other antipsychotics in the incidence (HRadj = 1.76; 95% CI 0.72–4.32) and prevalence (HRadj = 2.20; 95% CI 1.35–3.59) cohorts. There was no significant difference in all‐cause or cardiovascular mortality in the two cohorts. Cumulative use of clozapine was not associated with an increased cardiovascular mortality. Cumulative use of other antipsychotics for up to 1 year was associated with a lower all‐cause mortality and suicide risk than a similar period of clozapine use (all‐cause: HRadj = 0.73; 95% CI 0.63–0.85, suicide; HRadj = 0.65; 95% CI 0.46–0.91).ConclusionThe results indicate that the use of clozapine is not associated with increased cardiovascular mortality. We found opposing trends toward a lower risk of suicide during current use of clozapine and a higher risk of suicide associated with cumulative use up to 1 year. This suggests that clozapine cessation marks a period of high risk of suicide.
Highlights
Clozapine is an effective drug for treatment-resistant schizophrenia, but has some serious side effects such as agranulocytosis, myocarditis, and ileus.[1]
In a nationwide Danish cohort, whether mortality associated with current use or cumulative use of clozapine is lower than that associated with current use or cumulative use of other categories of antipsychotics, adjusting for somatic comorbidity and the treatment thereof
Our first objective was to investigate whether mortality associated with “current” use of clozapine was lower than that associated with “current” use of other antipsychotics
Summary
Clozapine is an effective drug for treatment-resistant schizophrenia, but has some serious side effects such as agranulocytosis, myocarditis, and ileus.[1]. A single study used an incidence cohort,[11] but it did not address survivor bias, because the results were not adjusted for duration since onset of illness. It is important to adjust the results for somatic comorbidity or treatment, because clinicians may prescribe clozapine more often to patients in better cardiovascular health and because mandatory monitoring may lead to more adequate treatment of somatic disorder. Only two studies on cardiovascular mortality used a measure of cumulative use.[4,12] The results of these studies showed no differences between cumulative use of clozapine and cumulative use of other antipsychotics, but the results were not adjusted for somatic comorbidity and the treatment thereof
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