Clozapine and mortality: A comparison with other antipsychotics in a nationwide Danish cohort study

To compare the mortality in people using clozapine to that of people using other antipsychotics.

Danish 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.

As for current drug use, the risk of suicide was higher among users of other antipsychotics in the incidence (HR_adj  = 1.76; 95% CI 0.72-4.32) and prevalence (HR_adj  = 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: HR_adj  = 0.73; 95% CI 0.63-0.85, suicide; HR_adj  = 0.65; 95% CI 0.46-0.91).

The 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.