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

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

METHODS: 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.

RESULTS: As 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).

CONCLUSION: 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.