TY - JOUR

T1 - Clozapine and mortality: A comparison with other antipsychotics in a nationwide Danish cohort study

AU - Zalm, Yvonne

AU - Foldager, Leslie

AU - Termorshuizen, Fabian

AU - Sommer, Iris E.

AU - Nielsen, Jimmi

AU - Selten, Jean‐paul

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.1111/acps.13267

DO - 10.1111/acps.13267

M3 - Journal article

C2 - 33306211

VL - 143

SP - 216

EP - 226

JO - Acta Psychiatrica Scandinavica. Supplementum

JF - Acta Psychiatrica Scandinavica. Supplementum

SN - 0065-1591

IS - 3

ER -