Clozapine-associated pulmonary embolism: Presenting features and outcomes, UK pharmacovigilance data, 1990-2022

Abstract

Background Pulmonary embolism is said to be more common in clozapine-treated patients than either in patients treated with other antipsychotics or in the general population. Aims To explore clinical features and outcomes of clozapine-related pulmonary embolism in the UK. Method We studied UK Yellow Card reports recorded as clozapine-related respiratory, thoracic and mediastinal disorders, 1990-2022. Results Of 474 unique reports of people with clozapine-associated pulmonary embolism, 339 (59% male) remained after applying strict exclusion criteria. Of these, 164 patients (48%) died. The mean clozapine dose was 336.7 (range 25-1000) mg d-1 (N = 126). There was no difference in dose between the fatal and non-fatal outcomes. The median age at onset of pulmonary embolism was 45 years (range 21-82 years; N = 309). The median duration of clozapine treatment until onset was 2.9 years (range 2 days-22.7 years; N = 306). Sixty-five (39%) non-fatal and 36 (22%) fatal emboli occurred within 1 year of treatment. People who died were more likely to be obese (adjusted odds ratio 2.61; 95% CI 1.44-4.91) and to be noted as sedentary (adjusted odds ratio 6.07; 95% CI 1.58, 39.9). The 3 year moving average of cases was 0-5 per year, 1990-1999, 26 in 2010 and 16 in 2022. There was no change in the proportion of deaths by year of report (p = 0.41). Conclusions Clozapine-related pulmonary embolism is a significant concern with a high fatality rate. This risk necessitates a proactive approach to not only prevention, but also early recognition and management.