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.