Clozapine associated pulmonary embolism: systematic review

Background: Clozapine is a second-generation antipsychotic used in refractory schizophrenia. Clozapine can lead to pulmonary embolism (PE) by various mechanisms including immobility, weight gain and increased platelet aggregation. Objectives: We performed a systematic review on published cases of PE associated with clozapine. Methods: Comprehensive search of Medline, Embase and Cochrane library was done for relevant articles from inception until June 2017 Results: Total of 34 cases from 24 articles were included in the analysis. The mean age was 43.2 years with male predominance (63.6%). The mean dosage of clozapine was 281.4 mg daily. Duration of intake ranged from few days to many years. Nearly half of patients (47.82%) had no other co-morbidities for PE other than clozapine. For those reporting treatment, anticoagulation was chosen in 80%, thrombolysis in 10% and inferior vena cava filter placement in 5%. Mortality was 36.36% with three dying on presentation and an additional 9 dying during the follow-up period. Of the 18 patients in which follow-up data of clozapine were available, the drug was discontinued in 14 patients. Conclusion: PE can occur at doses lower than usual dose of clozapine (300 mg daily). It is important to consider this association especially in patients with no other risk factors for PE.