Current antipsychotic agent use and risk of venous thromboembolism and pulmonary embolism: a systematic review and meta-analysis of observational studies

Abstract

Background: Antipsychotic agents (APS) are widely used drugs to treat psychotic symptoms and can effectively reduce both positive and negative symptoms of schizophrenia. For decades, some studies suggested that there is a relationship between using APS and the risk of venous thromboembolism (VTE) and pulmonary embolism (PE). However, results remain inconclusive. Method: This review has been registered in International Prospective Register of Systematic Reviews (PROSPERO, ID: CDR42020155620). Relevant studies were identified among observational studies published up to 1 October 2019 in the databases MEDLINE, EMBASE, and Cochrane Library. Random or fixed-effects models were used to calculate the pooled odds ratio (OR). Results: In total, 28 observational studies were included. The results showed that compared with non-users, current APS users have significantly increased risks of VTE [OR 1.55 95% confidence interval (CI) 1.36, 1.76] and PE (OR 3.68, 95% CI 1.23, 11.05). Subgroup analyses suggested that new users were associated with a higher risk of VTE (OR 2.06, 95% CI 1.81, 2.35). For individual drugs, increased risk of VTE and PE was observed in taking haloperidol, risperidone, olanzapine, prochlorperazine but not in chlorpromazine, quetiapine or aripiprazole. However, careful interpretation is needed because of high heterogeneity among studies and scarce data. Conclusion: The present comprehensive meta-analysis further indicates a significantly increased risk of VTE and PE in current APS users compared with non-users. Subgroup analyses suggest that new users are more likely to develop VTE. However, due to significant heterogeneity among studies, conclusions should be considered with caution.

Clozapine‐induced pulmonary embolism in a patient with no pre‐existing risk factors: A case report

“…A large US hospital database of 28,723,711 adults in 2006 demonstrated that the risk of PE was greater in antipsychotic users than in the total population ( p < 0.001), and clozapine in higher doses was associated with the greatest risk amongst all antipsychotics 11 . Meta‐analyses of observational studies have also reported significantly increased risks of PE in antipsychotic users, particularly in previously antipsychotic‐naive patients 14‐16 . Therefore, it is important to be aware of this rare but significant adverse effect.…”

Clinical Characteristics and Management of Asymptomatic Thromboembolism in Psychiatric Inpatients: A Retrospective Study

“…The possible mechanisms of this phenomenon may be attributed to that the hypercoagulable state induced by drugs through increasing platelet aggregation and antiphospholipid antibodies, hyperprolactinemia and metabolic disturbance [12,16]. However, a recent study showed that some individual drugs, such as quetiapine or aripiprazole, were not associated with the risk of VTE [27]. Selective serotonin reuptake inhibitor and serotonin norepinephrine reuptake inhibitors were also unlikely to contribute to VTE because of their potent inhibitory effects on the 5-hydroxytryptamine (5-HT) transporter to attenuate platelet activation and weaken the risk of thromboembolism formation [28].…”

Pulmonary Embolism or COVID-19 Pneumonia? A Case Report

“…This patient had several risk factors for developing PE that were overlooked by the physicians, including old age, being overweight, having hypertension, and prolonged limited mobility owing to dementia. Recent studies have also linked the current use of antipsychotics with the development of PE (7). As mentioned earlier, the patient had been using risperidone for two years before admission which may have increased the risk of PE.…”