Evaluating the association between clozapine and venous thromboembolism.

PURPOSE: The possible association between clozapine and venous thromboembolism (VTE) is discussed.
SUMMARY: Twenty-two cases of VTE associated with clozapine have been published. The average patient age at the time of occurrence was 38 years in the reported cases. Of the published cases with a known outcome, the mortality rate of a clotting complication while on clozapine was approximately 44%. The manufacturer of clozapine has calculated a mortality rate from pulmonary embolism to be one death per 3450 person years of use, approximately 28 times higher than the rate in the general population. The possible mechanism for the association between clozapine and VTE is probably multifactorial. A VTE usually occurs when one of three factors is present: damage to the vessel wall, static blood flow, or coagulation abnormalities. Clozapine, as well as other antipsychotics, has not been shown to cause direct damage to the vasculature in humans. However, static blood flow may be influenced by sedation and the sedentary lifestyle commonly associated with psychiatric disorders, their treatment, or both. Clozapine is associated with significant sedation and an average weight gain of 7-11 kg. There is also increasing evidence that clozapine and other antipsychotics may cause a variety of different coagulation abnormalities. Clozapine has been found to increase platelet adhesion as well as aggregation. Avoidance of risk factors, such as weight gain and sedentary lifestyle, may alleviate some of the risk of clozapine-induced VTE.
CONCLUSION: Available data indicate an association between clozapine and VTE; however, it is unknown whether the increased risk of VTE in patients receiving clozapine is because of prothrombotic effects of the drug. Risk of VTE versus the benefits of therapy should be considered when initiating clozapine therapy.