PE in schizophrenia

Q: 59 years female with schizophrenia presented to ED with Shortness of Breath (SOB). Wife reports that recently patient was having a bout of depression and spent all days lying on sofa watching TV. On EKG, the patient was found to have an increased QTc interval. Also, CT-Angiogram of the chest showed pulmonary Embolism (PE). What drug is the most probable culprit?

Answer: Clozapine

Clozapine is considered one of the mainstay drug treatments for schizophrenia. Unfortunately, it has an increased risk of venous thromboembolism. Moreover, mortality from clotting complications in these patients is very high, with almost half having a fatal outcome (44%). Risk factors include:

• Genetic factors (like factor V Leiden mutation or high concentration of factor VIII)
• Recent immobilization
• Recent surgery
• Pregnancy or the postpartum state
• Obesity

Although evidence is weak, aspirin and statins have been suggested in patients on Clozapine to reduce the risk of venous thromboembolism. Patients should also be advised to stay active and mobile while on Clozapine.

In the above question, increased QTc prolongation is given as a hint.

#pharmacology

#psychiatry

References:

1. Kortepeter C, Chen M, Knudsen JF, et al. Clozapine and venous thromboembolism. Am J Psychiatry 2002; 159:876.

2. Farah RE, Makhoul NM, Farah RE, Shai MD. Fatal venous thromboembolism associated with antipsychotic therapy. Ann Pharmacother 2004; 38:1435.

3. Paciullo CA. Evaluating the association between clozapine and venous thromboembolism. Am J Health Syst Pharm 2008; 65:1825.