A case of pulmonary thromboembolism and rhabdomyolysis during therapy with mirtazapine and risperidone.

Case report. In 2005, Mr. A, a nonobese 40-year-old man (body mass index = 26 kg/m), developed a syndrome consistent with schizophrenia. He was treated with high doses of risperidone (8 mg); after he subsequently developed a hypokinetic-rigid syndrome, biperiden (2 mg) was added. However, it soon became apparent that the psychosis was followed by a major depressive episode (his Hamilton Rating Scale for Depression [HAM-D] score was 30), and mirtazapine (45 mg) was added. Outpatient treatment failed, and he was admitted to our psychiatric day clinic (serum levels: risperidone was 5.1 μg/L and 9-OH-risperidone was 47.7 μg/L during therapy with risperidone 7 mg/day). Mirtazapine was increased to 60 mg and risperidone reduced to 3 mg daily. The patient improved, but 6 weeks after starting this combination therapy, he developed acute aching in his left leg and respiratory problems. These led to his admission to a medical hospital, where pulmonary embolism and rhabdomyolysis (creatine kinase level = 4795 U/L) were diagnosed. No hemostatic defect (no abnormalities were found in antithrombin III level, protein C activity, protein S antigen level, or activated protein C resistance) and no evidence for smoking, autoimmune activities, or malignant diseases were detected. During treatment with heparin followed by warfarin, Mr. A recovered. In parallel to the medical therapy, we replaced mirtazapine with reboxetine and replaced risperidone with aripiprazole and achieved a remission of the major depressive episode (his HAM-D score decreased by 24 points to 6). We successfully initiated vocational rehabilitation, and the patient was discharged in a euthymic state 8 weeks after the thromboembolism.