Deep vein thrombosis on the fourth day of risperidone therapy

Background

Antipsychotics constitute the first-line treatment of schizophrenia and other primary psychotic disorders. Sedation, extrapyramidal symptoms, constipation and weight gain are some of the common side effects of antipsychotics, but they also cause serious adverse effects like myocarditis and neuroleptic malignant syndrome. Deep vein thrombosis is a less common but serious adverse effect of antipsychotic therapy.

Risperidone is a second-generation atypical antipsychotic, and there have been only a few case reports of risperidone-associated deep vein thrombosis. These have been mostly reported a few weeks to a few months after initiation of therapy. However, deep vein thrombosis in the first few days of starting treatment with risperidone has been rarely reported. Here, we are reporting this case in which the complication was detected on the fourth day of initiation of risperidone. This case also warns us that deep vein thrombosis may not be a dose-related adverse effect and can occur even at a low dose.

Case presentation

A married male in his early forties presented to psychiatry emergency department with history of aggressive behaviour, delusions of persecution, third person auditory hallucinations and reduced social interaction. History was obtained from his wife and it was reliable. Total duration of illness was 12 years. He had a history of poor drug compliance. He had not taken any drug for the past 3 months. Prior to that, the only antipsychotic he had taken in the past 2 years was haloperidol. His symptoms had worsened in the past 1 month. Patient was not having any other comorbidities and was not on any other medication. He was a non-smoker. He gave no history suggestive of deep vein thrombosis in the past. There was no history of any deep vein thrombosis in the family also. His body mass index (BMI) was 23 kg/m². He was ambulant. After detailed clinical examination, he was diagnosed as having paranoid schizophrenia continuous according to ICD-10 classification. Risperidone 2 mg/day along with trihexyphenidyl 2 mg/day was prescribed and he was sent home the same day. On the fourth day, he came to psychiatry outpatient department with complaints of pain over right calf muscle and inability to walk. He was haemodynamically stable and had no clinical signs of dehydration. His right lower limb was swollen and edematous below knee. He had tenderness over the calf muscles. Homan’s sign was positive. It was confirmed that patient had taken risperidone as prescribed. He had never been physically restrained either at home or in the hospital. The clinical picture pointed towards deep vein thrombosis induced by risperidone, and the drug was immediately stopped. He was started on conventional antipsychotic haloperidol at a dose of 5 mg/day. He was referred to surgery outpatient department for further management.

Investigations

His haemoglobin was 150g/L, total leucocyte count was 5.9 x 10⁹/L and platelet count 350 x 10⁹/L . His random blood sugar was 88 mg/dL. Total cholesterol was 162 mg/dL, high density lipoprotein 46 mg/dL, low density lipoprotein 120 mg/dL and triglycerides 140 mg/dL. Serum sodium was 137 mEq/L and serum potassium was 4.1 mEq/L. Prothrombin time, international normalised ratio (INR) and activated partial thromboplastin time were found to be in normal reference range. His thyroid hormone profile was also in the normal range. D-dimer was 5732 ng/mL (laboratory reference range <500 ng/mL). Duplex ultrasound examination demonstrated deep vein thrombosis involving right popliteal and proximal posterior tibial veins.

Differential diagnosis

Cellulitis involving the right lower limb was a possible alternate diagnosis. This was especially relevant as risperidone has been reported to cause pedal oedema. However, clinical picture and an elevated D-dimer pointed towards deep vein thrombosis. Well’s score for pre-test probability was 4 suggesting deep vein thrombosis as ‘likely’.1 A duplex venous ultrasound scan has a high overall specificity of 93.8% for diagnosis of deep vein thrombosis.1 It can differentiate between oedema with cellulitis and deep vein thrombosis and in this case, it clearly demonstrated thrombosis of right popliteal and proximal posterior tibial veins.

Treatment

Patient was admitted in the general surgery ward and was started on heparin 5000 units bolus intravenously followed by 30 000 units per day as continuous infusion. He was concurrently started on oral anticoagulant warfarin. Heparin was given for 7 days until target INR range of 2–3 was reached. INR was 2.2 on the seventh day and he was discharged on warfarin. During the period of admission, he was continued on haloperidol, dose of which had to be increased to 10 mg/day for adequate control of psychotic symptoms. Trihexyphenidyl 2 mg/day was continued.

Outcome and follow-up

Symptoms of deep vein thrombosis was completely resolved. Patient was followed up in the psychiatry department for 6 months. He was well maintained on haloperidol 10 mg/day and trihexyphenidyl 2 mg/day. He had no recurrence of deep vein thrombosis during the follow-up period.