Clozapine-associated extrapyramidal reaction

OBJECTIVE: To report a case of extrapyramidal reaction associated with a do sage increase of clozapine. CASE SUMMARY: A 44-year-old white man with a 20-year history of chronic par anoid schizophrenia was admitted to an inpatient psychiatric facility. His prior medications restarted on admission were clozapine 650 mg at bedtime, haloperidol 10 mg at bedtime, clonazepam 2 mg/d, and aspirin 325 mg/d. Two days after admission (hospital day 3), clozapine and clonazepam were discon tinued, and he was prescribed haloperidol 5 mg every morning and 10 mg ever y evening. Stabilization occurred over the following 24 days, with progress ively lower dosages of haloperidol and increasing dosages of clozapine. Hal operidol was discontinued on day 24. On day 47, the patient was agitated an d making bizarre statements; thus, the morning dose of clozapine was increa sed by 50 mg (total 450 mg/d). On day 48 at 2200, a dystonic reaction was d iagnosed; he received intramuscular diphenhydramine 50 mg, which caused the reaction to subside. At the time of the adverse reaction, he was prescribe d clozapine 450 mg/d, Vitamin E 400 IU three times daily, aspirin 325 mg/d, and acetaminophen, milk of magnesia, and Maalox as needed. DISCUSSION: Although the risk of extrapyramidal symptoms (EPS) is significa ntly lower with clozapine man with conventional agents, elevated clozapine blood concentrations have been reported to cause EPS; other reports have ci ted severe dystonias and dyskinesias on abrupt clozapine withdrawal. Consid ering the medications prescribed at the time and the discontinuation of hal operidol 24 days before the event, clozapine was the most likely cause of t he extrapyramidal reaction. CONCLUSIONS: Regardless of anticipated safety associated with novel antipsy chotics such as clozapine, reports of dystonic reactions must be taken into account and patients monitored appropriately.