Abstract

A 35-year-old man with bipolar affective disorder presented during a manic episode and was treated with intramuscular haloperidol 20 mg/day and promethazine 100 mg/day in divided doses, along with lithium 800 mg/day. On the fourth day of treatment, he developed high-grade fever, generalized rigidity, tremors, mutism, echolalia, altered consciousness, and marked autonomic instability, including tachycardia and labile blood pressure. Serum creatine phosphokinase was 2800 U/L, with leukocytosis and elevated CK-MB; troponin I was normal. A diagnosis of Neuroleptic malignant syndrome (NMS) was made, and all psychotropic medications were discontinued. He was treated with intravenous fluids, external cooling, and bromocriptine 15 mg/day. The fever, rigidity, and autonomic abnormalities improved over approximately 72 hours. However, after resolution of the acute NMS manifestations, severe agitation, aggression, and insomnia persisted. Lorazepam and nitrazepam provided inadequate behavioural control, while electroconvulsive therapy was considered unsuitable because of ongoing autonomic instability. Clozapine was initiated at 25 mg/day with close clinical and laboratory monitoring. Within 48 hours, marked reduction in agitation was observed, followed by improved cooperation and sleep. By the fifth day, behavioural stabilization was evident, without recurrence of fever, rigidity, autonomic instability, or clinically significant CPK elevation. This case illustrates the therapeutic challenge of persistent manic agitation following NMS. Clozapine may be considered in carefully selected patients when conventional antipsychotic treatment is considered unsuitable and other interventions are ineffective or temporarily contraindicated. However, clozapine itself can cause NMS Its use following NMS should therefore involve complete clinical resolution of the acute syndrome, conservative dosing, and close monitoring.

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