Use of Intravenous Valproate in a Patient With Neuroleptic Malignant Syndrome

SIR: A 22-year-old woman was admitted through casualty, with a history of altered behavior for approximately 15 days and history of fever, rigidity, tremors, and one episode of incontinence for a few days. The patient had autonomic disturbances, was partly oriented to time and place, and general condition was moderate.

History given by a close relative about cheerfulness, excessive talkativeness, singing songs, reduced need for sleep, and grandiose ideation for approximately 2 weeks indicated an episode of mania. The patient received an injection of haloperidol intramuscularly to control the behavior a few days before, prior to the onset of new symptoms.

A clinical diagnosis of neuroleptic malignant syndrome (NMS) was made, although other differentials of delirium due to general medical condition, including meningitis, were also considered.

Baseline investigations were within normal limits, and total leukocytes count of 9000/cmm and the CSF study was inconclusive. Serum creatinine phosphokinase (CPK) levels were 3850 U/liter, suggestive of N.M.S. and this confirmed the diagnosis.

Injection valproate was administered intravenously 250 mg on the first day and then 250 mg 12 hourly from the next day. A clonazepam tablet was also administered when needed. The following day, dramatic improvement in this patient, was observed. She was well oriented to time, place and person, and the rigidity had markedly reduced. Tremors were minimal, and there was no fever. After 6 days, the patient had minimal rigidity and mild tremors. There were no behavioral disturbances barring mild euphoria.

Repeat serum CPK levels after 10 days was 30 U/liter (well within normal limits) and other baseline investigations were within normal limits. The patient was later switched to oral sodium valproate, and there were no features of NMS. The serum valproate level was 87 mcg/ml after 2 weeks.

Intravenous valproate has been used for catatonia.¹ In this isolated case (by chance), intravenous valproate was found to be effective in the symptoms of NMS.^2,3

There was no fear of the reemergence of psychotic features, which is common with bromocriptine. The strict monitoring as required for bromocriptine was also not needed. It serves a dual purpose for controlling manic features in patients of bipolar disorder.⁴ Even a substitute novel (atypical) antipsychotic (although less) carries the risk of NMS.