Disulfiram-Induced De Novo Convulsions without Alcohol Challenge: Case Series and Review of Literature

Abstract

Seizure induction by disulfiram (DSF) an adverse effect of therapeutic dosages of DSF is less understood. In our prospective case series of eight subjects with alcohol dependence a temporal, dose-dependent, and reversible epileptogenic potential due to DSF was noted. Mean duration of onset of first seizure was 2.13 ± 1.13 weeks after initiation of DSF therapy (125-500 mg/day) with no other detectable causes of seizures. Presence of alcohol withdrawal seizures (50%), DSF-induced hypertension (HTN) (37.5%), psychosis (12.5%) were noted, that may suggest common neurobiological underpinnings like dopamine-beta-hydroxylase inhibition. Various types of DSF-induced generalized seizures (tonic-clonic, 62.5%; myoclonic and tonic-clonic, 25%; myoclonic, 12.5%) were effectively managed by halving initial DSF dose (37.5%) even after cessation of antiepileptics, or stopping DSF (37.5%). Presence of alcohol withdrawal seizures, DSF-induced HTN/psychosis during DSF therapy may be early risk factors for dose-dependent and reversible adverse effect of DSF therapy — seizure induction, emphasizing caution.

Epileptic Seizure Due to Disulfiram Treatment

“…Kulkarni and Bairy 7) reported a prospective case series of eight subjects with alcohol dependence and various types of disulfiram-induced generalized seizures that were controlled with antiepileptics or discontinuation of disulfiram use. We did not find it ethical to give our patient disulfiram again because he discontinued alcohol use and was afraid of epileptic seizures.…”

Comment on: “Disulfiram-induced De novo Convulsions Without Alcohol Challenge: Case Series and Review of Literature” (Kulkarni and Bairy, Indian J Psychol Med, Jul-Sep; 37(3): 345-8, 2015)

“…We read with great interest the recently published article by Kulkarni and Bairy in the Indian J Psychol Med[ 1 ] regarding disulfiram (DSF)-induced convulsions in alcoholic patients, and we really find the issue very interesting. However, we would like to comment briefly on this report.…”

“…In addition, the main underlying mechanism suggested was the impairment of the metabolism of brain catecholamines, due to inhibition of dopamine-beta-hydroxylase (DBH), a copper-containing glycoprotein enzyme that catalyzes the conversion of dopamine to noradrenaline in the peripheral and central adrenergic neurons. [ 1 ]…”

“…This has been shown by others[ 4 5 ] and was also confirmed by Kulkarni and Bairy. [ 1 ] The precise mechanism by which DSF produces its neurotoxic side effects is not fully understood. A key role, however, has been attributed to the inhibition of DBH,[ 4 5 ] which was also suggested in the paper of Kulkarni and Bairy.…”

“…A key role, however, has been attributed to the inhibition of DBH,[ 4 5 ] which was also suggested in the paper of Kulkarni and Bairy. [ 1 ]…”