Indian Journal of Psychological Medicine
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LETTER TO EDITOR
Year : 2016  |  Volume : 38  |  Issue : 2  |  Page : 167-168  

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)


1 Department of Neurosurgery, Olympion General Hospital and Rehabilitation Center, Volou and Milihou, 26443, Patras, Greece
2 Department of Pharmacology, Medical School, University of Ioannina, 45110, Ioannina, Greece

Date of Web Publication16-Mar-2016

Correspondence Address:
Petros N Karamanakos
Department of Neurosurgery, Olympion General Hospital and Rehabilitation Center, Volou and Milihou, 26443, Patras
Greece
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0253-7176.178818

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How to cite this article:
Karamanakos PN, Marselos M. 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). Indian J Psychol Med 2016;38:167-8

How to cite this URL:
Karamanakos PN, Marselos M. 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). Indian J Psychol Med [serial online] 2016 [cited 2019 Sep 22];38:167-8. Available from: http://www.ijpm.info/text.asp?2016/38/2/167/178818

Sir,

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 the aforementioned paper, the authors present eight subjects with alcohol dependence who developed epileptic seizures while under therapy with DSF. Since no other causes of seizures were detected the convulsions were attributed to the use of DSF and the authors concluded that this was a dose-dependent phenomenon. 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]

In a previous work of our laboratory team increasing doses of DSF were administered to Wistar rats and the activity of the hepatic aldehyde dehydrogenase (ALDH) along with the levels of brain catecholamines were determined. [2] ALDH was inhibited by DSF in a dose-dependent way. Similarly, the detected changes in the levels of the brain catecholamines correlated well with the doses applied. As expected, the known inhibitory effect of DSF on DBH [3] resulted in an accumulation of dopamine and a respective decrease of the levels of noradrenaline. However, the lowest dose of DSF produced no effect on brain catecholamines. Our results clearly showed that the hepatic ALDH is highly sensitive to the inhibitory effect of DSF while on the contrary, the levels of brain catecholamines, and hence the activity of DBH, seemed to be more refractory to the action of this drug.

Neurological complications of DSF are usually dose-related and may be reversible if the offending agent is removed early. 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. [1]

In conclusion, we suggest that Kulkarni and Bairy should refer our work in their paper, in order to strengthen their findings regarding the dose-dependent nature of DSF-induced convulsions, as well as their assumption toward an implication of DBH inhibition in this phenomenon. In addition, we should keep in mind that DSF affects the level of brain biogenic amines at dose levels higher than those inhibiting the activity of ALDH and it seems reasonable to conclude that there is a safety margin in the dosage of DSF between therapeutic and toxic effects. Therefore, in clinical practice treatment of alcoholic patients with low DSF doses could retain the aversion effect toward ethanol, with a reduced risk of neurotoxicity (e.g., convulsions).

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Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Kulkarni RR, Bairy BK. Disulfiram-Induced de novo convulsions without alcohol challenge: Case series and review of literature. Indian J Psychol Med 2015; 37:345-8.  Back to cited text no. 1
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2.
Karamanakos PN, Pappas P, Stephanou P, Marselos M. Differentiation of disulfiram effects on central catecholamines and hepatic ethanol metabolism. Pharmacol Toxicol 2001;88:106-10.  Back to cited text no. 2
    
3.
Goldstein M, Anagnoste B, Lauber E, Mckeregham MR. Inhibition of dopamine-beta-hydroxylase by disulfiram. Life Sci 1964;3:763-7.  Back to cited text no. 3
    
4.
Borrett D, Ashby P, Bilbao J, Carlen P. Reversible, late-onset disulfiram-induced neuropathy and encephalopathy. Ann Neurol 1985;17:396-9.  Back to cited text no. 4
    
5.
Enghusen Poulsen H, Loft S, Andersen JR, Andersen M. Disulfiram therapy: Adverse drug reactions and interactions. Acta Psychiatr Scand Suppl 1992;369:59-65.  Back to cited text no. 5
    




 

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