Disulfiram Induced Psychosis

Abstract

Background: Disulfiram was widely used as an aversive agent for treatment of alcohol dependence since its discovery. Various adverse drug reactions have been documented. Psychosis due to disulfiram is not a common side effect. Methods & Discussion: We report two cases of disulfiram associated psychosis. We also highlight the biological mechanism of the psychosis associated with disulfiram use. The Dopamine (DA) hypothesis of schizophrenia states that an increase in DA activity in certain brain areas is associated with psychotic symptoms in schizophrenic patients. The possible explanation for the development of psychosis, might be inhibition of Dopamine-Betahydroxylase (DBH) enzyme due to metabolites of disulfiram. This enzyme catalyzes the metabolism of DA into norepinephrine. Inhibition of DBH increases dopamine level. Furthermore, alcoholics who developed psychosis due to disulfiram were found to have low levels of amine and monoamine oxidase, suggesting DBH blockage. Conclusion: Disulfiram induced psychosis is not an uncommon side effect. Biological mechanism of Disulfiram induced psychosis, probably via its DBH inhibiting effects, which lead to an increase in DA activity. Hence, careful monitoring is required for emergent of psychotic symptoms in vulnerable patients while on disulfiram treatment.

Disulfiram‐induced mania: A case report

“…Although the exact mechanism for disulfiram‐induced mania is unknown, disulfiram's main metabolite, diethyldithiocarbamate, has been implicated as the causative factor. Diethyldithiocarbamate inhibits dopamine beta‐hydroxylase, which is the enzyme that catalyzes the metabolism of dopamine to norepinephrine 1 . This results in increased dopamine concentrations in mesolimbic system which are thought to potentiate mania.…”

“…Unlike first‐line agents naltrexone and acamprosate, disulfiram does not reduce cravings, but instead serves as a deterrent from alcohol consumption. Mechanistically, it irreversibly inhibits aldehyde dehydrogenase, the primary liver enzyme responsible for alcohol metabolism, preventing the conversion of acetaldehyde to acetate 1 . The increase in acetaldehyde leads to uncomfortable effects such as flushing, nausea, vomiting, diaphoresis, and tachycardia, referred to as the disulfiram‐alcohol reaction 1 .…”

“…Mechanistically, it irreversibly inhibits aldehyde dehydrogenase, the primary liver enzyme responsible for alcohol metabolism, preventing the conversion of acetaldehyde to acetate 1 . The increase in acetaldehyde leads to uncomfortable effects such as flushing, nausea, vomiting, diaphoresis, and tachycardia, referred to as the disulfiram‐alcohol reaction 1 . These effects occur within 10–30 min of alcohol consumption and can persist for several hours, thus assisting with alcohol deterrence.…”

Acute Disulfiram Poisoning in a Child: A Case Report and Review of Literature

“…3 Symptoms of overdose include nausea, vomiting, pruritus, skin rash, headache, aggressive or psychotic behavior, drowsiness, coma, and ascending flaccid paralysis that can also involve cranial nerves. 2,4 Vykuntaraju and Ramalingaiah reported basal ganglia infarct, encephalopathy and extrapyramidal features with globus pallidus and substantia nigra involvement in 2-year-old child. 5 The exact mechanism of disulfiram-mediated encephalopathy is not known.…”