Effects of Disulfiram on Positron Emission Tomography and Neuropsychological Studies in Severe Chronic Alcoholism

Abstract

Disulfiram is an aldehyde dehydrogenase inhibitor that is widely used as an adjunctive agent in the treatment of patients with severe chronic alcoholism. Recent positron emission tomography (PET) studies of local cerebral metabolic rates for glucose (ICMRglc) and benzodiazepine receptor binding in alcoholic patients have shown regional cerebral abnormalities; however, some of the patients were studied while receiving disulfiram, which could influence the biochemical processes under investigation. In a retrospective investigation, we examined the influence of disulfiram administration on the results of PET studies of ICMRglc and benzodiazepine receptor binding and neuropsychological tests of cognition and executive function in patients with severe chronic alcoholism. [18F]Fluorodeoxyglucose was used to measure ICMRglc in 48 male patients, including 11 receiving and 37 not receiving disulfiram in therapeutic doses. [11C]Flumazenil was used to measure benzodiazepine receptor binding in 17 male patients, including 3 receiving and 14 not receiving disulfiram. All patients studied with FMZ were also examined with fluorodeoxyglucose. PET studies of ICMRglc revealed significantly decreased global values in the patients receiving disulfiram compared with those not receiving disulfiram. PET studies of benzodiazepine receptor binding revealed decreased flumazenil influx and distribution volume in patients receiving disulfiram. The neuropsychological tests demonstrated no differences between the two groups of subjects. The findings suggest that disulfiram may influence the results of PET studies of glucose metabolism and benzodiazepine receptor binding.

Effects of abstinence and relapse upon neuropsychological function and cerebral glucose metabolism in severe chronic alcoholism

“…Aditionally, Patients 3 and 6 were receiving disulfiram during their evaluations. Although disulfiram has not been found to affect cognitive functioning, a recent study by Gilman et al (1996) revealed that disulfiram can decrease global metabolism.…”

Alcohol: Effects on Neurobehavioral Functions and the Brain

“…Frontal lobe structure and function Although alcoholismrelated cortical changes have been documented throughout the brain, many studies consistently have found the frontal lobes to be more vulnerable to alcohol-related brain damage than other cerebral regions (Dirksen et al 2006;Gansler et al 2000;Gilman et al 1996;Oscar-Berman et al 2004;Pfefferbaum et al 1997;Ratti et al 2002). Neuropathological studies performed on the brains of deceased patients have revealed decreased neuron density in the frontal cortex of alcoholics (Harper and Matsumoto 2005).…”

Alcohol Abuse and Traumatic Brain Injury: Quantitative Magnetic Resonance Imaging and Neuropsychological Outcome

“…Research has related other physiological abnormalities in the human brain exposed to chronic alcohol use including abnormal EEG activity (Ronty et al, 1993), reduced cerebral blood flow (Berglund et al, 1987;Caspari et al, 1993;Dally et al, 1988;Dupont et al, 1996;Hata et al, 1987;Volkow et al, 1994), cerebral metabolic alterations (Adams et al, 1993;Gilman et al, 1996;Volkow et al, 1990), alteration in white matter fiber coherence as measured by diffusion tensor imaging (Mann et al 2001), and changes in evoked potential measurements (Baguley et al, 1997). Consistent with the structural and physiological changes noted above, there is further evidence for cognitive dysfunction manifested in long-term alcoholics without TBI, where impairments in abstraction, visual scanning, perceptuomotor speed, verbal memory, and mental flexibility have been demonstrated (Di Scalafani et al, 1995;Emsley et al, 1997;Nixon, 1993, 1998;Parsons and Stevens, 1986;Wang et al, 1993).…”