Richard K. Fuller

Disulfiram for the Treatment of Alcoholism: An Evaluation in 128 Men

One hundred twenty-eight alcoholic men were assigned randomly to receive either a regular dose of disulfiram (250 mg), a pharmacologically inactive dose (1 mg), or no disulfiram. There were no statistically significant differences among the three treatment groups in total abstinence, percentage of drinking days, days worked, family stability (living with same relative), or percent of scheduled appointments kept. However, 21% of those who received the regular dose of disulfiram and 25% who received the pharmacologically inactive dose remained abstinent, whereas only 12% of those who received no disulfiram did so. These results indicate that disulfiram may be of limited value in the treatment of alcoholism, fear of the disulfiram-ethanol reaction is important in preventing drinking, and patients willing to take disulfiram are more likely to be abstinent if given the drug. We also found that complete abstinence correlated significantly with compliance and obtaining employment.

Compliance with disulfiram treatment of alcoholism

One hundred twenty-four men were randomly assigned to receive disulfiram with a riboflavin marker or riboflavin alone. During a one year follow-up urine specimens were collected at each visit and analyzed for riboflavin. There was a strong relationship between excellent attendance and infrequent drinking. For subjects taking disulfiram there was a high correlation between a subject submitting 15 or more positive urines during follow-up and infrequent drinking. For the disulfiram patients there was also a strong relationship between continuous usage of disulfiram and infrequent drinking. However, the correlation between percentage of urine specimens positive for the riboflavin marker and infrequent drinking was slight. This occurred because a person who was drinking tended to return for follow-up only when he was not drinking and thus submitted only a few specimens of which the majority were positive. We conclude that (1) excellent attendance, (2) submission of a large number of positive urines and (3) a period of continuous compliance to the disulfiram regimen were highly associated with infrequent drinking.

Effect of parenteral amino acids on human pancreatic exocrine secretion

Parenteral administration of amino acids has been utilized for the nutritional support of patients with a variety of gastrointestinal disorders including protracted pancreatitis and pancreatic fistulae. However, the effect of parenteral amino acid administration alone on human pancreatic secretion has not been studied. We have studied the short-term effect of parenteral administration of amino acids on pancreatic exocrine secretion in seven healthy men. A double-lumen tube was placed in the duodenum and polyethylene glycol was perfused into the proximal duodenum at the rate of 10 ml/min. A second double-lumen tube was placed in the stomach and bromsulfthalein was perfused into the cardia. Samples of duodenal contents were aspirated and gastric contents recovered during one hour of intravenous saline infusion followed by two hours of an amino acid mixture infusion. Hourly outputs of protein and pancreatic enzymes were determined, correcting for duodenogastric reflux based on concentrations of both markers in the samples. Despite an average increase of 72% in the plasma concentration of the infused amino acids, the outputs of protein, trypsin and amylase did not change significantly during amino acid infusion; the output of lipase decreased significantly during amino acid infusion. Two subjects were given intravenous secretin and cholecystokinin following amino acids; this resulted in increased outputs of protein, trypsin, and amylase in both. We conclude that the parenteral administration of amino acids to healthy young men does not stimulate pancreatic enzyme secretion as measured by the method using duodenal marker perfusion at the rate of 10 ml/min.

Method for the detection of diethylamine, a metabolite of disulfiram, in urine

Disulfiram is a drug used in the treatment of chronic alcoholism in man. Accurate assessment of patient compliance is important in this treatment. This paper describes a method for the detection and quantitative analysis of diethylamine, a metabolite of disulfiram, in urine. The method involves conversion of the water-soluble diethylamine in the urine to a derivative, N,N-diethyl-3,5-dinitrobenzamide, that is soluble in an organic solvent. This derivative is extracted from urine with diethyl ether and then subjected to thin-layer chromatography. A spectrophotometric procedure is used for quantification. This method provides a means of determining whether or not a patient is taking his prescribed disulfiram.

Veterans administration cooperative study of disulfiram in the treatment of alcoholism: Study design and methodological considerations

Disulfiram treatment of alcoholism has been difficult to evaluate in controlled studies because the study design must contend with problems unique to this drug. The therapeutic effect may be a result of the patients fear of the disulfiram-ethanol reaction rather than a direct pharmacological effect on the craving for alcohol. Good outcome may not be directly related to compliance with the drug regimen; a patient may remain abstinent even if he does not take his medication. The Veterans Administration Cooperative Study Disulfiram in the Treatment of Alcoholism, is a multicenter, randomized, blinded, controlled clinical trial designed to evaluate the efficacy of disulfiram while addressing these issues. Two control groups are used. The members of one control group will not receive disulfiram and will be told they are not receiving disulfiram. The members of the other control group will be given disulfiram and will be told they are receiving disulfiram; however, the dose of their disulfiram will be measured by doing pill counts and obtaining urine specimens at each clinic visit and measuring urinary diethylamine, a metabolite of disulfiram, and riboflavin (a medication marker).