Monitoring relapse drinking during disulfiram therapy by assay of urinary 5-hydroxytryptophol.
Screening for recent alcohol use by testing urine for the ratio of 5-hydroxytryptophol (5HTOL) to 5-hydroxyindole-3-acetic acid (5HIAA) was performed in 10 methadone patients on disulfiram (Antabuse) maintenance therapy in an outpatient setting. Apart from alcohol ingestion, treatment with aldehyde dehydrogenase inhibitors such as disulfiram is the only known cause of an abnormally high 5HTOL/5HIAA ratio. After introduction of drug therapy, increased ratios were observed in all patients. The new higher level reached was relatively stable over time within the same patient but variable between patients. Four patients continued to consume alcohol, as evidenced by 5HTOL/5HIAA ratios well above the new individual plateau, while still taking 400 mg disulfiram 3 times per week under strict supervision. To try to achieve sobriety in two patients who drank frequently while on therapy, the disulfiram dose was doubled. Continued testing demonstrated this to increase the 5HTOL/5HIAA steady-state level further, and the absence of extreme values above this new baseline level indicated adherence to abstinence with possibly one single relapse. When disulfiram administration was discontinued, as planned, by five of the patients, four of them returned to drinking very soon. The present results show that during disulfiram maintenance the continuous inhibition of aldehyde dehydrogenase produces a new higher and dose-related 5HTOL to 5HIAA steady state level in urine, but relapse to drinking will still lead to further increased 5HTOL/5HIAA ratios. It is also suggested that an individual dose-titration regimen, whereby the disulfiram dose is raised gradually until 5HTOL/5HIAA testing indicates sobriety, will improve therapeutic effectiveness.
Helander
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Karolinska Institute, Department of Clinical Neuroscience, St. Görans Hospital, Stockholm, Sweden.
D000328:Adult; D000427:Alcohol Deterrents / Q000008:administration & dosage* / Q000009:adverse effects; D000437:Alcoholism / Q000534:rehabilitation* / Q000652:urine; D000553:Ambulatory Care; D004221:Disulfiram / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000652:urine; D006917:Hydroxytryptophol / Q000652:urine*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012016:Reference Values; D015813:Substance Abuse Detection; D016896:Treatment Outcome
D000427:Alcohol Deterrents; D006917:Hydroxytryptophol; D006897:Hydroxyindoleacetic Acid; D004221:Disulfiram