Abstract
Studies of the interactions of serotonin uptake inhibitors with ethanol may help determine the mechanism whereby ethanol intake is decreased by these drugs. In four separate studies, subjects were randomly assigned to receive ethanol dosed to maintain blood ethanol concentrations of 800–1000 mg/l or juice and drug or placebo: (1) single doses of zimelidine one hour after ethanol or juice; (2) single doses of amitriptyline 25 mg p.o. one hour after the ethanol or juice; (3) viqualine 75 mg b.i.d. for 3 days prior to ethanol or juice; (4) fluoxetine 40 mg p.o. or amitriptyline 50 mg p.o. for 14 nights. Acetaldehyde concentrations did not change and no aversive ethanol sensitizing reaction for any drug was detected. Ethanol-induced impairment in memory, body sway and a manual tracking task were further enhanced by zimelidine as was ethanol-induced decreased friendliness. Ethanol decreased the rate of zimelidine biotransformation by 46%. Concurrent ethanol increased mean amitriptyline concentrations 91–188% during amitriptyline absorption. Mean postural sway and memory were markedly impaired. In contrast neither viqualine nor chronic fluoxetine alone or chronic amitriptyline modified the deleterious effects of ethanol on any performance measure. Some subtle effects of fluoxetine on mood may exist. No kinetic interaction was detected with viqualine, or chronic fluoxetine or chronic amitriptyline. Specific and selective serotonin uptake inhibitors do not importantly increase ethanol induced impairment. Interaction profiles differ after repeat ethanol dosing and are affected by order of drug and ethanol administration. These studies provide no explanation for drug associated decrease in alcohol consumption in humans.
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E.M. Sellers
Both authors formerly Public Health Officers, Eastern Sydney Area Public Health Unit Previously general practitioner, Orange NSW, Australia.