EPOCH-MAKING THERAPY IN PROLONGED ALCOHOL WITHDRAWAL SYNDROME

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In our preliminary study, acute alcohol produced phase-shifts in the circadian rhythms of locomotor activity and body temperature, while chronic alcohol treatment induced changes in the periods of free-running rhythms in mammals. These data suggest that chronic administration of alcohol may cause disordered circadian rhythms in humans, for example, insomnia, secondary depression, alcohol withdrawal and prolonged alcohol withdrawal in alcoholism. In this study, we investigated that 81 (54%) of 150 inpatients with alcoholism had been treated under a diagnosis of alcohol withdrawal (delirium tremens) and 11 of these 81 cases (13.6%) had been diagnosed with prolonged alcohol withdrawal (prolonged delirium tremens). The clinical efficacy of specific benzodiazepine antagonist flumazenil for hepatic coma and prolonged delirium tremens was studied. Methods were as follows : 1) The level of hepatic coma was assessed by the stage of hepatic coma, alcohol withdrawal was assessed with CIWA and each subject was examined byelectroencephalogram(EEG) before and after flumazenil injection. Flumazenil was given as an iv infusion and continuously given as an 24-hr iv drip injection for a few days. As a result, all unconscious patients were clearly reversed in a few minutes, and EEG returned to normal ranges of alpha dominant activities at occipital sites and normal ranges persisted thereafter. Additionally, this may provide a clue to elucidating the theory that there may be abnormalities of the benzodiazepine receptor, or a possible inverse agonist ligand in alcohol withdrawal. We conclude that this clinical study may be very important to discovering a new therapy for prolonged alcohol withdrawal (prolonged delirium tremens) and for preventing transition to dementia associated with alcohol.