A Controlled Trial of Chlormethiazole and Chlordiazepoxide in the Treatment of the Acute Withdrawal Phase of Alcoholism

Abstract

In 1959 (Browne et al.) we published a regime for the treatment of the acute withdrawal phase of alcoholism developed at St. John of God Hospital, and employed in over 300 cases. We had been struck by the vagueness of advice about management of this phase in standard textbooks and by the pre-occupation with individual drugs in reports in the literature. We emphasised the importance of a standardized but flexible approach and used promazine and pentobarbitone as the basic drugs. Over the years as various other tranquillizers and sedatives were introduced, we substituted them within the same management regime. Utilizing our experience and the impressions of patients, some of whom inevitably having repeat courses and so acting as their own controls, we subjected the new drugs to uncontrolled trials, usually in series of 50 patients. It was not until we tried chlormethiazole in 1965 that we felt that we had found a drug that offered material improvement over those previously used, and we decided to use it from then on as the drug of choice.Innumerable reports have appeared in the literature in recent years regarding the value of specific drugs in the treatment of the alcohol withdrawal state but opinion, particularly in the American literature, has hardened in favour of chlordiazepoxide. Kaim et al. (1969), on the basis of a double blind, multi-hospital study claimed that chlordiazepoxide was the drug of choice in the treatment of this condition. An earlier report claimed that it had a clear advantage over diazepam (Chambers and Schultz 1965). British and continental reports, on the other hand, had favoured the use of chlormethiazole (Glatt 1965).As no double blind controlled trial of chlormethiazole and chlordiazepoxide had been published, we decided to carry one out. MethodAs the two preparations being tested were very different in presentation, one being a tablet and the other a capsule with Arachis oil, it was decided that both tablet and capsule would be given to each patient. For the purposes of the trial 192 mg chlormethiazole (base) in Arachis oil was regarded as equivalent to 25 mg chlordiazepoxide.One hundred consecutive admissions to a specialized unit for the treatment of alcoholism in a psychiatric hospital were allotted code numbers and in accordance with a list of randomised numbers received either active capsules and placebo tablets, or vice versa. The true nature of the medication was known only to the 81 "

Chlormethiazole‐mode of action

“…Chlormethiazole, which is derived from the thiazole moiety of thiamine, possesses sedative, hypnotic, anxiolytic and anticonvulsant properties (1)(2)(3). Chlormethiazole is widely used in some European countries for the treatment of ethanol withdrawal states including delirium tremens (4)(5)(6)(7)(8)(9). It is also widely used clinically as an anticonvulsant in different types of convulsive states.…”

Comparison of Clomethiazole and Diazepam in the Treatment of Alcohol Withdrawal Syndrome in Clinical Practice

“…Bonnet et al [38] and LaPierre et al [39] found clomethiazole and clonazepam/chlordiazepoxide to be equally effective and tolerable. Compared to chlordiazepoxide, McGrath [40] revealed a tendency of better symptom and delirium control using clomethiazole, while Burroughs et al [34] saw clomethiazole as the more flexibly usable drug. In the most recent study, Millas et al [41] compared oxazepam and clomethiazole.…”

Estrategias en el tratamiento de desintoxicación alcohólica

“…Presenta, sin embargo, tres serios riesgos: depresión respiratoria, hipersecreción bronquial y riesgo de rápi-da adicción, por lo que no debería utilizarse más que en medio hospitalario. Las benzodiacepinas son una alternativa válida y, en algunos casos, necesaria al clometiazol, aunque su eficacia, especialmente en el tratamiento del delirium tremens, sea inferior (54) . Los principios activos más empleados son diazepam, clordiazepóxido y clorazepato dipotásico.…”