High dose intravenous clonidine is superior to intravenous clomethiazole in severe alcohol withdrawal syndrome (delirium tremens)

Abstract

Background Delirium tremens develops in 3–15% of all alcoholics under acute withdrawal. At present the treatment consists mainly of sedatives and symptomatic therapy. In addition to benzodiazepines, neuroleptic drugs and carbamazepine, clomethiazole is widely used. Catecholamine turnover in the central nervous system increases in delirium tremens with corresponding clinical signs. Clonidine reduces the sympathetic tonus in the region of the nucleus of the tractus solitarius. Methods Ninety-two patients (11 female, 81 male) reaching > 10 points (median 14, 10–23) on a symptom scale of max 25 points were treated in an open, randomized study with high dose clonidine (n = 43; 46 years; average dose 2.3 ± 1.4 mg/day) or clomethiazole (n = 48; 43 years; average dose 5.2 ± 2.5 g/day). Criteria for the evaluation of efficacy were the duration of treatment (days) to normalisation of clinical symptoms, the necessity of parenteral nutrition after 5 days of treatment, the possible mobilisation of the patients and their delirium specific concomitant medication. Clinical examinations with scoring were done twice daily. Examinations for adverse events and overall tolerability were done daily, laboratory tests at baseline and termination of the study. Results See table. Both drugs were effective in the treatment of alcoholic delirium. Eighty-four percent of the patients on clonidine compared with 60% on clomethiazole reached normalisation of symptoms within 5 days (P < 0.01). There were less non-responders with clonidine. On day 4 of treatment only 19% of the patients on clonidine had respiratory complications compared to 44% on clomethiazole (P < 0.013). In contrast, bowel function was a problem in 44% of patients on clonidine compared to 19% on clomethiazole on day 4 (P < 0.012). More patients on clonidine needed additional sedative measures. The global clinical assessment of efficacy at the end of treatment was better for clonidine. Nevertheless in clonidine six serious adverse events were documented, but only two in clomethiazole treatment. Hypotension and bradycardia were main adverse reactions with clonidine whereas clomethiazole led to excessive bronchial hypersecretion. Conclusions In treatment of delirium tremens clonidine is superior to clomethiazole with regard to duration of therapy and respiratory function. The clonidine dose used (2.3 mg/day) was higher as recommended (1.5 mg/day) in alcohol withdrawal. The tolerability of clonidine was better rather than the tolerability of clomethiazole. Table Clonidine Clomethiazole Initial dose 0.56 ± 0.22 mg 0.78 ± 0.56 mg Maintenance dose   2.2 ± 1.5 mg/day   5.2 ± 2.5 mg/day Duration of treatment  ≤ 2 days 14 (32.6%) 7(14.6%)  3-5 days 22 (51.2%) 22 (45.8%)  6-10 days 3 (7.0%) 12 (25.0%) Non-responder (≥ 10 days) 4 (9.3%) 7 (14.6%) Enteral nutrition day 5 20 (46.5%) 12 (25%) Mobilisation  Regular respiration 35 (81.4%) 27 (56.3%)  Regular bowel function day 2 24 (55.8%) 36 (75%)  Regular bowel function day 4 24 (55.8%) 39 (81.3%) Additive sedatives necessary 36 (83.7%) 24 (50%)