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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%)