Parkhead Hospital, 81 Salamanca Street, Glasgow G31 5BA, UK
Received 27 November 1998; in revised form 30 September 1999; accepted 14 October 1999
We report on a pilot double-blind study on the effectiveness of divided doses of chlordiazepoxide and a single daily dose of diazepam in the treatment of the alcohol-withdrawal syndrome. While a variety of drugs (chlormethiazole, propranolol and clonidine) have been used for treatment of alcohol-withdrawal symptoms, benzodiazepines remain the drugs of choice for alcohol detoxification (Mayo-Smith, 1997). Diazepam and chlordiazepoxide are both longer-acting benzodiazepines, and preferred for detoxification (Williams and McBride, 1998
). Traditionally, chlordiazepoxide has been the benzodiazepine of choice due to its lower dependence and abuse potential, whereas diazepam has been used in patients with a history of alcohol-withdrawal seizures.
In view of the accent on community detoxification, we undertook this pilot study to evaluate the effectiveness of a single daily dose of diazepam in detoxification. Consecutive in-patients with severe alcohol-dependence syndrome, who gave informed consent, were included in the study. Patients with severe physical illness or psychiatric co-morbidity were excluded. All patients had a semi-structured alcohol history recorded and completed the Severity of Alcohol Dependence Questionnaire (SADQ) (Stockwell et al., 1983) to quantify the severity of dependence. Patients were randomly allocated, by pharmacy, to one of two double-blind alcohol withdrawal regimes administered four times a day: diazepam once a day (evening dose) with three placebo tablets or chlordiazepoxide four times a day. Both regimes were on a sliding scale over eight days, with a starting daily dose of either 40 mg of diazepam or 80 mg of chlordiazepoxide. Alcohol withdrawal was monitored four times a day using a modified alcohol-withdrawal chart (Sullivan et al., 1989
) (see Appendix). Pulse, temperature and blood pressure were also monitored four times a day prior to administration of medication. All patients received similar vitamin supplementation. If patients required additional benzodiazepines to overcome withdrawal symptoms, oxazepam 20 mg was available. All patients were prescribed chloral hydrate elixir, 10 ml nocte as a hypnotic, if required.
Twenty-three consecutive elective admissions for detoxification were assessed for inclusion in the study. Three patients, all male, were withdrawn at the time of assessment: one had a subdural haematoma, one had manifest agitation felt to be a feature of psychosis, and one patient took immediate self-discharge prior to medication being administered. The two populations were similar in age, duration of problem drinking, units of alcohol consumed per week, alcolmeter reading, and SADQ on admission (Table 1). No patient required any supplementary medication; neither oxazepam nor chloral hydrate elixir were needed and no adverse events were recorded. As shown in Figure 1
, the mean pulse rate in both groups showed no significant difference on days 1, 2, 5 or 8 although significance was noted on day 6 (P < 0.05) and day 7 (P < 0.05). This anomaly is difficult to explain; there was no record of clinical concern on these days and no significant difference in the scores for alcohol withdrawal. Both medications were effective with withdrawal symptoms (Fig. 2
). The difference noted on days 5, 6, and 8 (though not significant) is explained by the high scores of one particular patient, patient 5, which skewed the mean. While withdrawal scores for all patients improved consistently, patient 5 remained anxious with no clinical evidence of alcohol withdrawal (Table 2
).
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APPENDIX
FOOTNOTES
* Author to whom correspondence should be addressed.
REFERENCES
Mayo Smith, M. F. for the American Society of Addiction Medicine Working Group on Pharmacological Management of Alcohol Withdrawal (1997) Pharmacological management of alcohol withdrawal. A meta-analysis and evidence-based practice guideline. Journal of the American Medical Association 278, 144151.[Abstract]
Stockwell, T., Murphy, D. and Hodgson, R. (1983) The Severity of Alcohol Dependence questionnaire: its use, reliability and validity. British Journal of Addiction 78, 145155.[ISI][Medline]
Sullivan, J. T., Sykora, K., Schniderman, J., Naranjo, C. A. and Sellers, E. M. (1989) Assessment of alcohol withdrawal: the Revised Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar). British Journal of Addiction 84, 13531357.[ISI][Medline]
Williams, D. and McBride, A. J. (1998) The drug treatment of alcohol- withdrawal symptoms: a systematic review. Alcohol and Alcoholism 33, 103115.[Abstract]