212
P. JAUHAR and J. ANDERSON
IS DAILY SINGLE DOSAGE OF DIAZEPAM AS EFFECTIVE AS CHLORDIAZEPOXIDE
IN DIVIDED DOSES IN ALCOHOL WITHDRAWAL —
A PILOT STUDY
P. JAUHAR* and J. ANDERSON
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 alcoholwithdrawal 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
*Author to whom correspondence should be addressed.
feature of psychosis, and one patient took immediate selfdischarge 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).
The relatively small sample of this study precludes extrapolating significance from the results. Regrettably, limited
finance for placebo tablets necessitated that only 23 patients
could be included in the study. However during this pilot
study, no patients required adjuvant medication or developed
severe complications. We would suggest that the option of a
single daily dose of diazepam is attractive in uncomplicated
community detoxification with appropriate monitoring of
withdrawal symptoms.
Table 1. Comparative characteristics of patient populations
Characteristic
Chlordiazepoxide group
(n = 9)
mean ± SD
Mean age (years)
Duration of problem
drinking (years)
Units of alcohol per week
Alcolmeter reading on
admission
SADQ score on admission
46 ± 14
10 ± 8
221 ± 3
31 ± 66
38 ± 10
Diazepam group
(n = 11)
mean ± SD
41 ± 9
11 ± 8
244 ± 83
38 ± 74
37 ± 6
LETTERS TO THE EDITORS
213
Fig. 1. Mean pulse rates.
Fig. 2. Alcohol-withdrawal scores.
Table 2. Alcohol withdrawal scale score changes
Treatment/
Patient No.
Day 1
Day 2
Day 3
Day 4
Day 5
Day 6
Day 7
Day 8
1
2
3
4
5
6
7
8
9
10
11
12
20
27
12
23
21
23
8
12
19
26
18
14
5
10
47
21
24
18
7
14
16
16
1
3
1
23
7
17
16
6
8
11
9
0
1
0
13
0
14
5
6
1
0
11
0
0
0
27
0
9
2
5
2
8
8
0
0
2
15
0
15
2
1
4
7
0
0
0
0
9
0
10
0
0
2
6
0
5
0
0
32
0
6
0
0
0
5
1
2
3
4
5
6
7
8
9
17
21
12
7
15
16
33
17
24
14
12
3
6
1
3
14
7
21
6
7
0
8
0
0
13
5
6
10
5
1
4
0
0
14
2
3
13
0
0
0
0
0
3
5
0
6
0
0
0
0
1
2
0
0
3
0
0
0
1
0
0
0
0
4
0
0
0
1
0
0
0
0
Diazepam
Chlordiazepoxide
REFERENCES
Mayo Smith, M. F. for the American Society of Addiction Medicine
Working Group on Pharmacological Management of Alcohol
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withdrawal. A meta-analysis and evidence-based practice guideline. Journal of the American Medical Association 278,
144–151.
Stockwell, T., Murphy, D. and Hodgson, R. (1983) The Severity of
Alcohol Dependence questionnaire: its use, reliability and validity.
British Journal of Addiction 78, 145–155.
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 (CIWAAr). British Journal of Addiction 84, 1353–1357.
Williams, D. and McBride, A. J. (1998) The drug treatment of alcoholwithdrawal symptoms: a systematic review. Alcohol and Alcoholism
33, 103–115.
214
P. JAUHAR and J. ANDERSON
APPENDIX