Comparison of Clomethiazole vs. Clonazepam in Acute Alcohol Withdrawal

In This Article

Abstract and Introduction

Abstract

Aims: To compare two inpatient symptom-triggered pharmacological treatments of acute alcohol withdrawal (AWS) (clomethiazole vs. clonazepam).
Methods: Prospective observational comparison within a quality improvement project. Because of a need for extra precautions against complications such as seizures and severe respiratory complaints, patients with a history of withdrawal seizures or complications with clomethiazole in their history were automatically assigned to the clonazepam group. The remaining patients were alternately assigned either to the clonazepam group (n = 38 altogether) or the clomethiazole group (n = 36). Rescue medication could consist of adding either extra clonazepam or clomethiazole. Effectiveness was measured by Clinical Global Impression Scale, Revised Clinical Institute Withdrawal Assessment for Alcohol Scale, Mainz Alcohol Withdrawal Scale, Essen Self-Assessment-Alcohol Withdrawal and attrition rate. Safety and tolerability was estimated from adverse clinical events. Secondary outcome values were heart rate, blood and pulse pressure.
Results: There were no significant differences between the treatments with respect to primary and secondary effectiveness measures, safety or tolerability or duration of medication treatment. Both reduced the severity of initial withdrawal symptoms below 20% up to the ending of withdrawal medications. No withdrawal seizure or delirium occurred.
Conclusion: Both score-driven treatments were equally effective, safe and well tolerated in this setting. This is the first study demonstrating the utility of clonazepam in the treatment of AWS syndrome.

Introduction

Acute alcohol withdrawal (AWS) of at least moderate severity requires pharmacological treatment to avoid severe complications such as epileptic seizures or deliria. Most effective treatments used benzodiazepines (Kosten and O'Connor, 2003) and in Europe also clomethiazole (Majumdar, 1991; Morgan, 1995). Approved strategies were 'loading with diazepam' and 'fixed-dosing' or 'symptom-triggered' treatments with highly potent benzodiazepines (Hall and Zador, 1997; Kosten and O'Connor, 2003; Kumar et al., 2009).

Symptom-triggered treatments reduced both withdrawal medication and duration of treatment when compared with fixed-dose regimes in two studies (Daeppen et al., 2002; Mayo-Smith, 1997). Symptom-triggered treatments were usually driven by withdrawal scores (Kosten and O'Connor, 2003). Most detoxification units have specially trained nurses who administer medication when the score builds up to at least moderate severity (e.g. 'Revised Clinical Institute Withdrawal Assessment for Alcohol Scale' (CIWA-Ar) >10 or 'Score-Driven Treatment of Alcohol Withdrawal by Nurse Staff' (SAB-P) >4 points), the score being used to determine an individual initial amount of withdrawal medication over the span of the first 24 or 48 h of treatment followed tapering off ('score-driven treatment') (Banger et al., 1997; McKay et al., 2004; Sullivan et al., 1989).

There are pros and cons regarding the usual benzodiazepines diazepam, chlordiazepoxide, lorazepam and oxazepam (Daeppen et al., 2002; Holbrook et al., 1999; Kumar et al., 2009; Mayo-Smith, 1997; Ntais et al., 2005). We have used clonazepam as an alternative over many years as it has a relatively long biological half-life, which is important in the prevention of withdrawal seizures. It also has several advantages for the management of AWS: its mainly renal elimination, no pharmacologically active metabolites, no capacity to induce cytochrome P-450, and no sequestration in brain tissue (Greenblatt et al., 1987; Pachecka et al., 1990).

Alcohol detoxification in Germany is traditionally managed with oral clomethiazole in symptom-triggered regimes, whenever possible, score-driven (Mundle et al., 2006). This study compares the effectiveness and tolerability of clonazepam to clomethiazole. We hypothesized that both score-driven pharmacological treatments are equally potent, safe and tolerable when simple precautions are taken.

Cite this: Comparison of Two Oral Symptom-triggered Pharmacological Inpatient Treatments of Acute Alcohol Withdrawal: Clomethiazole vs. Clonazepam - Medscape - Jan 01, 2011.

Table 1. Baseline characteristics and alcohol history data
Characteristics	Clomethiazole	Clonazepam	P
N	36	38
Age	41.3 ± 10.5	44.5 ± 10.4	0.38
Gender (female/male)	9/27	14/24	0.37
ICD-10 criteria of alcohol-dependence (eight item)	7.4 ± 1.9	7.7 ± 1.7	0.46
BAC at baseline (%)	0.13 ± 0.11	0.18 ± 0.1.3	0.52
Daily alcohol consumption (g)	303 ± 140	326 ± 176	0.52
Years of drinking	14.8 ± 12.0	17.9 ± 10.7	0.25
Family history positive for alcoholism (yes/no)	13/23	18/20	0.33
Daily number of cigarettes	23 ± 14	26 ± 15	0.41
Prior delirium (yes/no)	1/35	2/36	>0.9
Prior epileptic seizures (yes/no)	0/33	12/26	<0.001*
Number of prior inpatient withdrawal treatments	2.2 ± 2.5	12.5 ± 15.9	<0.001*
Number of prior weaning therapies	0.5 ± 1.1	1.4 ± 1.5	0.01*
Visiting self-helping groups (yes/no)	5/31	14/24	0.024*
Compensated co-morbid mental diseases (yes/no)	10/26	4/34	0.058
Compensated co-morbid somatic diseases (yes/no)	5/31	2/36	0.21
MCV (fl)	93 ± 12	91 ± 10	0.28
GGT (U/l)	331 ± 488	186 ± 392	0.17
GPT (U/l)	74 ± 65	100 ± 123	0.26
Cholesterol (mg/dl)	216 ± 47	216 ± 68	>0.9
Triglycerides (mg/dl)	153 ± 102	158 ± 118	0.87
Magnesium (mM)	0.80 ± 0.2	0.81 ± 0.22	0.82

*Significant differences between the treatment groups according to t-test (Welch test in case of unequal variances) or χ ² test (P < 0.05).

Table 2. ACE throughout the whole study
	Clomethiazole (n = 36)	Clonazepam (n = 38)
Patients with ACE^a	13	15
Dizziness/somnolence	8	10
Vertigo/ataxia	8	9
Insomnia	8	5
Dysphoria/mood instability	5	6
Paresthesia	6	4
Nasal irritation (tingling in the nose/sneezing)	8	0
Nausea	3	3
Flu-like symptoms	3	3
Restlessness/anxiety	3	2
Seizure	0	0
Delirium	0	0

^aSeveral complaints at one patient are recorded in most cases.

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