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Three Part Question

In [Adult patients with withdrawal symptoms] is[Chlordiazepoxide better than chlormethiazole] at [treating withdrawal symptoms]?

Clinical Scenario

A patient arrives in the emergency department is suffering from withdrawal symptoms. You know benzodiazepines can be given but are not sure if its the best treatment choice

Search Strategy

Using the OVID interface:
Medline 1996 to June week 3 2007:
[chlordiazepoxide.mp. or exp Chlordiazepoxide or benzodiazepines.mp. or exp Benzodiazepines or chlormethiazole.mp. or exp Chlormethiazole] and [exp Alcohol Withdrawal Seizures or withdrawal.mp. or exp Alcohol Withdrawal Delirium/ or exp Substance Withdrawal Syndrome] and [ethanol.mp. or exp Ethanol or alcoholic.mp or exp Alcoholic Intoxication/ or exp Alcoholic Beverages or alcohol abuse.mp. or Alcoholism and limit to (humans and english language)
Embase 1996 to 2007 week 26:
[chlordiazepoxide.mp or exp Chlordiazepoxide or benzodiazepines.mp. or exp Benzodiazepines] AND [chlormethiazole.mp. or exp Chlormethiazole] and [exp Alcohol Withdrawal Seizures or withdrawal.mp. or exp Alcohol Withdrawal Delirium/ or exp Substance Withdrawal Syndrome] and limit to (humans and english language)
Cochrane Database of Systematic Reviews 2nd Quarter 2007:
[chlordiazepoxide.mp. or exp Chlordiazepoxide or benzodiazepines.mp. or exp Benzodiazepines or chlormethiazole.mp. or exp Chlormethiazole] and [exp Alcohol Withdrawal Seizures or withdrawal.mp. or exp Alcohol Withdrawal Delirium/ or exp Substance Withdrawal Syndrome] and [ethanol.mp. or exp Ethanol or alcoholic.mp or exp Alcoholic Intoxication/ or exp Alcoholic Beverages or alcohol abuse.mp. or Alcoholism and limit to (humans and english language)

Search Outcome

Medline found 153 papers, Embase found 155 papers, Cochrane found 8 papers. 4 of these papers were relevant

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Berglund M et al 2002 Sweden	Eighty-two RCTS were found mainly comparing Benzodiazepine effectiveness in Patients who presented to hospitals or health care centres.	Systematic Review	the effect of pharmacotherapy on withdrawal symptoms	Benzodiazepines said to be effective, Chlormethiazole said to be effective in delerium tremens	Limited studies available for chlormethiazole. Little data shown from studies analysed
Williams D and McBride JA 1998 United Kingdom	14 randomised double blinded placebo control trials and 22 double blinded comparison control trials	Systematic Review	Outcomes were measured using scales	2 trials showed chlormethiazole and chlordiazepoxide had equal efficacy in comparison to placebo	Different scales used to measure outcome
Ntais C et al 2005 United Kingdom	57 trials with a total of 4,051 people were included.	Systematic Review	Status of patients with regards to withdrawal symptoms	Benzodiazepines were better than placebo but of varying efficacy with regards to other drugs	Large variety of outcomes and rating scales makes synthesis difficult
Lucht M et al 2002 Germany	Specialist hospital for addictive disorders. 127 caucasian german patients with alcohol dependence according to ICD 10 criteria. Assigned to 1 of 4 treatment options depending on breath alcohol concentration.	Open label study	Alcohol Withdrawal Score	tiapride and carbamazepine are as effective as chlormethiazole and diazepam in intoxicated patients	Lack of blinding

Comment(s)

There have been many studies comparing mainly the benzodiazepines to placebo or other drugs. The benzodiazepines have also been shown to deal well with alcohol related seizures

Clinical Bottom Line

Benzodiazepines or Chlormethiazole can be given but there is more evidence availble to support administering a benzodiazepine.

References

1. Berglund M et al Treatment of alcohol abuse an evidence based review Alcoholism: Clinical and Experimental Research October 2003; Vol.27, No.10, pp.1645-1656
2. Williams D and McBride JA The drug treatment of alcohol withdrawal symptoms: A systematic review Alcohol & Alcoholism 1998; Vol.33, No.2, pp. 103-115.
3. Ntais C et al Benzodiazepines for Alcohol Withdrawal Cochrane Database of Systematic Reviews 2005, Issue 3. Art. No.: CD005063
4. Lucht M et al Alcohol Withdrawal Treatment in Intoxicated vs Non Intoxicated Patients: A controlled Open Label study with Tiapride/Carbamazepine, Clomethiazole and Diazepam Alcohol & Alcoholism 2003; Vol. 38, No. 2, pp.168-175