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Three Part Question

In [patients with alcohol dependency who exhibit withdrawal] does [repeated administration of chordiazepoxide] increase [the incidence of withdrawal fits]?

Clinical Scenario

A 48-year-old man attends the emergency department intoxicated and with a head injury. He is kept overnight and develops symptoms of alcohol withdrawal in the morning. He is a frequent attender to the emergency department with similar presentation and has been treated repeatedly with chlordiazepoxide in the past. You recently attended a postgraduate lecture where the “kindling effect” was discussed. You wonder whether his repeated treatments with chlordiazepoxide are actually having this effect and thereby increasing his risk of alcohol withdrawal seizures.

Search Strategy

Ovid MEDLINE(R) 1950 to September week 4 2009
Embase via the NHS Evidence interface 1980–30 September 2009
The Cochrane Library, Issue 3, 2009

Medline: (exp Kindling, Neurologic/OR kindling.mp.) AND (chlordiazepoxide.mp. OR exp Chlordiazepoxide/)

exp alcohol-related disorders/OR ethanol.mp. OR exp Ethanol/AND chlordiazepoxide.mp. OR exp Chlordiazepoxide/AND exp seizures/OR fits.mp. OR epilep$.mp.

Embase:(exp KINDLING/OR kindling ti, ab,) AND (exp CHLORDIAZEPOXIDE/OR Chlordiazepoxide.ti,ab)

(exp ALCOHOLISM/OR ethanol.ti,ab OR exp ALCOHOL/) AND (exp SEIZURE/OR fits.ti,ab OR epilep$.ti,ab) AND (chlordiazepoxide.ti,ab OR exp CHLORDIAZEPOXIDE/)

Cochrane:MeSH descriptor Kindling, Neurologic explode all trees.

Search Outcome

A total of 155 unique papers were found in all the searches of which two were relevant. These are shown in the table

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Worner T.M. July 1996, United States	360 alcoholics with at least two admissions for detoxification.Subjects with seizure history were treated with tapering doses of chlordiazepoxide and the rest had a standard dose.	Cohort study.	Seizure activity	No seizures were recorded in this study.	The study outcomes were not clearly defined at the start
Lechtenberg R., Worner T.M. 1990, USA	Cohort study study of 256 men and 45 women (alcoholics) voluntarily admitted into a structured 5 day detoxification program. EEGs were done on all patients.	Observational	EEG findings	Increased seizure activity was detected on EEG.
			Seizure activity	No seizures were recorded in the study

Comment(s)

No good evidence exists to answer our clinical scenario. One cohort study has suggested that there is seizure activity in the brain seen on EEG which is externally suppressed by chlordiazepoxide. Further work needs to be done in this area.

Clinical Bottom Line

There is no evidence to support the theory that recurrent alcohol detoxification with chlordiazepoxide will lead to kindling effect.

References

1. Worner T.M. Relative Kindling Effect of Readmission in Alcoholics . Alcohol and Alcoholism July 1996, vol./is. 31/4(375-380).
2. Lechtenberg R., Worner T.M. Seizure Risk with Recurrent Alcohol Detoxification. Archives of Neurology 1990, vol./is. 47/5(535-538).