Background: The objective of this retrospective study was to compare the effectivity and tolerability of diazepam and clomethiazole in the treatment of alcohol withdrawal syndrome (AWS) in a large clinical sample. Methods: The data of 566 patients admitted to an intensive care psychiatric unit in Germany (2010-2014) were evaluated. The course of withdrawal was analyzed on a matched sample (n = 152) consisting of a diazepam group (n = 76) and a clomethiazole group (n = 76). Medical assessment was based on a standardized point-based symptom rating scale called AESB (Alkoholentzugssymptom-Bogen), a German modified version of the Revised Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar). Results: Although the mean daily symptom reduction did not differ significantly, patients treated with clomethiazole were treated significantly shorter and needed less concomitant antipsychotic medication. Numbers of complications and adverse events did not show significant differences. Conclusion: Both clomethiazole and diazepam were effective and equally safe in the treatment of AWS. Clomethiazole provided a faster withdrawal and required less concomitant antipsychotic medication and therefore might be the more favorable option for patients and physicians. Taken into account the methodological limitations of the study (retrospective design, secondary matching, missing randomization, use of clomethiazole as drug of first choice), further studies are needed to confirm this result.

Tsai G, Gastfriend DR, Coyle JT: The glutamatergic basis of human alcoholism. Am J Psychiatry 1995;152:332-340.
Glue P, Nutt D: Overexcitement and disinhibition. Dynamic neurotransmitter interactions in alcohol withdrawal. Br J Psychiatry 1990;157:491-499.
Littleton J, Little H: Current concepts of ethanol dependence. Addiction 1994;89:1397-1412.
Adinoff B: The alcohol withdrawal syndrome. Neurobiology of treatment and toxicity. Am J Addict 1994;3:277-288.
de Witte P, Pinto E, Ansseau M, Verbanck P: Alcohol and withdrawal: from animal research to clinical issues. Neurosci Biobehav Rev 2003;27:189-197.
Saitz R, Mayo-Smith MF, Roberts MS, Redmond HA, Bernard DR, Calkins DR: Individualized treatment for alcohol withdrawal. A randomized double-blind controlled trial. JAMA 1994;272:519-523.
Victor M, Adams RD: The effect of alcohol on the nervous system. Res Publ Assoc Res Nerv Ment Dis 1953;32:526-573.
Turner RC, Lichstein PR, Peden JG Jr, Busher JT, Waivers LE: Alcohol withdrawal syndromes: a review of pathophysiology, clinical presentation, and treatment. J Gen Intern Med 1989;4:432-444.
Mayo-Smith MF: Pharmacological management of alcohol withdrawal. A meta-analysis and evidence-based practice guideline. American Society of Addiction Medicine Working Group on Pharmacological Management of Alcohol Withdrawal. JAMA 1997;278:144-151.
National Clinical Guideline Centre: Alcohol Use Disorders, Diagnosis and Clinical Management of Alcohol-Related Physical Complications. London, Royal College of Physicians, 2010. (accessed October 10, 2016).
Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften: S3-Leitlinie ‘Screening, Diagnose und Behandlung Alkoholbezogener Störungen' (S3-Guideline, ‘Screening, Diagnosis and Treatment of Alcohol-Related Disorders'), AWMF-Register Nr. 076-001, 2016. (accessed October 10, 2016).
Daeppen JB, Gache P, Landry U, Sekera E, Schweizer V, Gloor S, Yersin B: Symptom-triggered vs fixed-schedule doses of benzodiazepine for alcohol withdrawal: a randomized treatment trial. Arch Intern Med 2002;162:1117-1121.
Amato L, Minozzi S, Davoli M: Efficacy and safety of pharmacological interventions for the treatment of the alcohol withdrawal syndrome. Cochrane Database Syst Rev 2011;6:CD008537.
Shader RI, Greenblatt DJ: The use of benzodiazepines in clinical practice. Br J Clin Pharmacol 1981;11(suppl 1):5S-9S.
Danneberg P, Weber KH: Chemical structure and biological activity of the diazepines. Br J Clin Pharmacol 1983;16(suppl 2):231S-244S.
Greenblatt DJ, Divoll M, Abernethy DR, Ochs HR, Shader RI: Benzodiazepine kinetics: implications for therapeutics and pharmacogeriatrics. Drug Metab Rev 1983;14:251-292.
Holbrook AM, Crowther R, Lotter A, Cheng C, King D: Meta-analysis of benzodiazepine use in the treatment of acute alcohol withdrawal. CMAJ 1999;160:649-655.
Kaim SC, Klett CJ, Rothfeld B: Treatment of the acute alcohol withdrawal state: a comparison of four drugs. Am J Psychiatry 1969;125:1640-1646.
Sellers EM, Naranjo CA, Harrison M, Devenyi P, Roach C, Sykora K: Diazepam loading: simplified treatment of alcohol withdrawal. Clin Pharmacol Ther 1983;34:822-826.
Naranjo CA, Sellers EM, Chater K, Iversen P, Roach C, Sykora K: Nonpharmacologic intervention in acute alcohol withdrawal. Clin Pharmacol Ther 1983;34:214-219.
Ntais C, Pakos E, Kyzas P, Ioannidis JP: Benzodiazepines for alcohol withdrawal. Cochrane Database Syst Rev 2005;3:CD005063.
Amato L, Minozzi S, Vecchi S, Davoli M: Benzodiazepines for alcohol withdrawal. Cochrane Database Syst Rev 2010;3:CD005063.
Saitz R: Introduction to alcohol withdrawal. Alcohol Health Res World 1998;22:5-12.
Ritson B, Chick J: Comparison of two benzodiazepines in the treatment of alcohol withdrawal: effects on symptoms and cognitive recovery. Drug Alcohol Depend 1986;18:329-334.
Jostell KG, Agurell S, Allgen LG, Kuylenstierna B, Lindgren JE, Aberg G, Osterlof G: Pharmacokinetics of clomethiazole in healthy adults. Acta Pharmacol Toxicol (Copenh) 1978;43:180-189.
Cross AJ, Stirling JM, Robinson TN, Bowen DM, Francis PT, Green AR: The modulation by chlormethiazole of the GABAA-receptor complex in rat brain. Br J Pharmacol 1989;98:284-290.
Harrison NL, Simmonds MA: Two distinct interactions of barbiturates and chlormethiazole with the GABAA receptor complex in rat cuneate nucleus in vitro. Br J Pharmacol 1983;80:387-394.
Usala M, Thompson SA, Whiting PJ, Wafford KA: Activity of chlormethiazole at human recombinant GABA(A) and NMDA receptors. Br J Pharmacol 2003;140:1045-1050.
Pentikainen PJ, Neuvonen PJ, Jostell KG: Pharmacokinetics of chlormethiazole in healthy volunteers and patients with cirrhosis of the liver. Eur J Clin Pharmacol 1980;17:275-284.
Centerholt C, Ekblom M, Odergren T, Borga O, Popescu G, Molz K-H, Couturier A, Weil A: Pharmacokinetics and sedative effects in healthy subjects and subjects with impaired liver function after continuous infusion of clomethiazole. Eur J Clin Pharmacol 2003;59:117-122.
Majumdar SK: Chlormethiazole: current status in the treatment of the acute ethanol withdrawal syndrome. Drug Alcohol Depend 1991;27:201-207.
Glatt MM, George HR, Frisch EP: Controlled trial of chlormethiazole in treatment of the alcoholic withdrawal phase. Br Med J 1965;2:401-404.
Harfst MJ, Greene JG, Lassae FG: Controlled trial comparing amobarbital and clomethiazole in alcohol withdrawal symptoms. Q J Stud Alcohol 1967;28:641-648.
Burroughs AK, Morgan MY, Sherlock S: Double-blind controlled trial of bromocriptine, chlordiazepoxide and chlormethiazole for alcohol withdrawal symptoms. Alcohol Alcohol 1985;20:263-271.
Morgan MY: The management of alcohol withdrawal using chlormethiazole. Alcohol Alcohol 1995;30:771-774.
Dalen JE, Evans GL, Banas JS Jr, Brooks HL, Paraskos JA, Dexter L: The hemodynamic and respiratory effects of diazepam (Valium). Anesthesiology 1969;30:259-263.
Gregg E, Akhter I: Chlormethiazole abuse. Br J Psychiatry 1979;134:627-629.
Bonnet U, Lensing M, Specka M, Scherbaum N: Comparison of two oral symptom-triggered pharmacological inpatient treatments of acute alcohol withdrawal: clomethiazole vs. clonazepam. Alcohol Alcohol 2011;46:68-73.
Lapierre YD, Bulmer DR, Oyewumi LK, Mauguin ML, Knott VJ: Comparison of chlormethiazole (Heminevrin) and chlordiazepoxide (Librium) in the treatment of acute alcohol withdrawal. Neuropsychobiology 1983;10:127-130.
McGrath SD: A controlled trial of chlormethiazole and chlordiazepoxide in the treatment of the acute withdrawal phase of alcoholism. Br J Addict Alcohol Other Drugs 1975;70(suppl 1):81-90.
de Millas W, Ganzer F, Kuhn S, Haasen C: Oxazepam versus clomethiazol in alcohol withdrawal treatment. Eur Addict Res 2010;16:179-184.
Sullivan JT, Sykora K, Schneiderman J, Naranjo CA, Sellers EM: Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). Br J Addict 1989;84:1353-1357.
Shaw GK: Chlormethiazole in the management of alcohol withdrawal. Acta Psychiatr Scand Suppl 1986;329:162-166.
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