Comparing medications for alcohol withdrawal
It is interesting to look at other agents that aide in treating alcohol withdrawal (AW) (“Alcohol withdrawal: When to choose an adjunctive anticonvulsant,” Current Psychiatry, April 2010). However, it would be more important to stress using chlordiazepoxide instead of lorazepam as long as there are no contraindications, because there is conclusive evidence that patients receiving chlordiazepoxide are hospitalized for fewer days. Presumably, there should be less morbidity and a smoother withdrawal likely related to chlordiazepoxide’s longer half-life. What do the authors think about using chlordiazepoxide more often and what cutoff for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) would they suggest for not using chlordiazepoxide?
Corey Yilmaz, MD
Adult and child psychiatrist
The authors respond
Chlordiazepoxide and diazepam are time-honored choices for AW. Advantages include long half-lives, which allow for uniform blood levels across the day and reduce risk of withdrawal symptoms, including seizures, that may arise when blood levels drop. At the same time, this long half-life combined with the presence of active metabolites, dependence on Phase I metabolism, and higher lipophilicity could result in increased drug accumulation and redistribution into lipid storage reservoirs, which could complicate the clinical picture. Alternatively, lorazepam, an intermediate-acting benzodiazepine that depends primarily on Phase 2 metabolism, is less affected by liver disease. Additional advantages of lorazepam are its lower lipophilicity compared with chlordiazepoxide and diazepam, and no active metabolites. For these pharmacokinetic benefits, in a group where liver dysfunction is presumed, lorazepam has grown in favor.2
Although there is a dearth of head-to-head efficacy comparisons between lorazepam and chlordiazepoxide/diazepam, a study of chlordiazepoxide and lorazepam in AW supported that during detoxification the longer-acting diazepam produced no withdrawal seizures; the lorazepam group had patients who developed seizures. However, when the initial lorazepam dosage was increased in a later study, patients’ withdrawal was seizure-free. Efficacy was otherwise equal among treatment groups.1
The evidence seems to lead to an overall generalization that when dosed correctly, shorter- and longer-acting benzodiazepines (ie, lorazepam and chlordiazepoxide, respectively) are effective and safe, with the caveat that older patients and those with liver dysfunction should be treated with lorazepam.3 However, is there a reliable and quick assessment of liver dysfunction in patients with alcohol use disorders?
Although the Child-Pugh classification score can be used, it typically is used to assess prognosis of chronic liver disease.4 Using traditional serum biomarkers to predict hepatic dysfunction offers advantages and disadvantages. I offer the following guidelines: gamma-glutamyl transpeptidase (GGTP) ≥177 U/L, AST ≥63 U/L, and ALT ≥67 U/L, statistically separates (P < .001) heavy drinkers from moderate drinkers and abstainers; the former group is at greatest risk for alcoholic liver disease.5 The majority of long-term heavy drinkers develop fatty liver disease, but only 10% to 35% develop hepatitis and 8% to 20% progress to cirrhosis.6 Additionally, other limitations with using a priori serum biomarkers’ range include the role of genetics, gender, race, and medical comorbidities7 (ie, other causes of acute hepatitis, cholestasis, and liver congestion) in the development of alcoholic liver disease and their effect on these biomarkers.6
David R. Spiegel, MD
Associate professor of clinical psychiatry and behavioral sciences
Daiana Radac, MD
Eastern Virginia Medical School
1. Kumar CN, Andrade C, Murthy P. A randomized, double-blind comparison of lorazepam and chlordiazepoxide in patients with uncomplicated alcohol withdrawal. J Stud Alcohol Drugs. 2009;70:467-474.
2. Bird RD, Makela EH. Alcohol withdrawal: what is the benzodiazepine of choice? Ann Pharmacother. 1994;28:67-71.
3. Hoey LL, Nahum A, Vance-Bryan K. A prospective evaluation of benzodiazepine guidelines in the management of patients hospitalized for alcohol withdrawal. Pharmacotherapy. 1994;14(5):579-585.
4. Child-Pugh score. Available at: http://www.doctorslounge.com/gastroenterology/scores/child.htm. Accessed June 7, 2010.
5. Alatalo P, Koivisto H, Puukka K, et al. Biomarkers of liver status in heavy drinkers, moderate drinkers and abstainers. Alcohol Alcohol. 2009;44(2):199-203.
6. Gramenzi A, Caputo F, Biselli M, et al. Review article: alcoholic liver disease—pathophysiological aspects and risk factors. Aliment Pharmacol Ther. 2006;24(8):1151-1161.
7. Meuller S, Millonig G, Sarovska L, et al. Increased liver stiffness in alcoholic liver disease: differentiating fibrosis from steatohepatitis. World J Gastroenterol. 2010;16(8):966-972.