Managing alcohol withdrawal in the hospitalized patient


What about phenobarbital?

Phenobarbital has similar pharmacokinetics to the benzodiazepines frequently used for alcohol withdrawal, including simultaneous effects on gamma-aminobutyric acid (GABA) and N-methyl-D-aspartate (NMDA) receptors, and has been proposed as a treatment option for delirium tremens.

Dr. Erica Grabscheid, Mount Sinai Beth Israel, New York

Dr. Erica Grabscheid

In 2019, as reported in the American Journal of Emergency Medicine, Nelson et al. found that incorporating phenobarbital into a benzodiazepine-based protocol or as sole agent led to similar rates of ICU admission, length of stay, and need for mechanical ventilation in patients treated for alcohol withdrawal in the emergency department.9 The authors concluded that “phenobarbital (was) a safe and effective treatment alternative for alcohol withdrawal.” The systematic review by Hammond et al. in 2017 found that phenobarbital, either as monotherapy or in conjunction with benzodiazepines, could have comparable or superior results in comparison to other treatments, including benzodiazepines monotherapy.10 Further studies are needed to determine dosing and the most effective way to incorporate the use of phenobarbital in treatment of Alcohol Withdrawal Syndrome (AWS).

Should gabapentin or any other medications be added to his treatment regimen?

Chronic alcohol use induces a reduction in GABA activity (the major inhibitory neurotransmitter in the brain) and alcohol cessation results in decreased inhibitory tone. This physiologic imbalance contributes to the syndrome of alcohol withdrawal. As such, gabapentin has emerged as a promising treatment option in AWS and may help reduce the need for benzodiazepines.

Dr. Eve Merrill, Mount Sinai Beth Israel, New York

Dr. Eve Merrill

Gabapentin has few drug-drug interactions and is safe for use in patients with impaired liver function; however, dosage adjustment is required for renal dysfunction (CrCl less than 60 mL/min). Gabapentin’s neuroprotective effects may also help decrease the neurotoxic effects associated with AWS. Common side effects of gabapentin include dizziness, drowsiness, ataxia, diarrhea, nausea, and vomiting. The potential for misuse has been reported.

In several small studies, gabapentin monotherapy was found to be comparable to benzodiazepines in the treatment of mild to moderate AWS. Gabapentin is efficacious in reducing cravings as well as improving mood, anxiety, and sleep, and showed an advantage over benzodiazepines in preventing relapse with no difference in length of hospital stay.6,11 Given the small sample sizes of these studies and the differing methods, settings, and inclusion/ exclusion criteria used, the generalizability of these findings to patients with significant medical and/or psychiatric comorbidities remains limited. Additional studies are needed to standardize dosing protocols and treatment strategies for both inpatients and outpatients.

Dr. Kamana Pillay, Mount Sinai Beth Israel, New York

Dr. Kamana Pillay

Alternative agents such as antipsychotics (e.g., haloperidol), centrally acting alpha-2 agonists (e.g., clonidine), beta-blockers, and an agonist of the GABA-B receptor (e.g., baclofen) may also attenuate the symptoms of withdrawal. Since these all have limited evidence of their efficacy and have potential for harm, such as masking symptoms of progressive withdrawal and lowering seizure threshold, these agents are not routinely recommended for use. Valproic acid/divalproex, levetiracetam, topiramate, and zonisamide have also showed some efficacy in reducing symptoms of alcohol withdrawal in limited studies. The data on prevention of withdrawal seizures or delirium tremens when used as monotherapy is less robust.12


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