Original Research

Gabapentin Use in Acute Alcohol Withdrawal Management

Gabapentin’s anxiolytic and sedative properties along with its overall safety profile suggest that it may be a viable adjuvant to lorazepam in the management of acute alcohol withdrawal.

Fed Pract. 2018 March;35(3):40-45

Author(s):

Christopher Wilming, PharmD

Mariah Alford, PharmD

Lynnette Klaus, PharmD, BCPS

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References

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8. U.S. Department of Veteran Affairs, U.S. Department of Defense. VA/DoD clinical practice guideline for the management of substance use disorders. https://www.healthquality.va.gov/guidelines/MH/sud/VADODSUDCPGRevised22216.pdf. Published December 2015. Accessed January 10, 2018.

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The prevalence of alcohol dependence in the U.S. represents a significant public health concern. Alcohol use disorder (AUD) is estimated to affect 6.7% of Americans and is the fourth leading preventable cause of death.¹ Men and women who have served in the military are at an even higher risk of excessive alcohol use. More than 20% of service members report binge drinking every week.²This risk is further exacerbated in veterans who have experienced active combat or who have comorbid health conditions, such as posttraumatic stress disorder.³

Background

Individuals that regularly consume excessive amounts of alcohol can develop acute alcohol withdrawal syndrome (AWS) after abrupt discontinuation or significant reduction of alcohol intake. Patients admitted for acute alcohol withdrawal may experience complicated courses of treatment and extended lengths of hospitalization.^4,5Cessation from chronic alcohol intake elicits a pathophysiologic response from increased N-methyl-d-aspartate receptor activity and decreased γ-aminobutyric acid (GABA) receptor function.

Autonomic and psychomotor hyperactivity disturbances, such as anxiety, nausea, tremors, diaphoresis, and tachycardia, may occur as early as 6 to 8 hours after cessation of use. Within 48 to 72 hours of alcohol cessation, patients may be at an increased risk of experiencing tonic-clonic seizures, visual and auditory hallucinations, and delirium tremens (DTs), which may be accompanied by signs of extreme autonomic hyperactivity and agitation.⁶ Patients hospitalized within acute settings require frequent medical supervision for acute alcohol withdrawal, especially in patients at high risk for seizure or DTs because morbidity and mortality risk is increased.⁷

Benzodiazepines remain the standard of care for management of moderate-to-severe symptoms of AWS. Strong evidence supports the use of benzodiazepines to reduce withdrawal severity, incidence of delirium, and seizures in AWS by enhancing GABA activity.⁸ However, the adverse effect (AE) burden associated with benzodiazepines can be a major limitation throughout care. Benzodiazepines also may be limited in their use in select patient populations, such as in older adults or patients who present with hepatic dysfunction due to the risk of increased AEs or metabolite accumulation.⁶ A high dosing requirement of benzodiazepine for symptom management can lead to oversedation to the point of requiring intubation, increasing length of stay in the intensive care unit (ICU), and the risk of nosocomial infections.⁹

Anticonvulsants, such as carbamazepine, valproic acid, and gabapentin, have shown to be superior to placebo and equal in efficacy to benzodiazepines for symptom management in mild-to-moderate alcohol withdrawal in both inpatient and outpatient settings.^6-8 However, these agents are not recommended as first-line monotherapy due to the limited number of randomized trials supporting their efficacy over benzodiazepines in preventing severe symptoms of withdrawal, such as seizures or delirium.^10-12 Nonetheless, the mechanism of action of anticonvulsants may help raise seizure threshold in patients and provide a benzodiazepine-sparing effect by enhancing GABAergic activity and lowering neuronal excitability.¹³

Gabapentin makes an attractive agent for clinical use because of its anxiolytic and sedative properties that can be used to potentially target symptoms analogous with AWS when the use of benzodiazepines becomes a safety concern. Although similar in chemical structure, gabapentin is not metabolized to GABA and does not directly interact with the receptor. Gabapentin may increase GABA concentrations by direct synthesis of GABA and indirectly through interaction with voltage-gated calcium channels.¹³ In addition to its overall safety profile, gabapentin may be a viable adjuvant because emerging data may suggest a potential role in the management of acute alcohol withdrawal.^12,14,15

Gabapentin for Alcohol Withdrawal at VAPORHCS

Although not currently included in the alcohol withdrawal protocol at Veterans Affairs Portland Health Care System (VAPORHCS), gabapentin has been added to the standard of care in select patients per the discretion of the attending physician. Anecdotal reports of patients experiencing milder symptoms and less benzodiazepine administration have facilitated use of gabapentin in alcohol withdrawal management at VAPORHCS. However, routine use of gabapentin is not consistent among all patients treated for acute alcohol withdrawal, and dosing schedules of gabapentin seem highly variable. Standard symptom management for acute alcohol withdrawal should be consistent for all affected individuals, using evidence-based medicine in order to achieve optimal outcomes and improve harm reduction.

The objective of this quality assurance/quality improvement (QA/QI) project was to assess the amount of lorazepam required for symptom management in acute alcohol withdrawal when gabapentin is used as an adjunct to treatment and to evaluate the impact on symptom management using the Clinical Institute Withdrawal Assessment for Alcohol scale, revised version (CIWA-Ar) in patients admitted to the ICU and general medicine wards for acute alcohol withdrawal at VAPORHCS.¹⁶ If a possible adjunct for the treatment of alcohol withdrawal has the potential to reduce benzodiazepine requirements and minimize AEs, a thorough evaluation of the treatment should be conducted before its practice is incorporated into the current standard of care.