In this episode, I’ll discuss an article about using gabapentin for severe alcohol withdrawal.
Article
Lead author: Alexander Levine
Published in the journal Pharmacotherapy July 2019
Background
Gabapentin has beneficial effects on treating patients with alcohol use disorder including:
-decreased cravings
-increased abstinence
-improved sleep
Whether gabapentin can be used successfully to treat alcohol withdrawal syndrome is less clear, although by its mechanism of action it is plausible to think that gabapentin would be beneficial in this setting as well.
The authors of this study sought to evaluate the impact of high‐dose gabapentin on benzodiazepine requirements, alcohol withdrawal symptoms, and hospital length of stay in patients hospitalized with alcohol withdrawal syndrome.
Methods
The study was a retrospective cohort of 50 adult patients who received high dose gabapentin for alcohol withdrawal syndrome and 50 propensity score matched patients who did not. High‐dose gabapentin was defined as ≥ 1800 mg/day in the first 48 hours of hospital admission.
Results
Patients who received high‐dose gabapentin required on average nearly 20% less benzodiazepines than did controls. The average in lorazepam equivalents was 88.5 mg in the gabapentin group vs 109.5 mg in controls and this difference was statistically significant.
The mean CIWA‐Ar score was also lower in the gabapentin group at 7.7 vs 10.1 in controls.
The apparent severity of withdrawal, as measured by the maximum CIWA-Ar score on day 3 of hospitalization was also lower in the gabapentin group.
The high‐dose gabapentin regimen did not demonstrate an increased risk of oversedation.
Patients receiving high‐dose gabapentin had a shorter length of hospital stay by 1.4 days on average and a 22% absolute increase in the likelihood of being discharged home.
Conclusion
The authors concluded:
Early initiation of high‐dose gabapentin was associated with a significant reduction in benzodiazepine exposure, faster stabilization of alcohol withdrawal–related symptoms, and shorter hospital length of stay. Future studies evaluating gabapentin’s effect on long‐term safety and hospital readmission are warranted.
Discussion
Because gabapentin’s mechanism of action fits the pathophysiology of alcohol withdrawal, many investigators have sought to test gabapentin for this condition.
Chronic ethanol use affects receptors in the brain in two ways:
1. Ethanol causes reduced sensitivity to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).
2. Ethanol inhibits the excitatory effects of glutamate at the N-methyl-D-aspartate (NMDA) receptor resulting in additional NMDA receptors being produced.
When ethanol withdrawal occurs the result is both a decreased ability to inhibit from reduced GABA sensitivity and an increased effect of glutamate from an increased number of NMDA receptors.
Gabapentin works independently of GABA receptors to inhibit the release of excitatory neurotransmitters such as glutamate. It is from this mechanism that gabapentin is thought to help normalize CNS tone in alcohol withdrawal.
The protocol for this study involved giving gabapentin 600 mg q8h. About a third of patients also got a loading dose of 800 mg. As a retrospective study, this research suggests that gabapentin can be used in alcohol withdrawal and points the way for future randomized trials to prove whether this is indeed an effective strategy.
Members of my Hospital Pharmacy Academy have access to over 85 in-depth, practical trainings including one on the treatment of severe alcohol withdrawal. To get immediate access to these and more resources to help you in your practice go to pharmacyjoe.com/academy.
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