Same receptor, only different: Gabapentin for acute alcohol withdrawal.

Hi friends! IM HEAT is proud to present our very first guest post, from the person who had the least ability to refuse: Bill’s wife, Risa Fuller. Risa is an internal medicine resident at Penn, and will be an infectious diseases fellow at Mt. Sinai next year.

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And now,

PRN Ativan gabapentin for CIWA >8

As internal medicine residents, we’ve all admitted our fair share of acute alcohol withdrawal. At Penn, where Bill and I train, practices include administration of lorazepam as needed based on the Clinical Institute Withdrawal Assessment for Alcohol (CIWA) score, while other places prefer scheduled tapers of long-acting benzodiazepines.  These tried-and-true practices work just fine to prevent and treat the tremors, hallucinations, and in extreme cases death associated with acute alcohol withdrawal, but benzodiazepines do have a dark side. For starters, they potentiate the depressant effects of alcohol. Both benzos and alcohol are downers, and, when combined, they can bring someone at risk way, way down. Benzos also have strong abuse potential and high street value. Lastly, similar to alcohol, benzo overdose can result in death, as can withdrawal. In the controlled inpatient setting this isn’t always a huge deal because we have the luxury of watching the patient, controlling and overseeing every miligram of Ativan administered. But what about management of alcohol withdrawal in the outpatient setting? And what about that guy in the throes of alcohol withdrawal who insists on leaving AMA?

Enter: gabapentin. A 2015 metanalysis in the Annals of Pharmacotherapy by Jonathan Leung and colleagues reviews an impressive number of recent studies and trials on the use of gabapentin for alcohol withdrawal syndrome. To understand why gabapentin was considered, we must take a quick detour to understand alcohol withdrawal. Alcohol withdrawal syndrome is essentially the result of an imbalance of two hormones in the brain: GABA goes down, and N-methyl-d-aspartate glutamate activity goes up. Benzos work by enhancing GABA activity, restoring the balance. Gabapentin, as its name suggests, also increases GABA activity (though through a different mechanism). Unlike benzos, gabapentin has lower abuse potential and is not lethal in overdose. Sounds great on paper (“So does communism” – Bill). But how does it stack up?

The metanalysis included too many studies to review here, so I’ll just hit some of the highlights. First, a prospective observational study in which 800mg of gabapentin was given to 37 individuals with severe alcohol withdrawal syndrome (CIWA >15). Twenty-seven of these patients had significant reductions in CIWA. These patients were deemed “early responders” and were treated with tapering doses of gabapentin for the remainder of the study with good outcomes. The “non-responders” were treated with usual care (benzos) and did fine too. Interestingly, the authors noted that these non-responders had higher CIWA scores initially (>20) and more anxiety/depression from the start, which may help us understand which patients may be more likely to respond to gabapentin.

Next we have a double-blind randomized controlled trial that took place in the outpatient setting. This study included 100 individuals with alcohol withdrawal randomized to 4 groups: 600mg gabapentin, 900mg gabapentin, 1200mg gabapentin, or 6mg Ativan. These doses were gradually tapered over several days, and rescue medications (as-needed Ativan) were available to all groups. There was no difference in the use of rescue medications between the groups, and the 1200mg gabapentin group had statistically significant lower CIWA scores than the Ativan group (P= 0.009). They also discovered that the Ativan group was more likely to return to heavy drinking after the study was complete (P= 0.009). Overall, they concluded that gabapentin was superior to Ativan in an outpatient fixed dose scheme for alcohol withdrawal syndrome.

It’s important to note that all the studies reviewed had quite small sample sizes with high dropout rates, though the authors do state that these dropout rates are typical for studies on alcohol withdrawal syndrome. Three studies in the paper reported 5 adverse events in gabapentin groups, all of which were seizures or seizure-like activity. This likely represents an underdosing of gabapentin in those situations resulting in seizures from alcohol withdrawal.

Bottom line, gabapentin should certainly be considered for acute alcohol withdrawal syndrome over benzos, especially in the outpatient setting, as it has lower abuse potential, is non-habit forming, and does not enhance the depressant effects of alcohol as benzos do. Still, larger prospective RCTs are probably needed before institutions will be willing to change long standing policy, especially given concern for under dosing in the trials to date. In the meantime, suggest to your attending that you give 1200mg of gabapentin to your withdrawal patient with a CIWA of 15, and observe closely how there are now TWO people desperate for a dose of Ativan instead of one.

Read the study here.

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