Efficacy of Gabapentin for the Treatment of Alcohol Use Disorder in Patients With Alcohol Withdrawal Symptoms

Abstract

IMPORTANCEAlthough an estimated 30 million people meet criteria for alcohol use disorder (AUD), few receive appropriate pharmacotherapy. A more personalized, symptom-specific, approach might improve efficacy and acceptance.OBJECTIVE To examine whether gabapentin would be useful in the treatment of AUD, especially in those with the most alcohol withdrawal symptoms. DESIGN, SETTING, AND PARTICIPANTSThis double-blind randomized clinical trial conducted between November 2014 and June 2018 evaluated gabapentin vs placebo in community-recruited participants screened and treated in an academic outpatient setting over a 16-week treatment period. A total of 145 treatment-seeking individuals who met Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria for AUD and were not receiving other AUD intervention were screened, and 96 who also met recent alcohol withdrawal criteria were randomized to treatment after 3 abstinent days. Daily drinking was recorded, and percentage of disialo carbohydrate-deficient transferrin in the blood, a heavy drinking marker, was collected at baseline and monthly during treatment.INTERVENTIONS Gabapentin up to 1200 mg/d, orally, vs placebo along with 9 medical management visits (20 minutes each). MAIN OUTCOMES AND MEASURESThe percentage of individuals with no heavy drinking days and those with total abstinence were compared between treatment groups and further evaluated based on prestudy alcohol withdrawal symptoms. RESULTSOf 96 randomized individuals, 90 were evaluable (44 in the gabapentin arm and 46 in the placebo arm), with a mean (SD) age of 49.6 (10.1) years; 69 were men (77%) and 85 were white (94%). The evaluable participants had 83% baseline heavy drinking days (4 or more drinks/day for women, 5 or more for men) and met 4.5 alcohol withdrawal criteria from the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). More gabapentin-treated individuals had no heavy drinking days (12 of 44 participants [27%]) compared with placebo (4 of 46 participants [9%]), a difference of 18.6% (95% CI, 3.1-34.1; P = .02; number needed to treat [NNT], 5.4), and more total abstinence (8 of 44 [18%]) compared with placebo (2 of 46 [4%]), a difference of 13.8% (95% CI, 1.0-26.7; P = .04; NNT, 6.2). The prestudy high-alcohol withdrawal group had positive gabapentin effects on no heavy drinking days (P < .02; NNT, 3.1) and total abstinence (P = .003; NNT, 2.7) compared with placebo, while within the low-alcohol withdrawal group, there were no significant differences. These findings were similar for other drinking variables, where gabapentin was more efficacious than placebo in the high-alcohol withdrawal group only. Gabapentin caused more dizziness, but this did not affect efficacy.CONCLUSIONS AND RELEVANCE These data, combined with others, suggest gabapentin might be most efficacious in people with AUD and a history of alcohol withdrawal symptoms. Future studies should evaluate sleep changes and mood during early recovery as mediators of gabapentin efficacy.

Safety of Gabapentin Prescribed for Any Indication in a Large Clinical Cohort of 571,718 US Veterans with and without Alcohol Use Disorder

“…Similarly, we found less than 10% excess risk (not statistically significant) of adverse events associated with gabapentin exposure among patients with current AUD. However, a recent randomized controlled trial examining the efficacy of gabapentin on AUD treatment outcomes among 90 patients with alcohol withdrawal symptoms found significantly more reports of mild to moderate dizziness in those receiving gabapentin versus placebo (n = 25 vs. n = 15; p = 0.02) (Anton et al, 2020). Additionally, a multisite clinical trial evaluating the safety and efficacy of gabapentin enacarbil extended-release (GE-XR) in 346 participants with moderate to severe AUD reported no serious adverse events related to medication use, but did find significantly greater rates of fatigue (25.9% vs. 15.5%; p = 0.022), somnolence (17.6% vs 9.5%; p = 0.038), and tremor (5.9% vs. 0.6%; p = 0.010), as well as a nonsignificant increase for dizziness (21.2% vs. 13.7%; p = 0.085) in the GE-XR group versus placebo group (Falk et al, 2019).…”

“…Compared to overall rates, we found that patients with current AUD had greater rates of neurologic adverse events regardless of gabapentin exposure, suggesting that these patients represent a particularly vulnerable population at risk for falls, fractures, and altered mental status. Given the growing body of evidence supporting gabapentin's safety and efficacy in treating AUD (Anton et al, 2020;Kranzler et al, 2019;Mason et al, 2014), these baseline risks among individuals with current AUD should be considered alongside the potential benefits gabapentin treatment in this population. Among trials that found significantly greater rates of adverse events among gabapentin-exposed patients, these events were reported as mild to moderate (Anton et al, 2020;Falk et al, 2019;Pani et al, 2014).…”

“…Given the growing body of evidence supporting gabapentin's safety and efficacy in treating AUD (Anton et al, 2020;Kranzler et al, 2019;Mason et al, 2014), these baseline risks among individuals with current AUD should be considered alongside the potential benefits gabapentin treatment in this population. Among trials that found significantly greater rates of adverse events among gabapentin-exposed patients, these events were reported as mild to moderate (Anton et al, 2020;Falk et al, 2019;Pani et al, 2014). Furthermore, Anton and colleagues (2020) reported significantly more dizziness in those receiving gabapentin versus placebo, but the presence or absence of dizziness did not significantly account for gabapentin's effectiveness.…”

“…The widespread prescribing of gabapentin for various conditions, which contrasts with the limited use of FDA-approved medications for AUD, suggests that clinicians are familiar with gabapentin and may feel more comfortable prescribing it for AUD treatment. Such comfort with prescribing gabapentin paired with growing evidence to support its efficacy in treating AUD (Anton et al, 2020;Kranzler et al, 2019;Mason et al, 2014;Pani et al, 2014) may help expand the number of individuals with AUD receiving effective medication treatment. However, these possible benefits must be weighed against potential risks.…”

Alcohol Addiction, Gut Microbiota, and Alcoholism Treatment: A Review

“…The mechanism and effect of calcium carbimide are similar to disulfiram [ 48 ]. Topiramate, used to treat epilepsy and prevent migraines, is supported to treat alcohol-related illnesses, and gabapentin, also used to treat epilepsy, is supported to treat alcohol withdrawal [ 49 , 50 ].…”