Association Between Gabapentin Receipt for Any Indication and Alcohol Use Disorders Identification Test—Consumption Scores Among Clinical Subpopulations With and Without Alcohol Use Disorder

Rentsch, Christopher T; Fiellin, David A.; Bryant, Kendall; Justice, Amy C.; Tate, Janet P.

doi:10.1111/acer.13953

Cited by 13 publications

(8 citation statements)

References 66 publications

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“…Because such efforts require large samples of patients treated with a specific medication, the time and expense for which can be prohibitive, an electronic health record approach may be required. Such an approach was used to examine the effects of gabapentin on alcohol consumption using repeated measurements of the Alcohol Use Disorders Identification Test-Consumption score [ 30 ]. This approach could be paired with genome-wide genotype data in a sample such as that in the Million Veteran Program [ 31 ] to identify variants, which could be tested individually or as polygenic risk scores in prospective RCTs.…”

Section: Discussionmentioning

confidence: 99%

Prospective randomized pharmacogenetic study of topiramate for treating alcohol use disorder

Kranzler

Morris

Pond

et al. 2021

Neuropsychopharmacol.

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In a prior study, topiramate reduced heavy drinking among individuals who sought to reduce their drinking, with the effect moderated by a single nucleotide polymorphism (SNP; rs2832407) in GRIK1, which encodes the kainate GluK1 receptor subunit (Kranzler et al. 2014). The present study sought to replicate prospectively the effect of topiramate and rs2832407 in patients with DSM-5 alcohol use disorder (AUD) who sought to reduce or stop their drinking. We stratified the randomization on genotype (rs2832407*C-allele homozygotes vs. A-allele carriers) and assigned 170 European-American participants (71.2% male) to receive 12 weeks of treatment with topiramate (N = 85), at a maximal daily dosage of 200 mg, or matching placebo (N = 85). At each of nine treatment visits participants received brief counseling to reduce drinking and increase abstinent days. We hypothesized that topiramate-treated patients with the rs2832407*CC genotype would reduce heavy drinking days (HDDs) more than the other three groups. The rate of treatment completion was 91.8% in both groups. The mean number of HDDs per week in the placebo group was 1.67 (95% CI = (1.29, 2.16), p = 0.0001) times greater than in the topiramate group, which was confirmed by the topiramate group’s significantly greater reduction in the concentration of the liver enzyme γ-glutamyltransferase and lower alcohol-related problems score. There was no significant difference in topiramate’s effect on HDDs between genotype groups. Although consistent with other studies showing a reduction in heavy drinking with topiramate treatment, the prior finding of a moderating effect of rs2832407 genotype was not replicated in this prospective trial.

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Section: Discussionmentioning

confidence: 99%

Prospective randomized pharmacogenetic study of topiramate for treating alcohol use disorder

Kranzler

Morris

Pond

et al. 2021

Neuropsychopharmacol.

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“…This study reported increased risk of adverse outcomes starting at gabapentin doses of ≥ 1,800 mg/d, whereas we demonstrated increased risk at lower doses of ≥ 600 mg/d. These findings are particularly relevant when considering the use of gabapentin to treat AUD, as current evidence suggests greater impact of gabapentin on reducing alcohol consumption at higher doses of ≥ 1,500 mg/d (Mason et al, 2014;Rentsch et al, 2019). However, it is important to note that gabapentin has been shown to improve AUD outcomes even at doses as low as 900 mg/d (Mason et al, 2014), which may reduce the risk of adverse consequences.…”

Section: Discussionmentioning

confidence: 92%

“…Given the widespread prescribing of gabapentin and its potential utility in decreasing alcohol consumption among treatment-seeking and non-treatment-seeking populations (Rentsch et al, 2019), we sought to determine its association with events often linked with neurologic effects of dizziness, ataxia, and somnolence among patients receiving gabapentin for any indication, specifically falls or fractures (Ishida et al, 2018) and altered mental status. We further assessed whether these effects differed in demographic and clinical subpopulations at higher risk for these events, including patients with and without HCV, HIV, and AUD.…”

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confidence: 99%

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

Rentsch

Morford

Fiellin

et al. 2020

Alcoholism Clin & Exp Res

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Background Gabapentin is prescribed for seizures and pain and has efficacy for treating alcohol use disorder (AUD) starting at doses of 900 milligrams per day (mg/d). Recent evidence suggests safety concerns associated with gabapentin including adverse neurologic effects. Individuals with hepatitis C (HCV), HIV, or AUD may be at increased risk due to comorbidities and potential medication interactions. Methods We identified patients prescribed gabapentin for ≥ 60 days for any indication between 2002 and 2015. We propensity‐score matched each gabapentin‐exposed patient with up to 5 gabapentin‐unexposed patients. We followed patients for 2 years or until diagnosed with (i) falls or fractures, or (ii) altered mental status using validated ICD‐9 diagnostic codes. We used Poisson regression to estimate incidence rates and relative risk (RR) of these adverse events in association with gabapentin exposure overall and stratified by age, race/ethnicity, sex, HCV, HIV, AUD, and dose. Results Incidence of falls or fractures was 1.81 per 100 person‐years (PY) among 140,310 gabapentin‐exposed and 1.34/100 PY among 431,408 gabapentin‐unexposed patients (RR 1.35, 95% confidence interval [CI] 1.28 to 1.44). Incidence of altered mental status was 1.08/100 PY among exposed and 0.97/100 PY among unexposed patients, RR of 1.12 (95% CI 1.04 to 1.20). Excess risk of falls or fractures associated with gabapentin exposure was observed in all subgroups except patients with HCV, HIV, or AUD; however, these groups had elevated incidence regardless of exposure. There was a clear dose–response relationship for falls or fractures with highest risk observed among those prescribed ≥ 2,400 mg/d (RR 1.90, 95% CI 1.50 to 2.40). Patients were at increased risk for altered mental status at doses 600 to 2,399 mg/d; however, low number of events in the highest dose category limited power to detect a statistically significant association ≥ 2,400 mg/d. Conclusions Gabapentin is associated with falls or fractures and altered mental status. Clinicians should be monitoring gabapentin safety, especially at doses ≥ 600 mg/d, in patients with and without AUD.

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“…Gabapentin has been shown to be effective for AUD in doses up to 1800 mg (Mason et al, 2014) and 1200 mg (Anton et al, 2020), but an extended‐release formulation of gabapentin, with lower bioavailability, was not shown to be effective at a dose of 1200 mg/day (Falk et al, 2019). Large‐scale retrospective studies of gabapentin effects on alcohol consumption have shown benefit (Rentsch et al, 2019), but also the potential for harms (Rentsch et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Pilot randomized placebo‐controlled clinical trial of high‐dose gabapentin for alcohol use disorder

Mariani

Pavlicová

Basaraba

et al. 2021

Alcoholism Clin & Exp Res

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Background Despite advances in the development of pharmacotherapy for alcohol use disorder (AUD), there remains a need for medications that can be administered to actively drinking outpatients to promote a reduction in harmful alcohol consumption. The primary aim of this pilot study was to determine whether high‐dose gabapentin (3600 mg/daily) is more effective than placebo in reducing harmful alcohol consumption in outpatients with AUD. Methods Forty patients (27 men) who met DSM‐IV‐TR criteria for alcohol dependence and reporting at least 4 heavy drinking days (HDD) per week were recruited at a single site. Participants were actively drinking at study entry and received double‐blind gabapentin (3600 mg/day; n = 19) or placebo (n = 20) for 8 weeks. Study medication was titrated over 5 days and administered in three divided doses (1200 mg three times per day). The proportion of HDD (primary outcome) and percent days abstinent (PDA; secondary outcome) were analyzed using generalized longitudinal mixed models with the predictors being study arm, week, study arm by week interaction, and corresponding baseline drinking measure. Results There was a significant interaction between study arm and week for the proportion of HDD per week, F (7, 215) = 3.33, p = 0.002 . There was also a significant interaction between study arm and week for PDA per week, F (7, 215) = 3.11, p = 0.004. The overall retention rate was 67.5% with no significant difference in time‐to‐dropout between treatment groups. There were no serious adverse events. No participants were removed from the trial due to the development of moderate‐to‐severe alcohol withdrawal (CIWA‐Ar ≥ 13). Conclusions Gabapentin treatment rapidly titrated to a dosage of 3600 mg/day is associated with a reduction in the proportion of HDD per week and an increase in PDA per week in actively drinking outpatients with AUD. High‐dose gabapentin is potentially a feasible approach to treating AUD and deserving of further study.

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Association Between Gabapentin Receipt for Any Indication and Alcohol Use Disorders Identification Test—Consumption Scores Among Clinical Subpopulations With and Without Alcohol Use Disorder

Cited by 13 publications

References 66 publications

Prospective randomized pharmacogenetic study of topiramate for treating alcohol use disorder

Prospective randomized pharmacogenetic study of topiramate for treating alcohol use disorder

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

Pilot randomized placebo‐controlled clinical trial of high‐dose gabapentin for alcohol use disorder

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