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

Abstract

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.

Astrocytic GABAergic Regulation in Alcohol Use and Major Depressive Disorders

“…Most effective when implemented following the commencement of abstinence to maintain it, with its optimal performance likely observed in individuals with a track record of more intense alcohol withdrawal symptoms. [139,140,[150][151][152][153]…”

Helpful or Harmful? The Therapeutic Potential of Medications with Varying Degrees of Abuse Liability in the Treatment of Substance Use Disorders

“…These effects were sustained at the study’s Week 24 follow-up encounter [ 24 ]. Similarly, a more recent study of 40 participants with AUD found that high-dose gabapentin (3600 mg/day) was associated with decreased number of heavy drinking days ( p = 0.002) and increased percentage of days abstinent ( p = 0.004) [ 25 ].…”

“…However, to date, there has been no published data about related deaths when used for treatment of AUD. Clinical trials have had limited adverse events, with instances of abnormal cravings and abuse rare and limited to patients with co-occurring psychiatric conditions [ 39 , 43 ], and these may constitute risk factors for craving and abuse of GHB [ 25 ].…”

Pilot RCT comparing low-dose naltrexone, gabapentin and placebo to reduce pain among people with HIV with alcohol problems

“…It is licensed to treat post-herpetic neuralgia and seizures, but is more broadly used as an alternative for opioid medications despite lack of evidence of effectiveness for chronic pain in general, which is most often musculoskeletal in nature [ 29 ]. Like naltrexone, gabapentin also has demonstrated effectiveness for AUDs in some studies [ 30 , 31 ].…”