Anticonvulsants for the Treatment of Alcohol Withdrawal Syndrome and Alcohol Use Disorders

Abstract

Alcoholic patients suffer from harmful allostatic neuroplastic changes in the brain causing an acute withdrawal syndrome upon cessation of drinking followed by a protracted abstinence syndrome and an increased risk of relapse to heavy drinking. Benzodiazepines have long been the treatment of choice for detoxifying patients and managing alcohol withdrawal syndrome (AWS). Non-benzodiazepine anticonvulsants (NBACs) are increasingly being used both for alcohol withdrawal management and for ongoing outpatient treatment of alcohol dependence, with the goal of either abstinence or harm reduction. This expert narrative review summarizes the scientific basis and clinical evidence supporting the use of NBACs in treating AWS and for reducing harmful drinking patterns. There is less evidence in support of NBAC therapy for AWS, with few placebo-controlled trials. Carbamazepine and gabapentin appear to be the most promising adjunctive treatments for AWS, and they may be useful as monotherapy in select cases, especially in outpatient settings and for the treatment of mild-to-moderate low-risk patients with the AWS. The body of evidence supporting the use of the NBACs for reducing harmful drinking in the outpatient setting is stronger. Topiramate appears to have a robust effect on reducing harmful drinking in alcoholics. Gabapentin is a potentially efficacious treatment for reducing the risk of relapse to harmful drinking patterns in outpatient management of alcoholism. Gabapentin's ease of use, rapid titration, good tolerability, and efficacy in both the withdrawal and chronic phases of treatment make it particularly appealing. In summary, several NBACs appear to be beneficial in treating AWS and alcohol use disorders.

A case of gait disturbance caused by low-dose gabapentin

“…Several studies report that combined use of gabapentin and benzodiazepine enhances the effects of medications used to treat alcoholism. 10 – 12 Based on the abovementioned reports, in the present case, the effects of low-dose gabapentin were enhanced by sodium valproate and flunitrazepam, leading to gait disturbances, despite the low dose of gabapentin. Hepner and Claxton 13 warned that combined use of gabapentin and anticonvulsants for pain therapy could worsen the side effects of these drugs.…”

The Role of Pharmacotherapy in the Treatment of Adolescent Substance Use Disorders

“…To date, FDA has approved four medications for the treatment of AUD in adults:

naltrexone (oral),

extended-release injectable naltrexone (XR-naltrexone) (intramuscular),

disulfiram, and

acamprosate.

Additionally, non-benzodiazepine anticonvulsants (NBACs), including gabapentin and topiramate, have emerged as potential pharmacotherapy options in adults. 40 There is limited safety and efficacy data available on these medications in adolescent samples.…”

“…While a number of NBACs are being studied for the treatment of AWS and AUD in adults 40 , benzodiazepines currently remain the first line pharmacotherapy for treatment of AWS. 43 Consensus guidelines suggest that adolescents with severe AUD who present with moderate to severe AWS should be treated with benzodiazepines in inpatient treatment settings.…”

“…56, 57 Topiramate has been shown to be efficacious for reducing heavy drinking and relapse to alcohol for AUD in adults in a number of RCTs and prospective longitudinal studies as described in a recent systematic review. 40 …”

High‐Dose Gabapentin for the Treatment of Severe Alcohol Withdrawal Syndrome: A Retrospective Cohort Analysis

“…Although benzodiazepines are effective at acutely managing symptoms, they can lead to respiratory depression, delirium, and oversedation . Several adjunctive therapies have been used in the management of AWS to decrease distressing symptoms of withdrawal, reduce unnecessary exposure to benzodiazepines, and prevent alcohol withdrawal–related complications . Gabapentin, which is believed to indirectly modulate GABA neurotransmission by blocking the α2δ subunit of voltage‐dependent calcium channels, is a potentially attractive adjunctive agent to use in this setting because it possesses sedative, anticonvulsant, and anxiolytic effects, and it is generally well tolerated .…”