Treatment of alcohol withdrawal with gabapentin

doi:10.1016/S0278-5846(01)00234-2

Progress in Neuro-Psychopharmacology and Biological Psychiatry

Volume 26, Issue 1, January 2002, Pages 197-199

https://doi.org/10.1016/S0278-5846(01)00234-2 Get rights and content

Abstract

Gabapentin is an anticonvulsant agent, also effective in the treatment of mood disorders and anxiety disorders. Three cases of alcohol withdrawal treated with gabapentin are presented. All patients received gabapentin 400 mg tid for 3 days, 400 mg bid for 1 day, and finally 400 mg for 1 day. Withdrawal symptoms subsided and no adverse effects were observed. The possible effectiveness of gabapentin in the treatment of alcohol withdrawal warrants further investigation by systematic and well-designed studies.

Introduction

Gabapentin is a second-generation anticonvulsant, which does not bind to GABA_A or GABA_B receptors and does not interact with those sites affected by benzodiazepines. This drug binds α2δ-subunit of L-type calcium channels and increases the synthesis and nonsynaptic release of GABA in the brain (Kelly, 1998). In psychiatry, gabapentin is used mainly as an adjunctive to previous treatment-resistant patients suffering from bipolar disorder Erfurth et al., 1998, Knoll et al., 1998, Cabras et al., 1999, Perugi et al., 1999, Young et al., 1999. There are reports that it has also anxiolytic effects and that it can be successfully applied in anxiety disorder, e.g., in social phobia and generalized anxiety disorder Pollack et al., 1998, Pande et al., 1999. Gabapentin demonstrated a selective action in decreasing both convulsive and anxiety-related aspects of withdrawal behaviour in mice after chronic ethanol treatment in doses that had no sedative or ataxic effect on animals (Watson et al., 1997). Myrick et al. (1998) reported the effective use of gabapentin as monotherapy in the treatment of alcohol withdrawal in six outpatients. Also, the drug had beneficial effects in the treatment of moderate alcohol withdrawal in four inpatients in an add-on fashion to clomethiazole, although two of them did not need any adjunctive medication and in three of them gabapentin led to a radical reduction in clomethiazole administration compared with previous detoxifications (Bonnet et al., 1999).

In this paper, three cases of alcohol withdrawal treated with gabapentin are presented.

Section snippets

Case 1

Mr. A. is a 32-year-old, single, unemployed man with a type B alcohol dependence. He is described as introverted and emotionally restricted, has no close relationships, and avoids making a family. His history of alcohol consumption combined with occasional use of cannabis started when he was 14 years old. By the age of 23 and for the next 2 1/2 years, the patient showed only opioid dependence. Afterwards, he restarted the daily consumption of enormous quantities of alcohol, together with

Discussion

Chlordiazepoxide and diazepam are the standard therapy for alcohol withdrawal. The effectiveness of benzodiazepines is based on their pharmacologic cross-tolerance with ethanol for GABA_A receptors (Hyman et al., 1995). Carbamazepine was found to be an effective and safe alternative to benzodiazepine treatment for alcohol withdrawal, probably through an antikindling effect (Malcolm et al., 1989). A study of valproate has also been performed, but without conclusive results (Rosenthal et al., 1998)

Conclusion

Taken together, these preliminary data suggest that the possible effectiveness of gabapentin in the treatment of alcohol withdrawal warrants further investigation by systematic and well-designed studies.

References (17)

A. Erfurth et al.
An open label study of gabapentin in the treatment of acute mania
J. Psychiatr. Res.
(1998)
J. Knoll et al.
Clinical experience using gabapentin adjunctively in patients with history of mania or hypomania
J. Affective Disord.
(1998)
W.P. Watson et al.
The novel anticonvulsant, gabapentin, protects against both convulsant and anxiogenic aspects of the ethanol withdrawal syndrome
Neuropharmacology
(1997)
U. Bonnet et al.
Treatment of alcohol syndrome with gabapentin
Pharmacopsychiatry
(1999)
P.L. Cabras et al.
Clinical experience with gabapentin in patients with bipolar or schizoaffective disorder: results of an open-label study
J. Clin. Psychiatry
(1999)
T. Heffner
Preclinical models of anxiety: profile of gabapentin
S.E. Hyman et al.
Handbook of Psychiatric Drug Therapy
(1995)
K.M. Kelly
Gabapentin: antiepileptic mechanism of action
Neuropsychobiology
(1998)

There are more references available in the full text version of this article.

Cited by (74)

Novel Algorithms for the Prophylaxis and Management of Alcohol Withdrawal Syndromes–Beyond Benzodiazepines
2017, Critical Care Clinics
Citation Excerpt :
GAB has performed as well as barbiturates148 and BZDP, with subjects experiencing less craving, anxiety, and sedation.149 Clinical data supporting the use of GAB in the management of AWS are summarized in Table 5.139,150–152 Both lamotrigine and topiramate significantly reduced observer-rated and self-rated withdrawal severity, dysphoric mood, and supplementary diazepam administration when compared with placebo, and were as effective as diazepam.153
Withdrawal Seizures
2017, Models of Seizures and Epilepsy: Second Edition
Seizures induced by withdrawal from substances of abuse (i.e., withdrawal-induced seizures) are rooted in pharmacological dependence and often occur in individuals with no previous history of seizures. In the vast majority of reported cases, the seizures are caused by withdrawal from alcohol, benzodiazepines, barbiturates, and other sedatives. Withdrawal after chronic use of opioids can also cause seizures. However, withdrawal from the use of stimulants may not directly cause seizures. This chapter describes the procedures for inducing substance of abuse dependence, precipitating withdrawal, eliciting seizures, and discusses the results with respect to the pathophysiology of withdrawal seizures in rodent models.
Treatment-refractory substance use disorder: Focus on alcohol, opioids, and cocaine
2016, Progress in Neuro-Psychopharmacology and Biological Psychiatry
Citation Excerpt :
Gabapentin is used and approved for the treatment of epilepsy and neuropathic pain. The drug inhibits presynaptic voltage-gated Na+ and Ca2 + channels (Rogawski and Loscher, 2004) and prevents the release of various neurotransmitters, including glutamate (Bonnet et al., 1999; Bozikas et al., 2002; Myrick et al., 1998; Rustembegovic et al., 2004; Watson et al., 1997). It may reduce CNS hyperexcitability and anxiety during alcohol withdrawal (Watson et al., 1997).
Substance use disorders are common, but only a small minority of patients receive adequate treatment. Although psychosocial therapies are effective, relapse is common. This review focusses on novel pharmacological and other treatments for patients with alcohol, opioid, or cocaine use disorders who do not respond to conventional treatments.
Disulfiram, acamprosate, and the opioid antagonist naltrexone have been approved for the treatment of alcoholism. A novel, “as needed” approach is the use of the mu-opioid antagonist and partial kappa agonist nalmefene to reduce alcohol consumption. Other novel pharmacological approaches include the GABA-B receptor agonist baclofen, anticonvulsants such as topiramate and gabapentin, the partial nicotine receptor agonist varenicline, and other drugs. For opioid dependence, opioid agonist therapy with methadone or buprenorphine is the first-line treatment option. Other options include oral or depot naltrexone, morphine sulfate, depot or implant formulations, and heroin (diacetylmorphine) in treatment-refractory patients. To date, no pharmacological treatment has been approved for cocaine addiction; however, 3 potential pharmacological treatments are being studied, disulfiram, methylphenidate, and modafinil. Pharmacogenetic approaches may help to optimize treatment response in otherwise treatment-refractory patients and to identify which patients are more likely to respond to treatment, and neuromodulation techniques such as repeated transcranial magnetic stimulation and deep brain stimulation also may play a role in the treatment of substance use disorders.
Although no magic bullet is in sight for treatment-refractory patients, some novel medications and brain stimulation techniques have the potential to enrich treatment options at least for some patients.
Glutamatergic medications for the treatment of drug and behavioral addictions
2012, Pharmacology Biochemistry and Behavior
Citation Excerpt :
Gabapentin also acts on calcium channels containing a2d-1 subunits to block the ability of thrombospondin released from glial cells to promote excitatory synapse formation (Eroglu et al. 2009). Numerous studies have shown that gabapentin is efficacious in alleviating the somatic symptoms of alcohol withdrawal (Bonnet et al., 1999; Bozikas et al., 2002; Mariani et al., 2006; Martinez-Raga et al., 2004; Myrick et al., 1998; Rustembegovic et al., 2004; Voris et al., 2003), which often presents with moderate to severe CNS hyperexcitability and convulsions. Gabapentin has also been shown to be superior to the benzodiazepine lorazepam in reducing sleep disturbances associated with alcohol withdrawal (Malcolm et al., 2007).
Historically, most pharmacological approaches to the treatment of addictive disorders have utilized either substitution-based methods (i.e., nicotine replacement or opioid maintenance) or have targeted monoaminergic or endogenous opioidergic neurotransmitter systems. However, substantial evidence has accumulated indicating that ligands acting on glutamatergic transmission are also of potential utility in the treatment of drug addiction, as well as various behavioral addictions such as pathological gambling. The purpose of this review is to summarize the pharmacological mechanisms of action and general clinical efficacy of glutamatergic medications that are currently approved or are being investigated for approval for the treatment of addictive disorders. Medications with effects on glutamatergic transmission that will be discussed include acamprosate, N-acetylcysteine, d-cycloserine, gabapentin, lamotrigine, memantine, modafinil, and topiramate. We conclude that manipulation of glutamatergic neurotransmission is a relatively young but promising avenue for the development of improved therapeutic agents for the treatment of drug and behavioral addictions.
Comparative efficacy of various pharmacologic treatments for alcohol withdrawal syndrome: A systematic review and network meta-analysis
2024, International Clinical Psychopharmacology
Impact of Adjuvant Anticonvulsant Medications on Benzodiazepine Use and Delirium in Alcohol Withdrawal Syndrome
2021, Primary Care Companion for CNS Disorders

View all citing articles on Scopus

View full text

Treatment of alcohol withdrawal with gabapentin

Abstract

Introduction

Section snippets

Case 1

Discussion

Conclusion

J. Psychiatr. Res.

J. Affective Disord.

Neuropharmacology

Treatment of alcohol syndrome with gabapentin

Pharmacopsychiatry

Clinical experience with gabapentin in patients with bipolar or schizoaffective disorder: results of an open-label study

J. Clin. Psychiatry

Preclinical models of anxiety: profile of gabapentin

Handbook of Psychiatric Drug Therapy

Gabapentin: antiepileptic mechanism of action

Neuropsychobiology