Alcoholism and Gabapentin Treatment

Abstract

Gabapentin was designed as a GABA analog. Currently, used for its antiepileptic and analgesic properties, most likely antagonizes high-voltage-gated calcium channels. It is also proposed that gabapentin enhances inhibitory input of GABA-mediated pathways (e.g., reducing excitatory input) and antagonizes NMDA receptors and now recently being investigated for its treatment in abstinence from alcohol dependence disorder.

We report a case of an adult with alcohol use disorder (AUD) with major depressive disorder, narcissistic personality disorder, bipolar disorder, PTSD and anxiety whom has relapsed multiple times on alcohol trying to maintain abstinence. This gentleman has demonstrated sustained remission of alcoholic cravings and symptoms when exposed to gabapentin in the context of inpatient hospitalization. We review the scarce literature on the use of gabapentin for abstinence from alcohol in adults. This case demonstrates that gabapentin should be explored as a potential treatment option for adults with severe relapses of their alcohol dependence.

Keywords:

gabapentin, alcohol use disorder, alcoholism, anticonvulsant

Introduction

Alcohol use contributes to a significant problem of morbidity and mortality, not just in the United States but worldwide.

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It is estimated by the World Health Organization (WHO) that approximately six percent of deaths globally can be attributed to alcohol.

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Alcohol use is present across all medical specialties, with alcohol-related deaths, particularly associated with injury, cancer, cardiovascular disease, and liver cirrhosis; however, the implementation of medications remains limited.

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Gabapentin, a GABA-analog, with antagonistic properties at high-voltage-activated calcium channels has long been used for treatment of focal seizures and neuropathic pain; however, is now recently been investigated for its effects on alcoholic use disorder. Preclinical studies have found that gabapentin normalizes the stress-induced GABA activation in the amygdala that is associated with alcohol dependence and provides rational to investigate it as a treatment for alcohol dependence.

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Clinical studies have found that gabapentin has reduced cravings and sleep disturbance in patients with heavy alcohol use.

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Thus, gabapentin’s low abuse potential, favorable side effect profile and virtually no metabolism by the liver make its off label use an attractive option compared to benzodiazepines and other drugs.

Case Report

This patient is a 55-year-old-man with a psychiatric history significant for PTSD, major depressive disorder, bipolar disorder, schizophrenia spectrum disorder, substance use disorder, past suicide attempts and alcohol use disorder who has had severe episodes of emotional and behavioral outbursts involving his wife and family members. He presented to us with severe alcohol intoxication, suicidal ideation, disorganized organized and tangential thoughts, and responding to internal stimuli. He has experienced periods of sever anhedonia, often explained, as well as difficulty controlling his temper and dealing with stressful situations. Initial laboratory investigations included a CMP, a CBC, an alcohol breath test and a drug tox screen which was unremarkable except for a blood alcohol level of 0.17.

Review of this patient’s medical record has revealed a longstanding history of alcohol use. He currently has been drinking a pint or two of vodka 4 – 5 days per week for an unknown amount of time; however, he has never experienced major withdrawal symptoms such as seizures or delirium tremens, but states that he has a tremor and memory concerns.

When depressed, he would excessively drink and have anger surges. These severe outbursts, from alcohol, of aggression has led to a domestic assault charge, his wife asking for a divorce and a no-contact order, multiple DUI charges and his sister kicking him out of her home. Past medications and nonpharmacologic trials to address these problems included: antiepileptic drugs, antipsychotics, SNRIs, and SSRIs. None of these interventions had any substantial improvement in his recovery process. In the last one and a half years, he has required multiple chemical dependency treatments, some of which he never finished, inpatient mental health admissions due to his inability to be safe with his wife and family members at home and suicide ideation. Soon after his relapse, he became aggressive via punching holes in the walls and shooting his gun in the home.

On hospital stay day 1, the patient was agreeable to starting gabapentin (100 mg t.i.d) for anxiety along with naltrexone (25 mg) and trazadone (50 mg). In the following days, the patient’s dose of gabapentin was increased to 300 mg t.i.d. It was noted by the medical team that the intensity and frequent alcohol cravings and aggressive behaviors had lessened with the ability to control these cravings. The documentation showed that he mainly had major suicidality in the absence of alcoholic cravings and his emotions and behaviors did not escalate. During his time thus far, he has been able to talk about his life providing insight and therapeutic goals while on the inpatient psychiatric services, such as attaining help with finding a permanent residence and seeking long term treatment for alcohol use. Throughout his meetings with the medical team, he was able to speak and provide insight into his past about leading to his alcohol use disorder and make gains in his therapeutic goals.

Discussion

This case presents the opportunity to ponder current treatment for alcohol use disorder in a patient who has developed medical and social consequences of his drinking habits (i.e., legal issues with a divorce, multiple DUIs and MDD).

Currently, medications approved for AUD include the following: naltrexone, disulfiram and acamprosate.

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Also, there is off-labeled prescriptions, with less evidence but potential benefit, such as gabapentin, baclofen and topiramate.

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This case highlights the difficulties of prescribing pharmacological treatment, with the possibility of liver dysfunction and a severe mental health disorder, major depressive disorder. Given this situation, novel treatments are needed to prevent relapse of alcoholism to prevent future medical and social problems.

Naltrexone is an opioid antagonist and is thought to block endogenous opioids triggered by alcohol use.

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It has been shown to decrease the total number of drinking days; however, liver failure and acute hepatitis are contraindications for its use and must be used carefully in patients with liver dysfunction.

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Acamprosate is also currently approved for alcohol use disorder, most useful for maintaining abstinence, and thought to reducing cravings and/or relapse of heavy drinking.

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Also, this drug can be used in actively drinking individuals and those with liver disease.

Gabapentin, mostly used for its anticonvulsant and analgesic properties, is currently being delved into as a possible treatment for alcohol use disorder. Presently, there is not a significant amount of literature comparing it to naltrexone or acamprosate; however, in studies, it has been shown that gabapentin reduces alcoholic cravings and withdrawal symptoms, which may be beneficial to remaining abstinent.

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With its low risk of abuse and negligible side effects (favorable safety profile) gabapentin has gained support for alcohol withdrawal and dependence treatment.

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It is also not metabolized by the liver and therefore can be used in patients with liver dysfunction.

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The exact mechanism behind our patient’s sustained improvement from alcoholic cravings is unclear. It is hypothesized that the central nucleus of the amygdala (CeA) has an important role in the voluntary control of ethanol intake.

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Currently, activation of the CeA by gabapentin is thought to suppress alcohol-self administration by reducing a high-anxiety state that potentially drives excessive drinking in animal models.

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Therefore, gabapentin regulation of GABAergic neurotransmission, has potential to eradicate the high-anxiety behavior and thus normalize alcohol intake.

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Conclusion

Gabapentin is an effective FDA approved drug for the management of seizures and neuropathic pain. In conclusion, studies have found that gabapentin, specifically the 1800 mg dose

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, has been effective in the treatment of alcohol use disorder and in preventing relapse-associated symptoms such as cravings, mood and sleep disturbances. Gabapentin could be the preferred medication over benzodiazepines, a controlled and addictive substance, because of its low abuse potential, increased rates of abstinence, decreased number of heavy drinking days and relatively low side effect profile. However, at this time it is unclear how long these benefits may persist. This would provide primary care physicians an effective treatment for patients suffering from alcohol use disorder. Based on the evidence thus far, it appears that gabapentin is a novel treatment option in the management of alcohol dependence. In the future, this case proposes the need for more research using gabapentin as a first-line treatment for alcohol use disorder.

References

1. Young S, Wood E, Ahamad K. Pharmacotherapy for Alcohol Addiction in a Patient with Alcoholic Cirrhosis and Massive Upper Gastrointestinal Bleed: A Case Study. 2016;35(2):236-9.
2. Mason B, Quello S, Goodell V, Shadan F, Kyle M, Begovic A. Gabapentin Treatment for Alcohol Dependence: A Randomized Controlled Trial. 2014;174(1):70-7.
3. Roberto M, Glipin N, O’Dell L, Cruz M, Morse A, Siggins M, et al. Cellular and Behavioral Interactions of Gabapentin with Alcohol Dependence. [amygdala, ethanol dependence, IPSC, paired-pulse facilitation, anxiety, ethanol-self administration]. 2008;28(22):5762-71.
4. Myrick H, Malcolm R, Randall P, Boyle E, Anton R, Becker H, et al. A Double‐Blind Trial of Gabapentin Versus Lorazepam in the Treatment of Alcohol Withdrawal. [gabapentin, alcohol dependence, alcohol withdrawal, lorazepam]. 2009;33(9):1582-8.
5. Nichols T. Off-label use of gabapentin for management of alcohol use disorders. [gabapentin, alcohol use disorder, alcohol, detox, detoxification, dependence]. 2015;5(6):248-52.
6. Yesil B, Elbozan B. Gabapentin withdrawal in a depressed patient: A case report. [gabapentin, withdrawal, drug abuse]. 2016;17(3):61-3.
7. Rose MA, Kam PCA. Gabapentin: pharmacology and its use in pain management. [pharmacology, gabapentin, neuropathic]. 2002;57(5):451-62.