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Gabapentin for Alcohol Dependence

Gabapentin for Alcoholism

Gabapentin was originally approved by the FDA to treat seizure disorders.  It has also been found to be effective for a number of disorders in neurology (neuropathic pain, fibromyalgia, restless leg syndrome) and psychiatry (insomnia, anxiety disorders).

In recent years, evidence has been mounting for its effectiveness in treating Alcohol Use Disorders. In this 2014 study (1), Gabapentin was shown to:

  • Increase rates of abstinence.
  • Decrease rates of binge-drinking.
  • Decrease the number of drinks per week.
  • Reduce cravings.
  • Improve sleep, even in the presence of alcohol.
  • Improve mood disturbances associated with alcohol use.

At first glance, it might seem surprising that gabapentin would help treat alcoholism, given its benefits for seemingly unrelated disorders.   In order to understand why this makes sense from a pharmacological standpoint, it is helpful to know a little about how the brain works, how alcohol affects the brain, and how gabapentin works.

Unlike drugs such as opiates, cannabis, nicotine, and cocaine, there are no drug-specific receptors in our brains for alcohol

We do not have alcohol receptors in our brains.  Instead, alcohol affects a wide range of other receptors, each having specific effects on our behavior and cognition.  The most important are glutamate, adenosine, opiate, dopamine, serotonin, and gamma-amminobutric acid (GABA).  The most relevant receptor to gabapentin is GABA, which is a neurological inhibitor.

An easy way to think about inhibitors is that they function as brakes for neural impulses.  They slow things down and decrease communication among cells.  When you drink, the primary effect initially is a slowing down of brain function.  These inhibitory neurotransmitters underlie the familiar signs of intoxication, including drowsiness, decreased attention, poor memory, and confusion.  Given sufficient amounts, the user could lose consciousness, stop breathing, and die.

Maintaining the Status Quo

One of your body’s primary survival strategies is homeostasis, which in Latin means “the same state.”  Whenever an environmental change is applied to the body, the body responds to offset this and keep conditions exactly as they are.   Common examples include sweating when the body gets too warm (thermo-regulation) and frequent urination if excessive water is consumed.

The brain responds in a similar way to chronic alcohol exposure.  When an excessive amount of an inhibitory neurotransmitter (“brake”) such as GABA is activated because of alcohol use, the brain counters this by either reducing the number of receptors or the sensitivity of the receptors.   It attempts to reestablish equilibrium by offsetting GABA’s inhibition.  The brain presses the gas pedal. But when the chronic use of alcohol stops (as sobriety commences) and the brake is removed, all that remains is the pressed gas pedal, and the the brain is suddenly left in a hyper-aroused state characterized by anxiety, insomnia, agitation, and, in severe cases, seizures.

How Gabapentin Works

This is where gabapentin enters the picture. Although it is not known exactly known how gabapentin affects GABA, it is generally agreed that it either directly or indirectly increases the availability of GABA in the brain. In other words, it has something in common with alcohol.   Through its effects on GABA, gabapentin calms down the brain, which is exactly what is needed for the hyper-aroused state of a newly sober alcoholic (3).  This is believed to result in a reduction in anxiety and improve sleep (4, 5), both of which are associated with reduced cravings for alcohol.

Safety and Side Effects

Gabapentin is generally well tolerated, with dizziness, peripheral edema, etc. being the most common side effects.  It is not a controlled substance.

Beyond its ability to reduce drinking and improve secondary symptoms associated with alcohol dependence, there are specific characteristics of the medication that make it particularly suited to helping problem drinking, including:

  • It has no dangerous interactions with alcohol.
  • It is not metabolized by the liver.
  • It has no interactions with other medications that treat alcohol dependence or medications that treat depression and anxiety, two common co-morbidities.

Dosing

Gabapentin has a wide dosing range.  For seizures, patients may take up to 4800 mg daily.  For sleep, doses range from 300 to 1800 mg at bedtime.  For the treatment of alcohol use disorders, typical dosing used in alcohol dependence is between 900 and 1800 mg daily.  Higher doses are associated with greater benefit.

References

  1. Gabapentin Treatment for Alcohol Dependence: A Randomized Controlled Trial.

Importance—Approved medications for alcohol dependence are prescribed for fewer than 9% of US alcoholics.

Objective—To determine if gabapentin, a widely-prescribed generic calcium channel/GABA modulating medication, increases rates of sustained abstinence and no heavy drinking, and decreases alcohol-related insomnia, dysphoria and craving, in a dose-dependent manner.

Design, Participants and Setting—A 12-week, double-blind, placebo-controlled, randomized dose-ranging trial of 150 men and women over 18 years of age with current alcohol dependence, conducted 2004–2010 at a single-site outpatient clinical research facility adjoining a general medical hospital.

Interventions—Oral gabapentin (0, 900, 1800 mg/d) and concomitant manual-guided counseling.

Main Outcome Measures—Rates of complete abstinence and no heavy drinking (co-primary) and changes in mood, sleep and craving (secondary) over the 12-week study.

  1.  Gabapentin Combined With Naltrexone for the Treatment of Alcohol Dependence

Objective: Naltrexone, an efficacious medication for alcohol dependence, does not work for everyone. Symptoms Such as insomnia and mood instability that are most evident during early abstinence might respond better to a different pharmacotherapy. Gabapentin may reduce these symptoms and help prevent early relapse. This clinical trial evaluated whether the combination of naltrexone and gabapentin was better than naltrexone alone and/or placebo during the early drinking cessation phase (first 6 weeks), and if so, whether this effect persisted.

Method: A total of 150 alcohol-dependent individuals were randomly assigned to a 16-week course of naltrexone alone (50 m g/day [N=50]), naltrexone (50 m g/ day) with gabapentin (up to 1,200 m g/ day [N=50]) added for the first 6 weeks or double placebo (N=50). All participants received medical management.

Results: During the first 6 weeks, the naltrexone-gabapentin group had a longer interval to heavy drinking than the naltrexone-alone group, which had an interval similar to that of the placebo group; had fewer heavy drinking days than the naltrexone-alone group, which in turn had more than the placebo group; and had fewer drinks per drinking day than the naltrexone alone group and the placebo group. These differences faded over the remaining weeks of the study. Poor sleep was associated with more drinking in the naltrexone-alone group but not in the naltrexone-gabapentin group, while a history of alcohol withdrawal was associated with better response in the naltrexone-gabapentin group.

Conclusions: The addition of gabapentin to naltrexone improved drinking outcomes over naltrexone alone during the first 6 weeks after cessation of drinking. This effect did not endure after gabapentin was discontinued.

  1. Anxious to drink: gabapentin normalizes GABAergic transmission in the central amygdala and reduces symptoms of ethanol dependence.
  1. Gabapentin Treatment for Insomnia Associated With Alcohol Dependence
  1. Insomnia, Self-Medication, and Relapse to Alcoholism

Objective: This study was an investigation of the frequencies of insomnia and its self-medication with alcohol in a group of alcoholic patients, as well as the relationship of these variables to alcoholic relapse.

Method: The subjects were 172 men and women receiving treatment for alcohol dependence. They completed a sleep questionnaire, measures of alcohol problem severity and depression severity, and polysomnography after at least 2 weeks of abstinence.

Results: On the basis of eight items from the Sleep Disorders Questionnaire, 61% of the subjects were classified as having symptomatic insomnia during the 6 months before treatment entry. Compared to patients without insomnia, patients with insomnia were more likely to report frequent alcohol use for sleep (55% versus 28%), had significantly worse polysomnographic measures of sleep continuity, and had more severe alcohol dependence and depression. Among 74 alcoholics who were followed a mean of 5 months after treatment, 60% with baseline insomnia versus 30% without baseline insomnia relapsed to any use of alcohol, a significant difference. Insomnia remained a robust predictor of relapse after application of logistic regression analysis to control for other variables. A history of self-medicating insomnia with alcohol did not significantly predict subsequent relapse.

Conclusions: The majority of alcoholic patients entering treatment reported insomnia symptoms. Given the potential link between insomnia and relapse, routine questions about sleep in clinical and research settings are warranted.

  1. Alcohol Dependence: Neurobiology and Treatment

Abstract: The consequences of alcohol dependence concern serious health care, social and economic problems. The scope of many studies is to better understand mechanisms underlying alcohol addiction in order to work out new, more effective treatment strategies. Alcohol affects many neurotransmission systems within the brain. In general, acute alcohol enhances inhibitory transmission, up-regulating the GABAergic system and impairing glutamatergic function, therefore interfering the balance between excitatory and inhibitory synaptic inputs. Chronic alcohol consumption, meanwhile, in order to restore equilibrium leads to neuroadaptive changes causing both decreased GABAergic and increased glutamatergic activity. Also function of other neurotransmitters and modulators is modified by the presence of alcohol, including glycine, adenosine, serotonin and dopamine. Moreover, a significant impact of alcohol on the endogenous opioid system, nicotinic cholinergic transmission and the endocannabinoids system has been also established. At present, only four medications are approved for the treatment of alcohol dependence in Europe, that is naltrexone, acamprosate, disulfiram and the most recent nalmefene. Among other promising strategies the following drugs are mentioned: baclofen, topiramate, ondansetron, aripiprazole, rimonabant and varenicline. Additionally, the role of appetite-regulating hormones, neuroimmune modulators or the bodyís stress-response system modulators in reducing alcohol consumption is currently of great interest, however, further investigations are needed.

2018-04-20T21:02:15+00:00