Treatment for Alcohol Dependence With Gabapentin

Summary

Alcohol use disorders are present across medical specialties, with alcohol-related deaths particularly prevalent in the categories of injury, liver cirrhosis, cancer, cardiovascular disease, disorders of the peripheral nerves and of the central nervous system. Alcohol dependence, also referred to as alcohol use disorder, is a chronic, relapsing disorder marked by compulsive alcohol use, an inability to stop drinking despite harmful consequences, and the emergence of a withdrawal syndrome upon cessation of use. Early abstinence is associated with activation of brain stress systems in the extended amygdala. Clinically, protracted abstinence involves symptoms of craving, mood and sleep disturbance, all of which have been identified as risk factors for relapse. Nonetheless, implementation of alcohol-specific medications remains limited across most medical specialties. Medications for treating alcohol dependence primarily have been adjunctive interventions, and only three medications-disulfiram, naltrexone, and acamprosate-are approved for this indication by the United States Food and Drug Administration. Baclofen, an inhibitor of synaptic transmission through spinal reflex arcs via hyper polarization of primary afferent fiber terminals, was originally approved by the Food and Drug Administration in 1977 for use in spasticity associated with neurologic conditions, such as multiple sclerosis and spinal cord lesions. However, due to its pharmacologic properties it has also been investigated for the treatment of alcohol dependence. But in the clinical practice of study physicians, it was observed that most of the patients who were prescribed baclofen for alcohol dependence hit back to alcohol very soon despite being on the drug. Therefore there is a need to search for an alternative drug which could be beneficial for this population of patients. Gabapentin is Food and Drug Administration-approved for the management of epileptic seizures and neuropathic pain. It is believed to act by blocking a specific alpha-2d subunit of the voltage-gated calcium channel at selective presynaptic sites and, as a result, to indirectly modulate Gamma Butyric Acid neurotransmission. Pre-clinical findings indicate that gabapentin normalizes the stress-induced Gamma Butyric Acid activation in the amygdala that is associated with alcohol dependence, and provide an excellent pre-clinical rationale for evaluating gabapentin as a treatment for alcohol dependence. Earlier studies of gabapentin in alcohol dependent subjects, attempting to abstain following withdrawal support the safety and potential efficacy of gabapentin in alcohol dependent patients, but definitive conclusions were limited by either small sample size, methodological, or dosing issues.

Timeline

Start

2016-06

Primary completion

2018-04-23

Completion

2018-05-16

Publications

• Results Mason BJ, Quello S, Goodell V, Shadan F, Kyle M, Begovic A. Gabapentin treatment for alcohol dependence: a randomized clinical trial. JAMA Intern Med. 2014 Jan;174(1):70-7. doi: 10.1001/jamainternmed.2013.11950.
• Results Williams SH. Medications for treating alcohol dependence. Am Fam Physician. 2005 Nov 1;72(9):1775-80.
• Results Rehm J, Mathers C, Popova S, Thavorncharoensap M, Teerawattananon Y, Patra J. Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders. Lancet. 2009 Jun 27;373(9682):2223-33. doi: 10.1016/S0140-6736(09)60746-7.
• Results Mark TL, Kassed CA, Vandivort-Warren R, Levit KR, Kranzler HR. Alcohol and opioid dependence medications: prescription trends, overall and by physician specialty. Drug Alcohol Depend. 2009 Jan 1;99(1-3):345-9. doi: 10.1016/j.drugalcdep.2008.07.018. Epub 2008 Sep 25.
• Results Koob GF. A role for brain stress systems in addiction. Neuron. 2008 Jul 10;59(1):11-34. doi: 10.1016/j.neuron.2008.06.012.

Drugs

Indications