Alcohol abuse and dependence are known to contribute to more than 60 associated diseases and to cause injuries that lead to more than 2.5 million deaths annually.1 Alcohol abuse also leads to exorbitant social costs such as those related to violence, child neglect/abuse, and occupational challenges. While psychosocial intervention such as a 12-step program remains the mainstay of alcohol dependence management, established and emerging science show that pharmacotherapy as an adjunct to psychosocial intervention may significantly improve outcomes for some patients. At my practice, we are finding success with combinations of baclofen, gabapentin, and naltrexone. When you have patients struggling with the cessation or moderation of alcohol consumption, especially patients demonstrating alcohol withdrawal symptoms, please consider a referral to the offices of Neal S. Taub, MD.

Multiple medications are now approved for the treatment of alcohol dependence. These include disulfiram, acamprosate, and naltrexone. However, these medications have been shown to have moderate effect sizes.^2-6 Naltrexone, in particular, works as an opioid antagonist to reduce the reinforcing aspects of alcohol cues and consumption while reducing “slip” drinking.^7-9 Research over the past decade suggests that off-label prescription of other medications, especially gabapentin and baclofen, could further reduce alcohol withdrawal symptoms, reduce cravings, and improve success with alcohol moderation and abstinence.

These medications can complement the neurophysiological effects of naltrexone. Gabapentin and baclofen work to normalize GABA and glutamate balance, systems that play a role in reinforcement, extinction, cue-induced learning, anxiety, and regulation of emotional behavior.^10,11 Numerous studies now show that anticonvulsants in general and gabapentin in particular can moderate acute alcohol withdrawal symptoms and prevent relapse.^12-16 Of particular relevance is the work of Dr. Raymond Anton and colleagues demonstrating that, when combined with behavioral therapy, gabapentin plus naltrexone treats alcohol dependence better than naltrexone alone.16 Likewise, there is a body of evidence suggesting that baclofen can improve the maintenance of alcohol abstinence.¹⁷  Especially encouraging is evidence from three publications showing that daily baclofen improves 60-day abstinence success rates from 29% with placebo to 71% with baclofen among patients with liver cirrhosis,18 from 25% to 83% among patients with hepatitis C,19 and from 21% to 70% among a general group of alcohol-dependent patients.20

These various studies are finding the use of baclofen and gabapentin at normal doses to be safe, even when used with alcohol, and to have tolerable side effects including drowsiness, headaches, and vertigo. In addition to greater efficacy, baclofen and gabapentin offer the advantage of being excreted by the kidneys rather than the liver. The extrahepatic metabolism of these drugs removes the hepatic contraindications that sometimes limit the use of naltrexone. When you encounter patients struggling with management of alcohol dependence, please consider a referral to my practice.

References

1. World Health Organization. Global status report on alcohol and health. 2011. Geneva, Switzerland: World Health Organization: 2011.
2. Anton R, O’Malley S, Ciraulo D, et al. Combined pharmocotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA. 2006; 295 (17): 2003-2017.
3. Mann K Lehert P, Morgan M. The efficacy of acamprosate in the maintenance of abstinence in alcohol-dependent individuals: results of meta-analysis. Alcohol Clin Exp Res. 2004; 28(1): 51-63.
4. Fuller R, Branchey L, Brightwell D, et al. Disulfiram treatment of alcoholism. A Veterans Administration cooperateive study. JAMA. 1986; 256(11): 1449-1455.
5. Rosner S, Hackl-Herrwerth A, Leucht S, et al. Opioid antagonists for alcohol dependence. Chochrane Database Syst Rev. 2010; 12: CD001867.
6. Rosner S, Hackl-Herrwerth A, Leucht S, et al. Acamprosate for alcohol dependence. Cochrane Database Syst Rev. 2010; 9:CD004332.
7. O’Malley S, Krishnan-Sarin S, Farren C, et al. Naltrexone decreases craving and alcohol self-administration in alcohol-dependent subjects and activates the hypothalamo-pituitary-adrenocortical axis. Psychopharmacology (BERL) 2002; 160: 19-29.
8. Drobes D, Anton R, Thomas S, et al. A clinical laboratory paradigm for evaluating medication effects on alcohol consumption: naltrexone and nalmefene. Neurospychopharamacology. 2003; 28:755-764.
9. O’Malley S, Jaffe A, Rode S, et al. Experience of a “slip” among alcoholics treated with naltrexone or placebo. Am J Psychiatry. 1996; 153: 281-283.
10. Kalivas P, Volkow N. The neural basis of addiction, a pathology of motivation and choice. Am J Psychiatry. 2005; 162: 1403-1413.
11. Addorolatoo G, Leggio L, Cardone S, et al. Role of the GABAB receptor system in alcoholism and stress: focus on clinical studies and treatment perspectives. Alcohol. 2009; 43(7): 559-563.
12. Mariani J, Rosenthal R, Tross S, et al. A randomized, open-label, controlled trial of gabapentin and phenobarbital in the treatment of alcohol withdrawal. Am J Addict. 2006; 15: 76-94.
13. Myrick H, Malcolm R, Randall P, boyle E, et al. A double-blind trial of gabapentin verus lorazepam in the treatment of alcohol withdrawal.  Alcohol Clin Exp Res. 20-09; 33: 1582-1588.
14. Furieri F, Nakamura-Palacios E. Gabapentin reduces alcohol consumption and craving: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2007; 68: 1691-1700.
15. Anton R, Myrick H, Baros A, et al. Efficacy of a combination of flumazenil and gabapentin in the treatment of alcohol dependence: relationship too alcohol withdrawal symptoms. J Clin Psychopharmacol. 2009; 29: 334-342.
16. Anton R, Myrick H, Wright T, et al. Gabapentin combined with naltrexone for the treatment of alcohol dependence. Am J Psychiatry. 2011; 168 (7): 709-717.
17. Brennan J, Leung J, Gagliardi J, et al . Clinical effectivenss of baclofen for the treatment of alcohol dependence: a review. Clinical Pharmacology: Advances and Applications. 2013: 99-107.
18. Addolorato G, Leggio L, Ferruli A, et al. Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: a randomized, double-blind, controlled study. Lancet. 2007; 370 (9603): 1915-1922.
19. Leggio L, Ferruli A, Zambon A, et al. Baclofen promotes alcohol abstinence in alcohol dependent cirrhotic patients with hepatitis C viros infection. Addict Behav. 2012; 37: 561-564.
20. Addolorato G, Caputo F, Capristo E, et al. Baclofen efficacy in reducing alcohol craving and intake: a preliminary double-blind randomized controlled study. Alcohol and Alcoholism. 2002; 37: 504-508.