Gabapentin for the Treatment of Alcohol Use Disorder in Patients With Alcohol Withdrawal Symptoms | Clinical Pharmacy and Pharmacology | JN Learning | AMA Ed Hub [Skip to Content]
[Skip to Content Landing]

Efficacy of Gabapentin for the Treatment of Alcohol Use Disorder in Patients With Alcohol Withdrawal SymptomsA Randomized Clinical Trial

Educational Objective
To examine whether gabapentin would be useful in the treatment of alcohol use disorder (AUD), especially in those with the most alcohol withdrawal symptoms.
1 Credit CME
Key Points

Question  Is gabapentin efficacious in the treatment of alcohol use disorder in adults with a history of alcohol withdrawal symptoms?

Findings  In this randomized clinical trial, gabapentin compared with placebo significantly increased the number of people with total abstinence and reduced drinking. This effect was most significantly observed in those with greater pretreatment alcohol withdrawal symptoms—41% of participants with high alcohol withdrawal symptoms had total abstinence on gabapentin compared with 1% of participants in the placebo arm.

Meaning  This study showed that gabapentin is efficacious in promoting abstinence and reducing drinking in individuals with alcohol use disorder and especially so in those with more alcohol withdrawal symptoms.

Abstract

Importance  Although an estimated 30 million people meet criteria for alcohol use disorder (AUD), few receive appropriate pharmacotherapy. A more personalized, symptom-specific, approach might improve efficacy and acceptance.

Objective  To examine whether gabapentin would be useful in the treatment of AUD, especially in those with the most alcohol withdrawal symptoms.

Design, Setting, and Participants  This double-blind randomized clinical trial conducted between November 2014 and June 2018 evaluated gabapentin vs placebo in community-recruited participants screened and treated in an academic outpatient setting over a 16-week treatment period. A total of 145 treatment-seeking individuals who met Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria for AUD and were not receiving other AUD intervention were screened, and 96 who also met recent alcohol withdrawal criteria were randomized to treatment after 3 abstinent days. Daily drinking was recorded, and percentage of disialo carbohydrate-deficient transferrin in the blood, a heavy drinking marker, was collected at baseline and monthly during treatment.

Interventions  Gabapentin up to 1200 mg/d, orally, vs placebo along with 9 medical management visits (20 minutes each).

Main Outcomes and Measures  The percentage of individuals with no heavy drinking days and those with total abstinence were compared between treatment groups and further evaluated based on prestudy alcohol withdrawal symptoms.

Results  Of 96 randomized individuals, 90 were evaluable (44 in the gabapentin arm and 46 in the placebo arm), with a mean (SD) age of 49.6 (10.1) years; 69 were men (77%) and 85 were white (94%). The evaluable participants had 83% baseline heavy drinking days (4 or more drinks/day for women, 5 or more for men) and met 4.5 alcohol withdrawal criteria from the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). More gabapentin-treated individuals had no heavy drinking days (12 of 44 participants [27%]) compared with placebo (4 of 46 participants [9%]), a difference of 18.6% (95% CI, 3.1-34.1; P = .02; number needed to treat [NNT], 5.4), and more total abstinence (8 of 44 [18%]) compared with placebo (2 of 46 [4%]), a difference of 13.8% (95% CI, 1.0-26.7; P = .04; NNT, 6.2). The prestudy high–alcohol withdrawal group had positive gabapentin effects on no heavy drinking days (P < .02; NNT, 3.1) and total abstinence (P = .003; NNT, 2.7) compared with placebo, while within the low–alcohol withdrawal group, there were no significant differences. These findings were similar for other drinking variables, where gabapentin was more efficacious than placebo in the high–alcohol withdrawal group only. Gabapentin caused more dizziness, but this did not affect efficacy.

Conclusions and Relevance  These data, combined with others, suggest gabapentin might be most efficacious in people with AUD and a history of alcohol withdrawal symptoms. Future studies should evaluate sleep changes and mood during early recovery as mediators of gabapentin efficacy.

Trial Registration  ClinicalTrials.gov Identifier: NCT02349477

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 CME Credit™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

Article Information

Accepted for Publication: January 23, 2020.

Corresponding Author: Raymond F. Anton, MD, Addiction Sciences Division, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, 67 President St, MSC 861, Charleston, SC 29425 (antonr@musc.edu).

Published Online: March 9, 2020. doi:10.1001/jamainternmed.2020.0249

Author Contributions: Drs Anton and Hoffman had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Anton.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Anton, Book, Bristol.

Critical revision of the manuscript for important intellectual content: Anton, Latham, Voronin, Book, Hoffman, Prisciandaro.

Statistical analysis: Anton, Hoffman, Prisciandaro.

Obtained funding: Anton.

Administrative, technical, or material support: Anton, Latham, Voronin, Book, Prisciandaro, Bristol.

Study supervision: Anton, Book, Prisciandaro.

Conflict of Interest Disclosures: Dr Anton reported receiving grants from the National Institute on Alcohol Abuse and Alcoholism during the conduct of the study; receiving grants and consulting fees from Laboratorio Farmaceutico CT; receiving consulting fees from Alkermes, Allergan, Indivior, Insys, Life Epigenetics, XenoPort (Arbor Pharmaceuticals), and Alcohol Clinical Trials Initiative (ACTIVE) outside the submitted work; and serving as a member and chair of ACTIVE, which was partially supported by Alkermes, Amygdala Neurosciences, Arbor Pharmaceuticals, Ethypharm, Indivior, Lundbeck, Mitsubishi, and Otsuka. Dr Book reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Prisciandaro reported receiving grants and consulting fees from Farmaceutico Italiano and consulting fees from Laboratorio Farmaceutico CT outside the submitted work. No other disclosures were reported.

Funding/Support: Funding for this work was provided by the National Institute on Alcohol Abuse and Alcoholism (grant R01AA022364).

Role of the Funder/Sponsor: The National Institute on Alcohol Abuse and Alcoholism had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Data Sharing Statement: See Supplement 3.

Additional Contributions: Mark Ghent, BA, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, assisted in data collection, and Patrick Randall, PhD, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, assisted in initial power analyses and analytic planning and were compensated for their work.

References
1.
Grant  BF , Chou  SP , Saha  TD ,  et al.  Prevalence of 12-month alcohol use, high-risk drinking, and DSM-IV alcohol use disorder in the United States, 2001-2002 to 2012-2013: results from the National Epidemiologic Survey on Alcohol and Related Conditions.   JAMA Psychiatry. 2017;74(9):911-923. doi:10.1001/jamapsychiatry.2017.2161PubMedGoogle ScholarCrossref
2.
Rehm  J , Dawson  D , Frick  U ,  et al.  Burden of disease associated with alcohol use disorders in the United States.   Alcohol Clin Exp Res. 2014;38(4):1068-1077. doi:10.1111/acer.12331PubMedGoogle ScholarCrossref
3.
Litten  RZ , Wilford  BB , Falk  DE , Ryan  ML , Fertig  JB .  Potential medications for the treatment of alcohol use disorder: an evaluation of clinical efficacy and safety.   Subst Abus. 2016;37(2):286-298. doi:10.1080/08897077.2015.1133472PubMedGoogle ScholarCrossref
4.
Schuckit  MA , Smith  TL , Daeppen  JB ,  et al.  Clinical relevance of the distinction between alcohol dependence with and without a physiological component.   Am J Psychiatry. 1998;155(6):733-740.PubMedGoogle Scholar
5.
Caetano  R , Clark  CL , Greenfield  TK .  Prevalence, trends, and incidence of alcohol withdrawal symptoms: analysis of general population and clinical samples.   Alcohol Health Res World. 1998;22(1):73-79.PubMedGoogle Scholar
6.
Schuckit  MA , Danko  GP , Smith  TL , Hesselbrock  V , Kramer  J , Bucholz  K .  A 5-year prospective evaluation of DSM-IV alcohol dependence with and without a physiological component.   Alcohol Clin Exp Res. 2003;27(5):818-825. doi:10.1097/01.ALC.0000067980.18461.33PubMedGoogle ScholarCrossref
7.
Wright  TM , Myrick  H , Malcolm  R ,  et al.  Impact of lifetime alcohol quit attempts and medicated detoxifications on time to relapse during an index alcohol detoxification.   J Addict Med. 2007;1(1):15-20. doi:10.1097/ADM.0b013e318044ce4fPubMedGoogle ScholarCrossref
8.
Bonnet  U , Banger  M , Leweke  FM , Maschke  M , Kowalski  T , Gastpar  M .  Treatment of alcohol withdrawal syndrome with gabapentin.   Pharmacopsychiatry. 1999;32(3):107-109. doi:10.1055/s-2007-979203PubMedGoogle ScholarCrossref
9.
Mason  BJ , Light  JM , Williams  LD , Drobes  DJ .  Proof-of-concept human laboratory study for protracted abstinence in alcohol dependence: effects of gabapentin.   Addict Biol. 2009;14(1):73-83. doi:10.1111/j.1369-1600.2008.00133.xPubMedGoogle ScholarCrossref
10.
O’Malley  SS , Krishnan-Sarin  S , Farren  C , Sinha  R , Kreek  MJ .  Naltrexone decreases craving and alcohol self-administration in alcohol-dependent subjects and activates the hypothalamo-pituitary-adrenocortical axis.   Psychopharmacology (Berl). 2002;160(1):19-29. doi:10.1007/s002130100919PubMedGoogle ScholarCrossref
11.
Drobes  DJ , Anton  RF , Thomas  SE , Voronin  K .  Effects of naltrexone and nalmefene on subjective response to alcohol among non-treatment-seeking alcoholics and social drinkers.   Alcohol Clin Exp Res. 2004;28(9):1362-1370. doi:10.1097/01.ALC.0000139704.88862.01PubMedGoogle ScholarCrossref
12.
Anton  RF .  Naltrexone for the management of alcohol dependence.   N Engl J Med. 2008;359(7):715-721. doi:10.1056/NEJMct0801733PubMedGoogle ScholarCrossref
13.
Ray  LA , Hutchison  KE .  Effects of naltrexone on alcohol sensitivity and genetic moderators of medication response: a double-blind placebo-controlled study.   Arch Gen Psychiatry. 2007;64(9):1069-1077. doi:10.1001/archpsyc.64.9.1069PubMedGoogle ScholarCrossref
14.
Schacht  JP , Randall  PK , Latham  PK ,  et al.  Predictors of naltrexone response in a randomized trial: reward-related brain activation, OPRM1 genotype, and smoking status.   Neuropsychopharmacology. 2017;42(13):2640-2653. doi:10.1038/npp.2017.74PubMedGoogle ScholarCrossref
15.
Gass  JT , Olive  MF .  Glutamatergic substrates of drug addiction and alcoholism.   Biochem Pharmacol. 2008;75(1):218-265. doi:10.1016/j.bcp.2007.06.039PubMedGoogle ScholarCrossref
16.
Koob  GF , Kenneth Lloyd  G , Mason  BJ .  Development of pharmacotherapies for drug addiction: a Rosetta stone approach.   Nat Rev Drug Discov. 2009;8(6):500-515. doi:10.1038/nrd2828PubMedGoogle ScholarCrossref
17.
Littleton  J .  Neurochemical mechanisms underlying alcohol withdrawal.   Alcohol Health Res World. 1998;22(1):13-24.PubMedGoogle Scholar
18.
Gonzales  RA , Weiss  F .  Suppression of ethanol-reinforced behavior by naltrexone is associated with attenuation of the ethanol-induced increase in dialysate dopamine levels in the nucleus accumbens.   J Neurosci. 1998;18(24):10663-10671. doi:10.1523/JNEUROSCI.18-24-10663.1998PubMedGoogle ScholarCrossref
19.
Schacht  JP , Anton  RF , McNamara  PJ , Im  Y , King  AC .  The dopamine transporter VNTR polymorphism moderates the relationship between acute response to alcohol and future alcohol use disorder symptoms.   Addict Biol. 2019;24(5):1109-1118. doi:10.1111/adb.12676PubMedGoogle ScholarCrossref
20.
Addolorato  G , Leggio  L , Hopf  FW , Diana  M , Bonci  A .  Novel therapeutic strategies for alcohol and drug addiction: focus on GABA, ion channels and transcranial magnetic stimulation.   Neuropsychopharmacology. 2012;37(1):163-177. doi:10.1038/npp.2011.216PubMedGoogle ScholarCrossref
21.
Krystal  JH , Staley  J , Mason  G ,  et al.  Gamma-aminobutyric acid type A receptors and alcoholism: intoxication, dependence, vulnerability, and treatment.   Arch Gen Psychiatry. 2006;63(9):957-968. doi:10.1001/archpsyc.63.9.957PubMedGoogle ScholarCrossref
22.
Maneuf  YP , Luo  ZD , Lee  K .  Alpha2delta and the mechanism of action of gabapentin in the treatment of pain.   Semin Cell Dev Biol. 2006;17(5):565-570. doi:10.1016/j.semcdb.2006.09.003PubMedGoogle ScholarCrossref
23.
Zamponi  GW , Striessnig  J , Koschak  A , Dolphin  AC .  The physiology, pathology, and pharmacology of voltage-gated calcium channels and their future therapeutic potential.   Pharmacol Rev. 2015;67(4):821-870. doi:10.1124/pr.114.009654PubMedGoogle ScholarCrossref
24.
Hendrich  J , Van Minh  AT , Heblich  F ,  et al.  Pharmacological disruption of calcium channel trafficking by the alpha2delta ligand gabapentin.   Proc Natl Acad Sci U S A. 2008;105(9):3628-3633. doi:10.1073/pnas.0708930105PubMedGoogle ScholarCrossref
25.
Sills  GJ .  The mechanisms of action of gabapentin and pregabalin.   Curr Opin Pharmacol. 2006;6(1):108-113. doi:10.1016/j.coph.2005.11.003PubMedGoogle ScholarCrossref
26.
Yoshizumi  M , Parker  RA , Eisenach  JC , Hayashida  K .  Gabapentin inhibits γ-amino butyric acid release in the locus coeruleus but not in the spinal dorsal horn after peripheral nerve injury in rats.   Anesthesiology. 2012;116(6):1347-1353. doi:10.1097/ALN.0b013e318254e6fdPubMedGoogle ScholarCrossref
27.
Suto  T , Severino  AL , Eisenach  JC , Hayashida  K .  Gabapentin increases extracellular glutamatergic level in the locus coeruleus via astroglial glutamate transporter-dependent mechanisms.   Neuropharmacology. 2014;81:95-100. doi:10.1016/j.neuropharm.2014.01.040PubMedGoogle ScholarCrossref
28.
Cai  K , Nanga  RP , Lamprou  L ,  et al.  The impact of gabapentin administration on brain GABA and glutamate concentrations: a 7T 1H-MRS study.   Neuropsychopharmacology. 2012;37(13):2764-2771. doi:10.1038/npp.2012.142PubMedGoogle ScholarCrossref
29.
Mariani  JJ , Rosenthal  RN , Tross  S , Singh  P , Anand  OP .  A randomized, open-label, controlled trial of gabapentin and phenobarbital in the treatment of alcohol withdrawal.   Am J Addict. 2006;15(1):76-84. doi:10.1080/10550490500419110PubMedGoogle ScholarCrossref
30.
Myrick  H , Malcolm  R , Randall  PK ,  et al.  A double-blind trial of gabapentin versus lorazepam in the treatment of alcohol withdrawal.   Alcohol Clin Exp Res. 2009;33(9):1582-1588. doi:10.1111/j.1530-0277.2009.00986.xPubMedGoogle ScholarCrossref
31.
Furieri  FA , Nakamura-Palacios  EM .  Gabapentin reduces alcohol consumption and craving: a randomized, double-blind, placebo-controlled trial.   J Clin Psychiatry. 2007;68(11):1691-1700. doi:10.4088/JCP.v68n1108PubMedGoogle ScholarCrossref
32.
Karam-Hage  M , Brower  KJ .  Gabapentin treatment for insomnia associated with alcohol dependence.   Am J Psychiatry. 2000;157(1):151. doi:10.1176/ajp.157.1.151PubMedGoogle ScholarCrossref
33.
Karam-Hage  M , Brower  KJ .  Open pilot study of gabapentin versus trazodone to treat insomnia in alcoholic outpatients.   Psychiatry Clin Neurosci. 2003;57(5):542-544. doi:10.1046/j.1440-1819.2003.01161.xPubMedGoogle ScholarCrossref
34.
Anton  RF , Myrick  H , Baros  AM ,  et al.  Efficacy of a combination of flumazenil and gabapentin in the treatment of alcohol dependence: relationship to alcohol withdrawal symptoms.   J Clin Psychopharmacol. 2009;29(4):334-342. doi:10.1097/JCP.0b013e3181aba6a4PubMedGoogle ScholarCrossref
35.
Anton  RF , Myrick  H , Wright  TM ,  et al.  Gabapentin combined with naltrexone for the treatment of alcohol dependence.   Am J Psychiatry. 2011;168(7):709-717. doi:10.1176/appi.ajp.2011.10101436PubMedGoogle ScholarCrossref
36.
Roberto  M , Gilpin  NW , O’Dell  LE ,  et al.  Cellular and behavioral interactions of gabapentin with alcohol dependence.   J Neurosci. 2008;28(22):5762-5771. doi:10.1523/JNEUROSCI.0575-08.2008PubMedGoogle ScholarCrossref
37.
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;174(1):70-77. doi:10.1001/jamainternmed.2013.11950PubMedGoogle ScholarCrossref
38.
Falk  DE , Ryan  ML , Fertig  JB ,  et al; National Institute on Alcohol Abuse and Alcoholism Clinical Investigations Group (NCIG) Study Group.  Gabapentin enacarbil extended-release for alcohol use disorder: a randomized, double-blind, placebo-controlled, multisite trial assessing efficacy and safety.   Alcohol Clin Exp Res. 2019;43(1):158-169.PubMedGoogle Scholar
39.
Goldberg  JF , Burdick  KE .  Cognitive side effects of anticonvulsants.   J Clin Psychiatry. 2001;62(suppl 14):27-33.PubMedGoogle Scholar
40.
Schacht  JP , Randall  PK , Waid  LR ,  et al.  Neurocognitive performance, alcohol withdrawal, and effects of a combination of flumazenil and gabapentin in alcohol dependence.   Alcohol Clin Exp Res. 2011;35(11):2030-2038. doi:10.1111/j.1530-0277.2011.01554.xPubMedGoogle ScholarCrossref
41.
Bisaga  A , Evans  SM .  The acute effects of gabapentin in combination with alcohol in heavy drinkers.   Drug Alcohol Depend. 2006;83(1):25-32. doi:10.1016/j.drugalcdep.2005.10.008PubMedGoogle ScholarCrossref
42.
Myrick  H , Anton  R , Voronin  K , Wang  W , Henderson  S .  A double-blind evaluation of gabapentin on alcohol effects and drinking in a clinical laboratory paradigm.   Alcohol Clin Exp Res. 2007;31(2):221-227. doi:10.1111/j.1530-0277.2006.00299.xPubMedGoogle ScholarCrossref
43.
First  MB , Spitzer  RL , Gibbon  M , Williams  JBW .  Structured Clinical Interview for DSM-IV Axis I Disorders—Patient Edition. Version. 2.0. New York, NY: New York State Psychiatric Institute; 1997.
44.
Ahmed  S , Bachu  R , Kotapati  P ,  et al.  Use of gabapentin in the treatment of substance use and psychiatric disorders: a systematic review.   Front Psychiatry. 2019;10(228):228. doi:10.3389/fpsyt.2019.00228PubMedGoogle ScholarCrossref
45.
Sullivan  JT , Sykora  K , Schneiderman  J , Naranjo  CA , Sellers  EM .  Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar).   Br J Addict. 1989;84(11):1353-1357. doi:10.1111/j.1360-0443.1989.tb00737.xPubMedGoogle ScholarCrossref
46.
Pettinati  HM , Weiss  RD , Miller  WR , Donovan  D , Ernst  DB , Rounsaville  BJ .  Medical Management Treatment Manual: A Clinical Research Guide for Medically Trained Clinicians Providing Pharmacotherapy as Part of the Treatment for Alcohol Dependence. Bethesda, MD: National Institute on Alcohol Abuse and Alcoholism; 2004.
47.
Anton  RF , O’Malley  SS , Ciraulo  DA ,  et al; COMBINE Study Research Group.  Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial.   JAMA. 2006;295(17):2003-2017. doi:10.1001/jama.295.17.2003PubMedGoogle ScholarCrossref
48.
Johnson  BA , Ait-Daoud  N , Roache  JD .  The COMBINE SAFTEE: a structured instrument for collecting adverse events adapted for clinical studies in the alcoholism field.   J Stud Alcohol Suppl. 2005;(15):157-167. doi:10.15288/jsas.2005.s15.157PubMedGoogle Scholar
49.
Pittman  B , Gueorguieva  R , Krupitsky  E , Rudenko  AA , Flannery  BA , Krystal  JH .  Multidimensionality of the Alcohol Withdrawal Symptom Checklist: a factor analysis of the Alcohol Withdrawal Symptom Checklist and CIWA-Ar.   Alcohol Clin Exp Res. 2007;31(4):612-618. doi:10.1111/j.1530-0277.2007.00345.xPubMedGoogle Scholar
50.
Skinner  HA , Allen  BA .  Alcohol dependence syndrome: measurement and validation.   J Abnorm Psychol. 1982;91(3):199-209. doi:10.1037/0021-843X.91.3.199PubMedGoogle ScholarCrossref
51.
Anton  RF , Moak  DH , Latham  PK .  The obsessive compulsive drinking scale: a new method of assessing outcome in alcoholism treatment studies.   Arch Gen Psychiatry. 1996;53(3):225-231. doi:10.1001/archpsyc.1996.01830030047008PubMedGoogle ScholarCrossref
52.
Tonigan  JS , Miller  WR , Brown  JM .  The reliability of Form 90: an instrument for assessing alcohol treatment outcome.   J Stud Alcohol. 1997;58(4):358-364. doi:10.15288/jsa.1997.58.358PubMedGoogle ScholarCrossref
53.
Litten  RZ , Bradley  AM , Moss  HB .  Alcohol biomarkers in applied settings: recent advances and future research opportunities.   Alcohol Clin Exp Res. 2010;34(6):955-967. doi:10.1111/j.1530-0277.2010.01170.xPubMedGoogle ScholarCrossref
54.
Helander  A , Wielders  JP , Jeppsson  JO ,  et al; IFCC Working Group on Standardization of Carbohydrate-Deficient Transferrin (WG-CDT).  Toward standardization of carbohydrate-deficient transferrin (CDT) measurements: II. performance of a laboratory network running the HPLC candidate reference measurement procedure and evaluation of a candidate reference material.   Clin Chem Lab Med. 2010;48(11):1585-1592. doi:10.1515/CCLM.2010.322PubMedGoogle ScholarCrossref
55.
American Psychiatric Association.  Handbook of Psychiatric Measures. Washington, DC: American Psychiatric Association; 2000.
56.
Falk  D , Wang  XQ , Liu  L ,  et al.  Percentage of subjects with no heavy drinking days: evaluation as an efficacy endpoint for alcohol clinical trials.   Alcohol Clin Exp Res. 2010;34(12):2022-2034. doi:10.1111/j.1530-0277.2010.01290.xPubMedGoogle ScholarCrossref
57.
Center for Drug Evaluation and Research.  Alcoholism: Developing Drugs for Treatment. Guidance for Industry. Silver Spring, MD: Center for Drug Evaluation and Research; 2015.
58.
Anton  RF , Latham  PK , Voronin  KE ,  et al.  Nicotine-use/smoking is associated with the efficacy of naltrexone in the treatment of alcohol dependence.   Alcohol Clin Exp Res. 2018;42(4):751-760. doi:10.1111/acer.13601PubMedGoogle ScholarCrossref
59.
Laupacis  A , Sackett  DL , Roberts  RS .  An assessment of clinically useful measures of the consequences of treatment.   N Engl J Med. 1988;318(26):1728-1733. doi:10.1056/NEJM198806303182605PubMedGoogle ScholarCrossref
60.
Anton  RF , Lieber  C , Tabakoff  B ; CDTect Study Group.  Carbohydrate-deficient transferrin and gamma-glutamyltransferase for the detection and monitoring of alcohol use: results from a multisite study.   Alcohol Clin Exp Res. 2002;26(8):1215-1222. doi:10.1111/j.1530-0277.2002.tb02658.xPubMedGoogle Scholar
61.
Helander  A , Husa  A , Jeppsson  JO .  Improved HPLC method for carbohydrate-deficient transferrin in serum.   Clin Chem. 2003;49(11):1881-1890. doi:10.1373/clinchem.2003.023341PubMedGoogle ScholarCrossref
62.
Kranzler  HR , Feinn  R , Morris  P , Hartwell  EE .  A meta-analysis of the efficacy of gabapentin for treating alcohol use disorder.   Addiction. 2019;114(9):1547-1555. doi:10.1111/add.14655PubMedGoogle ScholarCrossref
63.
Leggio  L , Kenna  GA , Swift  RM .  New developments for the pharmacological treatment of alcohol withdrawal syndrome. a focus on non-benzodiazepine GABAergic medications.   Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(5):1106-1117. doi:10.1016/j.pnpbp.2007.09.021PubMedGoogle ScholarCrossref
64.
Griffin  WC  III , Haun  HL , Hazelbaker  CL , Ramachandra  VS , Becker  HC .  Increased extracellular glutamate in the nucleus accumbens promotes excessive ethanol drinking in ethanol dependent mice.   Neuropsychopharmacology. 2014;39(3):707-717. doi:10.1038/npp.2013.256PubMedGoogle ScholarCrossref
65.
Melendez  RI , McGinty  JF , Kalivas  PW , Becker  HC .  Brain region-specific gene expression changes after chronic intermittent ethanol exposure and early withdrawal in C57BL/6J mice.   Addict Biol. 2012;17(2):351-364. doi:10.1111/j.1369-1600.2011.00357.xPubMedGoogle ScholarCrossref
66.
Leggio  L , Lee  MR .  Treatment of alcohol use disorder in patients with alcoholic liver disease.   Am J Med. 2017;130(2):124-134. doi:10.1016/j.amjmed.2016.10.004PubMedGoogle ScholarCrossref
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_Multimedia_LoginSubscribe_Purchase
Close
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_Multimedia_LoginSubscribe_Purchase
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
Close
With a personal account, you can:
  • Track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
jn-learning_Modal_SaveSearch_NoAccess_Purchase
Close

Lookup An Activity

or

Close

My Saved Searches

You currently have no searches saved.

Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close