Cited by 444Substance Abuse Treatment and OutcomesAlcohol Consumption and Health EffectsAlcoholism and Thiamine Deficiency

The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.

Pharmacological Treatment of Alcohol Dependence: A Review of the Evidence

Garbutt, James C., West, Suzanne L., Carey, Timothy S., Lohr, Kathleen N., Crews, Fulton T.·1999·JAMA

DOI 10.1001/jama.281.14.1318

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Abstract

CONTEXT: Alcoholism affects approximately 10% of Americans at some time in their lives. Treatment consists of psychosocial interventions, pharmacological interventions, or both, but which drugs are most effective at enhancing abstinence and preventing relapse has not been systematically reviewed. OBJECTIVE: To evaluate the efficacy of 5 categories of drugs used to treat alcohol dependence--disulfiram, the opioid antagonists naltrexone and nalmefene, acamprosate, various serotonergic agents (including selective serotonergic reuptake inhibitors), and lithium. DATA SOURCES: Reports of randomized controlled trials, nonrandomized trials, and other study designs in English, French, and German identified from multiple searches of MEDLINE, EMBASE, and specialized databases; hand searching bibliographies of review articles; searches for unpublished literature; and discussions with investigators in the field. STUDY SELECTION: We included all studies on alcohol-dependent human subjects aged 18 years or older from all inpatient and outpatient settings between 1966 and December 1997 that met our inclusion criteria. DATA EXTRACTION: We abstracted the following information: study design and blinding, diagnostic instrument and severity assessment, drug interventions and cointerventions, demographic and comorbidity details about patients, compliance, and numerous outcome measures (eg, relapse, return to drinking, drinking or nondrinking days, time to first drink, alcohol consumed per unit of time, craving). We graded quality of the individual articles (scale, 0-100) independently from the strength of evidence for each drug class (A, strong and consistent evidence of efficacy in studies of large size and/or high quality; B, mixed evidence of efficacy; C, evidence of lack of efficacy; and I, insufficient evidence). DATA SYNTHESIS: Of 375 articles evaluated, we abstracted and analyzed data from 41 studies and 11 follow-up or subgroup studies. Naltrexone (grade A) reduces the risk of relapse to heavy drinking and the frequency of drinking compared with placebo but does not substantially enhance abstinence, ie, avoidance of any alcohol consumption. Acamprosate (grade A, from large-scale studies in Europe) reduces drinking frequency, although its effects on enhancing abstinence or reducing time to first drink are less clear. Controlled studies of disulfiram (grade B) reveal a mixed outcome pattern--some evidence that drinking frequency is reduced but minimal evidence to support improved continuous abstinence rates. The limited data on serotonergic agents were not very promising (grade I), although most studies were confounded by high rates of comorbid mood disorders. Lithium lacks efficacy (grade C) in the treatment of primary alcohol dependence. CONCLUSIONS: Recent reports documenting that naltrexone and acamprosate are more effective than placebo in the treatment of alcoholism justify clinical interest in use of these medications for alcohol-dependent patients. Use of disulfiram is widespread but less clearly supported by the clinical trial evidence; however, targeted studies on supervised administration of disulfiram may be warranted. Use of existing serotonergic agents or lithium for patients with primary alcohol dependence does not appear to be supported by the efficacy data available at this time; these medications may still have a positive effect in patients with coexisting psychiatric disorders.

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Background
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Background
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Background
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Background
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Background
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Background
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Background
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“disulfiram discourages alcohol use by causing uncomfortable physical symptoms when alcohol is consumed; however, rates of noncompliance are high.(65,66) For opioid use disorders, methadone, buprenorphine (with or without naloxone), and”
Background
The Sigma-2 receptor / transmembrane protein 97 (σ2R/TMEM97) modulator JVW-1034 reduces heavy alcohol drinking and associated pain states in male mice
Quadir, S. G., Tanino, S. M., Rohl, C. D., Sahn, J. J., Yao, E. J., Cruz, L. R., Cottone, P., Martin, S. F., & Sabino, V. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108409 · Cited by 33
“Medications currently available for AUD focus on reducing alcohol intake and/or relapse to it, but they rarely target the negative states present during alcohol withdrawal, which include intense pain states (Anton et al., 2006; Garbutt, 2009; Garbutt et al., 1999).”
Background
Development of an Ethanol Model Using Social Insects: III. Preferences for Ethanol Solutions
Abramson, C. I., Sheridan, A. B., Donohue, D., Kandolf, A., Božič, J., Meyers, J. E., & Benbassat, D. (2004) · Psychological Reports · doi:10.2466/pr0.94.1.227-239 · Cited by 35
Development of Novel Pharmacotherapies for the Treatment of Alcohol Dependence: Focus on Antiepileptics
Johnson, B. A., Swift, R. M., Ait‐Daoud, N., DiClemente, C. C., Javors, M. A., & Malcolm, R. J. (2004) · Alcoholism Clinical and Experimental Research · doi:10.1097/01.alc.0000113409.47937.6c · Cited by 35
Off-label and investigational drugs in the treatment of alcohol use disorder: A critical review
Fischler, P. V., Soyka, M., Seifritz, E., & Mutschler, J. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.927703 · Cited by 34
“Various meta-analyses and reviews have described the effectiveness of these medications in treating alcohol use disorder (Garbutt et al., 1999; Kenna et al., 2004a, 2004b; Soyka and Roesner, 2006; Jonas et al., 2014; Soyka and Mutschler, 2016).”
Background
Pharmacological Treatments for Alcoholism: Revisiting Lithium and Considering Buspirone
FAWCETT, J. A., Kravitz, H. M., McGuire, M., Easton, M., Ross, J. S., Pisani, V. D., Fogg, L., Clark, D. T., Whitney, M., Kravitz, G., et al. (2000) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2000.tb02038.x · Cited by 34
Organizational Predictors of Pharmacological Innovation Adoption: The Case of Disulfiram
Knudsen, H. K., Roman, P. M., Ducharme, L. J., & Johnson, J. A. (2005) · Journal of Drug Issues · doi:10.1177/002204260503500308 · Cited by 33
“Although there are traditions of both individual and group therapy in substance abuse treatment (Garbutt et al., 1999; Kranzer, 2000), centers can vary in the extent to which they emphasize these formats.”
Background
A Pilot Study of Oxcarbazepine Versus Acamprosate in Alcohol‐Dependent Patients
Croissant, B., Diehl, A., Klein, O., Zambrano, S., Nakovics, H., Heinz, A., & Mann, K. F. (2006) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2006.00082.x · Cited by 32
The Pharmacotherapy of Alcohol Dependence: A State of the Art Review
Sousa, A. D. (2010) · Mens Sana monographs · doi:10.4103/0973-1229.58820 · Cited by 31
Substance Misuse and Substance-Related Disorders in Forensic Psychiatry
Gendel, M. H. (2006) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2006.04.010 · Cited by 32
The renaissance in psychedelic research: What do preclinical models have to offer
Murnane, K. S. (2018) · Progress in brain research · doi:10.1016/bs.pbr.2018.08.003 · Cited by 35
Medication-Assisted Treatment for Substance use Disorders within a National Community Health Center Research Network
Rieckmann, T. R., Muench, J., McBurnie, M. A., Leo, M. C., Crawford, P. M., Ford, D., Stubbs, J., O’Cleirigh, C. M., Mayer, K. H., Fiscella, K. A., et al. (2016) · Substance Abuse · doi:10.1080/08897077.2016.1189477 · Cited by 31
“This medication helps patients with AUDs by decreasing cravings, reducing the urge for binge drinking during relapse, and supporting patients working towards abstinence.(52,53) Two additional medications for treating AUDs are acamprosate and disulfiram.”
Background
Gender Differences in Predictors of Treatment Attrition with High Dose Naltrexone in Cocaine and Alcohol Dependence
Suh, J. J., Pettinati, H. M., Kampman, K. M., & O’Brien, C. P. (2008) · American Journal on Addictions · doi:10.1080/10550490802409074 · Cited by 30
Amisulpride Does Not Prevent Relapse in Primary Alcohol Dependence: Results of a Pilot Randomized, Placebo-Controlled Trial
Marra, D., Warot, D., Berlin, I., Hispard, É., Notides, C., Tilikete, S., Payan, C., Lépine, J., Dally, S., & Aubin, H. (2002) · Alcoholism Clinical and Experimental Research · doi:10.1097/00000374-200210000-00012 · Cited by 31
Effective and cost-effective measures to reduce alcohol misuse in Scotland A literature review
Ludbrook, A., Godfrey, C., Wyness, L., & Executive, E. (. K. S. (2002) · OpenGrey (Institut de l'Information Scientifique et Technique) · Cited by 32
New pharmacotherapies for alcohol dependence
Graham, R., WODAK, A. D., & Whelan, G. (2002) · The Medical Journal of Australia · doi:10.5694/j.1326-5377.2002.tb04683.x · Cited by 31
Alcohol Consumption and Development of Acute Respiratory Distress Syndrome: A Population-Based Study
Thakur, L., Kojičić, M., Thakur, S., Pieper, M. S., Kashyap, R., Trillo-Alvarez, C., Javier, F., Cartin-Ceba, R., & Gajic, O. (2009) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph6092426 · Cited by 29
“The worldwide prevalence of alcohol abuse and dependence in hospitalized patients is similar [4,5].”
Background
Diagnosis and Management of Alcoholic Hepatitis
Sohail, U., & Satapathy, S. K. (2012) · Clinics in Liver Disease · doi:10.1016/j.cld.2012.08.005 · Cited by 29
Adoption of Medications in Substance Abuse Treatment: Priorities and Strategies of Single State Authorities
Rieckmann, T. R., Kovas, A. E., & Rutkowski, B. A. (2010) · Journal of Psychoactive Drugs · doi:10.1080/02791072.2010.10400546 · Cited by 27
“Naltrexone is a mu-opioid receptor antagonist that is approved for the treatment of alcohol dependence (Chick et al. 2000; Garbutt et al. 1999).”
Alcohol Use and Anxiety: Diagnostic and Management Issues
Brady, K. T., Tolliver, B. K., & Verduin, M. L. (2007) · American Journal of Psychiatry · doi:10.1176/ajp.2007.164.2.217 · Cited by 27
Use of naltrexone for alcohol use disorders in the Veterans’ Health Administration: A national study
Iheanacho, T., Issa, M. A., Marienfeld, C. B., & Rosenheck, R. A. (2013) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2013.01.016 · Cited by 27
DENTAL CARE OF PATIENTS WITH SUBSTANCE ABUSE
Bullock, K. (1999) · Dental Clinics of North America · doi:10.1016/s0011-8532(22)00806-0 · Cited by 27
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“Another important limitation is that acamprosate is approved for maintaining rather than inducing abstinence and is thought to dampen symptoms of prolonged alcohol withdrawal.(25,26) In this study, we administered acamprosate before alcohol discontinuation.”
Background
Open-Label Pilot Study of Extended-Release Naltrexone to Reduce Drinking and Driving Among Repeat Offenders
Lapham, S. C., & McMillan, G. P. (2010) · Journal of Addiction Medicine · doi:10.1097/adm.0b013e3181eb3b89 · Cited by 26
“168 C© 2011 American Society of Addiction Medicine XR-NTX, including nausea, headache, and fatigue (Garbutt et al., 1999).”
Background
Naltrexone Is Associated With Reduced Drinking by Alcohol Dependent Patients Receiving Antidepressants for Mood and Anxiety Symptoms: Results From VA Cooperative Study No. 425, “Naltrexone in the Treatment of Alcoholism”
Krystal, J. H., Gueorguieva, R. V., Cramer, J. A., Collins, J. F., Rosenheck, R. A., & The VA CSP No. 425 Study Team (2007) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2007.00555.x · Cited by 24
Pharmacotherapy of Alcohol Use Disorders
Buonopane, A., & Petrakis, I. L. (2005) · Substance Use & Misuse · doi:10.1080/10826080500294890 · Cited by 24
Recent Advances in Nicotinic Receptor Signaling in Alcohol Abuse and Alcoholism
Rahman, S., Engleman, E. A., & Bell, R. L. (2015) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2015.10.004 · Cited by 28
Involvement of delta opioid receptors in alcohol withdrawal-induced mechanical allodynia in male C57BL/6 mice
Alongkronrusmee, D., Chiang, T., & van Rijn, R. M. (2016) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2016.08.017 · Cited by 23
“Currently, the available drug treatments for AUD rarely combat the complexities of the withdrawal syndrome (Anton et al., 2006; Garbutt, 2009; Garbutt et al., 1999).”
Background
The use of atmospheric and room temperature plasma mutagenesis to create a brewing yeast with reduced acetaldehyde production
Liu, C., Li, Q., Niu, C., Tian, Y., Zhao, Y., & Yin, X. (2018) · Journal of the Institute of Brewing · doi:10.1002/jib.498 · Cited by 23
Efficacy of Naltrexone and Acamprosate for Alcoholism Treatment: A Meta-Analysis
Kranzler, H. R., & Kirk, J. V. (2001) · Alcoholism Clinical and Experimental Research · doi:10.1097/00000374-200109000-00014 · Cited by 23
Development of an Ethanol Model Using Social Insects: II. Effect of Antabuse® on Consumatory Responses and Learned Behavior of the Honey Bee ( Apis Mellifera L.)
Abramson, C. I., Fellows, G. W., Browne, B. L., Lawson, A. L., & Ortiz, R. N. M. (2003) · Psychological Reports · doi:10.2466/pr0.2003.92.2.365 · Cited by 23
Efficacy of Baclofen on Abstinence and Craving in Alcohol-dependent Patients: a Meta-analysis of Randomized Controlled Trials
Lesouef, N., Bellet, F., Mounier, G., & Beyens, M. (2014) · Therapies · doi:10.2515/therapie/2014038 · Cited by 22
Placebo Group Improvement in Trials of Pharmacotherapies for Alcohol Use Disorders
Re, A. C. D., Maisel, N. C., Blodgett, J. C., Wilbourne, P. L., & Finney, J. W. (2013) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e3182983e73 · Cited by 22
Pharmacologic Interventions for Pregnant Women Enrolled in Alcohol Treatment
Smith, E. J., Lui, S., & Terplan, M. (2009) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd007361.pub2 · Cited by 22
Building better strategies to develop new medications in Alcohol Use Disorder: Learning from past success and failure to shape a brighter future
Cannella, N., Ubaldi, M., Masi, A., Bramucci, M., Roberto, M., Bifone, A., & Ciccocioppo, R. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.05.014 · Cited by 24
Pharmacotherapy for Alcohol-Related Disorders: What Clinicians Should Know
Mariani, J. J., & LEVIN, F. R. (2004) · Harvard Review of Psychiatry · doi:10.1080/10673220490905697 · Cited by 22
Acamprosate for the Adjunctive Treatment of Alcohol Dependence
Overman, G. P., Teter, C. J., & Guthrie, S. K. (2003) · Annals of Pharmacotherapy · doi:10.1345/aph.1c351 · Cited by 21
Ondansetron and sertraline may interact with 5-HTTLPR and DRD4 polymorphisms to reduce drinking in non-treatment seeking alcohol-dependent women: Exploratory findings
Kenna, G. A., Zywiak, W. H., Swift, R. M., McGeary, J. E., Clifford, J. S., Shoaff, J. R., Fricchione, S., Brickley, M., Beaucage, K., Haass-Koffler, C. L., et al. (2014) · Alcohol · doi:10.1016/j.alcohol.2014.04.005 · Cited by 20

Authors: Garbutt, J. C., West, S. L., Carey, T. S., Lohr, K. N., & Crews, F. T.
Affiliations: University of North Carolina at Chapel Hill (US)
RTI International (US)
ORCID: West, Suzanne L.
Carey, Timothy S.
Lohr, Kathleen N.
Crews, Fulton T.
Venue: JAMA
Publisher: American Medical Association (AMA)
Published: 1999-04-14
Volume: 281
Issue: 14
Pages: 1318
ISSN: 0002-9955 (ISSN-L)
0098-7484
DOI: 10.1001/jama.281.14.1318
OpenAlex: W2082518171
Cited by: 444
References: 43
Citations by year: 2025: 3 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 3 · 2020: 11 · 2019: 13 · 2018: 12 · 2017: 13 · 2016: 11 · 2015: 17 · 2014: 13 · 2013: 15 · 2012: 19
FWCI: 21.16
Type: journal article
Language: en
Open access: closed
Locations: JAMA (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Public Health Service (290-97-0011)
Topics: Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
Health Sciences › Medicine › Clinical Neurology › Alcoholism and Thiamine Deficiency
Keywords: alcoholism, pharmacotherapy, disulfiram, naltrexone, nalmefene, acamprosate, selective serotonin reuptake inhibitors, lithium, relapse prevention, abstinence, drinking frequency, craving, treatment efficacy, quality of evidence grading, psychosocial interventions
MeSH terms: Acamprosate, Adult, Alcohol Deterrents, Alcoholism, Disulfiram, Humans, Lithium, Naltrexone, Narcotic Antagonists, Taurine, Serotonin Agents

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Pharmacological Treatment of Alcohol Dependence: A Review of the Evidence

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