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1
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Maisto SA, Moskal D, Firkey MK, Bergman BG, Borsari B, Hallgren KA, Houck JM, Hurlocker M, Kiluk BD, Kuerbis A, Reid AE, Magill M. From alcohol and other drug treatment mediator to mechanism to implementation: A systematic review and the cases of self-efficacy, social support, and craving. ALCOHOL, CLINICAL & EXPERIMENTAL RESEARCH 2024; 48:1677-1692. [PMID: 39182214 DOI: 10.1111/acer.15411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Accepted: 07/14/2024] [Indexed: 08/27/2024]
Abstract
Research designed to establish alcohol and other drug (AOD) mechanisms of behavioral change (MOBC) has centered on what variables mediate the relation between AOD treatment and outcomes. The purpose of this paper was to review this research evidence to identify empirically supported mediators of alcohol and other drug use and related outcomes and then to evaluate their potential as being AOD treatment MOBC. The first phase was a systematic review of reviews (2008-2023) to identify the variables with the strongest empirical support as mediators of AOD treatment effects. Eligible reviews focused on AOD treatment modalities, included empirically tested mediators, and targeted adult samples. The second phase was a systematic review of empirical studies (1990-2023) testing the hypothesis that variables identified in phase one were AOD treatment mediators/mechanisms and then evaluating each eligible stage two study according to the Kazdin and Nock (Journal of Child Psychology and Psychiatry, 44, 1116) criteria. Eligible articles included empirical studies with adult samples attending AOD treatment and empirically tested one of the three treatment mechanisms as a mediator of an AOD-related outcome. Databases were searched in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. This systematic review was not preregistered. The first review of 11 eligible review articles identified self-efficacy, social support, and craving as having the strongest empirical support. The second review captured 48 individual studies. An evaluation of each of these studies by the Kazdin and Nock criteria suggested that they likely are MOBC and therefore are ready for implementation. The implementation of self-efficacy, social support, and craving into clinical practice and training is warranted. Six directions for future research to solidify and generalize empirical support for the case that self-efficacy, social support, and craving are MOBC are presented, as are five implications for clinical practice and training.
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Affiliation(s)
| | - Dezarie Moskal
- VA Center for Integrated Healthcare, VA Western New York Healthcare System, Buffalo, USA
| | | | | | - Brian Borsari
- University of California-San Francisco, San Francisco, USA
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2
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Fischler PV, Soyka M, Seifritz E, Mutschler J. Off-label and investigational drugs in the treatment of alcohol use disorder: A critical review. Front Pharmacol 2022; 13:927703. [PMID: 36263121 PMCID: PMC9574013 DOI: 10.3389/fphar.2022.927703] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Accepted: 06/30/2022] [Indexed: 11/13/2022] Open
Abstract
Compounds known to be successful in the treatment of alcohol use disorder include the aversive agent, Disulfiram, the glutamatergic NMDA receptor antagonist, Acamprosate, and the opioid receptor antagonists, Naltrexone and Nalmefene. Although all four are effective in maintaining abstinence or reduction of alcohol consumption, only a small percentage of patients receive pharmacological treatment. In addition, many other medications have been investigated for their therapeutic potential in the treatment of alcohol use disorder. In this review we summarize and compare Baclofen, Gabapentin, Topiramate, Ondansetron, Varenicline, Aripiprazole, Quetiapine, Clozapine, Antidepressants, Lithium, Neuropeptide Y, Neuropeptide S, Corticotropin-releasing factor antagonists, Oxytocin, PF-05190457, Memantine, Ifenprodil, Samidorphan, Ondelopran, ABT-436, SSR149415, Mifepristone, Ibudilast, Citicoline, Rimonabant, Surinabant, AM4113 and Gamma-hydroxybutyrate While some have shown promising results in the treatment of alcohol use disorder, others have disappointed and should be excluded from further investigation. Here we discuss the most promising results and highlight medications that deserve further preclinical or clinical study. Effective, patient-tailored treatment will require greater understanding provided by many more preclinical and clinical studies.
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Affiliation(s)
- Pascal Valentin Fischler
- Department for Gynecology and Obstetrics, Women’s Clinic Lucerne, Cantonal Hospital of Lucerne, Lucerne, Switzerland
- *Correspondence: Pascal Valentin Fischler,
| | - Michael Soyka
- Psychiatric Hospital University of Munich, Munich, Germany
| | - Erich Seifritz
- Director of the Clinic for Psychiatry, Psychotherapy and Psychosomatics, Psychiatric University Clinic Zürich, Zürich, Switzerland
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3
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Vengeliene V, Foo JC, Kim J. Translational approach to understanding momentary factors associated with alcohol consumption. Br J Pharmacol 2020; 177:3878-3897. [PMID: 32608068 DOI: 10.1111/bph.15180] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 06/17/2020] [Accepted: 06/22/2020] [Indexed: 01/23/2023] Open
Abstract
Multiple interindividual and intra-individual factors underlie variability in drinking motives, challenging clinical translatability of animal research and limiting treatment success of substance use-related problems. Intra-individual variability refers to time-dependent continuous and discrete changes within the individual and in substance use research is studied as momentary variation in the internal states (craving, stressed, anxious, impulsive and tired) and response to external triggers (stressors, drug-associated environmental cues and social encounters). These momentary stimuli have a direct impact on behavioural decisions and may be triggers and predictors of substance consumption. They also present potential targets for real-time behavioural and pharmacological interventions. In this review, we provide an overview of the studies demonstrating different momentary risk factors associated with increased probability of alcohol drinking in humans and changes in alcohol seeking and consumption in animals. The review also provides an overview of pharmacological interventions related to every individual risk factor.
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Affiliation(s)
- Valentina Vengeliene
- Department of Neurobiology and Biophysics, Institute of Biosciences, Life Sciences Center, Vilnius, Lithuania
| | - Jerome Clifford Foo
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
| | - Jinhyuk Kim
- Department of Informatics, Graduate School of Integrated Science and Technology, Shizuoka University, Shizuoka, Japan
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4
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Topiramate Pharmacotherapy for Alcohol Use Disorder and Other Addictions: A Narrative Review. J Addict Med 2020; 13:7-22. [PMID: 30096077 DOI: 10.1097/adm.0000000000000443] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
: Topiramate is a non-benzodiazepine anticonvulsant medication with multi-faceted pharmacologic action. It has emerged as an efficacious pharmacotherapeutic option for the treatment of addiction, especially alcohol use disorder (AUD). We present a broad narrative review of the putative mechanism of action and clinical utility of topiramate with regard to AUD and other substance use disorders. Collective evidence suggests topiramate is an effective treatment option in AUD, with notable efficacy in reducing harmful drinking patterns in AUD. Though not currently approved by the United States Food and Drug Administration for the indication of AUD, topiramate should be considered as a pharmacological treatment option with high utility among AUD patients. Early pharmacogenetic studies raise the intriguing possibility of identifying patients likely to respond to topiramate using genetic testing, and initial studies show that topiramate may also be useful in treating cocaine use disorder, smoking cessation and behavioral addictions. However, further research is needed in all these areas.
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5
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Kazantseva AV, Enikeeva RF, Romanova AR, Malykh SB, Galyautdinova SI, Khusnutdinova EK. Stress-Associated Cognitive Functioning Is Controlled by Variations in Synaptic Plasticity Genes. RUSS J GENET+ 2020. [DOI: 10.1134/s1022795420010068] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Zastrozhin MS, Skryabin VY, Miroshkin SS, Bryun EA, Sychev DA. Pharmacogenetics of alcohol addiction: current perspectives. APPLICATION OF CLINICAL GENETICS 2019; 12:131-140. [PMID: 31372024 PMCID: PMC6628972 DOI: 10.2147/tacg.s206745] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Accepted: 06/10/2019] [Indexed: 12/31/2022]
Abstract
Genetics of alcohol addiction is currently a contradictive and complex field, where data in the most studies reflect methods’ limitations rather than meaningful and complementary results. In our review, we focus on the genetics of alcohol addiction, leaving genetics of acute alcohol intoxication out of the scope. A review of the literature on pharmacogenetic biomarkers development for the pharmacotherapy personalization reveals that today the evidence base concerning these biomarkers is still insufficient. In particular, now the researches with the design of randomized controlled trials and meta-analysis investigating the effect of the SNPs as biomarkers on the therapy efficacy are available for naltrexone only. For other medications, there are only a few studies in small samples. It decreases the possibilities to implement the pharmacogenetic algorithms for the pharmacotherapy personalization in patients with alcohol use disorders (AUD). In view of the importance of the precision approaches development not in addiction medicine only, but in other fields of medicine also to increase the efficacy and safety of the therapy, studies on pharmacogenetic biomarkers development for the medications used in patients with AUD (eg, naltrexone, disulfiram, nalmefene, acamprosate, etc.) remain relevant to this day.
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Affiliation(s)
- M S Zastrozhin
- Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare , Moscow 109390, Russian Federation.,Department of Addictology, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow 123995, Russian Federation
| | - V Yu Skryabin
- Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare , Moscow 109390, Russian Federation
| | - S S Miroshkin
- Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare , Moscow 109390, Russian Federation.,Department of Addictology, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow 123995, Russian Federation
| | - E A Bryun
- Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare , Moscow 109390, Russian Federation.,Department of Addictology, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow 123995, Russian Federation
| | - D A Sychev
- Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare , Moscow 109390, Russian Federation.,Department of Addictology, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow 123995, Russian Federation
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7
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Abstract
Zusammenfassung. Hintergrund: Unterschiede in der Therapiezielfindung bei der Behandlung von Alkoholkonsumstörungen, die sich zwischen völliger Abstinenz, vermindertem Konsum (Schadensvermeidung) und „kontrolliertem Konsum“ aufspannen, werden seit vielen Jahren z. T. kontrovers diskutiert. Ziel: Ziel der Stellungnahme der Dachgesellschaft Sucht ist es, vorhandene empirische Erkenntnisse zu diesem Themenbereich zusammenzutragen und daraus Empfehlungen für den praktischen Umgang mit verschiedenen Therapiezielen wie Trinkmengenreduktion oder Abstinenz für die Patienten oder Klienten abzuleiten. An der Erstellung des Positionspapiers haben sich Vertreter verschiedener Fachgesellschaften (DG Suchtmedizin, der DG Suchtforschung und Suchttherapie sowie die Deutsche Gesellschaft für Suchtpsychologie) beteiligt. Eine Reihe von Forschungsdesideraten wird benannt.
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Affiliation(s)
- Gallus Bischof
- Universität zu Lübeck, Klinik für Psychiatrie und Psychotherapie
| | - Nikolaus Lange
- Baden-Württembergischer Landesverband für Prävention und Rehabilitation (bwlv), Renchen
| | | | - Ulrich W. Preuss
- Vitos-Klinikum Psychiatrie und Psychotherapie, Herborn, Martin-Luther Universität, Halle-Wittenberg, Klinik für Psychiatrie, Psychotherapie und Psychosomatik
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8
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Obed A, Bashir A, Stern S, Jarrad A. Severe acute alcoholic hepatitis and liver transplant: A never-ending mournful story. Clin Mol Hepatol 2018; 24:358-366. [PMID: 30360030 PMCID: PMC6313024 DOI: 10.3350/cmh.2018.0044] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2018] [Accepted: 08/16/2018] [Indexed: 02/06/2023] Open
Abstract
Severe acute alcoholic liver disease (SAAH) unresponsive to medical therapy shows one-year-mortality rates of up to 90%. Most transplant centers request six months of alcohol abstinence prior to transplantation, the so-called "6-month rule." This regulation is not based on strong evidence, repeatedly making it a topic of controversial debates. The majority of patients with SAAH will die before fulfilling the 6-month rule. Therefore, liver transplantation (LT) protocols are becoming more flexible towards the rigid abstinence regulation, especially concerning SAAH patients. We conducted a literature review regarding LT in SAAH and its outcomes, including post-transplant mortality and recidivism. We studied available data on PubMed from 2011 and onwards whilst including articles dealing with genetic components, medical therapy and historic snapshots of alcoholism. Emerging studies recommend LT in SAAH not responding to medical therapies even without realizing the required abstinence period, since the majority of these patients would die within 6 months. SAAH without response to medical therapy has one-year-mortality rates of up to 90%. The 6-month rule is not based on strong evidence and is repeatedly a topic of controversial debates. There is genetic linkage to alcoholism and medical therapy is not as effective as estimated, yet. The 6-months-regulation has not shown to evidently decrease the risk of recidivism post-LT, which is a lifesaving treatment in SAAH patients. Insisting on rigid sobriety rules results in excluding patients with a low risk of recidivism from being transplanted. Moreover, the genetic linkage of alcoholism must be recognized.
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Affiliation(s)
- Aiman Obed
- Division of General, Hepatobiliary and Transplant Surgery, Jordan Hospital, Amman, Jordan
| | - Abdalla Bashir
- Division of General, Hepatobiliary and Transplant Surgery, Jordan Hospital, Amman, Jordan
| | - Steffen Stern
- Faculty of Law, Bielefeld University, Bielefeld, Germany
| | - Anwar Jarrad
- Division of Gastroenterology, Jordan Hospital, Amman, Jordan
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9
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Blanco-Gandía MC, Rodríguez-Arias M. Pharmacological treatments for opiate and alcohol addiction: A historical perspective of the last 50 years. Eur J Pharmacol 2018; 836:89-101. [DOI: 10.1016/j.ejphar.2018.08.007] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Revised: 07/13/2018] [Accepted: 08/03/2018] [Indexed: 12/17/2022]
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10
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Kowalczyk WJ, Moran LM, Bertz JW, Phillips KA, Ghitza UE, Vahabzadeh M, Lin JL, Epstein DH, Preston KL. Using ecological momentary assessment to examine the relationship between craving and affect with opioid use in a clinical trial of clonidine as an adjunct medication to buprenorphine treatment. THE AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE 2018; 44:502-511. [PMID: 29634425 PMCID: PMC6146282 DOI: 10.1080/00952990.2018.1454933] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/18/2017] [Revised: 01/05/2018] [Accepted: 03/13/2018] [Indexed: 01/30/2023]
Abstract
BACKGROUND In a recent clinical trial (NCT00295308), we demonstrated that clonidine decreased the association between opioid craving and moderate levels of stress and affect in patients receiving buprenorphine-based opioid agonist therapy. OBJECTIVES To examine the relationship between illicit opioid use and craving and affect during the evaluation of clonidine as an adjunct medication in buprenorphine treatment for opioid use disorder. Secondarily, to examine whether those relationships are driven by within- or between-participant factors. METHODS This was a secondary data analysis from our original trial. Participants (N = 108, female: n = 23, male n = 85) receiving buprenorphine were randomized to receive adjunct clonidine or placebo. Participants used portable electronic devices to rate stress, mood, and craving via ecological momentary assessment (EMA) four times randomly each day. To associate the EMA data with illicit opioid use, each EMA report was linked to participants' next urine drug screen (thrice weekly). We used generalized linear mixed models to examine the interaction between treatment group and illicit opioid use, as well as to decompose the analysis into within- and between-participant effects. RESULTS Craving for opioids and cocaine was increased when participants were using illicit opioids; this effect was greater in the clonidine group. For affect, mood was poorer during periods preceding opioid-positive urines than opioid-negative urines for clonidine-treated participants, whereas there was no difference for placebo participants. CONCLUSION This secondary analysis provides evidence that for participants maintained on opioid agonist therapy, clonidine minimized the behavioral impact of moderate levels of negative affect and craving.
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Affiliation(s)
- William J Kowalczyk
- a National Institute on Drug Abuse, Intramural Research Program , Clinical Pharmacology and Therapeutics Research Branch , Baltimore , MD, USA
- b Department of Psychology , Hartwick College , Oneonta , NY , USA
| | - Landhing M Moran
- a National Institute on Drug Abuse, Intramural Research Program , Clinical Pharmacology and Therapeutics Research Branch , Baltimore , MD, USA
| | - Jeremiah W Bertz
- a National Institute on Drug Abuse, Intramural Research Program , Clinical Pharmacology and Therapeutics Research Branch , Baltimore , MD, USA
| | - Karran A Phillips
- a National Institute on Drug Abuse, Intramural Research Program , Clinical Pharmacology and Therapeutics Research Branch , Baltimore , MD, USA
| | - Udi E Ghitza
- c National Institute on Drug Abuse, Center for Clinical Trials Network , Bethesda , MD , USA
| | - Massoud Vahabzadeh
- d National Institute on Drug Abuse, Intramural Research Program , Biomedical Informatics Section , Baltimore , MD , USA
| | - Jia-Ling Lin
- d National Institute on Drug Abuse, Intramural Research Program , Biomedical Informatics Section , Baltimore , MD , USA
| | - David H Epstein
- a National Institute on Drug Abuse, Intramural Research Program , Clinical Pharmacology and Therapeutics Research Branch , Baltimore , MD, USA
| | - Kenzie L Preston
- a National Institute on Drug Abuse, Intramural Research Program , Clinical Pharmacology and Therapeutics Research Branch , Baltimore , MD, USA
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11
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Ragia G, Veresies I, Veresie L, Veresies K, Manolopoulos VG. Association study of DRD2 A2/A1, DRD3 Ser9Gly, DβH -1021C>T, OPRM1 A118G and GRIK1 rs2832407C>A polymorphisms with alcohol dependence. Drug Metab Pers Ther 2017; 31:143-50. [PMID: 27447243 DOI: 10.1515/dmpt-2016-0015] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2016] [Accepted: 06/24/2016] [Indexed: 01/05/2023]
Abstract
BACKGROUND The reinforcing effects of alcohol are mediated through complex interactions between multiple neurochemical systems. Genes of dopaminergic (DRD2, DRD3 and DβH), opioid (OPRM1) and glutaminergic (GRIK1) systems mediate the dependent behavior via different mechanisms; however, they all target the serotonergic and dopaminergic pathways in the ventral tegmental area. METHODS In the present study, DRD2 A2/A1, DRD3 Ser9Gly, DβH -1021C>T, OPRM1 A118G and GRIK1 rs2832407C>A polymorphisms and their interactions were analyzed in 72 alcohol-dependent patients and 74 controls of Greek-Cypriot origin, using the PCR-RFLP method. RESULTS No differences were found in the genotype or allele distribution of DRD2 A2/A1, DRD3 Ser9Gly, DβH -1021C>T, OPRM1 A118G and GRIK1 rs2832407C>A between alcohol-dependent patients and controls. Additionally, we did not find any gene×gene interactions in association with alcohol dependence in the studied population. CONCLUSIONS Alcohol dependence is a complex interaction of genetic and environmental factors. In the present study, we have shown that DRD2 A2/A1, DRD3 Ser9Gly, DβH -1021C>T, OPRM1 A118G and GRIK1 rs2832407C>A are not associated with this dependent behavior alone or in interaction.
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12
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Isgro M, Doran N, Heffner JL, Wong E, Dinh E, Tibbs J, Russell K, Bittner T, Wehrle C, Worley MJ, Anthenelli RM. Type A/Type B Alcoholism Predicts Differential Response to Topiramate in a Smoking Cessation Trial in Dually Diagnosed Men. J Stud Alcohol Drugs 2017; 78:232-240. [PMID: 28317503 DOI: 10.15288/jsad.2017.78.232] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
OBJECTIVE Babor's A/B typology characterizes alcohol-dependence subtypes, which differ across multiple defining variables; however, differences in cigarette smoking and cessation between these subtypes have not been previously investigated. Topiramate reduces heavy drinking and has separately been found to help non-alcohol-dependent individuals quit smoking. This study tested the hypothesis that topiramate's effects on smoking would be moderated by alcohol-dependence subtype, and explored craving as a mediator of this response. METHOD One hundred twenty-nine abstinent alcohol-dependent outpatient male smokers participated in this 12-week, randomized controlled trial comparing topiramate (maximum dosage 200 mg/day) with placebo, both with brief counseling, for smoking cessation. Participants were followed for 24 weeks following end of treatment. RESULTS Of the 125 participants with sufficient subtyping data, k-means cluster analysis categorized 52 (42%) as Type A alcoholics and 73 (58%) as Type B. Types A and B did not differ on baseline smoking characteristics, urges to smoke, or smoking consequence scores. Longitudinal mixed-effects regression indicated that the effect of treatment on smoking was moderated by the Type × Time interaction. Specifically, during the nontreatment follow-up phase, Type B's treated with topiramate had relative suppressed levels of smoking compared with placebo-treated Type B's. This moderating effect of the Type × Time interaction was mediated by intention to smoke and craving related to relief of negative affect. CONCLUSIONS Type B alcoholics demonstrated suppressed levels of smoking in response to topiramate treatment as compared with placebo, but only during the nontreatment follow-up phase. This effect was mediated, in part, through intention to smoke and craving to smoke to relieve negative affect. Our findings extend other studies demonstrating a differential medication response by alcoholism subtype.
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Affiliation(s)
- Melodie Isgro
- Pacific Treatment and Research Center (Pac-TARC), San Diego Veterans Affairs Healthcare System, San Diego, California.,Department of Psychiatry, University of California, San Diego, Health Sciences, La Jolla, California
| | - Neal Doran
- Department of Psychiatry, University of California, San Diego, Health Sciences, La Jolla, California
| | | | - Esther Wong
- Department of Psychiatry, University of California, San Diego, Health Sciences, La Jolla, California
| | - Elizabeth Dinh
- Department of Psychiatry, University of California, San Diego, Health Sciences, La Jolla, California
| | - Jessie Tibbs
- Pacific Treatment and Research Center (Pac-TARC), San Diego Veterans Affairs Healthcare System, San Diego, California
| | - Katie Russell
- Pacific Treatment and Research Center (Pac-TARC), San Diego Veterans Affairs Healthcare System, San Diego, California.,Department of Psychiatry, University of California, San Diego, Health Sciences, La Jolla, California
| | - Tracy Bittner
- Department of Psychiatry, University of California, San Diego, Health Sciences, La Jolla, California
| | - Chris Wehrle
- Department of Psychiatry, University of California, San Diego, Health Sciences, La Jolla, California
| | - Matthew J Worley
- Pacific Treatment and Research Center (Pac-TARC), San Diego Veterans Affairs Healthcare System, San Diego, California.,Department of Psychiatry, University of California, San Diego, Health Sciences, La Jolla, California
| | - Robert M Anthenelli
- Pacific Treatment and Research Center (Pac-TARC), San Diego Veterans Affairs Healthcare System, San Diego, California.,Department of Psychiatry, University of California, San Diego, Health Sciences, La Jolla, California
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13
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Soyka M, Müller CA. Pharmacotherapy of alcoholism – an update on approved and off-label medications. Expert Opin Pharmacother 2017; 18:1187-1199. [DOI: 10.1080/14656566.2017.1349098] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Michael Soyka
- Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany
- Medical Park Chiemseeblick Fachklinik für Psychosomatik, Bernau, Germany
| | - Christian A. Müller
- Department of Psychiatry and Psychotherapy, Charité – Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany
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14
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Goh ET, Morgan MY. Review article: pharmacotherapy for alcohol dependence - the why, the what and the wherefore. Aliment Pharmacol Ther 2017; 45:865-882. [PMID: 28220511 DOI: 10.1111/apt.13965] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2016] [Revised: 11/29/2016] [Accepted: 01/12/2017] [Indexed: 12/20/2022]
Abstract
BACKGROUND The development of alcohol dependence is associated with significant morbidity and mortality. For the majority of affected people the most appropriate goal, in terms of drinking behaviour, is abstinence from alcohol. Psychosocial intervention is the mainstay of the treatment but adjuvant pharmacotherapy is also available and its use recommended. AIM To provide an updated analysis of current and potential pharmacotherapeutic options for the management of alcohol dependence. In addition, factors predictive of therapeutic outcome, including compliance and pharmacogenetics, and the current barriers to treatment, including doctors' unwillingness to prescribe these agents, will be explored. METHODS Relevant papers were selected for review following extensive, language- and date-unrestricted, electronic and manual searches of the literature. RESULTS Acamprosate and naltrexone have a substantial evidence base for overall efficacy, safety and cost-effectiveness while the risks associated with the use of disulfiram are well-known and can be minimised with appropriate patient selection and supervision. Acamprosate can be used safely in patients with liver disease and in those with comorbid mental health issues and co-occurring drug-related problems. A number of other agents are being investigated for potential use for this indication including: baclofen, topiramate and metadoxine. CONCLUSION Pharmacotherapy for alcohol dependence has been shown to be moderately efficacious with few safety concerns, but it is substantially underutilised. Concerted efforts must be made to remove the barriers to treatment in order to optimise the management of people with this condition.
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Affiliation(s)
- E T Goh
- UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College London, London, UK
| | - M Y Morgan
- UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College London, London, UK
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15
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Rinker JA, Fulmer DB, Trantham-Davidson H, Smith ML, Williams RW, Lopez MF, Randall PK, Chandler LJ, Miles MF, Becker HC, Mulholland PJ. Differential potassium channel gene regulation in BXD mice reveals novel targets for pharmacogenetic therapies to reduce heavy alcohol drinking. Alcohol 2017; 58:33-45. [PMID: 27432260 DOI: 10.1016/j.alcohol.2016.05.007] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2015] [Revised: 04/12/2016] [Accepted: 05/03/2016] [Indexed: 12/22/2022]
Abstract
Alcohol (ethanol) dependence is a chronic relapsing brain disorder partially influenced by genetics and characterized by an inability to regulate harmful levels of drinking. Emerging evidence has linked genes that encode KV7, KIR, and KCa2 K+ channels with variation in alcohol-related behaviors in rodents and humans. This led us to experimentally test relations between K+ channel genes and escalation of drinking in a chronic-intermittent ethanol (CIE) exposure model of dependence in BXD recombinant inbred strains of mice. Transcript levels for K+ channel genes in the prefrontal cortex (PFC) and nucleus accumbens (NAc) covary with voluntary ethanol drinking in a non-dependent cohort. Transcripts that encode KV7 channels covary negatively with drinking in non-dependent BXD strains. Using a pharmacological approach to validate the genetic findings, C57BL/6J mice were allowed intermittent access to ethanol to establish baseline consumption before they were treated with retigabine, an FDA-approved KV7 channel positive modulator. Systemic administration significantly reduced drinking, and consistent with previous evidence, retigabine was more effective at reducing voluntary consumption in high-drinking than low-drinking subjects. We evaluated the specific K+ channel genes that were most sensitive to CIE exposure and identified a gene subset in the NAc and PFC that were dysregulated in the alcohol-dependent BXD cohort. CIE-induced modulation of nine genes in the NAc and six genes in the PFC covaried well with the changes in drinking induced by ethanol dependence. Here we identified novel candidate genes in the NAc and PFC that are regulated by ethanol dependence and correlate with voluntary drinking in non-dependent and dependent BXD mice. The findings that Kcnq expression correlates with drinking and that retigabine reduces consumption suggest that KV7 channels could be pharmacogenetic targets to treat individuals with alcohol addiction.
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Ray LA, Bujarski S. Mechanisms of topiramate effects: refining medications development for alcoholism. Addict Biol 2016; 21:183-184. [PMID: 25876675 DOI: 10.1111/adb.12226] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Lara A. Ray
- Department of Psychology; University of California; Los Angeles CA 90095-1563 USA
| | - Spencer Bujarski
- Department of Psychology; University of California; Los Angeles CA 90095-1563 USA
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Magill M, Kiluk BD, McCrady BS, Tonigan JS, Longabaugh R. Active Ingredients of Treatment and Client Mechanisms of Change in Behavioral Treatments for Alcohol Use Disorders: Progress 10 Years Later. Alcohol Clin Exp Res 2015; 39:1852-62. [PMID: 26344200 PMCID: PMC4592447 DOI: 10.1111/acer.12848] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Accepted: 07/20/2015] [Indexed: 11/30/2022]
Abstract
BACKGROUND The current review revisits the article entitled: "Active Ingredients: How and Why Evidence-Based Alcohol Behavioral Treatment Interventions Work" published in Alcoholism: Clinical and Experimental Research. This work summarized proceedings from a 2004 Symposium of the same name that was held at the Annual Meeting of the Research Society on Alcoholism (RSA). A decade has passed, which provides occasion for an evaluation of progress. In 2014, an RSA symposium titled Active Treatment Ingredients and Client Mechanisms of Change in Behavioral Treatments for Alcohol Use Disorders: Progress 10 Years Later did just that. METHODS The current review revisits state-of-the-art research on the 3 treatments examined 10 years ago: cognitive behavioral therapy, alcohol behavior couples therapy, and 12-step facilitation. Because of its empirically validated effectiveness and robust research agenda on the study of process outcome, motivational interviewing has been selected as the fourth treatment modality to be discussed. For each of these 4 treatments, the reviewers provide a critical assessment of current theory and research with a special emphasis on key recommendations for the future. RESULTS Noteworthy progress has been made in identifying active ingredients of treatments and mechanisms of behavior change in these 4 behavioral interventions for alcohol and other drug use disorders. Not only have we established some of the mechanisms through which these evidence-based treatments work, but we have also uncovered some of the limitations in our existing frameworks and methods. CONCLUSIONS Further progress in this area will require a broader view with respect to conceptual frameworks, analytic methods, and measurement instrumentation.
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Affiliation(s)
- Molly Magill
- Center for Alcohol and Addiction Studies, Brown University, Providence, Rhode Island
| | - Brian D Kiluk
- Yale University School of Medicine, New Haven, Connecticut
| | - Barbara S McCrady
- Center on Substance Abuse, Alcoholism, and Addictions, University of New Mexico, Albuquerque, New Mexico
| | - J Scott Tonigan
- Center on Substance Abuse, Alcoholism, and Addictions, University of New Mexico, Albuquerque, New Mexico
| | - Richard Longabaugh
- Center for Alcohol and Addiction Studies, Brown University, Providence, Rhode Island
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Witkiewitz K, Finney JW, Harris AH, Kivlahan DR, Kranzler HR. Recommendations for the Design and Analysis of Treatment Trials for Alcohol Use Disorders. Alcohol Clin Exp Res 2015; 39:1557-70. [PMID: 26250333 PMCID: PMC4558228 DOI: 10.1111/acer.12800] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Accepted: 05/30/2015] [Indexed: 12/14/2022]
Abstract
BACKGROUND Over the past 60 years, the view that "alcoholism" is a disease for which the only acceptable goal of treatment is abstinence has given way to the recognition that alcohol use disorders (AUDs) occur on a continuum of severity, for which a variety of treatment options are appropriate. However, because the available treatments for AUDs are not effective for everyone, more research is needed to develop novel and more efficacious treatments to address the range of AUD severity in diverse populations. Here we offer recommendations for the design and analysis of alcohol treatment trials, with a specific focus on the careful conduct of randomized clinical trials of medications and nonpharmacological interventions for AUDs. METHODS This paper provides a narrative review of the quality of published clinical trials and recommendations for the optimal design and analysis of treatment trials for AUDs. RESULTS Despite considerable improvements in the design of alcohol clinical trials over the past 2 decades, many studies of AUD treatments have used faulty design features and statistical methods that are known to produce biased estimates of treatment efficacy. CONCLUSIONS The published statistical and methodological literatures provide clear guidance on methods to improve clinical trial design and analysis. Consistent use of state-of-the-art design features and analytic approaches will enhance the internal and external validity of treatment trials for AUDs across the spectrum of severity. The ultimate result of this attention to methodological rigor is that better treatment options will be identified for patients with an AUD.
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Affiliation(s)
- Katie Witkiewitz
- Department of Psychology and Center on Alcoholism, Substance Abuse, and Addictions, University of New Mexico
| | - John W. Finney
- Center for Innovation to Implementation, VA Palo Alto Health Care System, Menlo Park, CA
| | - Alex H.S Harris
- VA Substance Use Disorder Quality Enhancement Research Initiative, VA Palo Alto Health Care System, Menlo Park, CA
| | - Daniel R. Kivlahan
- Veterans Health Administration, Washington, DC and Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle
| | - Henry R. Kranzler
- Center for Studies of Addiction, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine and VISN4 MIRECC, Philadelphia VAMC, Philadelphia, PA
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Obed A, Stern S, Jarrad A, Lorf T. Six month abstinence rule for liver transplantation in severe alcoholic liver disease patients. World J Gastroenterol 2015; 21:4423-4426. [PMID: 25892898 PMCID: PMC4394109 DOI: 10.3748/wjg.v21.i14.4423] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2014] [Revised: 01/12/2015] [Accepted: 01/30/2015] [Indexed: 02/06/2023] Open
Abstract
Alcoholic liver disease (ALD) is the second most common diagnosis among patients undergoing liver transplantation (LT). The recovery results of patients transplanted for ALD are often at least as good as those of patients transplanted for other diagnoses and better than those suffering from hepatitis C virus, cryptogenic cirrhosis, or hepatocellular carcinoma. In the case of medically non-responding patients with severe acute alcoholic hepatitis or acute-on chronic liver failure, the refusal of LT is often based on the lack of the required alcohol abstinence period of six months. The obligatory abidance of a period of abstinence as a transplant eligibility requirement for medically non-responding patients seems unfair and inhumane, since the majority of these patients will not survive the six-month abstinence period. Data from various studies have challenged the 6-mo rule, while excellent survival results of LT have been observed in selected patients with severe alcoholic hepatitis not responding to medical therapy. Patients with severe advanced ALD should have legal access to LT. The mere lack of pre-LT abstinence should not be an obstacle for being listed.
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Hammond CJ, Niciu MJ, Drew S, Arias AJ. Anticonvulsants for the treatment of alcohol withdrawal syndrome and alcohol use disorders. CNS Drugs 2015; 29:293-311. [PMID: 25895020 PMCID: PMC5759952 DOI: 10.1007/s40263-015-0240-4] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Alcoholic patients suffer from harmful allostatic neuroplastic changes in the brain causing an acute withdrawal syndrome upon cessation of drinking followed by a protracted abstinence syndrome and an increased risk of relapse to heavy drinking. Benzodiazepines have long been the treatment of choice for detoxifying patients and managing alcohol withdrawal syndrome (AWS). Non-benzodiazepine anticonvulsants (NBACs) are increasingly being used both for alcohol withdrawal management and for ongoing outpatient treatment of alcohol dependence, with the goal of either abstinence or harm reduction. This expert narrative review summarizes the scientific basis and clinical evidence supporting the use of NBACs in treating AWS and for reducing harmful drinking patterns. There is less evidence in support of NBAC therapy for AWS, with few placebo-controlled trials. Carbamazepine and gabapentin appear to be the most promising adjunctive treatments for AWS, and they may be useful as monotherapy in select cases, especially in outpatient settings and for the treatment of mild-to-moderate low-risk patients with the AWS. The body of evidence supporting the use of the NBACs for reducing harmful drinking in the outpatient setting is stronger. Topiramate appears to have a robust effect on reducing harmful drinking in alcoholics. Gabapentin is a potentially efficacious treatment for reducing the risk of relapse to harmful drinking patterns in outpatient management of alcoholism. Gabapentin's ease of use, rapid titration, good tolerability, and efficacy in both the withdrawal and chronic phases of treatment make it particularly appealing. In summary, several NBACs appear to be beneficial in treating AWS and alcohol use disorders.
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Affiliation(s)
- Christopher J. Hammond
- Yale Child Study Center, Yale University School of Medicine, PO Box 207900, 230 South Frontage Road, New Haven, CT 06520, USA, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
| | - Mark J. Niciu
- Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, Bethesda, MD, USA
| | - Shannon Drew
- Veterans Affairs Connecticut Healthcare System-West Haven Campus, West Haven, CT, USA
| | - Albert J. Arias
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA, Veterans Affairs Connecticut Healthcare System-West Haven Campus, West Haven, CT, USA
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