A practice quit model to test early efficacy of medications for alcohol use disorder in a randomized clinical trial.
Alcohol use disorder
Cue-reactivity
Naltrexone
Pharmacotherapy
Varenicline
Journal
Psychopharmacology
ISSN: 1432-2072
Titre abrégé: Psychopharmacology (Berl)
Pays: Germany
ID NLM: 7608025
Informations de publication
Date de publication:
28 Nov 2023
28 Nov 2023
Historique:
received:
12
07
2023
accepted:
07
11
2023
medline:
28
11
2023
pubmed:
28
11
2023
entrez:
27
11
2023
Statut:
aheadofprint
Résumé
Screening novel medications for alcohol use disorder (AUD) requires models that are both efficient and ecologically-valid. Ideally, such models would be associated with the outcomes of a given medication in clinical trials. To test a novel human laboratory model in which individuals with intrinsic motivation to change their drinking engage in a "practice quit" attempt consisting of 6 days of complete abstinence from alcohol. Individuals with current AUD completed a randomized, double-blind, placebo-controlled study of naltrexone (50 mg), varenicline (2 mg bid), or matched placebo. Participants were titrated onto the study medication for 1 week prior to starting the 6-day practice quit attempt. During the practice quit attempt, participants completed daily interviews with research staff. All participants completed an alcohol cue-exposure paradigm before starting the study medication and after 2 weeks of study medication. There were no significant medication effect on drinks per drinking day (F(2,49) = 0.66, p = 0.52) or percent days abstinent (F(2,49) = 0.14, p = 0.87) during the 6-day practice quit period. There were no medication effects on alcohol cue-reactivity (F(2,44) = 0.80, p = 0.46). Notably, participants sharply reduced their drinking during the entire 13-day medication treatment period, as compared to reducing only during the 6-day practice quit period. During the total medication period, higher levels of motivation to change was associated with higher percent days abstinent (F(1,49) = 8.12, p < 0.01). This study reports mostly null findings, which challenges us to decompose its nuanced design to consider model refinements. Possible changes to the model include considering the requirement for intrinsic motivation for change, including a longer practice quit period, encompassing the medication administration timeframe in the practice quit period, increasing the required sample size for signal detection, and examining a post COVID-19 pandemic cohort.
Identifiants
pubmed: 38012333
doi: 10.1007/s00213-023-06504-6
pii: 10.1007/s00213-023-06504-6
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Références
Anton RF, Moak DH, Latham PK (1996) The Obsessive Compulsive Drinking Scale: A New Method of Assessing Outcome in Alcoholism Treatment Studies. Arch Gen Psychiatry 53:225–231
pubmed: 8611059
Beck AT, Epstein N, Brown G, Steer RA (1988) An inventory for measuring clinical anxiety: Psychometric properties. J Consult Clin Psychol 56:893–897
pubmed: 3204199
Beck AT, Steer RA, Brown G (1996) Beck depression inventory–II. Psychological assessment
Biener L, Abrams DB (1991) The Contemplation Ladder: validation of a measure of readiness to consider smoking cessation. Health Psychol 10:360–365
pubmed: 1935872
Bohn MJ, Krahn DD, Staehler BA (1995) Development and Initial Validation of a Measure of Drinking Urges in Abstinent Alcoholics. Alcohol Clin Exp Res 19:600–606
pubmed: 7573780
Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ (1989) The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 28:193–213
pubmed: 2748771
Cooney NL, Litt MD, Morse PA, Bauer LO, Gaupp L (1997) Alcohol cue reactivity, negative-mood reactivity, and relapse in treated alcoholic men. J Abnorm Psychol 106:243–250
pubmed: 9131844
Deci EL, Ryan RM (1985) The general causality orientations scale: self-determination in personality. J Res Pers 19(2):109–134
First MB, Williams JB, Karg RS, Spitzer RL (2015) Structured clinical interview for DSM-5—Research version (SCID-5 for DSM-5, research version; SCID-5-RV). American Psychiatric Association, pp 1–94
Flannery BA, Volpicelli JR, Pettinati HM (1999) Psychometric properties of the Penn Alcohol Craving Scale. Alcohol Clin Exp Res 23:1289–1295
pubmed: 10470970
Grant BF, Goldstein RB, Saha TD, Chou SP, Jung J, Zhang H, Pickering RP, Ruan WJ, Smith SM, Huang B, Hasin DS (2015) Epidemiology of DSM-5 Alcohol Use Disorder: Results From the National Epidemiologic Survey on Alcohol and Related Conditions III. JAMA Psychiatry 72:757–766
pubmed: 26039070
pmcid: 5240584
Grodin EN, Bujarski S, Venegas A, Baskerville W-A, Nieto SJ, Jentsch JD, Ray LA (2019) Reward, Relief and Habit Drinking: Initial Validation of a Brief Assessment Tool. Alcohol Alcohol 54:574–583
pubmed: 31557278
pmcid: 7306183
Haass-Koffler CL, Magill M, Cannella N, Brown JC, Aoun EG, Cioe PA, Sinha R, Swift RM, Ciccocioppo R, Leggio L (2023) Mifepristone as a pharmacological intervention for stress-induced alcohol craving: A human laboratory study. Addict Biol 28:e13288
pubmed: 37369125
Heatherton TF, Kozlowski LT, Frecker RC, Ko F (1991) The Fagerström test for nicotine dependence: a revision of the Fagerstrom Tolerance Questionnaire. Br J Addict 86:1119–1127
pubmed: 1932883
Hendershot CS, Wardell JD, Samokhvalov AV, Rehm J (2017) Effects of naltrexone on alcohol self-administration and craving: meta-analysis of human laboratory studies. Addict Biol 22:1515–1527
pubmed: 27411969
Ho D, Towns B, Grodin EN, Ray LA (2020) A novel human laboratory model for screening medications for alcohol use disorder. Trials 21:947
pubmed: 33225963
pmcid: 7681966
Jacobson AF, Goldstein BJ, Dominguez RA, Steinbook RM (1986) Interrater agreement and intraclass reliability measures of SAFTEE in psychopharmacologic clinical trials. Psychopharmacol Bull 22:382–388
pubmed: 3774931
Leggio L, Zywiak WH, McGeary JE, Edwards S, Fricchione SR, Shoaff JR, Addolorato G, Swift RM, Kenna GA (2013) A human laboratory pilot study with baclofen in alcoholic individuals. Pharmacol Biochem Behav 103:784–791
pubmed: 23262301
Leventhal AM, Cho J, Ray LA, Liccardo Pacula R, Lee BP, Terrault N, Pedersen E, Lee JO, Davis JP, Jin H, Huh J, Wilson JP, Whaley RC (2022) Alcohol use trajectories among U.S. adults during the first 42 weeks of the COVID-19 pandemic. Alcohol Clin Exp Res 46:1062–1072
pubmed: 35532741
pmcid: 9246926
Levine J, Schooler NR (1986) SAFTEE: a technique for the systematic assessment of side effects in clinical trials. Psychopharmacol Bull 22:343–381
pubmed: 3774930
Litten RZ, Egli M, Heilig M, Cui C, Fertig JB, Ryan ML, Falk DE, Moss H, Huebner R, Noronha A (2012) Medications development to treat alcohol dependence: a vision for the next decade. Addict Biol 17:513–527
pubmed: 22458728
pmcid: 3484365
Litten RZ, Falk DE, Ryan ML, Fertig JB (2016) Discovery, Development, and Adoption of Medications to Treat Alcohol Use Disorder: Goals for the Phases of Medications Development. Alcohol Clin Exp Res 40:1368–1379
pubmed: 27184259
pmcid: 4930402
Litten RZ, Ryan ML, Fertig JB, Falk DE, Johnson B, Dunn KE, Green AI, Pettinati HM, Ciraulo DA, Sarid-Segal O, Kampman K, Brunette MF, Strain EC, Tiouririne NA, Ransom J, Scott C, Stout R (2013) A double-blind, placebo-controlled trial assessing the efficacy of varenicline tartrate for alcohol dependence. J Addict Med 7:277–286
pubmed: 23728065
pmcid: 3914416
MacKillop J, Agabio R, Feldstein Ewing SW, Heilig M, Kelly JF, Leggio L, Lingford-Hughes A, Palmer AA, Parry CD, Ray L, Rehm J (2022) Hazardous drinking and alcohol use disorders. Nat Rev Dis Primers 8:80
pubmed: 36550121
pmcid: 10284465
Meredith LR, Burnette EM, Nieto SJ, Du H, Donato S, Grodin EN, Green R, Magill M, Baskerville WA, Ray LA (2023) Testing pharmacotherapies for alcohol use disorder with cue exposure paradigms: a systematic review and quantitative synthesis of human laboratory trial methodology. Alcohol Clin Exp Res (Hoboken). https://doi.org/10.1111/acer.15143
Miranda R Jr, O'Malley SS, Treloar Padovano H, Wu R, Falk DE, Ryan ML, Fertig JB, Chun TH, Muvvala SB, Litten RZ (2020) Effects of Alcohol Cue Reactivity on Subsequent Treatment Outcomes Among Treatment-Seeking Individuals with Alcohol Use Disorder: A Multisite Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Varenicline. Alcohol Clin Exp Res 44:1431–1443
pubmed: 32363592
pmcid: 7572549
Monti PM, Binkoff JA, Abrams DB, Zwick WR, Nirenberg TD, Liepman MR (1987) Reactivity of alcoholics and nonalcoholics to drinking cues. J Abnorm Psychol 96:122–126
pubmed: 3584660
Monti PM, Rohsenow DJ, Swift RM, Gulliver SB, Colby SM, Mueller TI, Brown RA, Gordon A, Abrams DB, Niaura RS, Asher MK (2001) Naltrexone and cue exposure with coping and communication skills training for alcoholics: treatment process and 1-year outcomes. Alcohol Clin Exp Res 25:1634–1647
pubmed: 11707638
Perkins KA (2012) Subjective reactivity to smoking cues as a predictor of quitting success. Nicotine Tob Res 14:383–387
pubmed: 22140145
Perkins KA (2014) Improving efficiency of initial tests for efficacy in smoking cessation drug discovery. Expert Opin Drug Discovery 9:1259–1264
Perkins KA, Lerman C (2014) An efficient early phase 2 procedure to screen medications for efficacy in smoking cessation. Psychopharmacology (Berl) 231:1–11
pubmed: 24297304
Perkins KA, Lerman C, Fonte CA, Mercincavage M, Stitzer ML, Chengappa KN, Jain A (2010) Cross-validation of a new procedure for early screening of smoking cessation medications in humans. Clin Pharmacol Ther 88:109–114
pubmed: 20485335
Perkins KA, Lerman C, Stitzer M, Fonte CA, Briski JL, Scott JA, Chengappa KN (2008) Development of procedures for early screening of smoking cessation medications in humans. Clin Pharmacol Ther 84:216–221
pubmed: 18388880
Perkins KA, Stitzer M, Lerman C (2006) Medication screening for smoking cessation: a proposal for new methodologies. Psychopharmacology (Berl) 184:628–636
pubmed: 16163529
Ray LA, Bujarski S, Roche DJO, Magill M (2018) Overcoming the "Valley of Death" in Medications Development for Alcohol Use Disorder. Alcohol Clin Exp Res 42:1612–1622
pubmed: 29969156
pmcid: 6146966
Ray LA, Bujarski S, Yardley MM, Roche DJO, Hartwell EE (2017) Differences between treatment-seeking and non-treatment-seeking participants in medication studies for alcoholism: do they matter? Am J Drug Alcohol Abuse 43:703–710
pubmed: 28426264
pmcid: 6159933
Ray LA, Chin PF, Miotto K (2010a) Naltrexone for the treatment of alcoholism: clinical findings, mechanisms of action, and pharmacogenetics. CNS Neurol Disord Drug Targets 9:13–22
pubmed: 20201811
Ray LA, Du H, Green R, Roche DJO, Bujarski S (2021) Do behavioral pharmacology findings predict clinical trial outcomes? A proof-of-concept in medication development for alcohol use disorder. Neuropsychopharmacology 46:519–527
pubmed: 33235284
Ray LA, Green R, Roche DJO, Magill M, Bujarski S (2019) Naltrexone effects on subjective responses to alcohol in the human laboratory: A systematic review and meta-analysis. Addict Biol 24:1138–1152
pubmed: 31148304
pmcid: 6819195
Ray LA, Hutchison KE, Tartter M (2010b) Application of human laboratory models to pharmacotherapy development for alcohol dependence. Curr Pharm Des 16:2149–2158
pubmed: 20482505
Rohn MC, Lee MR, Kleuter SB, Schwandt ML, Falk DE, Leggio L (2017) Differences Between Treatment-Seeking and Nontreatment-Seeking Alcohol-Dependent Research Participants: An Exploratory Analysis. Alcohol Clin Exp Res 41:414–420
pubmed: 28129451
pmcid: 6468994
Rollnick S, Miller WR (1995) What is motivational interviewing?. Behav Cogn Psychother 23(4):325–334
Skinner HA, Allen BA (1982) Alcohol dependence syndrome: measurement and validation. J Abnorm Psychol 91:199–209
pubmed: 7096790
Sobell MB, Sobell LC, Klajner F, Pavan D, Basian E (1986) The reliability of a timeline method for assessing normal drinker college students' recent drinking history: utility for alcohol research. Addict Behav 11:149–161
pubmed: 3739800
Sullivan JT, Sykora K, Schneiderman J, Naranjo CA, Sellers EM (1989) Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). Br J Addict 84:1353–1357
pubmed: 2597811
Upton GJ (1992) Fisher's exact test. J R Stat Soc A Stat Soc 155:395–402
Yardley MM, Ray LA (2016) Medications development for the treatment of alcohol use disorder: insights into the predictive value of animal and human laboratory models. Addict Biol 22(3):581–615. https://doi.org/10.1111/adb.12349