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Effect of Cognitive Bias Modification on Early Relapse Among Adults Undergoing Inpatient Alcohol Withdrawal TreatmentA Randomized Clinical Trial

Educational Objective
To test the hypothesis that cognitive bias modification (CBM) would increase the likelihood of abstaining from alcohol during the 2 weeks following discharge from inpatient withdrawal treatment.
1 Credit CME
Key Points

Question  Is computerized cognitive bias modification training during inpatient alcohol withdrawal treatment associated with the likelihood of relapse in the first 2 weeks after discharge?

Findings  In a randomized clinical trial of 300 patients with alcohol use disorder receiving inpatient withdrawal treatment, cognitive bias modification significantly increased the proportion who maintained abstinence during the follow-up period (54.4% vs 42.5% with sham training) in intention-to-treat analysis and by 17% (63.8% vs 46.8%) in per-protocol analysis.

Meaning  The findings of this trial show that cognitive bias modification during alcohol withdrawal helps prevent relapse during the high-risk early period following discharge from treatment; its implementation as an adjunctive intervention in this setting is recommended.


Importance  More than half of patients with alcohol use disorder who receive inpatient withdrawal treatment relapse within weeks of discharge, hampering subsequent uptake and effectiveness of psychological and pharmacologic interventions. Cognitive bias modification (CBM) improves outcomes after alcohol rehabilitation, but the efficacy of delivering CBM during withdrawal treatment has not yet been established.

Objective  To test the hypothesis that CBM would increase the likelihood of abstaining from alcohol during the 2 weeks following discharge from inpatient withdrawal treatment.

Design, Setting, and Participants  In a randomized clinical trial, 950 patients in 4 inpatient withdrawal units in Melbourne, Australia, were screened for eligibility between June 4, 2017, and July 14, 2019, to receive CBM or sham treatment. Patients with moderate or severe alcohol use disorder aged 18 to 65 years who had no neurologic illness or traumatic brain injury were eligible. Two-week follow-up, conducted by researchers blinded to the participant’s condition, was the primary end point. Both per-protocol and intention-to-treat analysis were conducted.

Interventions  Randomized to 4 consecutive daily sessions of CBM designed to reduce alcohol approach bias or sham training not designed to modify approach bias.

Main Outcomes and Measures  Primary outcome was abstinence assessed using a timeline followback interview. Participants were classified as abstinent (no alcohol use in the first 14 days following discharge) or relapsed (any alcohol use during the first 14 days following discharge or lost to follow-up).

Results  Of the 950 patients screened for eligibility, 338 did not meet inclusion criteria, 108 were discharged before being approached, and 192 refused. Of the 312 patients who consented (referred sample), 12 withdrew before being randomized. In the final population of 300 randomized patients (CBM, n = 147; sham, n = 153), 248 completed the intervention and 272 completed the follow-up. Of the 300 participants (173 [57.7%] men; mean [SD] age, 43.47 [10.43] years), 7 patients (3 controls, 4 CBM) withdrew after finding the training uncomfortable. Abstinence rates were 42.5% (95% CI, 34.3%-50.6%) in controls and 54.4% (95% CI, 46.0%-62.8%) in CBM participants, yielding an 11.9% (95% CI, 0.04%-23.8%; P = .04) difference in abstinence rates. In a per-protocol analysis including only those who completed 4 sessions of training and the follow-up, the difference in abstinence rate between groups was 17.0% (95% CI, 3.8%-30.2%; P = .008).

Conclusions and Relevance  The findings of this clinical trial support the efficacy of CBM for treatment of alcohol use disorder. Being safe and easy to implement, requiring only a computer and joystick, and needing no specialist staff/training, CBM could be routinely offered as an adjunctive intervention during withdrawal treatment to optimize outcomes.

Trial Registration  Australian New Zealand Clinical Trials Registry Identifier: ACTRN12617001241325

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Article Information

Accepted for Publication: August 28, 2020.

Published Online: November 4, 2020. doi:10.1001/jamapsychiatry.2020.3446

Corresponding Author: Victoria Manning, PhD, Turning Point, Eastern Health, 110 Church St, Richmond, VIC 3121, Australia (victoria.manning@monash.edu).

Author Contributions: Dr Reynolds had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Manning, Garfield, Staiger, Lubman, Lum, Reynolds, Hall, Lloyd-Jones, Wiers, Verdejo-Garcia.

Acquisition, analysis, or interpretation of data: Manning, Garfield, Lum, Reynolds, Bonomo, Lloyd-Jones, Piercy, Jacka, Verdejo-Garcia.

Drafting of the manuscript: Manning, Garfield, Lubman, Lum, Reynolds, Lloyd-Jones, Wiers, Piercy.

Critical revision of the manuscript for important intellectual content: Manning, Garfield, Staiger, Lubman, Reynolds, Hall, Bonomo, Lloyd-Jones, Piercy, Jacka, Verdejo-Garcia.

Statistical analysis: Lum, Reynolds.

Obtained funding: Manning, Staiger, Lubman, Lum, Reynolds, Hall, Verdejo-Garcia.

Administrative, technical, or material support: Manning, Garfield, Staiger, Lubman, Lum, Bonomo, Piercy, Jacka.

Supervision: Manning, Piercy.

Conflict of Interest Disclosures: Dr Manning reported receiving grants from the National Health and Medical Research Council (NHMRC) during the conduct of the study. Dr Garfield reported receiving salary support through an NHMRC grant during the conduct of the study. Dr Lubman has provided consultancy advice to Lundbeck and Indivior outside the submitted work; has received travel support and speaker honoraria from AstraZeneca, Camurus, Indivior, Janssen, Lundbeck, Shire, and Servier outside the submitted work; and has been an investigator on an untied education grant from Sequirus unrelated to the current work. Dr Reynolds reported receiving grants from the NHMRC during the conduct of the study, grants from AbbVie outside the submitted work, being a former employee of Novartis AG (2009-2012), and holding shares in Novartis AG and ALCON. Dr Bonomo has received research grants from St Vincent's Health Australia Research Foundation and the NHMRC unrelated to the current work; has received research support from Merck Sharp & Dohme, Victorian Medical Research Acceleration Fund, and Perpetual IMPACT Philanthropy Fund, all unrelated to the current work; has been on advisory boards for Indivior and Seqiris; and is a principal investigator for an industry-sponsored clinical trial of the pharmacokinetics of medicinal cannabis for Zelira Therapeutics unrelated to the current work. Dr Lloyd-Jones reported receiving personal fees from Indivior outside the submitted work. Mr Piercy reported salary support through an NHMRC grant during the conduct of the study. Dr Verdejo-Garcia reported receiving grants from the Australian Medical Research Future Fund and grants from the NHMRC during the conduct of the study, personal fees from Servier and Elsevier outside the submitted work, and being part of the Scientific Advisory Board of Monclarity/Brainwell, which produces cognitive training games, but does not receive any honorarium. No other disclosures were reported.

Funding/Support: This study was funded by grant 1124604 from the NHMRC.

Role of the Funder/Sponsor: The NHMRC 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: We appreciate the work done by research assistants and volunteers in collecting these data who are employed by Monash University and Eastern Health, including Katherine Mroz, JD, Samuel Campbell, MDS, Patrick Haylock, BSc (Hons), Kristina Vujcic, BA, and Nyssa Fergusson, MPH, who received a salary in compensation for their work, and Alexandra Turnbull, BHSc (Hons), a volunteer affiliated with Monash University who did not receive compensation for her involvement. Also included are honors students from the Monash University School of Psychological Sciences: Thomas Tolliday, BA (Hons), and Emily Darmanin, BSc (Hons), who did not receive compensation for supporting this research. We also thank the nursing, administrative, and other staff at the recruitment sites, including but not limited to Angela Fazio, BNurs, and Jennifer Kelly, RN (Depaul House, Saint Vincent’s Hospital Melbourne), Molly O’Reilly, DipSocSc (Windana Drug and Alcohol Recovery), Michelle Cody, Cert IV (Monash Health Community Residential Withdrawal Unit), and Alex Lebani, BSc, Trudy Trice, DipNurs, and Bernadette De Boer (Turning Point, Eastern Health). These staff did not receive compensation for supporting this study. Paul Sanfilippo, PhD, a biostatistician (Monash Addiction Research Centre, Monash University), assisted with statistical analyses and received no compensation beyond his salary for this work.

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