ALCO-VR Project: A randomized clinical trial evaluating virtual reality cue-exposure Therapy for Treatment-Resistant Alcohol Use Disorder patients
DOI:
https://doi.org/10.20882/adicciones.1958Keywords:
alcohol use disorder, alcohol craving, anxiety, virtual reality, cue-exposure therapy, clinical trialAbstract
The management of “treatment-resistant” alcohol use disorder (AUD) often presents significant challenges. Virtual reality (VR) applications, specifically VR cue exposure therapy (VR-CET), offer a potentially complementary approach to the standard treatment (TAU). This randomized clinical trial (RCT) aimed to assess VR-CET’s effectiveness when added to TAU, compared to TAU alone, in reducing alcohol craving and anxiety among individuals with treatment-resistant AUD. The study also sought to determine anxiety and craving levels during VR-CET sessions and to explore long-term effects. Eighty-five AUD patients from the Clinic Hospital of Barcelona participated. They were randomly assigned to either an experimental group (EG), receiving VR-CET plus TAU, or a control group (CG), receiving TAU alone. The EG completed six VR-CET sessions alongside TAU, while the CG continued with only TAU. Alcohol craving and anxiety were assessed before and after treatment for both groups, and during VR-CET sessions for the EG. Relapses were monitored at 3-, 6-, and 12-months post-treatment. Results indicated no significant main effects of “type of treatment” (EG vs. CG) on craving or anxiety. However, a significant “time” factor was observed, showing reductions in craving and anxiety from pre-test to post-test, regardless of the treatment type. Within VR-CET sessions, EG participants reported minimal anxiety and craving by the end of the therapy. Importantly, no statistically significant differences in relapse rates were found between the EG and CG at any follow-up period (3, 6, 12 months). The clinical implications of the study, limitations, and research directions are further discussed.References
American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed): DSM-5. Arlington, VA: American Psychiatric Association.
Andersson, H. W., Wenaas, M. & Nordfjærn, T. (2019). Relapse after inpatient substance use treatment: A prospective cohort study among users of illicit substances. Addictive Behaviors, 90, 222–228. https://doi.org/10.1016/j.addbeh.2018.11.008
Anker, J. J., Kummerfeld, E., Rix, A., Burwell, S. J. & Kushner, M. G. (2018). Causal Network Modeling of the determinants of drinking behavior in comorbid alcohol use and anxiety disorder. Alcoholism, Clinical and Experimental Research, 43, 91–97. https://doi.org/10.1111/acer.13914
Association, W. M. (2001). World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. Bulletin of the World Health Organization, 79(4), 373–374. https://doi.org/10.1111/ddg.13528
Babor, T. F., Biddle-Higgins, J. C., Saunders, J. B. & Monteiro, M. G. (2001). AUDIT: The Alcohol Use Disorders Identification Test: Guidelines for Use in Primary Health Care. Geneva, Switzerland: World Health Organization. https://iris.who.int/handle/10665/67205
Bados, A., Gómez-Benito, J. & Balaguera, G. (2010). The State-Trait Anxiety Inventory, Trait Version: Does it really measure anxiety? Journal of Personality Assessment, 92, 560-567
Bakker, M., van Dijk, A. & Wicherts, J. M. (2012). The Rules of the Game Called Psychological Science. Perspectives on Psychological Science, 7(6), 543–554. https://doi.org/10.1177/1745691612459060
Bernard, L., Cyr, L., Bonnet-Suard, A., Cutarella, C. & Bréjard, V. (2021). Drawingalcohol craving process: A systematic review of its association with thoughtsuppression, inhibition and impulsivity. Heliyon, 7, e05868.https://doi.org/10.1016/j.heliyon.2020.e05868
Bogenschutz, M. P., Ross, S., Bhatt, S., Baron, T., Forcehimes, A. A., Laska, E., Mennenga, S. E., O’Donnell, K., Owens, L. T., Podrebarac, S., Rotrosen, J., Tonigan, J. S. & Worth, L. (2022). Percentage of heavy drinking days following Psilocybin-Assisted Psychotherapy vs Placebo in the treatment of adult patients with Alcohol Use Disorder: A randomized clinical trial. JAMA Psychiatry, 79(10), 953–962. https://doi.org/10.1001/jamapsychiatry.2022.2096
Brecht, M. L. & Herbeck, D. (2014). Time to relapse following treatment for methamphetamine use: A long-term perspective on patterns and predictors. Drug and Alcohol Dependence, 139, 18–25. https://doi.org/10.1016/j.drugalcdep.2014.02.702
Byrne, S. P., Haber, P., Baillie, A., Giannopolous, V. & Morley, K. (2019). Cue exposure therapy for alcohol use disorders: What can be learned from exposure therapy for anxiety disorders?. Substance use & misuse, 54(12), 2053-2063. https://doi.org/10.1080/10826084.2019.1618328
Carroll, K. M., Kiluk, B. D., Nich, C., DeVito, E. E., Decker, S., LaPaglia, D., Duffey, D., Babuscio, T. A. & Ball, S. A. (2014). Toward empirical identification of a clinically meaningful indicator of treatment outcome: Features of candidate indicators and evaluation of sensitivity to treatment effects and relationship to one year follow up cocaine use outcomes. Drug and Alcohol Dependence, 137, 3–19. https://doi.org/10.1016/j.drugalcdep.2014.01.012
Cohen, L., Manion, L. & Morrison, K. (2007). Research methods in education (6th Ed.). New York, NY: Routledge.
Conklin, C. A. & Tiffany, S. T. (2002). Applying extinction research and theory to cue-exposure addiction treatments. Addiction (Abingdon, England), 97(2), 155–167. https://doi.org/10.1046/j.1360-0443.2002.00014.x
Contel, M., Gual, A. & Colom, J. (1999). Test para la identificación de transtornos poruso de alcohol (AUDIT): Traducción y validación del AUDIT al catalán ycastellano. Adicciones, 11(4), 337-347.
Donovan, D. M., Kivlahan, D. R., Doyle, S. R., Longabaugh, R. & Greenfield, S. F. (2006). Concurrent validity of the Alcohol Use Disorders Identification Test (AUDIT) and AUDIT zones in defining levels of severity among out‐patients with alcohol dependence in the COMBINE study. Addiction, 101(12), 1696-1704.
Drummond, D. C. (2001). Theories of drugs craving, ancient and modern. Addiction, 96, 33–46. https://doi.org/10.1080/09652140020016941
Durl, J., Dietrich, T., Pang, B., Potter, L. E. & Carter, L. (2017). Utilising virtual reality in alcohol studies: A systematic review. Health Education Journal, 77(2), 212-225.https://doi.org/10.1177/0017896917743534
Faul, F., Erdfelder, E., Lang, G. A. & Buchner, A. (2007). G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical. Behavior Research Methods, 39(2), 175–191.
Ferrer-García, M., Gutiérrez-Maldonado, J., Pla-sanjuanelo, J., Vilalta-abella, F., Riva, G., Clerici, M., Ribas-Sabate, J., Andreu-Garcia, A., Fernandez-Aranda, F., Forcano, L., Riesco, N., Sanchez, I., Escadon-Nagel, N., Gomez-Tricio, O., Tena, V. & Dakanalis, A. (2017). A randomised controlled comparison of second‐level treatment approaches for treatment‐resistant adults with bulimia nervosa and binge eating disorder: assessing the benefits of virtual reality cue exposure therapy. European Eating Disorder Review, 25(6), 479–490. https://doi.org/10.1002/erv.2538
Freeman, D., Reeve, S., Robinson, A., Ehlers, A., Clark, D., Spanlang, B. & Slater, M. (2017). Virtual reality in the assessment, understanding, and treatment of mental health disorders. Psychological Medicine, 47(14), 2393–2400. https://doi.org/10.1017/S003329171700040X
Ghiţă, A. & Gutiérrez-Maldonado, J. (2018). Applications of virtual reality in individuals with alcohol misuse: A systematic review. Addictive Behaviors, 81, 1–11. https://doi.org/10.1016/j.addbeh.2018.01.036
Ghiţă, A., Hernández-Serrano, O., Fernández-Ruiz, Y., Monras, M., Ortega, L., Mondon, S., Teixidor, L., Gual, A., Porras-García, B., Ferrer-García, M. & Gutiérrez-Maldonado, J. (2019b). Cue-elicited anxiety and alcohol craving as indicators of the validity of ALCO-VR software: A Virtual Reality study. Journal of Clinical Medicine, 8(8), 1153–1168. https://doi.org/10.3390/jcm8081153
Ghiţă, A., Teixidor, L., Monras, M., Ortega, L., Mondon, S., Gual, A., Paredes, S. M., Villares Urgell, L., Porras-Garcia, B., Ferrer-Garcia, M. & Gutiérrez-Maldonado, J. (2019a). Identifying triggers of alcohol craving to develop effective virtual environments for cue exposure therapy. Frontiers in Psychology, 10, 1–11. https://doi.org/10.3389/fpsyg.2019.00074
Guardia-Serecigni, J., Luquero, E., Siñol, N., Burguete, T. & Cardús, M. (2006). Utilidad de la Escala Multidimensional de Craving de Alcohol (EMCA) en la práctica clínica. Adicciones, 18, 265-273.
Guardia-Serecigni, J., Segura, L., Gonzalvo, B., Trujols, J., Tejero, A., Suárez, A. & Martí, A. (2004). Estudio de validación de la Escala Multidimensional de Craving de Alcohol. Medicina Clínica, 123(6), 211–216. https://doi.org/10.1157/13064414
Guillén-Riquelme, A. & Buela-Casal, G. (2011). Psychometric revision and differential item functioning in the State Trait Anxiety Inventory (STAI). Psicothema, 23(3), 510–515. https://doi.org/10.5260/chara.14.1.16
Hedeker, D. & Gibbons, R.D. (2006). Longitudinal Data Analysis. John Wiley & Sons, New Jersey.
Hernández-Serrano, O., Ghiţă, A., Fernández-Ruiz, J., Monràs, M., Gual, A., Gacto, M., Porras-García, B., Ferrer-García, M. & Gutiérrez-Maldonado, J. (2021). Determinants of Cue-Elicited Alcohol Craving and Perceived Realism in Virtual Reality Environments among Patients with Alcohol Use Disorder. Journal of Clinical Medicine, 10(11), 2241. http://dx.doi.org/10.3390/jcm10112241
Hernández-Serrano, O., Ghiţă, A., Figueras-Puigderrajols, N., Fernández-Ruiz, J., Monras, M., Ortega, L., Mondon, S., Teixidor, L., Gual, A., Ugas-Ballester, L., Fernández, M., Montserrat, R., Porras-Garcia, B., Ferrer-Garcia, M. & Gutiérrez-Maldonado, J. (2020). Predictors of changes in alcohol craving levels during a Virtual Reality Cue Exposure Treatment among patients with alcohol use disorder. Journal of Clinical Medicine, 9(9), 3018-undefined. https://doi.org/10.3390/jcm9093018
Hone-Blanchet, A., Wensing, T. & Fecteau, S. (2014). The use of virtual reality in craving assessment and cue-exposure therapy in substance use disorders. Frontiers in Human Neuroscience, 8(844), 1–15. https://doi.org/10.3389/fnhum.2014.00844
Kang, M., Ragan, B. G. & Park, J. H. (2008). Issues in outcomes research: an overview of randomization techniques for clinical trials. Journal of athletic training, 43(2), 215–221. https://doi.org/10.4085/1062-6050-43.2.215
Kiyak, C., Simonetti, M. E., Norton, S. & Deluca, P. (2023). The efficacy of cue exposure therapy on alcohol use disorders: A quantitative meta-analysis and systematic review. Addictive behaviors, 139, 107578. https://doi.org/10.1016/j.addbeh.2022.107578
Kothgassner, O. D., Goreis, A., Kafka, J. X., Van Eickels, R. L., Plener, P. L. & Felnhofer, A. (2019). Virtual reality exposure therapy for posttraumatic stress disorder (PTSD): A meta-analysis. In European Journal of Psychotraumatology (Vol. 10, Issue 1, pp. 1654782-undefined). Taylor and Francis Ltd. https://doi.org/10.1080/20008198.2019.1654782
Kranzler, H. R. & Soyka, M. (2018). Diagnosis and pharmacotherapy of alcohol use disorder: A review. Journal of the American Medical Association, 320(8), 815–824. https://doi.org/10.1001/jama.2018.11406
Kuntsche, E., Kuntsche, S., Thrul, J. & Gmel, G. (2017). Binge drinking: Health impact, prevalence, correlates and interventions. Psychology and Health, 32(8), 976–1017. https://doi.org/10.1080/08870446.2017.1325889
Malbos, E., Borwell, B., EinigIscain, M., Korchia, T., Cantalupi, R., Boyer, L. & Lancon, C. (2023). Virtual reality cue exposure therapy for tobacco relapse prevention: A comparative study with standard intervention. Psychological Medicine, 53, 5070–5080. https://doi.org/10.1017/S0033291722002070
Manchery, L., Yarmush, D. E., Luehring-Jones, P. & Erblich, J. (2017). Attentional bias to alcohol stimuli predicts elevated cue-induced craving in young adult social drinkers. Addictive Behaviors, 70, 14–17. https://doi.org/10.1016/j.addbeh.2017.01.035
Mann, K. & Hermann, D. (2010). Individualised treatment in alcohol-dependent patients. European Archives of Psychiatry and Clinical Neuroscience, 260, 116–120. https://doi.org/10.1007/s00406-010-0153-7
McCaul, M. E., Hutton, H. E., Stephens, M. A. C., Xu, X. & Wand, G. S. (2017). Anxiety, anxiety sensitivity, and perceived stress as predictors of recent drinking, alcohol craving, and social stress response in heavy drinkers. Alcoholism: Clinical and Experimental Research, 41(4), 836–845. https://doi.org/10.1111/acer.13350
McCormick, E. (2021). Multi-Level Multi-Growth Models: New opportunities for addressing developmental theory using advanced longitudinal designs with planned missingness. Developmental Cognitive Neuroscience, 51, 101001. https://doi.org/10.1016/j.dcn.2021.101001.
Mellentin, A. I., Nielsen, B., Nielsen, A. S., Yu, F. & Stenager, E. (2016). A randomized controlled study of exposure therapy as aftercare for alcohol use disorder: study protocol. BMC Psychiatry, 16, 112–120. https://doi.org/10.1186/s12888-016-0795-8
Mellentin, A. I., Skøt, L., Nielsen, B., Schippers, G. M., Nielsen, A. S., Stenager, E. & Juhl, C. (2017). Cue exposure therapy for the treatment of alcohol use disorders: A meta-analytic review.Clinical Psychology Review, 57, 195-207.https://doi.org/10.1016/j.cpr.2017.07.006
Morean, M. E., L’Insalata, A., Butler, E. R., McKee, A. & Krishnan-Sarin, S. (2018). Age at drinking onset, age at first intoxication, and delay to first intoxication: Assessing the concurrent validity of measures of drinking initiation with alcohol use and related problems. Addictive Behaviors, 79, 195–200. https://doi.org/10.1016/j.addbeh.2017.12.017
Mystakidou, K., Tsilika, E., Parpa, E., Sakkas, P. & Vlahos, L. (2009). The psychometric properties of the Greek version of the State-Trait Anxiety Inventory in cancer patients receiving palliative care. Psychology and Health, 24, 1215-1228.
Naqvi, N. H. & Morgenstern, J. (2015). Cognitive Neuroscience Approaches to Understanding Behavior Change in Alcohol Use Disorder Treatments. Alcohol research : current reviews, 37(1), 29–38.
Parsons, T. D. (2015). Virtual Reality for Enhanced Ecological Validity and Experimental Control in the Clinical, Affective and Social Neurosciences. Frontiers in human neuroscience, 9, 660. https://doi.org/10.3389/fnhum.2015.00660
Patterson Silver Wolf, D. A., BlackDeer, A. A., Beeler-Stinn, S., Zheng, K. & Stazrad, K. (2021). Performance-based practice: Clinical dashboards for addiction treatment retention. Research on Social Work Practice, 31(2), 205–211. doi:https://doi.org/10.1177/1049731520972798
Patterson Silver Wolf, D., Dulmus, C. N., Maguin, E., Linn, B. K. & Hales, T. W. (2019). Therapist–patient demographic profile matching: A movement toward performance-based practice. Research on Social Work Practice, 29(6), 677–683. doi:https://doi.org/10.1177/1049731518783582
Patterson Silver Wolf, D. A., Dulmus, C. N., Wilding, G. E., Yu, J., Barczykowski, A. L., Shi, T., Diebold, J. R., Harvey, S. J., Tomasello, N. M. & Linn, B. K. (2022). Treatment resistant alcohol use disorder. Alcoholism Treatment Quarterly, 40(2), 205–216. https://doi.org/10.1080/07347324.2021.1989994
Segawa, T., Baudry, T., Bourla, A., Blanc, J. V., Peretti, C. S., Mouchabac, S. & Ferreri, F. (2020). Virtual Reality (VR) in assessment and treatment of addictive disorders: A systematic review. Frontiers in Neuroscience, 13, 1–14. https://doi.org/10.3389/fnins.2019.01409
Simon, J., Etienne, A. M., Bouchard, S. & Quertemont, E. (2020). Alcohol Craving in Heavy and Occasional Alcohol Drinkers After Cue Exposure in a Virtual Environment: The Role of the Sense of Presence. Frontiers in human neuroscience, 14, 124. https://doi.org/10.3389/fnhum.2020.00124
Sliedrecht, W., de Waart, R., Witkiewitz, K. & Roozen, H. G. (2019). Alcohol use disorder relapse factors: A systematic review. Psychiatry Research, 278, 97–115. https://doi.org/10.1016/j.psychres.2019.05.038
Spielberger, C. D., Gorsuch, R. L. & Lushene, R. (1982). Manual del Cuestionario de Ansiedad Estado/Rasgo (STAI). Madrid, España: TEA Ediciones
Steele, F. (2008). Multilevel Models for Longitudinal Data. Journal of the Royal Statistical Society, Series A, 171, 5-19.
Stohs, M. E., Schneekloth, T. D., Geske, J. R., Biernacka, J. M. & Karpyak, V. M. (2019). Alcohol craving predicts relapse after residential addiction treatment. Alcohol & Alcoholism, 1–5. https://doi.org/10.1093/alcalc/agy093/5363992
Sullivan, G. M. & Feinn, R. (2012). Using Effect Size-or Why the P Value Is NotEnough. Journal of graduate medical education, 4(3), 279–282. https://doi.org/10.4300/JGME-D-12-00156.1
Suresh, K. (2011). An overview of randomization techniques: An unbiased assessment of outcome in clinical research. Journal of Human Reproductive Sciences, 4, 8–11. https://doi.org/10.4103/0974-1208.82352
Trahan, M. H., Maynard, B. R., Smith, K. S., Farina, A. S. J. & Khoo, Y. M. (2019). Virtual Reality Exposure Therapy on Alcohol and Nicotine: A Systematic Review. Research on Social Work Practice, 29(8), 876–891. https://doi.org/10.1177/1049731518823073
Witkiewitz, K., Litten, R. Z. & Leggio, L. (2019). Advances in the science and treatment of alcohol use disorder. Science Advances, 5(9), eaax4043. https://doi.org/10.1126/sciadv.aax4043
Witkiewitz, K., Roos, C. R., Pearson, M. R., Hallgren, K. A., Maisto, S. A., Kirouac, M., Forcehimes, A. A., Wilson, A. D., Robinson, C. S., McCallion, E., Tonigan, J. S. & Heather, N. (2017). How much is too much? Patterns of drinking during alcohol treatment and associations with post-treatment outcomes across three alcohol clinical trials. Journal of Studies on Alcohol and Drugs, 78, 59–69. https://doi.org/10.15288/jsad.2017.78.59


