Wiebren, Markus

Kraan A.E., Markus W., Schellekens A.F., Dijkstra B.A.

Abstract Although manual-based treatments are widely available in mental health care, they are often not delivered according to protocol. Treatment-, therapist- and organizational-related determinants are known to affect therapist adherence to treatment protocols, and subsequently treatment success. This study examined which determinants are associated with therapist adherence to the Community Reinforcement Approach (CRA) manual, an evidence-based behavioural treatment programme commonly used in addiction care. Using a cross-sectional design, adherence to the CRA manual and potential contributing determinants were assessed through a self-report survey among therapists (N = 69) working in out-patient addiction care. Correlation analysis and backward stepwise regression analysis were used to examine which treatment-, therapist- and organizational-related determinants were associated with CRA adherence. Significant associations with self-reported CRA adherence were found for nine out of 16 determinants examined. Three independent determinants explained 43% of the variance in CRA manual adherence, namely compatibility with the working method therapists were used to, perceived outcome expectations, and perceived adoption of CRA procedures by colleagues. These determinants should be considered when implementing CRA in addiction care, for example by investing in training and taking into account therapists’ previous treatment experience. This also accounts for creating positive outcome expectations and the use of descriptive norms by making experiences explicit of therapists and teams that excel. Future research should investigate which other determinants contribute to therapists’ adherence and focus on clarifying causality between determinants and adherence. Key learning aims (1) To understand the importance of treatment, therapist and organizational determinants influencing therapist adherence to the CRA manual. (2) To explain the three determinants that make the largest contribution to self-reported therapists’ adherence to the CRA manual, namely: compatibility with the working method, perceived outcome expectations, and perceived adoption of CRA procedures by colleagues. (3) To reflect on the clinical implications regarding therapist training, implementation of manual-based treatments and future research.

Brynte C., Aeschlimann M., Barta C., Begeman A.H., Bäcker A., Crunelle C.L., Daigre C., De Fuentes-Merillas L., Demetrovics Z., Dom G., López L.G., Icick R., Johnson B., Joostens P., Kapitány-Fövény M., et. al.

Substance use disorders (SUD) often co-occur with attention deficit hyperactivity disorder (ADHD). Although the short-term effects of some specific interventions have been investigated in randomized clinical trials, little is known about the long-term clinical course of treatment-seeking SUD patients with comorbid ADHD. This paper presents the protocol and baseline clinical characteristics of the International Naturalistic Cohort Study of ADHD and SUD (INCAS) designed and conducted by the International Collaboration on ADHD and Substance Abuse (ICASA) foundation. The overall aim of INCAS is to investigate the treatment modalities provided to treatment-seeking SUD patients with comorbid ADHD, and to describe the clinical course and identify predictors for treatment outcomes. This ongoing study employs a multicentre observational prospective cohort design. Treatment-seeking adult SUD patients with comorbid ADHD are recruited, at 12 study sites in nine different countries. During the follow-up period of nine months, data is collected through patient files, interviews, and self-rating scales, targeting a broad range of cognitive and clinical symptom domains, at baseline, four weeks, three months and nine months. A clinically representative sample of 578 patients (137 females, 441 males) was enrolled during the recruitment period (June 2017-May 2021). At baseline, the sample had a mean age (SD) of 36.7 years (11.0); 47.5% were inpatients and 52.5% outpatients; The most prevalent SUDs were with alcohol 54.2%, stimulants 43.6%, cannabis 33.1%, and opioids 14.5%. Patients reported previous treatments for SUD in 71.1% and for ADHD in 56.9%. Other comorbid mental disorders were present in 61.4% of the sample: major depression 31.5%, post-traumatic stress disorder 12.1%, borderline personality disorder 10.2%. The first baseline results of this international cohort study speak to its feasibility. Data show that many SUD patients with comorbid ADHD had never received treatment for their ADHD prior to enrolment in the study. Future reports on this study will identify the course and potential predictors for successful pharmaceutical and psychological treatment outcomes. ISRCTN15998989 20/12/2019.

Arissen C., van der Helm L., Dijkstra B., Markus W.

This study aimed to identify facilitators and barriers for implementation of virtual reality therapy (VRT), used to train communication and problem-solving skills aiding relapse prevention, when integrated with addiction treatment (Treatment as Usual; TAU). Mixed methods were used in an observational, partly prospective, design. A total of 21 therapists and 113 patients from three inpatient addiction clinics were assessed. Therapists filled in questionnaires to gauge expectancies and experiences regarding facilitators and barriers at baseline, after a try-out period, halfway, and at the end of the pilot lasting 6–12 months. They also participated in focus-group interviews. Patients filled in similar questionnaires before an initial, and after they finished a third, VRT session. In addition, nine patients were interviewed. All VRT sessions were logged, with patients answering additional questions. Acceptability of VRT was high in both groups. It was feasible to integrate VRT with TAU and integration showed potential effectiveness. Barriers included incidental motion sickness, technical difficulties, costs, and device setup time. Both therapists and patients advocated VRT use to augment addiction treatment. Findings suggest a clinical effectiveness study is warranted.

Belgers M., Van Eijndhoven P., Markus W., Schene A., Schellekens A.

(1) Background: Current evidence-based treatments for alcohol use disorder (AUD) are moderately effective. Studies testing repetitive transcranial magnetic stimulation (rTMS) in AUD commonly apply a limited number of rTMS sessions with different rTMS settings, showing inconsistent effects on craving for alcohol. This study tested the efficacy of a robust rTMS protocol on craving and alcohol use. (2) Methods: In a single-blind randomized controlled trial in recently detoxified patients with AUD, ten days of high-frequency rTMS over the right dorsolateral prefrontal cortex on top of treatment as usual (n = 14) was compared with sham rTMS (n = 16). Outcome measures were alcohol craving and use over a follow-up period of one year. Analysis was performed by means of repeated measures multivariate analysis of variance. (3) Results: The results showed a main group-by-time interaction effect on craving (Wilks’ Λ = 0.348, F (12, 17) = 2.654, p = 0.032) and an effect of group on alcohol use (Wilk’s Λ = 0.44, F (6, 23) = 4.9, p = 0.002), with lower alcohol craving and use in the group with active rTMS compared to the control group. Differences in craving between groups were most prominent three months after treatment. At 12 months follow-up, there was no effect of rTMS on craving or abstinence. (4) Conclusions: This small-scale randomized controlled trial showed the efficacy of high-frequency rTMS over the right dlPFC diminished alcohol craving and use in recently detoxified patients with AUD during the first months after detoxification. These findings suggest that rTMS might be an effective add-on in treating patients with AUD and warrant replication in future large-scale studies.

Langener S., Van Der Nagel J., van Manen J., Markus W., Dijkstra B., De Fuentes-Merillas L., Klaassen R., Heitmann J., Heylen D., Schellekens A.

(1) Background: Virtual reality (VR) has been investigated in a variety of psychiatric disorders, including addictive disorders (ADs); (2) Objective: This systematic review evaluates the current evidence of immersive VR (using head-mounted displays) in the clinical assessment and treatment of ADs; (3) Method: PubMed and PsycINFO were queried for publications up to November 2020; (4) Results: We screened 4519 titles, 114 abstracts and 85 full-texts, and analyzed 36 articles regarding the clinical assessment (i.e., diagnostic and prognostic value; n = 19) and treatment (i.e., interventions; n = 17) of ADs. Though most VR assessment studies (n = 15/19) showed associations between VR-induced cue-reactivity and clinical parameters, only two studies specified diagnostic value. VR treatment studies based on exposure therapy showed no or negative effects. However, other VR interventions like embodied and aversive learning paradigms demonstrated positive findings. The overall study quality was rather poor; (5) Conclusion: Though VR in ADs provides ecologically valid environments to induce cue-reactivity and provide new treatment paradigms, the added clinical value in assessment and therapy remains to be elucidated before VR can be applied in clinical care. Therefore, future work should investigate VR efficacy in randomized clinical trials using well-defined clinical endpoints.

van Tongeren M.J., Markus W., Stringer B., de Man J.M., de Jong C.A., van Meijel B.

To investigate the ability of case managers, working in ambulatory treatment settings specialized in addiction care, to clinically judge demoralization in substance-dependent patients.In a cross-sectional study, clinical judgments of case managers were compared with the patients' scores on the Demoralization Scale, by calculating the sensitivity and specificity scores.Case managers identified demoralization in 85% of the cases (sensitivity), the specificity of 62% suggests that demoralization was overestimated by case managers.Demoralization is a frequently occurring phenomenon in patients. Methods should be developed that allow professionals and patients to identify demoralization collaboratively, and to develop tailored interventions to prevent demoralization and its negative consequences.

Snoek A., Dijkstra B.A., Markus W., Van der Meer M., De Wert G., Horstkötter D.

Parental alcohol dependency is associated with risks for the well-being of their children. However, guiding these families to support is often complicated. We interviewed 10 alcohol dependent parents, and held 3 focus group interviews with child welfare social workers, and alcohol and other drug workers. We identified a reluctance to act among professional and non-professional bystanders. Family members, neighbours, teachers, and general practitioners are often aware of parental drinking problems, but are reluctant to discuss them with the parents or to alert services designed to support families. The aim of this paper is to share the experiences of parents and show that parents appreciate interventions if done in a certain manner. Although parents were reluctant to discuss their drinking problem, they considered these problems as symptoms of underlying severe distress. They were highly motivated to get help for these underlying problems and wondered why they were not questioned about their distress by those around them. The silence of others reinforced pre-existing feelings of worthlessness and hopelessness. In this paper we analyse other's hesitation to intervene as a form of the bystander effect, and make suggestions on how this bystander effect can be overcome.

Heitmann J., van Hemel-Ruiter M.E., Huisman M., Ostafin B.D., Wiers R.W., MacLeod C., DeFuentes-Merillas L., Fledderus M., Markus W., de Jong P.J.

Background Attentional bias for substance-relevant cues has been found to contribute to the persistence of addiction. Attentional bias modification (ABM) interventions might, therefore, increase positive treatment outcome and reduce relapse rates. The current study investigated the effectiveness of a newly developed home-delivered, multi-session, internet-based ABM intervention, the Bouncing Image Training Task (BITT), as an add-on to treatment as usual (TAU). Methods Participants (N = 169), diagnosed with alcohol or cannabis use disorder, were randomly assigned to one of two conditions: the experimental ABM group (50%; TAU+ABM); or the control group (50%; split in two subgroups the TAU+placebo group and TAU-only group, 25% each). Participants completed baseline, post-test, and 6 and 12 months follow-up measures of substance use and craving allowing to assess long-term treatment success and relapse rates. In addition, attentional bias (both engagement and disengagement), as well as secondary physical and psychological complaints (depression, anxiety, and stress) were assessed. Results No significant differences were found between conditions with regard to substance use, craving, relapse rates, attentional bias, or physical and psychological complaints. Conclusions The findings may reflect unsuccessful modification of attentional bias, the BITT not targeting the relevant process (engagement vs. disengagement bias), or may relate to the diverse treatment goals of the current sample (i.e., moderation or abstinence). The current findings provide no support for the efficacy of this ABM approach as an add-on to TAU in alcohol or cannabis use disorder. Future studies need to delineate the role of engagement and disengagement bias in the persistence of addiction, and the role of treatment goal in the effectiveness of ABM interventions.

van Minnen M., Markus W., Blaauw E.

Eye movement desensitization and reprocessing (EMDR) therapy is an evidence-based treatment for posttraumatic stress disorder (PTSD). Preliminary findings suggest the application of an adapted, addiction-focused EMDR procedure, AF-EMDR therapy, may also be helpful in treating addictions, such as gambling disorder (GD). In this study eight participants with GD received AF-EMDR therapy, using modules from Markus and Hornsveld's Palette of EMDR Interventions in Addiction (PEIA). A multiple baseline design was used to investigate whether AF-EMDR therapy reduced gambling urge and increased experienced self-control. Six weekly AF-EMDR sessions (treatment phase) were preceded by a 3- to 7-week non-treatment baseline phase. During both phases, participants kept a daily diary. Visual inspection as well as an interrupted time series analysis demonstrated mixed findings. Results showed that three participants experienced spontaneous recovery during the baseline period, two did not respond to treatment, and three others showed improvements during the EMDR phase. No adverse effects were noted. In sum, AF-EMDR therapy may have potential in the treatment of gambling addiction. However, more research is needed regarding the efficacy, contra-indications, focus, and application as well as the optimal dose of AF-EMDR therapy using the PEIA modules.

Markus W., Hornsveld H.K., Burk W.J., de Weert – van Oene G.H., Becker E.S., DeJong C.A.

BackgroundThis study examined the feasibility, safety, and efficacy of addiction‐focused eye movement desensitization and reprocessing (AF‐EMDR) treatment, as an add‐on intervention to treatment as usual (TAU).MethodsAdult outpatients with alcohol use disorder (AUD) (N = 109) who already received or had just started with TAU (Community Reinforcement Approach) were recruited at 6 outpatient addiction care facilities. They were randomly assigned to either TAU + 7 weekly 90‐minute sessions of AF‐EMDR (N = 55) or TAU‐only (N = 54). Assessments were made at baseline, after AF‐EMDR therapy (+ 8 weeks in the TAU‐only group), and at 1‐ and 6‐month follow‐up. The primary outcomes were changes in drinking behavior as reported by the participant and biomarker indices.ResultsData were analyzed as intent‐to‐treat with linear mixed models. Additionally, sensitivity analyses were performed. No group or interaction effects were found for any of the outcome variables. Only limited change over time was seen with regard to indices of personal and societal recovery and in some secondary indices of clinical recovery (craving, desire thinking, and rumination). Reliable Change Index calculations showed that more TAU‐only participants showed clinical improvement with regard to alcohol consumption while a somewhat higher proportion of participants in the TAU + AF‐EMDR group experienced less craving. The acceptability, safety, and feasibility of the treatments received in both groups were comparable.ConclusionsThere was no add‐on effect of AF‐EMDR on TAU with regard to drinking behavior in outpatients with an AUD. Possible explanations are discussed. Future studies should first establish proof of principle regarding the potential of AF‐EMDR therapy to disrupt operant learning and habits relevant in addiction.

Markus W., de Kruijk C., Hornsveld H.K., de Weert–van Oene G.H., Becker E.S., DeJong C.A.

Alcohol use disorder (AUD) treatment presents a serious challenge. While there are evidence-based treatment options available, there is still a substantial group of treatment-seeking patients who do not complete regular AUD treatment. In addition, accomplished reductions in drinking behavior during treatment are often lost posttreatment. Therefore, both feasibility and effectiveness of AUD treatment are important. Innovative interventions, such as addiction-focused eye movement desensitization and reprocessing (AF-EMDR) therapy (Markus & Hornsveld, 2017), may hold promise as adjunctive treatments. Here the results of a feasibility study of adjunctive AF-EMDR therapy in outpatients with AUD and without comorbid posttraumatic stress disorder (PTSD) are described. A multiple baseline design across four participants was used. They received AF-EMDR alongside treatment as usual (TAU). The results suggest that, while challenging, AF-EMDR therapy in outpatients with AUD can be safe, acceptable, and feasible. Whether it is effective, under what conditions and for whom, requires further study however.

Markus W., Hornsveld H.K.

La consommation de tabac, d'alcool et de drogues illicites est très répandue et a des conséquences négatives importantes pour les individus, leurs familles et la collectivité à laquelle ils appartiennent. Un nombre important d'usagers développent un trouble de dépendance. Le traitement à visée curative de la dépendance est difficile, sur le plan de la fidélisation des patients et du taux de rechute. Nous discutons ici du potentiel de la thérapie EMDR (désensibilisation et retraitement par les mouvements oculaires) dans le traitement de la dépendance. On distingue deux approches : l'EMDR axée sur les traumatismes et l'EMDR axée sur l'addiction. Nous faisons ici un examen critique des protocoles EMDR adaptés déjà existants et des recherches sur ces deux types d'approche. Malgré vingt ans de développement et de recherche, la faisabilité et l'efficacité de la thérapie EMDR axée sur les addictions n'ont guère encore été étudiées. Nous discutons ici les nouvelles possibilités passionnantes offertes par les recherches sur la théorie de la mémoire de travail. Nous présentons dans cet article la palette des interventions EMDR en toxicomanie (PIET), une vue d'ensemble de toutes les interventions visant au traitement de la toxicomanie par apport de ressources et thérapie EMDR. L'article se conclut par des recommandations pour les recherches futures dans ce domaine.

Bruijnen C.J., Dijkstra B.A., Walvoort S.J., Markus W., VanDerNagel J.E., Kessels R.P., DE Jong C.A.

AbstractIntroduction and AimsCognitive impairments in substance use disorder predict treatment outcome and are assumed to differ between substances. They often go undetected, thus the current study focuses on the prevalence of and differences in cognitive functioning across substances by means of a cognitive screen at the early stage of addiction treatment.Design and MethodsThe Montreal Cognitive Assessment was administered to outpatients seeking treatment for substance use disorder. Patient characteristics (age, years of regular use, polysubstance use, severity of dependence/abuse, depression, anxiety and stress) were also taken into account.ResultsA total of 656 patients were included (n = 391 used alcohol, n = 123 used cannabis, n = 100 used stimulants and n = 26 used opioids). The prevalence of cognitive impairments was 31%. Patients using alcohol had a lower total‐ and memory domain score than those using cannabis. Patients using opioids scored lower on visuospatial abilities than those using cannabis or stimulants. Younger patients scored higher than older patients. No effect was found for the other investigated characteristics.Discussion and ConclusionsGiven the high prevalence of cognitive impairments, standard screening at an early stage of treatment is important to determine the course of treatment and maximise treatment outcome. Caution is needed in interpreting results about opioids due to an underrepresentation of this patient group, and more research is needed on the effect of age on Montreal Cognitive Assessment performance.

Knuijver T., Belgers M., Markus W., Verkes R., van Oosteren T., Schellekens A.

Kraan A.E., Dijkstra B.A., Markus W.

Treatment model adherence is an important predictor of treatment outcome. In clinical practice evidence-based treatments are delivered in widely varying degrees. This study examines which Community Reinforcement Approach (CRA) procedures are delivered by addiction care therapists and how this is associated with therapist characteristics.The study integrated two observational designs. Firstly, using a prospective design, 24 therapists registered every CRA procedure delivered during every patient contact over a six month period. Secondly, using a cross-sectional design, personal characteristics of 69 therapists were assessed including their self-reported delivery of CRA procedures and their perceptions with regard to the meaningfulness and complexity of these procedures.The number of CRA procedures delivered varied substantially among therapists both at session and patient level. More experienced therapists and those that had received advanced training previously, delivered more CRA procedures. Finally, the delivery of CRA procedures was positively associated with experienced meaningfulness and negatively associated with difficulty.The results confirm the relation between treatment delivery and experienced meaningfulness and difficulty of CRA procedures and provides support for advanced training to enhance the delivery of a wider range of CRA procedures.

Bogdanov S., Koss K., Hook K., Moore Q., Van der Boor C., Masazza A., Fuhr D.C., Roberts B., May C., Fedorets O., Bayer O., Karachevskyy A., Nadkarni A.

Larsen J.K., Markus W., Wiers R.W., de Jongh A.

Lei J., Li T., Cui C., Ren K., Shi Y., Yao Y., Luo G., Li M., Peng X., Yang X., Yang J., Zhang P., Tian B.

Michel A., Kang D., Fillingim R.B., Balderston N.L., Bond D.S., Steele V.R.

Both substance use disorders (SUD) and chronic pain are highly prevalent, require new effective interventions, and share similar underlying neurocircuitry. A promising intervention for both is repetitive transcranial magnetic stimulation (rTMS) which is a tool to modulate brain circuits. In this narrative review, we surveyed the current state of rTMS used to address SUDs and chronic pain by focusing on 132 reports published since 2010. The field agrees that rTMS application in these clinical samples is safe and potentially effective, even in co-occurring disease or with recent substance use. Overall, the pain field has come to a stronger consensus about how best to apply rTMS to reduce diverse chronic pain conditions compared to the SUD field. We argue for standardization of methods within fields to rapidly address each clinical group. Such a standardization will require a concerted effort to test applications head-to-head to evaluate relative efficacy across applications. A coordinated effort in this regard is needed between research groups and funding agencies to accomplish this goal. One of the most effective steps the field can take toward this goal is to measure the neuromechanisms that underlie SUD and pain before and after an rTMS intervention. Only 18% of reviewed reports included any brain measurement such as functional magnetic resonance imaging, electroencephalography, and event-related potentials. We argue that such measurements are essential for optimizing rTMS as an intervention for clinical populations. If rTMS is ostensibly applied to modulate neurocircuits, measurement of those circuits to verify, iterate, and optimize application is fundamental for developing effective treatments.

Mistler C.B., Shrestha R., Copenhaver M.M.

Truter I., Regnart J., Meyer A.

Background: The brain reward circuitry is thought to underlie the co-occurrence of attention-deficit/hyperactivity disorder (ADHD) and substance use disorder (SUD) and to possibly impact mood disorders. This study aimed to establish if any difference existed in the severity of depression symptomology between SUD comorbidity with and without ADHD. Methods: A multi-centre, cross-sectional comparison study design drew study participants from substance use treatment facilities within South Africa. The participants were screened for ADHD and depression, with the selective application of a confirmatory ADHD diagnostic interview. The participants were diagnostically grouped according (SUD + ADHD, SUD − ADHD) to an application of a 2 x 2 x 3 ANOVA model. Results: A significant main effect of ADHD diagnosis and gender on depressive symptoms was identified. Post hoc analysis revealed that only male ADHD subjects had significantly higher scores on the Beck scale than non-ADHD males. Conclusions: Co-occurring disorder (COD) prevalence rates were higher than most other South African studies. The aggravation of ADHD on mood disorder symptom severity is consistent with the existing literature; however, further investigation is warranted to determine if the interaction of gender remains only significant for men with a lager sample size. The identified COD prevalence rate may contrast with other South Africa studies, emphasising the need for comprehensive psychiatric comorbidity screening in SUD treatment settings.

Praharaj S.K., Menon V., Ameen S.

Li J.Y., Nahmias J., Lekawa M., Dolich M.O., Burruss S.K., Park F.S., Grigorian A.

Grassi G., Moradei C., Cecchelli C.

AbstractBackgroundAttention deficit hyperactivity disorder (ADHD) and behavioral addictions (BAs) are highly comorbid but little is known about the effect of anti-ADHD medications on behavioral addiction symptoms. Thus, the aim of this naturalistic prospective study was to investigate the long-term changes on BAs symptoms among methylphenidate-treated adults with a primary diagnosis of ADHD.Methods37 consecutive adult ADHD outpatients completed a baseline and follow-up assessment of ADHD, mood and BAs symptoms (internet, shopping, food, sex addictions and gambling disorder) after one year of methylphenidate (flexible dose) treatment.ResultsInternet addiction test scores pre-treatment were significantly higher than post-treatment scores (p < 0.001). The same trend was seen for the shopping addiction (p = 0.022), food addiction scores (p = 0.039) and sex addiction scores (p = 0.047). Gambling disorder scores did not differ pre and post treatment since none of the included patients reported significant gambling symptoms at baseline. The rate of ADHD patients with at least one comorbid BA was reduced after methylphenidate treatment (51.4% vs 35.1%). The correlation analyses showed a moderate positive correlation between the changes in sluggish cognitive tempo symptoms, cognitive impulsivity, mood and anxiety symptoms and changes in internet addiction symptoms.ConclusionsThis is the first study showing that after one-year of treatment with methylphenidate, adult ADHD patients show a significant reduction on internet, food, shopping and sex addiction symptoms. Further controlled studies with larger samples should replicate these preliminary results and elucidate the role of methylphenidate and other moderator factors (such as concomitant psychological treatments or lifestyle habits changes) on BAs improvements.

Tsamitros N., Gutwinski S., Beck A., Lange Mussons S., Sebold M., Schöneck R., Wolbers T., Bermpohl F., Heinz A., Lütt A.

AbstractNew therapeutic approaches for alcohol dependence (AD) include virtual reality (VR)-based treatments offering scalable options for cue exposure (CE), a well-established strategy in cognitive behavioral therapy. This study aimed to evaluate the feasibility and tolerability of a new VR-CE paradigm. On an explorative basis, factors influencing the induction of craving were examined. This single-arm monocentric clinical study included n = 21 patients with AD in inpatient rehabilitation treatment, that completed one VR-CE session including confrontation with alcohol-associated stimuli. Measurements of subjective craving before, during and after exposure, affective states, VR side effects as cybersickness and the sense of presence in VR were conducted. Craving levels during and directly after VR-CE were significantly higher than before the intervention. Craving levels 20 min after VR-CE did not significantly differ compared to those before VR-CE. Patients described a pronounced sense of presence and only mild symptoms of cybersickness. Craving was significantly correlated with cybersickness. While positive affect decreased throughout the VR exposure, negative affect did not differ significantly in pre-post-comparisons. This study shows that craving induction through our VR-CE paradigm is feasible and well-tolerated by patients with AD in long-term rehabilitation. These results contribute to the development and future research of therapeutic VR-CE approaches.

Treiber M., Tsapakis E., Fountoulakis K.

Aims We aimed to evaluate the immediate and up to 3 months' effect of multiple-session repetitive transcranial magnetic stimulation (rTMS) on alcohol craving in AUD. Methods We performed a systematic review and random effects meta-analysis. We included randomized controlled trials with at least 10 sessions of rTMS and postintervention alcohol craving assessment. We evaluated the immediate and up to 3 months' effects of active rTMS versus sham stimulation. Results Twelve studies met inclusion criteria, including 475 participants across both treatment and control groups. rTMS reduced alcohol craving over sham stimulation immediately post-treatment (SMD = −0.79, 95% CI: −1.53 to −0.04, P = 0.04, I 2 = 93%). Concerning a maintenance effect, our meta-analysis revealed a medium effect for active rTMS in reduction of alcohol craving at 3-month follow-up (SMD = −0.44, 95% CI: −0.77 to 0.11, P < 0.01, I 2 = 38%). Our subgroup analysis revealed that rTMS targeting the medial prefrontal cortex (SMD = −2.12, 95% CI: −4.34 to 0.09, P = 0.06, I 2 = 94%) may be more effective than stimulating the right dorsolateral prefrontal cortex (SMD = −1.04, 95% CI: −2.56 to 0.48, P = 0.18, I 2 = 96%) or left dorsolateral prefrontal cortex (SMD = −0.27, 95% CI: −0.60 to 0.05, P = 0.10, I 2 = 0%) immediately after treatment. Conclusion A minimum of 10 sessions of rTMS reduced alcohol craving immediately after treatment; this effect seems to be sustained over a 3-month period. We provide limited evidence of superiority for rTMS targeting the medial prefrontal cortex.

Koomen A.P., Kaag A.M., Jongenelen K.A., Wouters R., van Marle H.J., van den Heuvel O.A., van der Werf Y.D., De Vries T.J.

IntroductionImproved effectiveness and treatment adherence is needed in smoking cessation (SC) therapies. Another important challenge is to disrupt maladaptive drug-related memories. To achieve these goals, we developed a novel treatment strategy on the basis of motion-assisted memory desensitization and reprocessing (3MDR).MethodsIn this study, the added effect of a distractor task following memory recall during a newly designed 3-day SC version of 3MDR (3MDR-SC) protocol on reducing smoking cue–elicited craving was investigated in abstinent chronic smokers. Chronic smokers were randomly allocated to an active 3MDR-SC group (receiving 3MDR-SC with a working memory distractor task) (n = 42) or a control 3MDR-SC group (receiving 3MDR-SC with a non-distracting task) (n = 39). Smoking cue–induced craving and physiological measures were assessed at baseline (T0) and 1 day after the intervention (T4), and smoking behavior was measured at T0 and 2-week (FU1) and 3-month (FU2) follow-up.ResultsSignificant decreases in cue-induced craving from T0 to T4 and daily cigarette use from T0 to FU1 and FU2 were observed but not differ between the two experimental groups. Cue-induced changes in heart-rate variability and skin conductance, which did not differ from T0 to T4, and relapse at FU2 were also not different between groups. Dropout rate during intervention was 2.5%.ConclusionsThe 3-day 3MDR-SC intervention resulted in a reduction in cue-induced craving and smoking behavior and showed very good treatment adherence. There was no added effect of the distractor task on 3MDR-SC efficacy. Further studies, including a treatment as usual control, are needed to confirm 3MDR-SC as an effective SC therapy.

Visontay R., Squeglia L.M., Sunderland M., Devine E.K., Byrne H., Mewton L.

Staudt J., De Haan H., Walvoort S., Rensen Y., Egger J., Dijkstra B.

Abstract Introduction and aims Repeatedly undergoing supervised, medical, detoxification from chronic alcohol use may contribute to impairments in neurocognitive functioning of patients with an alcohol use disorder (AUD). Unsupervised, non-medical, detoxification, however, may also contribute to neurocognitive impairments, given the absence of first choice prescription medication to counteract severe withdrawal effects. So far, findings from previous studies are inconclusive and specifically effects of non-medical detoxifications are not investigated yet. Using an association modeling approach, this study investigates whether intelligence, speed, attention, and executive functioning are influenced by previous medical and/or non-medical detoxifications. Methods A total of 106 participants with AUD underwent a clinical medical supervised detoxification. Basic characteristics of the patient were recorded including the number of previous medical and non-medical detoxifications. Neuropsychological assessment was conducted after 6 weeks of abstinence. Results The amount of previous medical detoxifications (F (1, 87) = 4.108, P = .046) and the group of medical detoxifications (F(1, 87) = 4734, P = .032), predicted performance on one out of 14 dependent variables, i.e. the “d2 Number of Signs” task. Though “Age of onset of daily alcohol use” contributed significantly to this relationship, the change of the regression coefficient of the model was ˂10%. The number of non-medical or total amount of previous detoxifications did not predict any of the dependent variables. Conclusion The results indicate limited evidence of a linear association between either medical, non-medical, or total amount of previous detoxifications and measures of intelligence, speed, attention, or executive functioning, while controlling for relevant confounders.

Larsen J.K., Hollands G.J., Moritz S., Wiers R.W., Veling H.

Imaginal retraining (IR) is an emerging intervention technique in which people imagine avoidance behaviors towards imagined foods or other substances, such as throwing them away. Although IR shows promise in reducing initial craving for a range of substances, including alcohol and tobacco, effects appear less robust for craving for energy-dense foods. This raises the question of how IR for food craving can be improved. Here, we address this question informed by emerging findings from IR dismantling studies and the field of regular cognitive bias modification training paradigms. Based on current insights, we suggest the most optimal 'craving-reduction' effects for energy-dense food can likely be expected for IR that includes an overt motor movement. While it is not yet clear what movement works best for food, we suggest a tailored movement or Go/No-Go-based stop movement has the potential to be most effective. The most likely mechanism in reducing craving is cue-devaluation of trained vivid craving images regarding specific energy-dense food products. Future work is needed that investigates and assess the underlying mechanisms (e.g., updating beliefs; cue-devaluation), task characteristics (e.g., IR instructions; specific motor movements) and individual characteristics (e.g., perceived craving; vividness of food imagination) that determine IR effects.

Harel M., Perini I., Kämpe R., Alyagon U., Shalev H., Besser I., Sommer W.H., Heilig M., Zangen A.

AbstractBackgroundAlcohol addiction is associated with a high disease burden, and treatment options are limited. In a proof-of-concept study, we used deep repetitive transcranial magnetic stimulation (dTMS) to target circuitry associated with the pathophysiology of alcohol addiction. We evaluated clinical outcomes and explored associated neural signatures using functional magnetic resonance imaging.MethodsThis was a double-blind, randomized, sham-controlled trial. A total of 51 recently abstinent treatment-seeking patients with alcohol use disorder (moderate to severe) were randomized to sham or active dTMS, using an H7 coil targeting midline frontocortical areas, including the medial prefrontal and anterior cingulate cortices. Treatment included 15 sessions over 3 weeks, followed by five sessions over 3 months of follow-up. Each session delivered 100 trains of 30 pulses at 10 Hz. The primary predefined outcome was reduction in percentage of heavy drinking days, obtained using timeline follow-back interviews. Secondary analyses included self-reports of craving, ethyl glucuronide in urine, and brain imaging measures.ResultsBoth craving after treatment and percentage of heavy drinking days during follow-up were significantly lower in the active versus sham control group (percentage of heavy drinking days = 2.9 ± 0.8% vs. 10.6 ± 1.9%, p = .037). Active dTMS was associated with decreased resting-state functional connectivity of the dorsal anterior cingulate cortex with the caudate nucleus and decreased connectivity of the medial prefrontal cortex to the subgenual anterior cingulate cortex.ConclusionsWe provide initial proof-of-concept for dTMS targeting midline frontocortical structures as a treatment for alcohol addiction. These data strongly support a rationale for a full-scale confirmatory multicenter trial. Therapeutic benefits of dTMS appear to be associated with persistent changes in brain network activity.

Riva G.

From a technological viewpoint, virtual reality (VR) is a set of fancy technologies: a helmet, trackers, and a 3D visualizing system. However, from a psychological viewpoint, VR is simultaneously a simulative, a cognitive, and an embodied technology. These features make VR the perfect tool for experiential assessment and learning with great clinical potential. This potential is already supported by clinical outcomes. Two recent meta-reviews assessing more than 53 systematic reviews and meta-analyses support its use in anxiety disorders, pain management, and eating and weight disorders, with long-term effects that generalize to the real world. Recent studies have also provided preliminary support for the use of VR in the assessment and treatment of psychosis, addictions, and autism.

Song S., Zilverstand A., Gui W., Pan X., Zhou X.

Non-invasive brain stimulation has shown potential in clinical applications aiming at reducing craving and consumption levels in individuals with drug addiction or overeating behaviour. However, it is unclear whether these intervention effects are maintained over time. This study aimed to measure the immediate, short- and long-term effects of excitatory transcranial direct current stimulation (tDCS) and high-frequency repetitive transcranial magnetic stimulation (rTMS) targeting at dorsolateral prefrontal cortex (dlPFC) in people with drug addiction or overeating.A systematic review and random effects meta-analysis. We included 20 articles (total of 22 studies using randomized controlled trials: 3 alcohol dependence, 3 drug dependence, 12 smoking, 4 overeating; total: 720 participants) from January 2000 to June 2020, which reported at least one follow-up assessment of craving, consumption or abstinence levels after the intervention. We compared effects of active versus sham stimulation immediately after the intervention and at the last follow-up assessment, as compared with baseline.Excitatory neuromodulation of dlPFC activity reduced craving and consumption immediately after the intervention (craving: g = 0.734, CI = 0.447-1.021, P < 0.001; consumption: g = 0.527, CI = 0.309-0.745; P < 0.001), as well as during short-, mid- and long-term abstinence (craving: g = 0.677, CI = 0.440-0.914, P < 0.001; consumption: g = 0.445, CI = 0.245-0.645, P < 0.001; abstinence levels: g = 0.698, CI = 0.433-0.963, P < 0.001; average time of follow-up: 84 ± 83 days after last stimulation). Additional analysis demonstrated that the intervention effects were sustained in all populations studied (food, nicotine, alcohol or drug abuse) and with both stimulation techniques used (rTMS, tDCS). Interventions targeting at the left (vs right) hemisphere may be more effective.Excitatory neuromodulation targeting the dorsolateral prefrontal cortex appears to lead to a sustained reduction of craving and consumption in individuals with addiction or overeating behaviour.

Langener S., Van Der Nagel J., van Manen J., Markus W., Dijkstra B., De Fuentes-Merillas L., Klaassen R., Heitmann J., Heylen D., Schellekens A.

(1) Background: Virtual reality (VR) has been investigated in a variety of psychiatric disorders, including addictive disorders (ADs); (2) Objective: This systematic review evaluates the current evidence of immersive VR (using head-mounted displays) in the clinical assessment and treatment of ADs; (3) Method: PubMed and PsycINFO were queried for publications up to November 2020; (4) Results: We screened 4519 titles, 114 abstracts and 85 full-texts, and analyzed 36 articles regarding the clinical assessment (i.e., diagnostic and prognostic value; n = 19) and treatment (i.e., interventions; n = 17) of ADs. Though most VR assessment studies (n = 15/19) showed associations between VR-induced cue-reactivity and clinical parameters, only two studies specified diagnostic value. VR treatment studies based on exposure therapy showed no or negative effects. However, other VR interventions like embodied and aversive learning paradigms demonstrated positive findings. The overall study quality was rather poor; (5) Conclusion: Though VR in ADs provides ecologically valid environments to induce cue-reactivity and provide new treatment paradigms, the added clinical value in assessment and therapy remains to be elucidated before VR can be applied in clinical care. Therefore, future work should investigate VR efficacy in randomized clinical trials using well-defined clinical endpoints.

Maatoug R., Bihan K., Duriez P., Podevin P., Silveira-Reis-Brito L., Benyamina A., Valero-Cabré A., Millet B.

Alcohol use disorder (AUD) ranks among the leading causes of decrements in disability-adjusted life-years. Long-term exposure to alcohol leads to an imbalance of activity between frontal cortical systems and the striatum, thereby enhancing impulsive behaviours and weakening inhibitory control. Alternative therapeutic approaches such as non-invasive and invasive brain stimulation have gained some momentum in the field of addictology by capitalizing on their ability to target specific anatomical structures and correct abnormalities in dysfunctional brain circuits. The current review, covers original peer-reviewed published research on the use of brain stimulation methods for the rehabilitation of AUD. A broad and systematic search was carried out on four electronic databases: NCBI PubMed , Web of Science , Handbooks and the Cochrane Library . Any original article in English or French language, without restrictions of patient age or gender, article type and publication outlet, were included in the final pool of selected studies. The outcomes of this systematic review suggest that the dorsolateral prefrontral cortex (DLPFC) is a promising target for treating AUD with high frequency repetitive transcranial magnetic stimulation. Such effect would reduce feelings of craving by enhancing cognitive control and modulating striatal function. Existing literature also supports the notion that changes of DLPFC activity driven by transcranial direct current stimulation, could decrease alcohol craving and consumption. However, to date, no major differences have been found between the efficacy of these two non-invasive brain-stimulation approaches, which require further confirmation. In contrast, beneficial stronger evidence supports an impact of deep brain stimulation reducing craving and improving quality of life in AUD, effects that would be mediated by an impact on the nucleus accumbens, a central structure of the brain's reward circuitry. Overall, neurostimulation shows promise contributing to the treatment of AUD. Nonetheless, progress has been limited by a number of factors such as the low number of controlled randomized trials, small sample sizes, variety of stimulation parameters precluding comparability and incomplete or questionable sham-conditions. Additionally, a lack of data concerning clinical impact on the severity of AUD or craving and the short follow up periods precluding and accurate estimation of effect duration after discontinuing the treatment, has also limited the clinical relevance of final outcomes. Brain stimulation remains a promising approach to contribute to AUD therapy, co-adjuvant of more conventional procedures. However, a stronger therapeutic rational based on solid physio-pathological evidence and accurate estimates of efficacy, are still required to achieve further therapeutic success and expand clinical use. • Long term exposure to alcohol leads to an imbalance of activity between frontal cortical systems and the striatum. • Brain dysfunction secondary to alcohol enhance impulsive behaviours and weaken inhibitory control. • Brain stimulation techniques have gained momentum by capitalizing on their ability to target specific anatomical structures. • Progress in neurostimulation has been limited by the diversity of stimulation parameters and questionable sham-conditions.

Emmelkamp P.M., Meyerbröker K.

Initially designed for the treatment of phobias, the use of virtual reality in phobic disorders has expanded to other mental health disorders such as posttraumatic stress disorder, substance-related disorders, eating disorders, psychosis, and autism spectrum disorder. The goal of this review is to provide an accessible understanding of why this approach is important for future practice, given its potential to provide clinically relevant information associated with the assessment and treatment of people suffering from mental illness. Most of the evidence is available for the use of virtual reality exposure therapy in anxiety disorders and posttraumatic stress disorder. There is hardly any evidence that virtual reality therapy is effective in generalized anxiety disorder and obsessive-compulsive disorder. There is increasing evidence that cue exposure therapy is effective in addiction and eating disorders. Studies into the use of virtual reality therapy in psychosis, autism spectrum disorder, and attention deficit hyperactivity disorder (ADHD) are promising.

Antonelli M., Fattore L., Sestito L., Di Giuda D., Diana M., Addolorato G.

Substance Use Disorder (SUD) is a chronic and relapsing disease characterized by craving, loss of control, tolerance and physical dependence. At present, the combination of pharmacotherapy and psychosocial intervention is the most effective management strategy in preventing relapse to reduce dropout rates and promote abstinence in SUD patients. However, only few effective medications are available. Transcranial Magnetic Stimulation (TMS) is a non-invasive brain stimulation technique that modulates the cellular activity of the cerebral cortex through a magnetic pulse applied on selected brain areas. Recently, the efficacy of TMS has been investigated in various categories of SUD patients. The present review analyzes the application of repetitive TMS in patients with alcohol, tobacco, and cocaine use disorder. Although the number of clinical studies is still limited, repetitive TMS yields encouraging results in these patients, suggesting a possible role of TMS in the treatment of SUD.

Ward H.B., Yip A., Siddiqui R., Morales O.G., Seiner S.J., Siddiqi S.H.

• Comorbid personality disorders are common in patients with major depressive disorder (MDD). • Individuals with comorbid borderline personality disorder (BPD) may be less responsive to electroconvulsive therapy (ECT), but it remains unclear whether BPD affects responsiveness to transcranial magnetic stimulation (TMS). • We performed a retrospective analysis of individuals receiving TMS to investigate the association between BPD and treatment response. As a control analysis, we also investigated the association between BPD and response to ECT. • For individuals receiving TMS, BPD traits did not independently predict QIDS score (p = 0.29). In the control analysis with ECT, BPD traits independently predicted QIDS score after controlling for the effect of the number of treatments (p < 10−6). • TMS may be an appropriate treatment for depression in individuals with comorbid BPD. Comorbid personality disorders are common in patients with major depressive disorder (MDD). Individuals with comorbid borderline personality disorder (BPD) may be less responsive to electroconvulsive therapy (ECT), but it remains unclear whether BPD affects responsiveness to transcranial magnetic stimulation (TMS). We sought to investigate the association between BPD and response to TMS. We conducted a retrospective analysis of individuals receiving TMS (n=356) at McLean Hospital. We also included individuals receiving ECT (n=1434) as a control. All individuals completed the McLean Screening Instrument for BPD (MSI-BPD) at baseline. Response to treatment was measured by the Quick Inventory of Depression Symptomatology Self-Report (QIDS-SR). We performed general linear models (GLMs) to assess the effect of BPD on treatment response to TMS and ECT. At baseline, the ECT group had a higher average QIDS-SR score (21.4 vs. 20.3, p

Rossi S., Antal A., Bestmann S., Bikson M., Brewer C., Brockmöller J., Carpenter L.L., Cincotta M., Chen R., Daskalakis J.D., Di Lazzaro V., Fox M.D., George M.S., Gilbert D., Kimiskidis V.K., et. al.

This article is based on a consensus conference, promoted and supported by the International Federation of Clinical Neurophysiology (IFCN), which took place in Siena (Italy) in October 2018. The meeting intended to update the ten-year-old safety guidelines for the application of transcranial magnetic stimulation (TMS) in research and clinical settings (Rossi et al., 2009). Therefore, only emerging and new issues are covered in detail, leaving still valid the 2009 recommendations regarding the description of conventional or patterned TMS protocols, the screening of subjects/patients, the need of neurophysiological monitoring for new protocols, the utilization of reference thresholds of stimulation, the managing of seizures and the list of minor side effects. New issues discussed in detail from the meeting up to April 2020 are safety issues of recently developed stimulation devices and pulse configurations; duties and responsibility of device makers; novel scenarios of TMS applications such as in the neuroimaging context or imaging-guided and robot-guided TMS; TMS interleaved with transcranial electrical stimulation; safety during paired associative stimulation interventions; and risks of using TMS to induce therapeutic seizures (magnetic seizure therapy). An update on the possible induction of seizures, theoretically the most serious risk of TMS, is provided. It has become apparent that such a risk is low, even in patients taking drugs acting on the central nervous system, at least with the use of traditional stimulation parameters and focal coils for which large data sets are available. Finally, new operational guidelines are provided for safety in planning future trials based on traditional and patterned TMS protocols, as well as a summary of the minimal training requirements for operators, and a note on ethics of neuroenhancement.

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.

Background/Objective: Determining the predictive variables associated with levels of alcohol craving can ease the identification of patients who can benefit from treatments. This study aimed to describe changes (improvement or no change/deterioration) in alcohol craving levels and explore the predictors of these changes from admission to discharge in outpatients with alcohol use disorder (AUD) undergoing treatment-as-usual (TAU), or treatment-as-usual supplemented with virtual reality cue-exposure therapy (TAU + VR-CET). Method: A prospective cohort study was conducted amongst 42 outpatients with AUD (n = 15 TAU + VR-CET and n = 27 TAU) from a clinical setting. Changes in the levels of alcohol craving between admission and discharge were assessed with the Multidimensional Alcohol Craving Scale. Sociodemographic characteristics (age, gender, education, and socioeconomic and civil status), cognitive-affective behavioral patterns (AUD severity, abstinence duration, psychiatric comorbidity, state anxiety, attentional bias, and substance use), and type of treatment (TAU + VR-CET and only TAU) were also evaluated. Results: The TAU + VR-CET group showed greater changes of improvement in the levels of alcohol craving than the TAU group (χ2 = 10.996; p = 0.001). Intragroup changes in alcohol craving from pre to post-treatment were significant in the TAU + VR-CET group (χ2 = 13.818; p = 0.003) but not within the TAU group (χ2 = 2.349; p = 0.503). The odds of an improvement in any of the craving levels between pre- and post-test was 18.18 (1/0.055) times higher in the TAU + VR-CET group with respect to the TAU group. The use of illicit drugs in the month prior to the test increased the odds of having a positive change by 18.18 (1/0.055) with respect to not having consumed. Conclusions: Including VR-CET in TAU programs may provide benefits in the treatment of AUDs mainly among patients with intense alcohol craving and individuals having used illicit substances prior to treatment.

MARLOTH M., CHANDLER J., VOGELEY K.

AbstractRecent improvements in virtual reality (VR) allow for the representation of authentic environments and multiple users in a shared complex virtual world in real time. These advances have fostered clinical applications including in psychiatry. However, although VR is already used in clinical settings to help people with mental disorders (e.g., exposure therapy), the related ethical issues require greater attention. Based on a thematic literature search the authors identified five themes that raise ethical concerns related to the clinical use of VR: (1) reality and its representation, (2) autonomy, (3) privacy, (4) self-diagnosis and self-treatment, and (5) expectation bias. Reality and its representation is a theme that lies at the heart of VR, but is also of specific significance in a clinical context when perceptions of reality are concerned, for example, during psychosis. Closely associated is the autonomy of VR users. Although autonomy is a much-considered topic in biomedical ethics, it has not been sufficiently discussed when it comes to applications of VR in psychiatry. In this review, the authors address the different themes and recommend the development of an ethical framework for the clinical use of VR.

Ding X., Li Y., Li D., Li L., Liu X.

Background The aim of this study was to evaluate whether machine learning (ML) can be used to distinguish patients with methamphetamine dependence from healthy controls by using their surface electroencephalography (EEG) and galvanic skin response (GSR) in a drug-simulated virtual reality (VR) environment. Methods A total of 333 participants with methamphetamine (METH) dependence and 332 healthy control subjects were recruited between January 2018 and January 2019. EEG (five electrodes) and GSR signals were collected under four VR environments: one neutral scenario and three METH-simulated scenarios. Three ML classification techniques were evaluated: random forest (RF), support vector machine (SVM), and logistic regression (LR). Results The MANOVA showed no interaction effects among the two subject groups and the 4 VR scenarios. Taking patient groups as the main effect, the METH user group had significantly lower GSR, lower EEG power in delta (pÂ

Nabors L., Monnin J., Jimenez S.

The goals for this scoping review were to evaluate interventions using virtual reality (VR) environments for individuals with intellectual disabilities (IDs) and to discuss these interventions in terms of their educational value. The authors conducted a scoping review of articles examining VR interventions for individuals with IDs. The authors searched seven databases between 2000 and 2019 using virtual reality and intellectual disability/disabilities as search terms. The search yielded 123 articles and 15 articles were reviewed. A search of critical journals in 2020 yielded one additional article for review. Interventions addressed different skills, such as increasing physical activity, teaching letter and number literacy, preparing individuals for court testimony, and learning routes. Researchers need to assess participants for level of cognitive functioning and understand how to modify interventions for individuals with different levels of impairment. Moreover, examining whether interventions are related to improvement of skills in in vivo situations will be important for understanding generalizability of skills. The review revealed positive findings for use of VR interventions, with a need for caregiver support and possible technology support to implement interventions. Using a participatory approach may improve abilities to implement interventions in real-world settings. Directions for future research include examining what interventions work for individuals with different levels of impairment and defining when and how to implement interventions.

de Bruijn G., de Vries J., Bolman C., Wiers R.

Cue-Exposure Therapy (CET) is considered an effective strategy to combat cigarette cravings and smoking relapses, but evidence is mixed. In this lab-based experimental study, we manipulated levels of realism for smoking scenarios in Virtual Environments (VE) and randomly exposed smokers and recent-quitters to one of two versions (low versus high realism) of these scenarios. Prior and after scenario exposure, valid measures of cigarette craving were obtained. Prior to exposure, we assessed nicotine dependence and smoking status (current smokers versus recent-quitter). Within-subject repeated measures analysis of covariance showed that there was an interaction of experimental condition with smoking status on cigarette craving. Amongst recent-quitters, high realistic scenarios produced stronger increases in craving than low realistic scenarios, but this effect was reversed in current smokers. It is concluded that VE technologies are a potentially relevant tool for smoking CET that warrant further exploration.

Mellentin A.I., Nielsen A.S., Ascone L., Wirtz J., Samochowiec J., Kucharska-Mazur J., Schadow F., Lebiecka Z., Skoneczny T., Mistarz N., Bremer T., Kühn S.

The approach-avoidance training program (AATP) has shown preliminary promise as an add-on to standard treatment for alcohol dependence. However, knowledge is lacking as to whether the effectiveness of AATP can be enhanced further when performed in a typical drinking situation. The main aim of this study is to investigate whether approach-avoidance training implemented in a virtual reality bar environment is superior to the classical joystick PC-version of the AATP. The study will be implemented as a randomized controlled trial. A total of 204consecutively enrolled alcohol use disorder (AUD) patients, recruited from alcohol inpatient clinics in Germany, Poland and Denmark, will be randomized into one of three groups at the start of standard alcohol treatment: group A) stimuli-relevant AATP + treatment as usual (TAU); group B) stimuli-relevant AATP in virtual reality + TAU, and group C) TAU only (control group). Treatment outcomes will be assessed at pre-treatment, post-treatment and 3-month follow-up. Repeated-measures ANOVA will be applied to compare the trajectories of the groups over time on drinking, craving and impulsiveness outcomes. It is hypothesized that the two experimental groups will achieve better treatment outcomes compared to group C and that group B will achieve better outcomes than group A. This study is the first trial examining the effectiveness of stimuli-relevant AATP delivered in a VR environment. The use of VR has shown promise in enhancing the effectiveness of other psychological treatments and since AATP has already been shown effective as add-on treatment, it is of interest to investigate whether these effects can be further enhanced by implementing the program in more ecologically valid environments. If proven effective, the AATP-VR can, like the AATP, be implemented easily and cheaply as add-on treatment or continued care to enhance the effectiveness of current evidence-based treatment. ClinicalTrials.gov ID: NCT04283305 Registration date: 24.02.20