Virtual Reality-Based Cue Exposure and Aversion Therapy for Alcohol Dependence: A Randomized Controlled Trial.

Alcohol dependence (AD) is characterized by a high relapse rate. Virtual reality (VR) technology can provide immersive cue exposure therapy (VR-CET) and aversion therapy (VR-AT). This study aimed to evaluate the efficacy of VR-CET, VR-AT and their combination on craving, emotional and sleep states, attentional bias and relapse rate in patients with AD. In this single-centre randomized controlled trial, male inpatients with AD were randomly assigned to one of four groups: control, VR-CET, VR-AT or combined VR-CET + AT (target n = 25 per group; 80 completed, 20 per group). The interventions spanned 15 days with eight sessions (VR-CET + AT ~20 min/session; others ~10 min). Assessments were conducted before and after treatment using the Visual Analogue Scale (VAS), the Pennsylvania Alcohol Craving Scale (PACS), the Hamilton Depression Scale (HAMD), the Hamilton Anxiety Scale (HAMA) and the Pittsburgh Sleep Quality Index (PSQI). Eye-tracking and grasping indices in VR environments were used to assess attentional bias (e.g., alcohol-cue fixation time ratio). Relapse was evaluated by telephone at 4 and 12 weeks post-treatment. Statistical analyses used Shapiro-Wilk tests and ANOVA/Kruskal-Wallis tests with appropriate post hoc comparisons (α = 0.05). All groups showed significant pre- to post-treatment improvements in PACS, HAMD, HAMA, PSQI and VAS scores (all p < 0.001). Between-group comparisons at post-treatment revealed significant differences in alcohol-cue fixation time ratio (p < 0.05), with the VR-CET + AT group showing a lower fixation time ratio than the control group. VAS scores also differed among groups (p < 0.05), with the control group showing higher values than the VR-CET + AT group. Changes in alcohol-cue fixation time ratio from pre- to post-treatment were significantly greater in the VR-CET + AT group than in the control group. Relapse rates at 4 and 12 weeks (47/80 reached by telephone follow-up) did not significantly differ among groups (both p > 0.05). Combining VR-CET with VR-AT reduced craving (VAS) and attentional bias (alcohol-cue fixation time ratio) beyond standard care, whereas all groups improved on clinical scales. Larger and longer trials are warranted to further clarify relapse outcomes. Trial Registration: Chinese Clinical Trial Registry, ChiCTR2500110026. Registered 29 September 2025 (retrospectively registered).