Study protocol on the efficacy of exergames-acceptance and commitment therapy program for the treatment of major depressive disorder: comparison with acceptance and commitment therapy alone and treatment-as-usual in a multicentre randomised controlled trial.

BACKGROUND: The prevalence of major depressive disorder (MDD) is on the rise globally, and the use of antidepressant medications for its treatment does not usually result in full remission. However, the combination of physical exercise and psychotherapy for the treatment of MDD increase the rate of full remission among patients. This three-armed, parallel-group, double-blinded randomised controlled trial (RCT) aims to assess and compare the effects between the combination of exergame and acceptance and commitment therapy (e-ACT) programme, ACT only and treatment-as-usual (TAU) control groups on the severity of depression and anxiety symptoms, the degree of experiential avoidance and quality of life (QoL) and the serum levels of depression biomarkers (such as brain-derived neurotrophic factor, C-reactive protein and vascular endothelial growth factor) among patients with MDD across three time points. METHODS AND ANALYSIS: This RCT will recruit 126 patients with MDD who will be randomised using stratified permuted block randomisation into three groups, which are the combined e-ACT programme, ACT-only and TAU control groups in a 1:1:1 allocation ratio. The participants in the e-ACT and ACT-only intervention groups will undergo once a week intervention sessions for 8 weeks. Assessments will be carried out through three time points, such as the pre-intervention assessment (t0), assessment immediately after completion of the intervention at 8 weeks (t1) and assessment at 24 weeks after completion of the intervention (t2). During each assessment, the primary outcome to be assessed includes the severity of depression symptoms, while the secondary outcomes to be assessed are the severity of anxiety symptoms, experiential avoidance, QoL and depression biomarkers. ETHICS AND DISSEMINATION: Approval of this study was obtained from the Human Research Ethics Committee of Universiti Sains Malaysia (USM/JEPeM/PP/23050420). The findings of the study will be published in academic peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05812001 (ClinicalTrials.gov). Registered on 12 April 2023.

Research protocol of the efficacy of probiotics for the treatment of alcohol use disorder among adult males: A comparison with placebo and acceptance and commitment therapy in a randomized controlled trial.

BACKGROUND AND AIM: Primarily, this study compares the efficacy of probiotic and acceptance and commitment therapy (ACT) in alleviating the severity of alcohol craving and alcohol use disorder (AUD) among patients who had undergo two weeks of in-patient detoxification. Secondarily, this study compares the efficacy of probiotic and ACT in mitigating the severity of comorbid depression and anxiety symptoms; decreasing serum level of pro-inflammatory cytokines, such as interleukin 1ß (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α); changing the event-related potential in electroencephalogram (EEG) and restoring microbiota flora in the gut of AUD patients. METHODS AND ANALYSIS: Initially, during Phase I of the study, the serum level of IL-1ß, IL-6 and TNF-α; ERP changes in the EEG and fecal microbiota content will be compared between 120 AUD patients and 120 healthy controls. Subsequently in Phase II of the study, 120 AUD patients will be randomized by stratified permuted block randomization into the probiotic, ACT and placebo groups in a 1:1:1 ratio. Participants in the probiotic and placebo groups will be administered one sachet per day of Lactobacillus spp. probiotic and placebo, respectively for 12 weeks. While those in the ACT group will receive one session per week of ACT for 8 weeks. Outcome measures will be administered at four timepoints, such as t0 = baseline assessment prior to intervention, t1 = 8 weeks after intervention began, t2 = 12 weeks after intervention and t3 = 24 weeks after intervention. Primary outcomes are the degrees of alcohol craving, alcohol withdrawal during abstinence and AUD. Secondary outcomes to be assessed are the severity of co-morbid depression and anxiety symptoms; the serum levels of IL-1ß, IL-6 and TNF-α; changes in ERP and fecal microbiota content. TRIAL REGISTRATION NUMBER: NCT05830708 (ClinicalTrials.gov). Registered on April 25, 2023.

Effects of virtual reality-based cue exposure therapy on craving and physiological responses in alcohol-dependent patients-a randomised controlled trial.

BACKGROUND: Cue exposure therapy is used to treat alcohol dependence. However, its effectiveness is controversial due to the limitations of the clinical treatment setting. Virtual reality technology may improve the therapeutic effect. The aim of this study is to explore whether virtual reality-based cue exposure therapy can reduce the psychological craving and physiological responses of patients with alcohol dependence. METHODS: Forty-four male alcohol-dependent patients were recruited and divided into the study group (n = 23) and the control group (n = 21) according to a random number table. The control group received only conventional clinical treatment for alcohol dependence. The study group received conventional clinical treatment with the addition of VR cue exposure (treatment). The primary outcome was to assess psychological craving and physiological responses to cues of patients before and after treatment. RESULTS: After virtual reality-based cue exposure therapy, the changes in VAS and heart rate before and after cue exposure in the study group were significantly lower than those in the control group (P < 0.05), while the changes in skin conductance and respiration between the study group and the control group were not significantly different (P > 0.05). The changes in VAS and heart rate before and after cue exposure in the study group were significantly lower than those before treatment (P < 0.05), while the changes in skin conductance and respiration were not significantly different from those before treatment (P > 0.05). The changes in VAS, heart rate, skin conductance and respiration before and after cue exposure in the control group were not significantly different from those before treatment (P > 0.05). CONCLUSION: Virtual reality-based cue exposure therapy can reduce the psychological craving and part of the physiological responses of alcohol-dependent patients during cue exposure in the short term and may be helpful in the treatment of alcohol dependence. TRIAL REGISTRATION: The study protocol was registered at the China Clinical Trial Registry on 26/02/2021 ( www.chictr.org.cn ; ChiCTR ID: ChiCTR2100043680).

The efficacy of virtual reality exposure therapy for the treatment of alcohol use disorder among adult males: a randomized controlled trial comparing with acceptance and commitment therapy and treatment as usual.

Background: This multicenter, three-armed, parallel, single-blind randomized controlled trial (RCT) primarily aims to compare the efficacy of virtual reality exposure therapy (VRET) with that of acceptance and commitment therapy (ACT) and treatment as usual (TAU) to depreciate the degree of alcohol craving among alcohol use disorder patients who have undergone in-patient detoxification across four timelines (t0 = baseline prior to intervention, t1 = 4 weeks after baseline, t2 = 12 weeks after baseline, and t3 = 24 weeks after baseline). The secondary aims of this RCT are to compare the efficacy of VRET with that of ACT and TAU to alleviate the severity of alcohol use disorder, dissipate comorbid depressive and anxiety symptoms, and normalize event-related potential (ERP) in electroencephalogram (EEG) monitoring across the four timelines. Methods: Initially, after 2 weeks of in-patient detoxification, 120 patients with alcohol use disorder will be randomized into three groups (VRET, ACT, and TAU control groups) via stratified permuted block randomization in a 1:1:1 ratio. Baseline assessment (t0) commences, whereby all the participants will be administered with sociodemographic, clinical, and alcohol use characteristics questionnaire, such as Alcohol Use Disorder Identification Test (AUDIT), Penn Alcohol Craving Scale (PACS), Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Rating Scale (HAM-D), while event-related potential (ERP) detection in electroencephalogram (EEG) will also be carried out. Then, 4 weeks of VRET, ACT, and non-therapeutic supportive activities will be conducted in the three respective groups. For the subsequent three assessment timelines (t1, t2, and t3), the alcohol use characteristic questionnaire, such as AUDIT, PACS, HAM-D, HAM-A, and ERP monitoring, will be re-administered to all participants. Discussion: As data on the effects of non-pharmacological interventions, such as VRET and ACT, on the treatment of alcohol craving and preventing relapse in alcohol use disorder are lacking, this RCT fills the research gap by providing these important data to treating clinicians. If proven efficacious, the efficacy of VRET and ACT for the treatment of other substance use disorders should also be investigated in future. Clinical trial registration: NCT05841823 (ClinicalTrials.gov).