Interventions combining mindfulness training with non-invasive brain stimulation and their impact on mental health outcomes: Protocol for a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Mindfulness training programs and non-invasive brain stimulation are both evidence-based interventions that have applications in mental health disorders. While both have showed promising results on a range of symptoms related to mental health, their combination has more recently grabbed the attention of researchers. There is a theoretical framework for their synergistic effects, and these effects can be tested through a variety of neurophysiological and clinical outcomes. This emerging field of research, which is regularly extended with new trials, has not yet been systematically reviewed. This systematic review protocol aims to present a rationale for combining these two interventions and to document the methodical approach to our systematic review before data extraction. METHODS AND ANALYSIS: Four electronic databases (Medline, EMBASE, CENTRAL, PsycINFO) and three clinical trial registries (Clinical Trials, EU Trials, WHO ICTRP) were searched. All randomized controlled trials testing the combination of mindfulness-based interventions and non-invasive brain stimulation in humans will be included. As primary outcome, data on change in anxiety and depression symptoms from baseline, and, as secondary outcomes, other mental health outcomes data will be gathered. Data will be extracted independently by two authors using a predefined extraction form. Depending on the clinical heterogeneity of the included studies, the research team will decide whether a quantitative synthesis is appropriate for each of the predefined outcomes. If there is considerable statistical heterogeneity, subgroup analyses and meta-regression will be performed. Bias will be assessed using a revised Cochrane risk-of-bias tool for randomized trials and the strength of evidence in our review will be assessed using the GRADE form in GRADEPro. We started our scoping searches in November 2022. This systematic review and meta-analysis protocol was finished and submitted before the end of the independent full-text selection process by two members of the team. ETHICS AND DISSEMINATION: Ethics approval and consent to participate were not applicable to our systematic review. Our dissemination plan includes the publication of our systematic review and meta-analysis in an international peer-reviewed journal as well as international communication of our results. TRIAL REGISTRATION: PROSPERO registration number CRD42022353971.

Mindfulness interventions for craving reduction in substance use disorders and behavioral addictions: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: High-quality evidence is still required to affirm the efficacy of mindfulness-based interventions (MBIs) in craving reduction. MBIs may be particularly appropriate for this purpose given the neurobiological mechanisms of addiction with automatic behavior in response to the negative affect. In this systematic review and meta-analysis, we aimed to study the efficacy of MBIs in craving reduction and to synthetize the newly published data. METHODS: We searched four databases and three clinical trial registries for randomized controlled trials (RCTs) up to August 2023, including studies with MBIs in all types of substance use disorders or behavioral addictions. We chose as our outcome of interest the change from the baseline of craving measures at posttreatment. Standardized mean difference was used as an effect size estimator. RESULTS: We included 17 RCTs with 1228 participants. The overall effect size was estimated at -0.70 (95% CI -1.15, -0.26) in favor of MBIs. CONCLUSION: Due to the high inconsistency (I2 = 92%), we were unable to conclude that there is a medium to large effect size. Overall risk of bias was high for most studies, and the GRADE approach detected a low quality of evidence. Previous clinical and fundamental research suggest that MBIs have a promising potential in addiction medicine. However, further investigation of whether MBIs effectively reduce craving is needed, and innovative solutions for resolving methodological limitations in MBI research are warranted. TRIAL REGISTRATION: PROSPERO registration ID CRD42020221141.

Prevalence of internet addiction in Africa: A systematic review and meta-analysis.

Background and aim: In the last two decades, the proportion of internet users has greatly increased worldwide. Data regarding internet addiction (IA) are lacking in Africa compared to other continents. This systematic review and meta-analysis aimed to estimate the pooled prevalence of IA in African countries. Methods: We systematically sought relevant articles in PubMed/MEDLINE, EMBASE, PsycINFO and Cochrane database published before September 25, 2021. The risk of bias was assessed using the Joanna Briggs Institute tool, and we estimated the pooled prevalence of IA using a random-effects meta-analytic model. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Results: We included 22 studies (13,365 participants), and collected data from Egypt, Ethiopia, Morocco, Nigeria, South Africa, Tanzania and Tunisia between 2013 and 2021. The mean age of participants ranged from 14.8 to 26.1 years, and the most used tool for IA screening was the Young's 20-item Internet Addiction Test. The pooled prevalence rate of IA was 40.3% (95% CI: 32.2%-48.7%), with substantial heterogeneity. The pooled prevalence for Northern Africa was 44.6% (95% CI: 32.9%-56.7%), significantly higher than the prevalence in sub-Saharan Africa, which was 31.0% (95% CI: 25.2%-37.1%). The risk of bias was moderate for most studies, the certainty was very low, and we found no publication bias. Discussion and conclusions: Four in every ten individuals was considered to have IA in Africa. Further research with methodological optimization seems needed, especially for IA screening tools and the representativity of some subregions.

Non-invasive brain stimulation for smoking cessation: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Non-invasive brain stimulation (NIBS) methods have showed promising results for the treatment of tobacco use disorder, but little is known about the efficacy of NIBS on sustained tobacco abstinence. We aimed to assess its effectiveness for long-term smoking cessation. METHODS: Systematic review and meta-analysis of randomized controlled trials (RCT). PubMed, Cochrane library, Embase, PsycINFO and clinical trials registries were systematically searched for relevant studies up to May 2021. Relevant studies included adult smokers seeking smoking cessation, included in an RCT using NIBS [specifically repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS)], and with follow-up of more than 4 weeks. There were no restrictions on location. Abstinence rates in the active NIBS groups were compared with abstinence rates in sham NIBS or in usual treatment groups, from 4 weeks to 12 months following the quit attempt. Smoking abstinence was measured on an intention-to-treat basis and we used risk ratios (RRs) as measures of effect size. RESULTS: Seven studies were included (n = 699 patients). In all included studies, the control groups were receiving sham NIBS and only data from 3 to 6 months were analysable. By pooling the seven included studies, the RR of sustained abstinence of any form of NIBS relative to sham NIBS was 2.39 [95% confidence interval (CI) = 1.26-4.55; I2  = 40%]. Subgroup analyses found that the RR was even higher when excitatory rTMS was used on the left dorsolateral prefrontal cortex (RR = 4.34; 95% CI = 1.69-11.18; I2  = 0%) or when using deep rTMS targeting the lateral prefrontal cortex and insula bilaterally (RR = 4.64; 95% CI = 1.61-13.39; I2  = 0%). A high risk of bias was found in four included studies. We also determined, using grades of recommendation, assessment, development and evaluation, that overall there was a low level of confidence in the results. CONCLUSION: Non-invasive brain stimulation (NIBS) may improve smoking abstinence rates from 3 to 6 months after quitting smoking, compared with sham NIBS or usual treatment.

Efficacy of repetitive transcranial magnetic stimulation (rTMS) for reducing consumption in patients with alcohol use disorders (ALCOSTIM): study protocol for a randomized controlled trial.

BACKGROUND: The number of people with an alcohol use disorder (AUD) was recently estimated to be 63.5 million worldwide. The global burden of disease and injury attributable to alcohol is considerable: about 3 million deaths, namely one in 20, were caused by alcohol in 2015. At the same time, AUD remains seriously undertreated. In this context, alternative or adjunctive therapies such as brain stimulation could play an important role. The early results of studies using repetitive transcranial magnetic stimulation (rTMS) suggest that stimulations delivered to the dorsolateral prefrontal cortex significantly reduce cravings and improve decision-making processes in various addictive disorders. We therefore hypothesize that rTMS could lead to a decrease in alcohol consumption in patients with AUD. METHODS/DESIGN: We report the protocol of a randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy of rTMS on alcohol reduction in individuals diagnosed with AUD. The study will be conducted in 2 centers in France. Altogether, 144 subjects older than 18 years and diagnosed with AUD will be randomized to receive 5 consecutive twice-daily sessions of either active or sham rTMS (10 Hz over the right DLPFC, 2000 pulses per day). The main outcomes of the study will be changes in alcohol consumption within the 4 weeks after the rTMS sessions. Secondary outcome measures will include changes in alcohol consumption within the 24 weeks, alcohol cravings, clinical and biological improvements, effects on mood and quality of life, and cognitive and safety assessments, and, for smokers, an assessment of the effects of rTMS on tobacco consumption. DISCUSSION: Several studies have observed a beneficial effect of rTMS on substance use disorders by reducing craving, impulsivity, and risk-taking behavior and suggest that rTMS may be a promising treatment in addiction. However, to date, no studies have included sufficiently large samples and sufficient follow-up to confirm this hypothesis. The results from this large randomized controlled trial will give a better overview of the therapeutic potential of rTMS in AUD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04773691. Registered on 26 February 2021 https://clinicaltrials.gov/ct2/show/NCT04773691?term=trojak&draw=2&rank=5 .

High-Frequency Neuronavigated rTMS in Auditory Verbal Hallucinations: A Pilot Double-Blind Controlled Study in Patients With Schizophrenia.

INTRODUCTION: Despite extensive testing, the efficacy of low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) of temporo-parietal targets for the treatment of auditory verbal hallucinations (AVH) in patients with schizophrenia is still controversial, but promising results have been reported with both high-frequency and neuronavigated rTMS. Here, we report a double-blind sham-controlled study to assess the efficacy of high-frequency (20 Hz) rTMS applied over a precise anatomical site in the left temporal region using neuronavigation. METHODS: Fifty-nine of 74 randomized patients with schizophrenia or schizoaffective disorders (DSM-IV R) were treated with rTMS or sham treatment and fully evaluated over 4 weeks. The rTMS target was determined by morphological MRI at the crossing between the projection of the ascending branch of the left lateral sulcus and the superior temporal sulcus (STS). RESULTS: The primary outcome was response to treatment, defined as a 30% decrease of the Auditory Hallucinations Rating Scale (AHRS) frequency item, observed at 2 successive evaluations. While there was no difference in primary outcome between the treatment groups, the percentages of patients showing a decrease of more than 30% of AHRS score (secondary outcome) did differ between the active (34.6%) and sham groups (9.1%) (P = .016) at day 14. DISCUSSION: This controlled study reports negative results on the primary outcome but demonstrates a transient effect of 20 Hz rTMS guided by neuronavigation and targeted on an accurate anatomical site for the treatment of AVHs in schizophrenia patients.

Effects of Transcranial Magnetic Stimulation on the Hypothalamic-Pituitary Axis in Depression: Results of a Pilot Study.

Some studies have reported that repetitive transcranial magnetic stimulation (rTMS) applied to the dorsolateral prefrontal cortex (DLPFC) is able to induce changes in the hypothalamic-pituitary axis in subjects with major depression. The causes of these neuroendocrine effects are unknown and deserve to be studied. The authors monitored neuroendocrine hormones in 15 subjects with major depression treated by 1-Hz rTMS on the right DLPFC and explored a correlation with mood improvement. Unlike previous studies, no changes in serum cortisol, prolactin, and thyroid hormone levels were found. However, the authors did observe short-term changes in growth hormone levels in nonresponsive subjects.

Efficacy of transcranial direct current stimulation (tDCS) in reducing consumption in patients with alcohol use disorders: study protocol for a randomized controlled trial.

BACKGROUND: Approximately 15 million persons in the European Union and 10 million persons in the USA are alcohol-dependent. The global burden of disease and injury attributable to alcohol is considerable: worldwide, approximately one in 25 deaths in 2004 was caused by alcohol. At the same time, alcohol use disorders remain seriously undertreated. In this context, alternative or adjunctive therapies such as brain stimulation may play a prominent role. The early results of studies using transcranial direct current stimulation found that stimulations delivered to the dorsolateral prefrontal cortex result in a significant reduction of craving and an improvement of the decision-making processes in various additive disorders. We, therefore, hypothesize that transcranial direct current stimulation can lead to a decrease in alcohol consumption in patients suffering from alcohol use disorders. METHODS/DESIGN: We report the protocol of a randomized, double-blind, placebo-controlled, parallel-group trial, to evaluate the efficacy of transcranial direct current stimulation on alcohol reduction in patients with an alcohol use disorder. The study will be conducted in 14 centers in France and Monaco. Altogether, 340 subjects over 18 years of age and diagnosed with an alcohol use disorder will be randomized to receive five consecutive twice-daily sessions of either active or placebo transcranial direct current stimulation. One session consists in delivering a current flow continuously (anode F4; cathode F3) twice for 13 minutes, with treatments separated by a rest interval of 20 min. Efficacy will be evaluated using the change from baseline (alcohol consumption during the 4 weeks before randomization) to 24 weeks in the total alcohol consumption and number of heavy drinking days. Secondary outcome measures will include alcohol craving, clinical and biological improvements, and the effects on mood and quality of life, as well as cognitive and safety assessments, and, for smokers, an assessment of the effects of transcranial direct current stimulation on tobacco consumption. DISCUSSION: Several studies have reported a beneficial effect of transcranial direct current stimulation on substance use disorders by reducing craving, impulsivity, and risk-taking behavior, and suggest that transcranial direct current stimulation may be a promising treatment in addiction. However, to date, no studies have included sufficiently large samples and sufficient follow-up to confirm the hypothesis. Results from this large randomized controlled trial will give a better overview of the therapeutic potential of transcranial direct current stimulation in alcohol use disorders. TRIAL REGISTRATION: Clinical Trials Gov, NCT02505126 (registration date: July 15 2015).

Transcranial Magnetic Stimulation Combined With Nicotine Replacement Therapy for Smoking Cessation: A Randomized Controlled Trial.

BACKGROUND: Further evidence suggests that repetitive Transcranial Magnetic Stimulation (rTMS) is an effective method to reduce tobacco craving among smokers. HYPOTHESIS: As relapse is common within a few days after smoking cessation, we hypothesized that combining the anti-craving effects of rTMS with Nicotine replacement therapy (NRT) to attenuate withdrawal symptoms could increase abstinence rates in smokers with severe nicotine dependence who quit smoking. METHODS: Thirty-seven smokers who failed to quit with the usual treatments were randomly assigned to two treatment groups to receive either active (n = 18) or sham (n = 19) 1-Hz rTMS of the right dorsolateral prefrontal cortex. The day after quitting smoking, each patient combined NRT (21-mg patch) with active or sham rTMS (10 sessions) for 2 weeks. Cessation support was then continued with NRT alone using lower-dose patches. Abstinence rates and self-report craving scales were used to assess the therapeutic results during the combined treatment and for up to 12 weeks after quitting. RESULTS: At the end of the combined treatment, there were significantly more abstinent participants in the active rTMS group (n = 16) than in the sham rTMS group (n = 9) (P = 0.027). The craving scales analysis revealed that active rTMS (P = 0.011) but not sham rTMS (P = 0.116) led to a significant decrease in the compulsive factor. However, no lasting rTMS effect was found. CONCLUSIONS: 1-Hz rTMS combined with NRT improved the success rate of abstinence in smokers during tobacco cessation. The stimulation-induced reduction in compulsivity may explain this result.

Interest of targeting either cortical area Brodmann 9 or 46 in rTMS treatment for depression: a preliminary randomized study.

OBJECTIVE: To assess the interest of specifically targeting Brodmann Areas (BA) 9 or 46 for rTMS treatment of depression. METHODS: Patients with Treatment-Resistant Depression were randomly assigned to two treatment groups to receive either rTMS on BA 9 or on BA 46. Each patient underwent 10 sessions of 1Hz-rTMS for 2weeks. The Hamilton and Montgomery-Asberg Depression Rating Scales (HDRS, MADRS) were used under blind conditions to assess the therapeutic response (50% improvement). A Wilcoxon signed-rank test was used to compare the depression rating scales scores obtained before and after the 10 rTMS sessions for each of the two groups. The therapeutic results in the two groups were compared using the Mann-Whitney-Wilcoxon test. We also reported the effect sizes using Hedges's g. RESULTS: Fifteen patients were included. Stimulation of both BA 9 (n=7) and BA 46 (n=8) led to similar therapeutic responses in the two groups (with moderate effect size), such as the mean decrease in HDRS (BA 9: p=0.015; BA 46: p=0.010) and MADRS (BA 9: p=0.042; BA 46: p=0.038) scores. CONCLUSION: Our results do not come out in favor of one or the other BA. SIGNIFICANCE: Stimulation of BA 9 and BA 46 appears to be equally effective in the treatment of depression.

Stroke with neuropsychiatric sequelae after cannabis use in a man: a case report.

INTRODUCTION: The outcome of cerebral ischemic stroke associated with cannabis use is usually favorable. Here we report the first case of cannabis-related stroke followed by neuropsychiatric sequelae. CASE PRESENTATION: A 24-year-old Caucasian man was discovered in a deeply comatose non-reactive state after cannabis use. A magnetic resonance imaging scan of his brain showed bilateral multiple ischemic infarcts. The patient remained deeply comatose for four days, after which time he developed other behavioral impairments and recurrent seizures. CONCLUSION: Stroke related to cannabis use can be followed by severe neuropsychiatric sequelae. Concomitant alcohol intoxication is essential neither to the occurrence of this neurologic event nor to its severity.