Prazosin and cyproheptadine in combination in the treatment of alcohol use disorder: A randomized, double-blind, placebo-controlled trial.

BACKGROUND AND AIMS: Pre-clinical studies suggest that the simultaneous blockade of the α1b and 5HT2A receptors may be effective in reducing alcohol consumption. This study aimed to assess the efficacy and safety of prazosin (α1b blocker) and cyproheptadine (5HT2A blocker) combination in decreasing total alcohol consumption (TAC) in alcohol use disorder (AUD). DESIGN, SETTING AND PARTICIPANTS: This was a double-blind, parallel group, placebo-controlled, Phase 2, randomized clinical trial conducted in 32 addiction treatment centres in France. A total of 108 men and 46 women with severe AUD took part. INTERVENTION: Participants were randomly assigned to one of the following 3-month treatments: (1) low-dose group (LDG) receiving 8 mg cyproheptadine and 5 mg prazosin extended-release (ER) formulation daily; (2) high-dose group (HDG) receiving 12 mg cyproheptadine and 10 mg prazosin ER daily; and (3) placebo group (PG) receiving placebo of cyproheptadine and prazosin ER. A total of 154 patients were randomized: 54 in the PG, 54 in the LDG and 46 in the HDG. MEASUREMENTS: The primary outcome was TAC change from baseline to month 3. FINDINGS: A significant main treatment effect in the change in TAC was found in the intent-to-treat population (P = 0.039). The HDG and LDG showed a benefit in the change in TAC from baseline to month 3 compared with PG: -23.6 g/day, P = 0.016, Cohen's d = -0.44; -18.4 g/day, P = 0.048 (Bonferroni correction P < 0.025), Cohen's d = -0.36. In a subgroup of very high-risk drinking-level participants (> 100 g/day of pure alcohol for men and > 60 g/day for women), the difference between the HDG and the PG in the primary outcome was -29.8 g/day (P = 0.031, Cohen's d = -0.51). The high and low doses were well-tolerated with a similar safety profile. CONCLUSIONS: A randomized controlled trial of treatment of severe alcohol use disorder with a cyproheptadine-prazosin combination for 3 months reduced drinking by more than 23 g per day compared with placebo. A higher dose combination was associated with a larger magnitude of drinking reduction than a lower dose combination while showing similar safety profile.

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 .

Factors of Interest in Extended-Release Buprenorphine: Comparisons Between Incarcerated and Non-Incarcerated Patients with Opioid Use Disorder.

PURPOSE: Extended-release buprenorphine (XR-BUP) covers a range of formulations of buprenorphine-based treatments for opioid use disorder (OUD) that release the medication over a period of one week, one month, or six months. OUD is particularly prevalent among incarcerated populations, and previous findings have shown that incarcerated subjects were not less interested in XR-BUP than non-incarcerated subjects. However, no study has ever investigated whether the factors of interest in XR-BUP were similar in incarcerated and non-incarcerated populations. PATIENTS AND METHODS: We carried out post-hoc analyses using data from the "AMBRE" survey, which was conducted among 366 individuals with OUD, that were recruited in 68 French addiction settings, including six prison medical centers. The reasons for interest in XR-BUP were compared between incarcerated and non-incarcerated interviewees, using logistic regressions models, which provided raw and adjusted odds ratios (aORs) and 95% confidence intervals (95% CI). Adjustment variables were gender, age category, level of education, and type of current medication for OUD, respectively. RESULTS: Data from 317 participants (ie, 221 non-incarcerated, and 96 incarcerated individuals) were included in the analyses. Adjusted comparisons found that "no longer taking a daily treatment" (aOR= 2.91; 95% CI= 1.21-6.98) and "having a more discreet medication" (aOR= 1.76; 95% CI= 1.01-3.10) were reasons that appealed more to incarcerated participants than to non-incarcerated ones. On the other hand, the potential reduction of withdrawal symptoms (aOR= 0.54; 95% CI= 0.29-0.99) or the risk of misuse (aOR= 0.56; 95% CI= 0.34-0.94) associated with XR-BUP treatment were considered more important by non-incarcerated individuals than by incarcerated ones. CONCLUSION: Incarcerated interviewees were interested in XR-BUP for different reasons than those outside prison. In particular, incarcerated patients were more interested in practicability and discretion features, and less in improving recovery or reducing misuse than non-incarcerated patients.

Determinants of interest in extended-released buprenorphine: A survey among 366 French patients treated with buprenorphine or methadone.

AIM: To explore the factors determining the interest in extended-release buprenorphine (XR-BUP) injections among patients receiving opioid agonist treatment (OAT) in France. METHODS: 366 patients receiving OAT for opioid use disorder, recruited in 66 French centers, were interviewed from 12/2018 to 05/2019. A structured questionnaire assessed their interest in XR-BUP using a [1-10] Likert scale. 'More' vs. 'less' interested groups were defined using the median score of interest, and their characteristics were explored using adjusted odds ratios (aORs) and 95 % confidence interval (95 %CI). Independent variables were as follows: sociodemographic characteristics, OAT-related features (e.g., type of OAT and prescriber, dosing, or duration of treatment), OAT representations, and personal objectives of treatment. RESULTS: The median interest in XR-BUP was 7 (interquartile range: 3-9) out of 10. The participants who were 'more interested' (i.e. those scoring ≥7) showed no substantial difference in sociodemographic characteristics, relative to the 'less interested' participants. However, they more frequently reported forgetting to take their OAT (OR = 1.81; CI95 % = 1.06-3.10) or reported experiencing situations where taking their OAT was impractical (aOR = 1.69; CI95 % = 1.05-2.73). Their treatment objective was more focused on stopping illicit drugs (aOR = 1.67; 95 %CI = 1.02-2.70), reducing health risks (aOR = 3.57; 95 %CI = 1.67-7.69) and craving (aOR = 2.38; 95 %CI = 1.39-4.02) or improving family (aOR = 1.81; 95 %CI = 1.03-3.13) or professional (aOR = 2.22; 95 %CI = 1.43-3.85) recovery. CONCLUSIONS: In France, where the access to OAT is relatively unrestricted, the majority of participants were interested in XR-BUP formulations. Being interested was associated with treatment objectives focused on abstinence and recovery, and with experiencing constraints in taking a daily oral OAT.

[Prolonged-release buprenorphine formulations: Perspectives for clinical practice]. / Buprénorphine d'action prolongée : quelles perspectives pour la pratique clinique ?

Buprenorphine and methadone are the two main opioids agonist treatments approved for opioid use disorder. Buprenorphine is a partial agonist of the mu-opioid receptors, which has been merely available through sublingual form until now. In practice, the use of buprenorphine is smoother than that of methadone, and it induces reduced risks of overdose. However, sublingual buprenorphine also exposes to risks (e.g., withdrawal, misuse) and constraints (e.g., daily intake). Three new galenic formulations of prolonged-release buprenorphine (PRB) are being commercialized and should allow some improvements in patients' comfort and safety. This narrative review aims to describe the main technical features and efficacy and safety data of these PRBs, as well as patients' and professionals' expectancies and concerns, using data of the scientific literature and the regulatory texts. PRBs consist of one subcutaneous implant and two subcutaneous injection depots. Sixmo®/Probuphine® is a six-month-long implant which needs to be surgically placed and removed and is approved for subjects previously treated with a maximum daily dose of 8mg of sublingual buprenorphine, and can be used only for two successive periods of six months before the subject needs to be switched back to sublingual form. Sublocade® is a one-month-long depot formulation that is indicated in switch from sublingual buprenorphine, and which proposes only two dose schemes, i.e., 100 and 300mg monthly. Buvidal®/Brixadi® is a one-week- or one-month-long depot formulation with multiple dosages, which can be used in initiation or in switched from sublingual formulations. While opioid users report some concerns with a risk of coercive use of long-acting forms of buprenorphine, both users and professionals deem that these new specialties could be particularly appreciated in stabilized patients bothered with the daily intake of the treatments, or specific situations at risk of treatment dropout (e.g., following hospital discharge or prison release).

Behavioral and Neural Arguments of Motivational Influence on Decision Making During Uncertainty.

The scientific world is increasingly interested in motivation, primarily due to the suspected impact on decision-making abilities, particularly in uncertain conditions. To explore this plausible relationship, 28 healthy participants were included in the study and performed decision-making and motivational tasks while their neural activity was recorded. All participants performed the Iowa Gambling Task (IGT) and were split into two groups based on their score, one favorable group with 14 participants who performed advantageously and one undecided group with 14 participants who failed to develop the correct strategy on the IGT. In addition, all participants performed the Effort Expenditure for Reward Task (EEfRT), which defines the motivational level of each participant by the effort that participants agree to do in function of reward magnitudes and probabilities to receive these reward (10, 50, and 90%). The completion of both tasks allowed for the exploration of the relationship between the motivational level and decision-making abilities. The EEfRT was adapted to electroencephalography (EEG) recordings to explore how motivation could influence reward experience. Behavioral results showed no difference in EEfRT performances on the whole task between the two groups' performances on the IGT. However, there was a negative correlation between the difficulty to develop an optimal strategy on the IGT and the percentage of difficult choices at the 90% condition on the EEfRT. Each probability condition has been previously associated to different motivational and emotional states, with the 90% condition associated to the reward sensitivity. This behavioral result leads to the hypothesis that reward sensitivity may induce an inability to develop an optimal strategy on the IGT. Group analysis demonstrated that only the undecided group showed a P300 during the processing of the outcome, whereas the favorable group showed a blunted P300. Similarly, there was a negative correlation between the P300 amplitude and the ability to develop an optimal strategy on the IGT. In conclusion, behavioral and neuronal data provides evidence that the propensity to focus only on the immediate outcomes is related to the development of an inefficient strategy on the IGT, without influence of motivation.

Prolonged-release buprenorphine formulations: Perspectives for clinical practice.

Buprenorphine and methadone are the two main opioid agonist treatments approved for opioid use disorder. Buprenorphine is a partial agonist of the mu opioid receptors, which has been merely available through sublingual form until now. In practice, the use of buprenorphine is smoother than that of methadone, and it induces reduced risks of overdose. However, sublingual buprenorphine also exposes to risks (e.g., withdrawal, misuse) and constraints (e.g., daily intake). Three new galenic formulations of prolonged-release buprenorphine (PRB) are being commercialized and should allow some improvements in patients' comfort and safety. This narrative review aims to describe the main technical features and efficacy and safety data of these PRBs, as well as patients' and professionals' expectancies and concerns, using data of the scientific literature and the regulatory texts. PRBs consist of one subcutaneous implant and two subcutaneous injection depots. Sixmo®/Probuphine® is a six-month-long implant which needs to be surgically placed and removed and is approved for subjects previously treated with a maximum daily dose of 8mg of sublingual buprenorphine, and can be used only for two successive periods of six months before the subject needs to be switched back to sublingual form. Sublocade® is a one-month-long depot formulation that is indicated in switch from sublingual buprenorphine, and which proposes only two dose schemes, i.e., 100 and 300mg monthly. Buvidal®/Brixadi® is a one-week- or one-month-long depot formulation with multiple dosages, which can be used in initiation or in switched from sublingual formulations. While opioid users report some concerns with a risk of coercive use of long-acting forms of buprenorphine, both users and professionals deem that these new specialties could be particularly appreciated in stabilized patients bothered with the daily intake of the treatments, or specific situations at risk of treatment dropout (e.g., following hospital discharge or prison release).

Event-Related Potentials (ERP) Indices of Motivation during the Effort Expenditure for Reward Task.

Dynamic and temporal facets of the various constructs that comprise motivation remain to be explored. Here, we adapted the Effort Expenditure for Reward Task, a well-known laboratory task used to evaluate motivation, to study the event-related potentials associated with reward processing. The Stimulus Preceding Negativity (SPN) and the P300 were utilized as motivation indicators with high density electroencephalography. The SPN was found to be more negative for difficult choices compared to easy choices, suggesting a greater level of motivation, at a neurophysiological level. The insula, a structure previously associated with both effort discounting and prediction error, was concomitantly activated during the generation of the SPN. Processing a gain significantly altered the amplitude of the P300 compared to an absence of gain, particularly on centroparietal electrodes. One of the generators of the P300 was located on the vmPFC, a cerebral structure involved in the choice between two positive results and their predictions, during loss processing. Both the SPN and the P300 appear to be reliable neural markers of motivation. We postulate that the SPN represents the strength of the motivational level, while the P300 represents the impact of motivation on updating memories of the feedback.

Behavioral and Electrophysiological Arguments in Favor of a Relationship between Impulsivity, Risk-Taking, and Success on the Iowa Gambling Task.

The aim of the present study was to investigate the relationship between trait impulsivity, risk-taking, and decision-making performance. We recruited 20 healthy participants who performed the Iowa Gambling Task (IGT) and the Balloon Analog Risk Task (BART) to measure decision-making and risk-taking. The impulsivity was measured by the Barratt Impulsiveness Scale. Resting-state neural activity was recorded to explore whether brain oscillatory rhythms provide important information about the dispositional trait of impulsivity. We found a significant correlation between the ability to develop a successful strategy and the propensity to take more risks in the first trials of the BART. Risk-taking was negatively correlated with cognitive impulsivity in participants who were unable to develop a successful strategy. Neither risk-taking nor decision-making was correlated with cortical asymmetry. In a more exploratory approach, the group was sub-divided in function of participants' performances at the IGT. We found that the group who developed a successful strategy at the IGT was more prone to risk, whereas the group who failed showed a greater cognitive impulsivity. These results emphasize the need for individuals to explore their environment to develop a successful strategy in uncertain situations, which may not be possible without taking risks.

[Mood disorders: When should we use repetitive transcranial magnetic stimulation?] / Troubles de l'humeur : quand recourir à la stimulation magnétique transcrânienne ?

Repeated transcranial magnetic stimulation (rTMS) is still a recent treatment in psychiatry. This article aims at updating the clinicians'knowledge about rTMS in the treatment of mood disorders (uni and bipolar depressive disorders, manic/mixed states, suicidal risk, catatonia). It is intended for clinicians who are required to indicate and/or use rTMS in their current practice. rTMShas the highest level of evidence for the treatment of unipolar depression, provided that effective parameters are used, that is to say, for classical high frequency protocols: 20 to 30 sessions, 1000 pulses/session, 5 to 20Hz, and 110 % of the motor threshold. Low frequency protocol are also efficient and well tolerated. The duration of the efficacy varies with relapses rates around 50 % at one year. Pharmacological treatment generally remains associated. With regard to manic states, and mixed states the results are preliminary and limited to a possible reduction in symptoms. In the suicidal risk associated with mood disorders, the interest of rTMS is still to demonstrate, as well as in catatonia. The current place of the rTMS is no longer disputed in the curative treatment of major depressive disorder, preferentially used after one or two lines of antidepressants upstream. Further studies are needed to confirm preliminary positive findings in other aspects of mood disorders.

Oral health in schizophrenia patients: A French Multicenter Cross-Sectional Study.

OBJECTIVE: The aim of this study was to assess the oral health status of a sample of patients with schizophrenia (PWS) in Côte d'Or region (France) and to determine the factors associated with dental status. MATERIAL AND METHODS: A multicenter cross-sectional descriptive study was performed. PWS were selected using a random stratified method. Dental status was investigated using the Decayed, Missing, or Filled Teeth (DMFT) index, based on 32 teeth. The Simplified Oral Hygiene Index (OHI-S), the Xerostomia Index (XI) and the Global Oral Health Assessment Index (GOHAI) for Oral Health-related Quality of Life (OHrQoL) were recorded. RESULTS: Among the 302 persons identified, 109 were included (acceptance rate was 49.1%). Of these, 61.5% were men. The mean age was 46.8 years±12.0 years. The majority (78%) had completed a secondary education (SE). The mean duration of mental illness (DMI) was 17.9±9.4 years, and 55.5% were taking drugs. The mean DMFT was 16.6±8.1. There was a significant relationship between age, SE, oral health variables, medical conditions and OHrQoL. CONCLUSIONS: PWS describe a poor OHrQoL. The dental and hygiene index scores are poor. We observed a lack of brushing and of dental visit for these persons and a gap in oral health between PWS and general population.

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.

[Biopsychosocial approach to caregiving burden: Why should we care about caregivers' health?] / Impact biopsychosocial de la charge des aidants : pourquoi faut-il porter une attention spécifique envers la santé des aidants ?

There are 11 million family caregivers in France and some estimates indicate that there will be 17 million in 2020. Caregiving is a source of chronic stress that requires adaptation and coping strategies. Caregiving may benefit the health of a caregiver with a positive coping style and altruistic goals. However, the caregiver's burden is frequently associated with negative effects in terms of biopsychosocial imbalance and medical conditions, with frequent anxiety and depression. The management of the caregiving burden starts with the recognition of health professionals - caregivers may benefit from consultation-liaison psychiatry and multidisciplinary medico-social strategies, in addition to constant support from their GPs.

Cognitive effects of labeled addictolytic medications.

INTRODUCTION: Alcohol, tobacco, and illegal drug usage is pervasive throughout the world, and abuse of these substances is a major contributor to the global disease burden. Many pharmacotherapies have been developed over the last 50years to target addictive disorders. While the efficacy of these pharmacotherapies is largely recognized, their cognitive impact is less known. However, all substance abuse disorders are known to promote cognitive disorders like executive dysfunction and memory impairment. These impairments are critical for the maintenance of addictive behaviors and impede cognitive behavioral therapies that are regularly administered in association with pharmacotherapies. It is also unknown if addictolytic medications have an impact on preexisting cognitive disorders, and if this impact is modulated by the indication of prescription, i.e. abstinence, reduction or substitution, or by the specific action of the medication. METHOD: We reviewed the cognitive effects of labeled medications for tobacco addiction (varenicline, bupropion, nicotine patch and nicotine gums), alcohol addiction (naltrexone, nalmefene, baclofen, disulfiram, sodium oxybate, acamprosate), and opioid addiction (methadone, buprenorphine) in human studies. Studies were selected following MOOSE guidelines for systematic reviews of observational studies, using the keywords [Cognition] and [Cognitive disorders] and [treatment] for each medication. RESULTS: 971 articles were screened and 77 studies met the inclusion criteria and were reported in this review (for alcohol abuse, n=21, for tobacco n=22, for opioid n=34. However, very few comparative clinical trials have explored the chronic effects of addictolytic medications on cognition in addictive behaviors, and there are no clinical trials on the cognitive impact of nalmefene in patients suffering from alcohol use disorders. DISCUSSION: Although some medications seem to enhance cognition in patients suffering from cognitive disorders, others could promote cognitive impairments, and our work highlights a lack of literature on this subject. In conclusion, more comparative clinical trials are needed to better understand the cognitive impact of addictolytic medications.

A Rasch Analysis between Schizophrenic Patients and the General Population.

BACKGROUND: The aim of this study was to test the General Oral Health Assessment Index Questionnaire (GOHAI) items for differential item functioning (DIF) according to demographic characteristics (gender, age) and mental health status (schizophrenic disorders versus general population) using Rasch analysis. METHODS: This is a cross-sectional study using aggregated baseline data from a validation study of the GOHAI in the French general population (GP) and similar validation study in persons with schizophrenia (PWS). DIF was tested using the Partial Credit Model. DIF were estimated in different groups of patients. RESULTS: The cohort comprised 363 persons: 65% were female, 83% were 25-45 years old and 30% were PWS.Five of the 12 items exhibited DIF. DIF effects were observed with schizophrenia for 3 items, with age for 3 items and with gender for 1 item. The variable "age" gave a significant explanation of the latent variable: the latent variable decreased with age (-0.40±0.08-p<0.001 for each increase of the age of 10 years). This decrease represented an effect size of 0.27 which can be qualified of a small to medium effect. The status of the individuals (GP versus PWS) and the gender did not significantly explain differences in the values of the latent variable. CONCLUSION: The GOHAI scores may not be comparable across sub-groups defined by health status, age and gender without accounting for DIF. In the future, other studies should explore this way with other Oral Health related Quality of Life assessment tools and populations with mental illness.

A Randomized, Placebo-Controlled Study of High-Dose Baclofen in Alcohol-Dependent Patients-The ALPADIR Study.

AIMS: Alcohol dependence is a major public health issue with a need for new pharmacological treatments. The ALPADIR study assessed the efficacy and safety of baclofen at the target dose of 180 mg/day for the maintenance of abstinence and the reduction in alcohol consumption in alcohol-dependent patients. METHODS: Three hundred and twenty adult patients (158 baclofen and 162 placebo) were randomized after alcohol detoxification. After a 7-week titration, the maintenance dose was provided for 17 weeks, then progressively decreased over 2 weeks before stopping. RESULTS: The percentage of abstinent patients during 20 consecutive weeks (primary endpoint) was low (baclofen: 11.9%; placebo: 10.5%) and not significantly different between groups (OR 1.20; 95%CI: 0.58 to 2.50; P = 0.618). A reduction in alcohol consumption was observed from month 1 in both groups, but the difference of 10.9 g/day at month 6 between groups, in favour of baclofen, was not statistically significant (P = 0.095). In a subgroup of patients with high drinking risk level at baseline, the reduction was greater with a difference at month 6 of 15.6 g/day between groups in favour of baclofen (P = 0.089). The craving assessed with Obsessive-Compulsive Drinking Scale significantly decreased in the baclofen group (P = 0.017). No major safety concern was observed. CONCLUSIONS: This study did not demonstrate the superiority of baclofen in the maintenance of abstinence at the target dose of 180 mg/day. A tendency towards a reduction in alcohol consumption and a significantly decreased craving were observed in favour of baclofen. SHORT SUMMARY: Baclofen was assessed versus placebo for maintenance of abstinence and reduction in alcohol consumption in alcohol-dependent patients. This study did not demonstrate the superiority of baclofen in the maintenance of abstinence. A tendency towards a reduction in alcohol consumption and a significantly decreased craving were observed in favour of baclofen.