Effect of sensorimotor rehabilitation based on an immersive virtual reality model on mental health.

The aim of this study was to determine the immersive virtual reality-based sensorimotor rehabilitation (IVR-SRB) effect on mental health (global mental health, depression, anxiety and well-being) in older adults. METHODS: This study was experimental, with a sample of 111 older adults (control-experimental), considering an application of IVR-SRB in four different virtual settings with exteroceptive synchronization, proprioceptive and vestibular stimuli, for 6 weeks. OUTCOME VARIABLES: symptoms associated with depression and anxiety; positive mental health (psychological well-being). A descriptive and inferential approach was used to analyze the data, and the ANCOVA test was used to compare the post-intervention groups, controlled by the baseline; In case of baseline moderation, a linear regression model was applied to identify the level of moderation and a region of significance analysis. RESULTS: An IVR-SRB positive net effect was found in the reduction of symptoms of global mental health (p < 0.0001) and depression (p < 0.0001), without baseline moderation. The anxiety scores showed moderation at the beginning (p < 0.0001; b = -0.53), identifying that the greater the presence of anxiety symptoms, the greater the effect of IVR-SRB in reducing these symptoms; its effect is present from scores of 2.9 (Goldberg-12). There were no changes in well-being. CONCLUSION: IVR-SRB is recognized as a great intervention tool among elderly population, showing its multidimensional approach capacity, properly responding to the reduction of symptoms associated with mental disorders.

Assessing the relationship between psychosocial stressors and psychiatric resilience among Chilean disaster survivors.

BACKGROUND: According to the stress inoculation hypothesis, successfully navigating life stressors may improve one's ability to cope with subsequent stressors, thereby increasing psychiatric resilience. AIMS: Among individuals with no baseline history of post-traumatic stress disorder (PTSD) and/or major depressive disorder (MDD), to determine whether a history of a stressful life event protected participants against the development of PTSD and/or MDD after a natural disaster. METHOD: Analyses utilised data from a multiwave, prospective cohort study of adult Chilean primary care attendees (years 2003-2011; n = 1160). At baseline, participants completed the Composite International Diagnostic Interview (CIDI), a comprehensive psychiatric diagnostic instrument, and the List of Threatening Experiences, a 12-item questionnaire that measures major stressful life events. During the study (2010), the sixth most powerful earthquake on record struck Chile. One year later (2011), the CIDI was re-administered to assess post-disaster PTSD and/or MDD. RESULTS: Marginal structural logistic regressions indicated that for every one-unit increase in the number of pre-disaster stressors, the odds of developing post-disaster PTSD or MDD increased (OR = 1.21, 95% CI 1.08-1.37, and OR = 1.16, 95% CI 1.06-1.27 respectively). When categorising pre-disaster stressors, individuals with four or more stressors (compared with no stressors) had higher odds of developing post-disaster PTSD (OR = 2.77, 95% CI 1.52-5.04), and a dose-response relationship between pre-disaster stressors and post-disaster MDD was found. CONCLUSIONS: In contrast to the stress inoculation hypothesis, results indicated that experiencing multiple stressors increased the vulnerability to developing PTSD and/or MDD after a natural disaster. Increased knowledge regarding the individual variations of these disorders is essential to inform targeted mental health interventions after a natural disaster, especially in under-studied populations.

[Psychological factors influencing weight regain after bariatric surgery]. / Recuperación de peso perdido en pacientes que han tenido cirugía bariátrica: Una mirada psicológica.

Background Approximately 15 to 40% of bariatric patients regain a significant percentage of their weight lost after surgery. Among psychological variables, control and self-efficacy loci are associated with behaviors related to weight loss. Also, family support can be a risk or protection factor for the maintenance of weight loss. Aim To evaluate the association between psychological variables with weight maintenance or regain after bariatric surgery. Material and Methods We evaluated 97 patients at 4.1 ± 3.4 years after their bariatric surgery. They answered questionnaires about self-efficacy to lose weight, locus of weight control and family functioning style. Regain after surgery was also calculated, through self-report. Results Seventeen percent of patients gained weight. Locus of control (Z = -3.09, p < 0.01), family identity (Z = -3.71, p < 0.01) and self-efficacy (Z = -2.44, p = 0.01), differentiated patients who maintained weight loss from those who re-gained at least 15% of their lost weight. An inverse and significant relationship was observed between the percentage of weight regain and locus of control (r = -0.42, p < 0.01), family identity (r = -0.36, p < 0.01) and self-efficacy (r = -0.34, p <0.01). Conclusions The psychological variables "locus of weight control" and "family identity" are inversely and moderately associated with weight regain in patients subjected to bariatric surgery.

[Psychometric characteristics of the Patient Health Questionnaire (PHQ-9)]. / Propiedades psicométricas del PHQ-9 (Patient Health Questionnaire) en centros de atención primaria de Chile.

BACKGROUND: Simple and brief questionnaires with adequate psychometric properties are useful for the early detection of depressive disorders. AIM: To analyze the psychometric behavior of the Patient Health Questionnaire (PHQ-9) in Chile. MATERIAL AND METHODS: Data were collected from 1,738 adult patients, consulting in primary health care centers. The values obtained in the PHQ-9 were compared with those of the Composite International Diagnostic Interview (CIDI). RESULTS: The mean score of PHQ-9 was 4.85 ± 5.57. Internal consistency indices were high. McDonald's ω coefficient of was 0.90 and Cronbach alpha 0.89. A confirmatory factor analysis showed a good fit of the one-dimensional model. Using a cutoff score of seven determined with the receiver operating characteristic (ROC) curve, the sensitivity and specificity of the instrument were 0.8 and 0.7, when compared with CIDI diagnoses. CONCLUSIONS: PHQ-9 is a useful instrument for the screening of depressive disorders in primary health care centers in Chile.

Mental health in the Americas: an overview of the treatment gap.

OBJECTIVE: To understand the mental health treatment gap in the Region of the Americas by examining the prevalence of mental health disorders, use of mental health services, and the global burden of disease. METHODS: Data from community-based surveys of mental disorders in Argentina, Brazil, Canada, Chile, Colombia, Guatemala, Mexico, Peru, and the United States were utilized. The World Mental Health Survey published data were used to estimate the treatment gap. For Canada, Chile, and Guatemala, the treatment gap was calculated from data files. The mean, median, and weighted treatment gap, and the 12-month prevalence by severity and category of mental disorder were estimated for the general adult, child-adolescent, and indigenous populations. Disability-adjusted Life Years and Years Lived with Disability were calculated from the Global Burden of Disease study. RESULTS: Mental and substance use disorders accounted for 10.5% of the global burden of disease in the Americas. The 12-month prevalence rate of severe mental disorders ranged from 2% - 10% across studies. The weighted mean treatment gap in the Americas for moderate to severe disorders was 65.7%; North America, 53.2%; Latin America, 74.7%; Mesoamerica, 78.7%; and South America, 73.1%. The treatment gap for severe mental disorders in children and adolescents was over 50%. One-third of the indigenous population in the United States and 80% in Latin America had not received treatment. CONCLUSION: The treatment gap for mental health remains a public health concern. A high proportion of adults, children, and indigenous individuals with serious mental illness remains untreated. The result is an elevated prevalence of mental disorders and global burden of disease.

[Concepción inventory: Development of a screening instrument for depression in primary care in Chile]. / Inventario Concepción: Desarrollo y validación de un instrumento de tamizaje de depresión para atención primaria.

BACKGROUND: Screening instruments are required for the detection of depressive disorders by primary care practitioners. AIM: To develop a screening instrument to detect depression, based on data gathered interviewing patients attending primary health care settings. MATERIAL AND METHODS: The instrument was constructed with data about factors associated or triggering a depressive disorder obtained from 3,000 patients consulting for general morbidity. All patients answered the Composite International Diagnostic Interview, (version 2.1, section depression) and an inventory containing 39 risk factors for depression, obtained from the literature. A multiple imputation method using chained equations was carried out. Using a binary logistic regression with backward selection, an equation for depression screening was obtained. The c-index was calculated to estimate discriminating power of the model. A shrinkage factor was estimated to adjust the predictive model. RESULTS: Estimations were carried out with data from 2,552 patients with a median age of 47 years (73% women). Fifty five percent lived with a partner and 45% had basic studies. The method selected 14 significant predictors, with a shrinkage value of 0.861 and a c-index of 0.838 (95% confidence intervals 0.82-0.86). CONCLUSIONS: The instrument has adequate psychometric properties as a screening tool for depression in primary health care.

[Association between serotonin transporter and monoamine oxidase A gene polymorphisms and depression]. / Asociación entre los polimorfismos 5HTTLPR, uMAOA y depresión en una cohorte de pacientes de atención primaria.

BACKGROUND: Serotonin plays a central role regulating mood and on the development of depressive disorders. AIM: To study whether 5HTTLPR functional polymorphisms in the serotonin transporter gene or the Monoamine oxidase A gene (uMAOA) were risk markers for depression. MATERIAL AND METHODS: The Composite International Diagnostic Interview (CIDI) was applied to 1,062 consultants in primary health care centers aged between 18 and 75 years to establish the diagnosis of depression. A sample of saliva was obtained for DNA extraction and genetic analyses. RESULTS: No association between the presence of depressive disorders and 5HTTLPR (ss) or uMAOA (3/3) risk genotypes was found. Psychological abuse and the presence of two or more life events were found to be predictors of depression in the studied sample. CONCLUSIONS: In this study, 5HTTLPR and uMAOA polymorphisms were not risk factors for depression. However, psychological abuse and the presence of two or more life events were risk factors for depressive disorders.

The Maristán stigma scale: a standardized international measure of the stigma of schizophrenia and other psychoses.

BACKGROUND: People with schizophrenia face prejudice and discrimination from a number of sources including professionals and families. The degree of stigma perceived and experienced varies across cultures and communities. We aimed to develop a cross-cultural measure of the stigma perceived by people with schizophrenia. METHOD: Items for the scale were developed from qualitative group interviews with people with schizophrenia in six countries. The scale was then applied in face-to-face interviews with 164 participants, 103 of which were repeated after 30 days. Principal Axis Factoring and Promax rotation evaluated the structure of the scale; Horn's parallel combined with bootstrapping determined the number of factors; and intra-class correlation assessed test-retest reliability. RESULTS: The final scale has 31 items and four factors: informal social networks, socio-institutional, health professionals and self-stigma. Cronbach's alpha was 0.84 for the Factor 1; 0.81 for Factor 2; 0.74 for Factor 3, and 0.75 for Factor 4. Correlation matrix among factors revealed that most were in the moderate range [0.31-0.49], with the strongest occurring between perception of stigma in the informal network and self-stigma and there was also a weaker correlation between stigma from health professionals and self-stigma. Test-retest reliability was highest for informal networks [ICC 0.76 [0.67 -0.83]] and self-stigma [ICC 0.74 [0.64-0.81]]. There were no significant differences in the scoring due to sex or age. Service users in Argentina had the highest scores in almost all dimensions. CONCLUSIONS: The MARISTAN stigma scale is a reliable measure of the stigma of schizophrenia and related psychoses across several cultures. A confirmatory factor analysis is needed to assess the stability of its factor structure.

[Development of an algorithm to predict the incidence of major depression among primary care consultants]. / Desarrollo y validación de un algoritmo para predecir riesgo de depresión en consultantes de atención primaria en Chile.

BACKGROUND: The reduction of major depression incidence is a public health challenge. AIM: To develop an algorithm to estimate the risk of occurrence of major depression in patients attending primary health centers (PHC). MATERIAL AND METHODS: Prospective cohort study of a random sample of 2832 patients attending PHC centers in Concepción, Chile, with evaluations at baseline, six and twelve months. Thirty nine known risk factors for depression were measured to build a model, using a logistic regression. The algorithm was developed in 2,133 patients not depressed at baseline and compared with risk algorithms developed in a sample of 5,216 European primary care attenders. The main outcome was the incidence of major depression in the follow-up period. RESULTS: The cumulative incidence of depression during the 12 months follow up in Chile was 12%. Eight variables were identified. Four corresponded to the patient (gender, age, depression background and educational level) and four to patients' current situation (physical and mental health, satisfaction with their situation at home and satisfaction with the relationship with their partner). The C-Index, used to assess the discriminating power of the final model, was 0.746 (95% confidence intervals (CI = 0,707-0,785), slightly lower than the equation obtained in European (0.790 95% CI = 0.767-0.813) and Spanish attenders (0.82; 95% CI = 0.79-0.84). CONCLUSIONS: Four of the factors identified in the risk algorithm are not modifiable. The other two factors are directly associated with the primary support network (family and partner). This risk algorithm for the incidence of major depression provides a tool that can guide efforts towards design, implementation and evaluation of effectiveness of interventions to prevent major depression.

Challenges for psychiatric recruitment and training in Chile.

This paper aims to describe the current challenges to recruitment of psychiatrists in Chile, and investigate factors related to interest in psychiatry from medical students of the Chilean Biobío Region. An online survey was completed by 39 medical students currently performing the internship. This survey included questions regarding socio-demographic aspects, probability of choosing a medical speciality, influencing factors on the choice of the medical speciality, and personal features. Students were separated in two groups for the analysis based on their likelihood of choosing psychiatry as a career. A total of 35.9% of the respondents showed some degree of interest in psychiatry. Factors considered important by the respondents were academic opportunities, training vacancies, and balance between job and personal life. The low participation in the study does not allow the extrapolation of data to the national situation, and may represent response bias to those already interested in psychiatry as a career. However, Chile has an average psychiatrist rate per number of inhabitants for the region, but an uneven distribution of this resource. National policies must be focused on this issue in order to reduce the gap in mental healthcare.

[Suicidal behavior and psychiatric disorders in Chile. A population-based study]. / Conducta suicida y trastornos psiquiátricos en Chile, un estudio poblacional.

BACKGROUND: Suicidal behavior ranges from ideation to consummation of suicide. In Chile, rates of suicide increased from 4.8 to 12.7/100,000 in the period 1992-2009. AIM: To evaluate the prevalence of suicidal behavior and its relationship with sociodemographic factors and psychiatric diseases. MATERIAL AND METHODS: The Composite International Diagnostic Interview (CIDI), was applied to a representative sample of 2,978 Chilean participants. The prevalence of four suicidal behaviors (thinking about or wishing death, suicide ideation and suicide attempts) and of psychiatric diseases according to the revised third version of the Diagnostic and Statistical Manual of Mental Disorders (DSM III-R), was calculated. RESULTS: The lifetime prevalence of suicidal conception was 14.3% and the suicide attempt 7.7%, the latest associated with sex, age, school years, smoking habits, being married or having a relationship, depressive disorders, dysthymia, and alcohol, drug and tobacco dependence. CONCLUSIONS: Rates founded exceed international prevalence data and extrapolated to current rates of completed suicide, higher levels of suicidal behavior should be expected. Considering the associated disorders we can infer that it is essential a correct diagnosis and treatment of mood disorders and substance consumption to any other specific interventions.

Increased academic stress is associated with decreased plasma BDNF in Chilean college students.

Introduction: Academic stress (AS) is a prevalent challenge faced by university students, potentially affecting molecular indicators such as brain-derived neurotrophic factor (BDNF) and global DNA methylation (G-DNA-M). These indicators could illuminate the physiological ramifications of academic stress. Study Design and Methods: This research followed a quantitative, non-experimental, longitudinal panel design spanning two academic semesters, observing phenomena in their natural context. Students from the Medical Technology program at Universidad de Concepción, Chile were involved, with assessments at the beginning and during heightened academic stress periods. Sample: Of the total participants, 63.0% were females, with an average age of 21.14 years at baseline, and 36.92% were males, averaging 21.36 years. By the study's conclusion, female participants averaged 21.95 years, and males 22.13 years. Results: Significant differences were observed between initial and final assessments for the SISCO-II Inventory of Academic Stress and Beck Depression Inventory-II, notably in stressor scores, and physical, and psychological reactions. Gender differences emerged in the final physical and psychological reactions. No significant changes were detected between the two assessments in plasma BDNF or G-DNA-M values. A refined predictive model showcased that, on average, there was a 3.56% decrease in females' plasma BDNF at the final assessment and a 17.14% decrease in males. In the sample, the G-DNA-M percentage at the final assessment increased by 15.06% from the baseline for females and 18.96% for males. Conclusions: The study underscores the physiological impact of academic stress on university students, evidenced by changes in markers like BDNF and G-DNA-M. These findings offer an in-depth understanding of the intricate mechanisms regulating academic stress responses and highlight the need for interventions tailored to mitigate its physiological and psychological effects.

Interaction of Val66Met BDNF and 5-HTTLPR polymorphisms with prevalence of post-earthquake 27-F PTSD in Chilean population.

Post-traumatic stress (PTSD) disorder is a mental health condition that can occur after experiencing or witnessing a traumatic event. The 27-F earthquake that struck Chile in 2010 was one such event that had a significant impact on the mental health of the population. A study was conducted to investigate the prevalence of PTSD and its associated factors among survivors of this earthquake. The study was a longitudinal design, involving a sample of 913 patients aged 18 to 75 years who attended 10 Primary Care Centers in Concepción, Chile. The Composite International Diagnostic Interview (CIDI) was used to assess both depressive episodes (DE) and PTSD before and after the earthquake. The study also involved genotyping studies using saliva samples from the participants, specifically focusing on the Val66Met and 5-HTTLPR polymorphisms. Statistical analysis was performed to examine the association between different variables and the presence of PTSD. These variables included demographic factors, family history of psychiatric disorders, DE, childhood maltreatment experiences, and critical traumatic events related to the earthquake. The results showed that the incidence of post-earthquake PTSD was 11.06%. No significant differences were found between the groups of participants who developed post-earthquake PTSD regarding the Val66Met or 5-HTTLPR polymorphisms. However, a significant association was found between the concomitant diagnosis of DE and the development of post-earthquake PTSD. The presence of DE doubled the risk of developing post-earthquake PTSD. The number of traumatic events experienced also had a statistically significant association with an increased risk of developing post-earthquake PTSD. The study's limitations include the potential interference of different DE subtypes, the complexity of quantifying the degree of earthquake exposure experienced by each individual, and events entailing social disruption, such as looting, that can profoundly influence distress. In conclusion, the study found that PTSD following the 27-F earthquake in Chile was associated with a concomitant diagnosis of DE and the number of traumatic events experienced. The study did not find a significant association between PTSD and the Val66Met or 5-HTTLPR polymorphisms. The researchers recommend that mental health professionals should prioritize the detection and treatment of concomitant depressive episodes and exposure to critical traumatic events in survivors of disasters. They also suggest that further research is needed to better understand the relationship between genetic factors and post-disaster PTSD.

Prevalence of child and adolescent mental disorders in Chile: a community epidemiological study.

BACKGROUND: In Latin America, there is limited research on the prevalence of mental disorders in children and adolescents. This Chilean survey is the first national representative survey in the Latin American region to examine the prevalence of diagnostic and statistical manual-IV (DSM-IV) psychiatric disorders in the region in children and adolescents. METHODS: Subjects aged 4-18 were selected using a stratified multistage design. The diagnostic interview schedule for children version IV (DISC-IV) was used to obtain 12-month DSM-IV diagnoses of affective, anxiety, conduct and substance use disorders, and supplemented with questionnaires examining family risk factors, family income, and service utilization. The parent or the primary caretaker was interviewed for children, aged 4-11, using the DISC-IV; however, adolescents, aged 12-18, were directly interviewed. RESULTS: A sample of 1558 children and adolescents was evaluated. Using the most stringent DISC-IV impairment algorithm, the prevalence rate for any psychiatric disorders was 22.5% (19.3% for boys and 25.8% for girls). The prevalence rate was higher among the children, aged 4-11, in comparison with adolescents, aged 12-18 (27.8% and 16.5%, respectively). Less than half of the subjects in need of services sought some form of assistance. Nearly a quarter of those using services did not present with a psychiatric diagnosis in the past year. Comorbidity was found in 24.8% of those with a disorder, but only 6.3% had three or more diagnoses. CONCLUSIONS: The prevalence of psychiatric disorders in Chile is high among children and adolescents. This study highlights the increasing need to reevaluate mental health services provided to children and adolescents in Latin America.

Prevalence of child and adolescent psychiatric disorders in Santiago, Chile: a community epidemiological study.

PURPOSE: To determine the prevalence of DSM-IV psychiatric disorders in a representative sample of children and adolescents living in Santiago, Chile, as part of a national sample. METHOD: Subjects aged 4-18 were selected using a stratified multistage design. First, ten municipalities/comunas of Santiago were selected; then the blocks, homes, and child or adolescent to be interviewed were chosen. Psychology graduate students administered the Spanish-language, computer-assisted version of DISC-IV that estimated DSM-IV 12-month prevalence. RESULTS: A total of 792 children and adolescents were evaluated, with a participation rate of 76.7%. The most stringent impairment DSM-IV DISC algorithm for psychiatric disorders revealed a prevalence of 25.4% (20.7% for boys and 30.3% for girls). The majority of the diagnoses corresponded to anxiety and affective disorders. Prevalence was higher in children aged 4-11 (31.9%) than in adolescents aged 12-18 (18.2%). This difference was mainly accounted for by disruptive disorders in the younger age group. Anxiety disorders had the highest prevalence, although impairment was low. In contrast, most children and adolescents with affective disorders were impaired. CONCLUSIONS: In Santiago, the prevalence of psychiatric disorders in children and adolescents was high. This study helps raise awareness of child and adolescent mental health issues in Spanish-speaking Latin America and serves as a basis for improving mental health services.

[Prevalence of psychiatric disorders among Chilean children and adolescents]. / Salud mental infanto-juvenil en Chile y brechas de atención sanitarias.

BACKGROUND: Psychiatric disorders that appear during childhood or adolescence should be a public health priority. AIM: To report the results of a national representative survey in the Latin American region examining the prevalence of DSM-IV psychiatric disorders in children and adolescents. MATERIAL AND METHODS: Subjects aged 4 to 18 years were selected using a stratified multistage design. The Diagnostic Interview Schedule for Children Version IV (DISC-IV) was used to obtain 12-month DSM-IV diagnoses, and was supplemented with questionnaires examining family risk factors, socioeconomic status and service use. RESULTS: A sample of 1558 children and adolescents (51% males) was evaluated. Fifty three percent of the sample were children aged 4 to 11 years and the rest were adolescents aged 12 to 18 years. The prevalence rate for any psychiatric disorder without impairment was 38.3% (33.5% for boys and 43.3% for girls). The prevalence rate was higher among children as compared to adolescents (42.9% and 33.2%, respectively). A third of participants receiving a diagnosis sought some form of assistance. Nearly a quarter of those using services, did not have a psychiatric diagnosis in the past year. Comorbidity was found in 27% of those with a disorder, but only 7% had three or more diagnoses. CONCLUSIONS: The prevalence of psychiatric disorders in Chile is high among children and adolescents. This study highlights the increasing need to re-evaluate mental health services provided to children and adolescents in our country.

[Analysis of a scale for the assessment of attention deficit disorder with hyperactivity in Chilean children]. / Análisis de la escala para la evaluación del trastorno por déficit de atención con hiperactividad en población escolar Chilena.

BACKGROUND: Epidemiologic studies may be used as a starting point to improve interventions and improve diagnosis, with instruments that are both reliable and adequate. AIM: To analyze the psychometric properties of the Attention Deficit Disorder Evaluation Scale (ADDES) in Chilean primary and high school students. MATERIAL AND METHODS: The ADDES was applied by 142 teachers to 254 students. Attention Defcit Disorder was already diagnosed in 144 students. Explanatory and confirmatory factorial analyses were carried out. RESULTS: Confirmatory Factorial Analysis (CFA) proved that the model suggested by the authors could not be replicated in the Chilean sample. Exploratory Factorial Analysis (EFA) showed that three new factors came out of the analysis. CFA was applied to the new model and modification indexes suggested the introduction of new saturations. Based on the model with the best goodness-of-fit, psychometric characteristics were evaluated. CONCLUSIONS: The ADDES adapted to the Chilean context has a high reliability and a strong discrimination ability, allowing the evaluation of behavior disorders, hyperactivity/impulsivity and attention deficit.

Etifoxine is non-inferior than clonazepam for reduction of anxiety symptoms in the treatment of anxiety disorders: a randomized, double blind, non-inferiority trial.

OBJECTIVE: To determine whether etifoxine, a non-benzodiazepine drug of the benzoxazine family, is non-inferior compared with clonazepam in the treatment of anxiety disorders. METHOD: A randomized controlled double blind trial with parallel groups was conducted. A total of 179 volunteer patients with a diagnosis of anxiety disorder (DSM-IV), between 18 and 64 years of age, participated in this study. The experimental group received 150 mg/day of etifoxine and the control 1 mg/day of clonazepam, both in three daily doses for 12 weeks. This treatment was completed by 87 participants, and 70 were available for follow-up at 24 weeks from start of treatment. The primary objective was a non-inferiority comparison between etifoxine and clonazepam in the decrease of anxiety symptoms (HAM-A) at 12 weeks of treatment. Secondary outcomes included the evaluation of medication side effects (UKU), anxiety symptoms at 24 weeks of treatment, and clinical improvement (CGI). Data analysis included multiple imputation of missing data. The effect of etifoxine on the HAM-A, UKU, and CGI was evaluated with the intention of treatment, and a sensitivity analysis of the results was conducted. Non-inferiority would be declared by a standardized mean difference (SMD) between clonazepam and etifoxine not superior to 0.31 in favour of clonazepam. RESULTS: Using imputed data, etifoxine shows non-inferiority to clonazepam on the reduction of anxiety symptoms at the 12-week (SMD = 0.407; 95% CI, 0.069, 0.746) and 24-week follow-ups (SMD = 0.484; 95% CI, 0.163, 0.806) and presented fewer side effects (SMD = 0.58; 95% CI, 0.287, 0.889). LOCF analysis shows that etifoxine is non-inferior to clonazepam on reduction of anxiety symptoms and adverse symptoms even when no change was assigned as result to participant whom withdrew. Non-inferiority could be declared for clinical improvement (SMD = 0.326; 95% CI, - 0.20, 0.858). CONCLUSION: Etifoxine was non-inferior to clonazepam on reduction of anxiety symptoms, adverse effects, and clinical improvement.

Gabapentin Inhibits Multiple Steps in the Amyloid Beta Toxicity Cascade.

Oligomeric ß-amyloid peptide (Aß) is one of the main neurotoxic agents of Alzheimer's disease (AD). Oligomers associate to neuronal membranes, forming "pore-like" structures that cause intracellular calcium and neurotransmitter dyshomeostasis, leading to synaptic failure and death. Through molecular screening targeting the C terminal region of Aß, a region involved in the toxic properties of the peptide, we detected an FDA approved compound, gabapentin (GBP), with neuroprotective effects against Aß toxicity. At micromolar concentrations, GBP antagonized peptide aggregation over time and reduced the Aß absorbance plateau to 28% of control. In addition, GBP decreased Aß association to membranes by almost half, and the effects of Aß on intracellular calcium in hippocampal neurons were antagonized without causing effects on its own. Finally, we found that GBP was able to block the synaptotoxicity induced by Aß in hippocampal neurons, increasing post-synaptic currents from 1.7 ± 0.9 to 4.2 ± 0.7 fC and mean relative fluorescence intensity values of SV2, a synaptic protein, from 0.7 ± 0.09 to 1.00 ± 0.08. The results show that GBP can interfere with Aß-induced toxicity by blocking multiple steps, resulting in neuroprotection, which justifies advancing toward additional animal and human studies.