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IntroductionNon-Medical Use of Anxiolytics (NMUA) and sedatives is a focus of scientific interest worldwide. In Tunisia, no national epidemiological data related to this issue, are published.ObjectivesWe aimed to determine the prevalence of NMUA in Tunisian adolescents and assess specificities from a gender scope.MethodsData from the 2021-Mediterranean school Survey on Alcohol and other Drugs (MedSPAD) were used. Based on random sampling method (three-stage stratification), high school teenagers in first and second year of secondary education, were enrolled. Data were collected using a self-administered standardized questionnaire assessing socio-demographic characteristics, and specific questions related to NMUA (among adolescents and close environment), perceived accessibility and initiation age. We studied weighted prevalence estimates of NMUA at least once in a lifetime, presented with 95% Confidence Interval (CI). Epi data software was used for data entry and statistical analysis was performed with STATA software.ResultsThe survey included 6.201 adolescents with a mean age of 16.8 years and sex ratio F/M equal to 1.5. Only half of surveyed adolescents, perceived accessibility to NMUA as “impossible” and almost 20% had at least one family member or friend using a nonmedical prescription of anxiolytics. The overall prevalence of NMUA was (8.4%; 95% CI [7.6-9.2]), significantly higher among girls (9.8% Vs 6.1%, p-value<10-4). Initiation age was over 13 years for almost 70% of consumers.ConclusionsOur study highlighted high prevalence of NMUA, mainly among girls. Although COVID mental health impact might have a role in explaining our findings; however, decisions makers should be aware of non-medically prescribed anxiolytics accessibility especially among this vulnerable population. Audit prescription monitoring programs should be reinforced, and multisectoral collaboration should be reinforced to promote adolescents mental well being and avoid falling into addiction trap.Disclosure of InterestNone Declared

Dental anxiety is an acute anxiety reaction that often occurs in several individuals. Severe cases of dental anxiety may negatively affect oral health because of the avoidance of and delays in dental treatments. Medical therapy has been the first-line therapy in managing dental anxiety. However, it can cause respiratory depression and prolonged sedation. The present study aimed to identify the effects of auricular laser puncture at the depressing, tranquilizer, and master cerebral points on anxiety levels using the Spielberger State-Trait Anxiety Inventory Moreover, the effects were compared between the treatment (sham auricular laser puncture) and control groups. In the treatment group, the same procedure was performed, except for the laser pen that was turned off. Results showed that the mean score of the treatment group (15.56 ± 7.188) was higher than that of the control group (5.39 ± 3.867). Auricular laser puncture is more effective than sham laser puncture in decreasing the anxiety levels in patients with dental anxiety.

The predominant inhibitory neurotransmitter in the brain, γ-aminobutyric acid (GABA), acts at ionotropic GABAA receptors to counterbalance excitation and regulate neuronal firing. GABAA receptors are heteropentameric channels comprised from subunits derived from 19 different genes. GABAA receptors have one of the richest and well-developed pharmacologies of any therapeutic drug target, including agonists, antagonists, and positive and negative allosteric modulators (PAMs, NAMs). Currently used PAMs include benzodiazepine sedatives and anxiolytics, barbiturates, endogenous and synthetic neurosteroids, and general anesthetics. In this article, I will review evidence that these drugs act at several distinct binding sites and how they can be used to alter the balance between excitation and inhibition. I will also summarize existing literature regarding (1) evidence that changes in GABAergic inhibition play a causative role in major depression, anxiety, postpartum depression, premenstrual dysphoric disorder, and schizophrenia and (2) whether and how GABAergic drugs exert beneficial effects in these conditions, focusing on human studies where possible. Where these classical therapeutics have failed to exert benefits, I will describe recent advances in clinical and preclinical drug development. I will also highlight opportunities to advance a generation of GABAergic therapeutics, such as development of subunit-selective PAMs and NAMs, that are engendering hope for novel tools to treat these devastating conditions.

A mechanistic understanding of anxiety is required to advance the development of next-generation therapies for anxiety disorders. In this Review, Calhoon and Tye discuss recent insights into the circuit physiology driving anxiety-like behavior gained through the application of modern approaches in neuroscience. Although anxiety disorders represent a major societal problem demanding new therapeutic targets, these efforts have languished in the absence of a mechanistic understanding of this subjective emotional state. While it is impossible to know with certainty the subjective experience of a rodent, rodent models hold promise in dissecting well-conserved limbic circuits. The application of modern approaches in neuroscience has already begun to unmask the neural circuit intricacies underlying anxiety by allowing direct examination of hypotheses drawn from existing psychological concepts. This information points toward an updated conceptual model for what neural circuit perturbations could give rise to pathological anxiety and thereby provides a roadmap for future therapeutic development.

IntroductionWe present the case of a 41-year-old male patient with multiple psychiatric diagnoses, he was diagnosed with agenesis of the corpus callosum, which explains his clinical presentation.ObjectivesThe objective is to carry out a brief review of the symptoms associated with the agenesis of the corpus callosum.MethodsThe patient has been diagnosed with ADHD, cyclothymia, depressive anxiety disorder and social phobia. He has been treated with a multitude of drugs such as antidepressants, anxiolytics, stimulants and even low-dose antipsychotics. Despite the pharmacological treatments received, as well as the therapies, the patient’s functionality has progressively worsened, to the point of restricting going out of the home or maintaining a stable job.Biographical data were collected, including psychomotor retardation and inappropriate laughter. He showed mannerisms such as fluttering and low frustration tolerance. He was slow to respond to his name and showed little affective resonance with his sister and parents. Restrictive interests, especially with English culture, for which he later studied English philology. On the other hand, his mother explains that he had no symbolic play and that, from early childhood, he had difficulties in relationships with peers.Due to the aforementioned clinical manifestations, the functional worsening and the examination carried out in the consultation room, it was decided to extend the study with a brain MRI, where an agenesis of the corpus callosum was observed.ResultsAgenesis of the corpus callosum is a malformation of the central nervous system, which affects one in every 4000 births. It can be partial or complete, and occurs between the 7th-20th week of gestation.Agenesis of the corpus callosum presents with a triad of symptoms:- Reduced interhemispheric communication of sensory-motor information.- Increased information processing time- Difficulty in abstract thinking.This triad causes difficulties not only cognitively, but also socially. There is difficulty in integrating and learning new verbal and visual information. Tendency to literalism, with difficulty in understanding double meanings. They also have difficulty understanding non-verbal language and reading emotions, which makes interaction with peers difficult. All these symptoms can sometimes be confused with symptoms compatible with Autism Spectrum Disorder.ConclusionsAfter the diagnosis and after focusing the patient’s treatment on the most limiting symptoms of his daily life, an integrated approach was initiated, not only at a pharmacological level, with the use of antidepressants and anxiolytics, but also from a psychotherapeutic point of view, working on those areas in which the patient is most dysfunctional. He was accompanied in the disability application process, as well as helped in the search for associations for adults with ASD, finding there the answer to his symptoms and difficulties.Disclosure of InterestNone Declared

Objective: Antipsychotic compounds are known to induce sedation somnolence and have expanded clinical indications beyond schizophrenia to regulatory approval in bipolar disorder, treatment-resistant depression, and is being repurposed in infectious diseases and oncology. However, the medical sciences literature lacks a comprehensive association between sedation and somnolence among a wide-range of antipsychotic compounds. The objective of this study is to assess the disproportionality of sedation and somnolence among thirty-seven typical and atypical antipsychotics. Materials and Methods: Patient adverse drug reactions (ADR) cases were obtained from the United States Food and Drug Administration Adverse Events Reporting System (FAERS) between January 01, 2004 and September 30, 2020 for a wide-array of clinical indications and off-label use of antipsychotics. An assessment of disproportionality were based on cases of sedation and somnolence and calculated using the case/non-case methodology. Statistical analysis resulting in the reporting odds-ratio (ROR) with corresponding 95% confidence intervals (95% CI) were conducted using the R statistical programming language. Results: Throughout the reporting period, there were a total of 9,373,236 cases with 99,251 specific ADRs reporting sedation and somnolence. Zuclopenthixol ( n = 224) ROR = 13.3 (95% CI, 11.6–15.3) was most strongly associated of sedation and somnolence and haloperidol decanoate long-acting injection (LAI) was not statistically associated sedation and somnolence. Further, among atypical antipsychotic compounds, tiapride and asenapine were the top two compounds most strongly associated with sedation and somnolence. Comprehensively, the typical antipsychotics ROR = 5.05 (95%CI, 4.97–5.12) had a stronger association with sedation and somnolence when compared to atypical antipsychotics ROR = 4.65 (95%CI, 4.47–4.84). Conclusion: We conducted a head-to-head comparison of thirty-seven antipsychotics and ranked the compounds based on the association of sedation and somnolence from ADR data collected throughout 16 years from the FAERS. The results are informative and with recent interests in repurposing phenothiazine antipsychotics in infectious disease and oncology provides an informative assessment of the compounds during repurposing and in psychopharmacology.

Phenolic compounds, present in plants, are considered to be indispensable parts of human dietary sources. Sinapic acid, is a natural herbal compound containing phenolic acid. It is found in oranges, grapefruits, and cranberries and in herbs like canola, mustard seed and rapeseed. Sinapic acid is chemically studied as a cinnamic acid derivative that contains 3, 5-dimethoxyl and 4-hydroxyl substitutions in the phenyl group of cinnamic acid. Sinapic acid has been pharmacologically evaluated for its potent antioxidant, anti-inflammatory, anti-cancer, hepatoprotective, cardioprotective, renoprotective, neuroprotective, anti-diabetic, anxiolytic and anti-bacterial activities. In this review we have summarized the potential pharmacological and therapeutic effects of Sinapic acid in various models.

Benzodiazepines (BZDs) are a class of widely prescribed psychotropic drugs that target GABAA receptors (GABAARs) to tune inhibitory synaptic signaling throughout the central nervous system. Despite knowing their molecular target for over 40 years, we still do not fully understand the mechanism of modulation at the level of the channel protein. Nonetheless, functional studies, together with recent cryo-EM structures of GABAA(α1)2(βX)2(γ2)1 receptors in complex with BZDs, provide a wealth of information to aid in addressing this gap in knowledge. Here, mechanistic interpretations of functional and structural evidence for the action of BZDs at GABAA(α1)2(βX)2(γ2)1 receptors are reviewed. The goal is not to describe each of the many studies that are relevant to this discussion nor to dissect in detail all the effects of individual mutations or perturbations but rather to highlight general mechanistic principles in the context of recent structural information.

Emotional disorders are highly prevalent in primary care. We aimed to determine whether a transdiagnostic psychological therapy plus treatment-as-usual (TAU) is more efficacious than TAU alone in primary care adult patients. A randomized, two-arm, single-blind clinical trial was conducted in 22 primary care centres in Spain. A total of 1061 adult patients with emotional disorders were enrolled. The transdiagnostic protocol ( = 527) consisted of seven 90-min sessions (8-10 patients) delivered over a 12-14-week period. TAU ( = 534) consisted of regular consultations with a general practitioner. Primary outcome measures were self-reported symptoms of anxiety, depression, and somatizations. Secondary outcome measures were functioning and quality of life. Patients were assessed at baseline, post-treatment, and at 3, 6, and 12 months. Intention-to-treat and per-protocol analyses were performed. Post-treatment primary outcomes were significantly better in the transdiagnostic group compared to TAU (anxiety: < 0.001; Morris's = -0.65; depression: < 0.001; = -0.58, and somatic symptoms: < 0.001; = -0.40). These effects were sustained at the 12-month follow-up (anxiety: < 0.001; = -0.44; depression: < 0.001; = -0.36 and somatic symptoms: < 0.001; = -0.32). The transdiagnostic group also had significantly better outcomes on functioning ( = 0.16-0.33) and quality of life domains ( = 0.24-0.42), with sustained improvement at the 12-month follow-up in functioning ( = 0.25-0.39) and quality of life ( = 0.58-0.72). Reliable recovery rates showed large between-group effect sizes ( > 0.80) in favour of the transdiagnostic group after treatment and at the 12-month follow-up. Adding a brief transdiagnostic psychological intervention to TAU may significantly improve outcomes in emotional disorders treated in primary care. isrctn.org identifier: ISRCTN58437086.