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An octogenarian woman showed increased sexual function after replacing alprazolam with clomethiazole, a sedative-hypnotic drug commonly prescribed in French-speaking Switzerland for the treatment of anxiety and insomnia in elderly patients. The patient's sexual symptoms did not improve after resuming alprazolam, but disappeared after interrupting clomethiazole, and did not reappear when alprazolam was discontinued. Considering the chronology of the events, increased sexual function was likely a manifestation of the introduction of clomethiazole. However, because alprazolam was interrupted when clomethiazole was introduced, we cannot exclude an association between increased sexual function and alprazolam interruption., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Anxiety disorders, an increasingly prevalent global mental health illness, affected approximately 301 million individuals worldwide in 2019. There is an unmet need for the treatment of anxiety disorders, as current therapies are associated with limited response rates, residual symptoms, and adverse effects., Objectives: To evaluate the efficacy, safety, and pharmacokinetics of nanodispersible cannabidiol (CBD) oral solution versus placebo for the treatment of mild to moderate anxiety disorders., Methods: This phase 3 prospective, randomized, double blind, parallel group, placebo-controlled, 15-week cohort study took place at multiple sites across India. Eligible participants were randomly assigned to one of the two treatment arms (CBD or placebo) in a 1:1 ratio., Results: 178 participants were randomized to receive CBD (n=89) or placebo (n=89). The study met both primary (GAD-7 and HAM-A scores) and secondary outcomes (CGI-I, CGI-S, PHQ-9 and PSQI scores). The GAD-7 score difference between the end of treatment and baseline for the CBD versus the placebo was -7.02 (S.E: 0.25, 95% CI -7.52; -6.52), p<0.0001. Similarly, the HAM-A score difference at the end of treatment compared to baseline for the CBD versus the placebo was -11.9 (S.E: 0.33, 95% CI -12.6; -11.3), p<0.0001., Conclusions: Nanodispersible CBD was therapeutically safe with no serious adverse events, well tolerated, and effective for the treatment of mild to moderate anxiety disorders, as well as associated depression and sleep quality disturbances. These results pave way for probable prospective use of nanodispersible CBD formulation for various psychiatry disorders alone or in conjunction with other drugs., Competing Interests: Declaration of Competing Interest CK is the Board member and CEO of Leiutis Pharmaceuticals LLP, KSDK is the Chief Medical Officer of Biophore Pharma, Inc., PRG is the Lead Investigator of the Clinical Trial. NB, SSRY, AN, RT are employees of Leiutis Pharmaceuticals LLP., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: From 2000-2021, U.S. suicide deaths have risen 36 %. Identification of pharmacological agents associated with increased suicide risk and safer alternatives may help reduce this trend., Methods: An exposure-only within-subject time-to-event pharmacoepidemiologic study of the dynamic association between alprazolam treatment and suicide attempts over 2-years. Parallel analyses were conducted for diazepam, lorazepam and buspirone. Data for 2,495,520 patients were obtained from U.S. private insurance medical claims MarketScan from 2010 to 2019., Findings: Alprazolam was associated with over a doubling of risk of suicide attempts (HR=2.21, 95 % CI=2.06,2.38). A duration-response analysis for the modal dose (0.5 mg) revealed a 5 % increase in suicidal events per additional month of treatment (HR=1.05, 95 % CI=1.04,1.07). Parallel analyses with long-acting (diazepam) and short-acting (lorazepam), found similar associations (diazepam HR=2.87, 95 % CI=2.56,3.21; lorazepam HR=1.83, 95 % CI=1.69,2.00), whereas the non-benzodiazepine anxiolytic, buspirone, showed significantly less risk (HR=1.25, 95 % CI=1.13,1.38), and no increased risk in patients with an attempt history (HR=1.05, 95 % CI=0.70,1.59)., Interpretation: This study confirmed an earlier signal linking alprazolam to increased suicide attempt risk. The increased risk extends to benzodiazepines in general, regardless of half-life and risk of withdrawal seizure. Buspirone appears to be a safer treatment than benzodiazepines, particularly in patients at increased risk for suicide., Competing Interests: Declaration of competing interest Dr. Gibbons has served as an expert witness in cases related to suicide for the US Department of Justice, and Pfizer, Wyeth, and GSK pharmaceutical companies and founded the company Adaptive Testing Technologies that distributes computerized adaptive mental health tests. These activities have been reviewed and approved by the University of Chicago in accordance with its conflict-of-interest policies. This study was reviewed and deemed exempt from review by the University of Chicago institutional review board. Dr. Mann receives royalties from the Research Foundation for Mental Hygiene for commercial use of the C-SSRS., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aim: To review the literature data on the prevalence of benzodiazepines abuse and poisoning in older adults; the prevalence of polypharmacy with benzodiazepines in this demographic; and determine whether benzodiazepine anxiolytics or hypnotics were more frequently implicated in the cases of abuse and poisoning., Methods: We searched PubMed and Scopus for relevant studies published from January 1, 2013, to May 1, 2023. Twelve studies were included in the final selection., Results: The review highlights the diverse prevalence rates of benzodiazepine abuse and poisoning in the older adult population. Benzodiazepine anxiolytics were more frequently associated with negative outcomes than benzodiazepine hypnotics. Concurrent use of benzodiazepines, benzodiazepine-related medications, and opioids was reported, although these medications were not the only ones commonly used by the elderly., Conclusion: It is essential to increase awareness about adhering to prescribed pharmacological therapies to mitigate issues related to drug abuse and poisoning among older adults.

Ethnopharmacological Relevance: Achyranthes ferruginea (A. ferruginea) Roxb. is a common plant used in traditional medicine in Asia and Africa. It has a variety of local names, including "Gulmanci" in Nigeria, "Dangar" in Pakistan, "Thola" in Ethiopia, and "Roktoshirinchi" in Bangladesh. It is edible and has several ethnomedical uses for a wide range of illnesses, including hysteria, dropsy, constipation, piles, boils, asthma, and shigellosis. However, the neuropharmacological and analgesic potential of A. ferruginea remains uninvestigated., Aim of the Study: To assess the neuropharmacological and analgesic potential of A. ferruginea through a multifaceted approach encompassing both experimental and computational models., Materials and Methods: Methanol was used to extract the leaves of A. ferruginea. It was then fractionated with low to high polar solvents (n-hexane, chloroform, ethyl acetate, and water) to get different fractions, including chloroform fraction (CLF). The study selected CLF at different doses and conducted advanced chemical element and proximate analyses, as well as phytochemical profiling using GC-MS. Toxicological studies were done at 300 μg per rat per day for 14 days. Cholinesterase inhibitory potential was checked using an in-vitro colorimetric assay. Acetic acid-induced writhing (AAWT) and formalin-induced licking tests (FILT) were used to assess anti-nociceptive effects. The forced swim test (FST), tail suspension test (TST), elevated plus maze (EPM), hole board test (HBT), and light and dark box test (LDB) were among the behavioral tests used to assess depression and anxiolytic activity. Network pharmacology-based analysis was performed on selected compounds using the search tool for interacting chemicals-5 (STITCH 5), Swiss target prediction tool, and search tool for the retrieval of interacting genes and proteins (STRING) database to link their role with genes involved in neurological disorders through gene ontology and reactome analysis., Results: Qualitative chemical element analysis revealed the presence of 15 elements, including Na, K, Ca, Mg, P, and Zn. The moisture content, ash value, and organic matter were found to be 11.12, 11.03, and 88.97%, respectively. GC-MS data revealed that the CLF possesses 25 phytoconstituents. Toxicological studies suggested the CLF has no effects on normal growth, hematological and biochemical parameters, or cellular organs after 14 days at 300 μg per rat. The CLF markedly reduced the activity of both acetylcholinesterase and butyrylcholinesterase (IC 50 : 56.22 and 13.22 μg/mL, respectively). Promising dose-dependent analgesic activity (p < 0.05) was observed in chemically-induced pain models. The TST and FST showed a dose-dependent substantial reduction in immobility time due to the CLF. Treatment with CLF notably increased the number of open arm entries and time spent in the EPM test at doses of 200 and 400 mg/kg b.w. The CLF showed significant anxiolytic activity at 200 mg/kg b.w. in the HBT test, whereas a similar activity was observed at 400 mg/kg b.w. in the EPM test. A notable increase in the amount of time spent in the light compartment was observed in the LDB test by mice treated with CLF, suggesting an anxiolytic effect. A network pharmacology study demonstrated the relationship between the phytochemicals and a number of targets, such as PPARA, PPARG, CHRM1, and HTR2, which are connected to the shown bioactivities., Conclusions: This study demonstrated the safety of A. ferruginea and its efficacy in attenuating cholinesterase inhibitory activity, central and peripheral pain, anxiety, and depression, warranting further exploration of its therapeutic potential., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Benzodiazepines (BZDs) are drugs commonly used for treating insomnia and anxiety. Although they are known to induce cognitive and psychomotor impairments, their effect on the risk of causing accidents at work remains understudied. The objective of this study is to estimate this risk by differentiating between the recommended use and overuse of these drugs (i.e., uninterrupted use for four months). The data come from the French National Health Data System, which provide a population composed of French people who had at least one work accident (WA) from 2017 to 2019 (approximately 2.5 million people). A linear probability model with two-way fixed effects is used to deal with time-constant heterogeneity and the time effect independent of individuals. The results show a reduction in the risk of WA after a short period of BZD use (one month) compared with no use at all, but the risk of WA increases when treatment exceeds the recommended duration. The intensity of use results in a greater risk of WAs: a 1% increase in BZD use (expressed as the amount reimbursed) leads to a 4.4% (p<0.001) increase in the monthly risk of WAs. Moreover, we see an increase in risk in the month following the treatment discontinuation (+3.6%, p<0.001), which could be due to rebounding and catch-up effects. Health professionals and BZD users should be made aware of the WA risk induced by the use of BZDs, particularly after prolonged use and after discontinuation of treatment. This study provides more evidence for the need to limit the duration of BZD treatment., Competing Interests: The author has declared that no competing interests exist., (Copyright: © 2024 François-Olivier Baudot. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Polycystic ovary syndrome (PCOS) is associated with symptoms of moderate to severe anxiety and depression. Hyperandrogenism is a key feature together with lower levels of the adipocyte hormone adiponectin. Androgen exposure leads to anxiety-like behavior in female offspring while adiponectin is reported to be anxiolytic. Here we test the hypothesis that elevated adiponectin levels protect against the development of androgen-induced anxiety-like behavior. Pregnant mice overexpressing adiponectin (APNtg) and wildtypes were injected with vehicle or dihydrotestosterone to induce prenatal androgenization (PNA) in the offspring. Metabolic profiling and behavioral tests were performed in 4-month-old female offspring. PNA offspring spent more time in the closed arms of the elevated plus maze, indicating anxiety-like behavior. Intriguingly, neither maternal nor offspring adiponectin overexpression prevented an anxiety-like behavior in PNA-exposed offspring. However, adiponectin overexpression in dams had metabolic imprinting effects, shown as lower fat mass and glucose levels in their offspring. While serum adiponectin levels were elevated in APNtg mice, cerebrospinal fluid levels were similar between genotypes. Adiponectin overexpression improved metabolic functions but did not elicit anxiolytic effects in PNA-exposed offspring. These observations might be attributed to increased circulating but unchanged cerebrospinal fluid adiponectin levels in APNtg mice. Thus, increased adiponectin levels in the brain are likely needed to stimulate anxiolytic effects., (© 2024. The Author(s).)

Objective: To investigate the efficacy and safety of Aviandr in the treatment of anxiety in patients with adjustment disorders after COVID-19., Material and Methods: A multicenter prospective open-label study included 109 patients of both sexes aged 18 to 65 years (70 women, 39 men, average age - 41.4±13.18 years) with a leading complaint of anxiety (Hamilton scale score, HAM-A ≥18 - ≤24), which arose after acute coronavirus infections. Clinical manifestations had to meet the diagnostic criteria F43.2 ICD-10. The drug Aviander was prescribed 20 mg 2 times a day for 4 weeks. At the end of taking the drug, patients were monitored for another 1 week (a delayed follow-up visit). Psychopathological, statistical and parametric research methods were used using standardized HAM-A, Montgomery-Asberg scales (MADRS), visual analog asthenia scale (VASH-A), Sheehan Disability Scale (SDS), digital character substitution test (DSST), general clinical impression scale (CGI)., Results: Data from 109\110 patients were analyzed to evaluate efficacy\safety. Aviandr was administered 20 mg 2 times daily for 4 weeks. Patients were followed for 1 week (delayed follow-up visit) at the end of treatment. Reducing the intensity of anxiety on the HAM-A scale was - 14.2±4.92 or 69.4±22.66% by the end of treatment. The response rate to therapy (responders are patients with a decrease in the total score on the HAM-A ≥50%) was 83.49%. Remission was achieved (sum of HAM-A scores ≤7) by the end of treatment 68.81% of patients, and 79.8% of patients at the follow-up visit. Significant changes were obtained on the MADRS, VAS-A, SDS and DSST scales. According CGI 45.9% of patients had «much improved» and 43.1% of patients had «very much improved» by the end of treatment; 58.7% of patients had «much improved» and of 33.9% patients had «very much improved» at the follow-up visit. 38 adverse events were reported in 27 (24.55%) patients during the study. A definite association with study drug was reported between 5 mild adverse events in 4 (3.64%) patients. No subjects withdrew from the study due to an adverse event. Positive dynamics (reduction of anxiety symptoms, decrease in asthenia) persisted after discontinuation of the study drug. No cases of withdrawal syndrome were observed., Conclusion: According to the results of the study, the anxiolytic, antidepressant, antiasthenic and pro-cognitive effects of Aviandr were observed. An increase in the social activity of patients was observed.

Background: Novel psychoactive substances, such as designer benzodiazepines (DBZD), are a growing public health concern. There are about 30 different DZBDs reported, which can vary widely in their effect and potential for harmful outcomes, ranging from agitation to confusion to coma. Despite the scope of this widespread phenomena, little information on the management of DBZD dependence is available in the literature., Case: In this case report, we present a patient with DBZD dependence requesting assistance tapering off the DBZD, clonazolam. He began self-medicating with clonazolam seven years prior for panic attacks to the point he was using 40 drops per day and having significant withdrawal during the day. He was prescribed gabapentin for his underlying anxiety while he tapered his clonazolam dose. Once he achieved a 75% reduction in his use of clonazolam, he had trouble managing withdrawal and anxiety symptoms and could not taper further., Discussion: We discuss the challenges of treating patients with DBZD use disorder in an outpatient setting. Switching a patient from a DZBD to a prescription benzodiazepine for the purposes of a taper can be dangerous as an outpatient due to the inability to monitor at-home DBZD usage and the resulting risk of overdose. DBZDs can also be highly potent and make it difficult to achieve success using current withdrawal guidelines.

Background: Williams syndrome (WS) is a rare genetic disorder associated with a high prevalence of anxiety disorders. Evidence-based pharmacologic treatments for anxiety in WS are lacking. The purpose of this study is to provide naturalistic data on the use of buspirone for the treatment of anxiety in WS., Research Design and Methods: Medical records of 24 individuals with Williams syndrome (ages 7-47 years) and anxiety who received treatment with buspirone were reviewed. Treatment response to buspirone was rated by assigning a retrospective Clinical Global Impression Improvement subscale (CGI-I) score., Results: Twenty-three of 24 (96%) patients completed at least a 16-week treatment course with buspirone. Sixteen patients (67%; 95% CI 47%, 82%) were treatment responders (CGI-I ≤ 2). Only 1 (4%) patient discontinued buspirone due to a treatment-emergent side effect (nausea and vomiting). The most common side effect was nausea (13%). Twenty (84%) patients remained on buspirone at the time of their most recent follow-up visit., Conclusions: In this retrospective study, the majority of patients responded to a 16-week course of buspirone. Prospective studies are warranted to further assess the efficacy and tolerability of buspirone for anxiety in WS.

Background: Preoperative anxiety management is gaining particular attention in paediatric anaesthesia. Pharmacological and non-pharmacological resorts can be implemented to address this special issue. Despite the various approaches currently used for preoperative sedation in children, the different sedative and anti-anxiety effects between the newly marketed anaesthetic, S-ketamine, and the traditional sedative, midazolam, are still unclear., Methods: This is a patient- and assessor-blinded randomized controlled clinical trial. Participants (n = 110) will receive S-ketamine (0.5 mg/kg) or midazolam (0.08 mg/kg) intravenously administrated at a ratio of 1:1 in the anaesthesia holding area. The primary outcome of this study is the sedative effect evaluated via the change in the modified Yale preoperative anxiety scale. It will be performed at two timepoints: in the pre-anaesthetic holding area before premedication (baseline, marked as T0) and about 5 min after premedication in the operating room without the existence of their guardians (marked as T1). Our secondary objectives include the parent separation anxiety score, postoperative agitation, caregivers' and anaesthesia care providers' satisfaction, and mask compliance., Discussion: This randomized controlled trial is the first study to compare the anti-anxiety effect of intravenous S-ketamine and midazolam. We will provide a new approach for the clinical management of preoperative anxiety in preschool children posted for elective surgery., Trial Registration: ChiCTR2300069998. Registered on 30 March 2023., (© 2023. The Author(s).)

Rationale: Selective serotonin reuptake inhibitors (SSRIs), one of the commonly used anti-anxiety drugs, may have impacts on bone metabolism and potentially lead to drug-induced osteoporosis. The traditional approach of oral implantation in individuals with both anxiety disorder and drug-induced osteoporosis poses a significant challenge. To address this issue, concentrated growth factor (CGF) has been utilized in patients undergoing concurrent alveolar ridge augmentation during oral implantation, resulting in favorable clinical outcomes. Consequently, combining CGF with guided bone regeneration (GBR) in alveolar bone increment may represent a promising new surgical approach for such patients. In this report, we present a case study of a 25-year-old male with anxiety disorder and drug-induced osteoporosis, in who CGF combined with GBR was employed in alveolar bone increment., Patient Concerns: This article reports the case of a 25-year-old male who underwent cone beam computed tomography (CBCT) due to the absence of his right lower second molar for a period of six months. The CBCT scan revealed significant bone defects, which were attributed to the tooth loss and prolonged use of anti-anxiety drugs. Consequently, the patient sought medical assistance from our department., Diagnoses: Based on the patient's self-report, he was diagnosed with an anxiety disorder. Additionally, the CBCT scan confirmed the loss of the right mandibular second molar and revealed the presence of dental irregularity and an alveolar bone defect., Interventions: During the patient's course of treatment with anti-anxiety medication, a combination of CGF and GBR was employed for the simultaneous implantation of the missing right mandibular second molar, along with bone augmentation., Outcomes: The patient had a follow-up visit two weeks after the surgical procedure, and the wound in the operation area had healed satisfactorily. Six months later, CBCT images revealed excellent osseointegration. The buccal and lingual width of the alveolar bone measured 6.95mm, which was an increase of 1.35mm compared to the pre-implantation stage., Lessons: This article presents a case study in which CGF combined with GBR were utilized to address alveolar bone augmentation during the implantation phase in patients taking anti-anxiety medication. The results demonstrated that CGF combined with GBR, as a cutting-edge platelet concentrate technique, could effectively stimulate bone tissue proliferation in individuals who have been on long-term anti-anxiety medication, specifically in oral implant areas. This approach can help prevent poor osseointegration, promote higher osseointegration rates, and facilitate wound healing., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Patient anxiety can complicate surgical outcomes by elevating blood pressure, increasing the need for postoperative pain management, and reducing overall patient satisfaction. Despite the use of anxiolytic medications in outpatient procedures, there is limited comparative evidence on the efficacy and safety of these agents in Mohs micrographic surgery., Objective: To compare the effectiveness and safety of different preprocedural anxiolytic agents in Mohs surgery on perioperative patient anxiety and patient satisfaction., Materials and Methods: A double-blinded, randomized, placebo-controlled trial was conducted of 6 different preprocedural anxiolytic agents (lorazepam, diazepam, alprazolam, gabapentin, pregabalin, and melatonin) in 350 patients undergoing Mohs surgery. Anxiety and vital signs were recorded., Results: Diazepam demonstrated a statistically significant, sustained reduction in anxiety levels compared with placebo ( p = .03). Gabapentin significantly reduced early anxiety ( p = .02). Alprazolam showed a trend to early anxiety reduction ( p = .08). Lorazepam ( p = .73), pregabalin ( p = .53), and melatonin ( p = .24) failed to reduce patient anxiety compared with placebo at any time point. No anxiolytic significantly impacted any patient vital sign or cognition., Conclusion: Although short-acting benzodiazepines and gamma-aminobutyric acid medications may have transient anxiolytic effects, a single oral dose of 5 mg of diazepam can provide a sustained anxiolytic effect in Mohs surgery, with excellent patient safety., (Copyright © 2023 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Benzodiazepines (BZDs) are commonly prescribed for pancreatic cancer patients. To investigate the correlation between BZDs and survival outcomes a recent study by Cornwell et al. found that lorazepam (LOR) correlates with poor survival. The mechanistic study shows that LOR increases interleukin 6 (IL6) expression in cancer-associated fibroblasts via GPR68., Competing Interests: Declaration of interests None are declared by the authors., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Anxiety and anxiety disorders are important modifiable risk factors for cardiovascular and other common chronic non-communicable diseases and complications. Anxiety disorders significantly reduce the motivation and adherence of patients to lifestyle changes and drug therapy, significantly worsen the quality of life, and increase the risk of disability and the costs of the health care system. The issues of diagnosis and therapy of anxiety are relevant for the practice of physicians and cardiologists due to the high incidence of anxiety disorders in patients with cardiovascular diseases, a decrease in the quality of life and an increase in adverse outcomes, and also due to the insufficient awareness of the risks associated with the psycho-emotional state of patients. Therapy of anxiety disorders includes both drug and non-drug methods. The first-line drugs in treating most anxiety disorders are selective serotonin reuptake inhibitors or selective serotonin-norepinephrine reuptake inhibitors. The risk of possible side effects of these agents in patients with cardiovascular diseases should be considered. Sedative and anti-anxiety drugs, including non-benzodiazepine tranquilizers, are more commonly used. The most studied drug from this class in therapeutic and cardiological practice is fabomotizole. The efficacy and safety of fabomotizole, including long-term use, have been studied in numerous studies in patients with cardiovascular diseases and a wide range of anxiety disorders.

Introduction: We report on a meta-analysis of Silexan, a proprietary active substance produced from Lavandula angustifolia, in subthreshold anxiety, mixed anxiety and depressive disorder (MADD), and generalized anxiety disorder (GAD)., Methods: The present analyses are based on all currently completed 5 double-blind, randomized, placebo-controlled trials investigating Silexan in adult out-patients who received Silexan 1 × 80 mg/day or placebo for ten weeks according to random assignment (n = 1213). Efficacy was assessed based on the Hamilton Anxiety Rating Scale (HAMA), several anxiety self-rating scales, the Clinical Global Impression (CGI) scale, and the Short Form-36 (SF-36) health status questionnaire., Results: After ten weeks' treatment, Silexan was significantly superior to placebo in reducing the HAMA total score (including the psychic and somatic anxiety sub-scores) and self-rated anxiety. Based on a ≥ 50% HAMA total score reduction, the responder rate ratio was 1.34 favoring Silexan, and the rate ratio of subjects much or very much improved according to the CGI was 1.51. Silexan was also significantly superior in improving the physical and mental health summary scores of the SF-36. There were no significant between-group differences concerning the occurrence of adverse events (AEs), serious AEs, and premature withdrawal due to AEs., Conclusions: This meta-analysis demonstrates that Silexan exerts significant anxiolytic effects in subthreshold anxiety, GAD and MADD that were consistently reflected in investigator ratings and patient-reported outcomes, including improvement of health-related life-quality, while showing favorable tolerability and safety., (© 2023. The Author(s).)

Anxiety disorders (ADs) represent the sixth leading cause of disability worldwide, resulting in a significant global economic burden. Over 50% of individuals with ADs do not respond to standard therapies, making the identification of more effective anxiolytic drugs an ongoing research priority. In this work, we review the preclinical literature concerning the effects of lysergic acid diethylamide (LSD) on anxiety-like behaviors in preclinical models, and the clinical literature on anxiolytic effects of LSD in healthy volunteers and patients with ADs. Preclinical and clinical findings show that even if LSD may exacerbate anxiety acutely (both in "microdoses" and "full doses"), it induces long-lasting anxiolytic effects. Only two randomized controlled trials combining LSD and psychotherapy have been performed in patients with ADs with and without life-threatening conditions, showing a good safety profile and persisting decreases in anxiety outcomes. The effect of LSD on anxiety may be mediated by serotonin receptors (5-HT1A/1B, 5-HT2A/2C, and 5-HT7) and/or transporter in brain networks and circuits (default mode network, cortico-striato-thalamo-cortical circuit, and prefrontal cortex-amygdala circuit), involved in the modulation of anxiety. It remains unclear whether LSD can be an efficacious treatment alone or only when combined with psychotherapy, and if "microdosing" may elicit the same sustained anxiolytic effects as the "full doses". Further randomized controlled trials with larger sample size cohorts of patients with ADs are required to clearly define the effective regimens, safety profile, efficacy, and feasibility of LSD for the treatment of ADs., (© 2023. Springer Nature Switzerland AG.)

Purpose of Review: The aim of this review is to discuss recent developments in paediatric anaesthesia, which have evolved in an undulating fashion., Recent Findings: The role and efficacy of pharmacological premedication is reevaluated. The anxiolytic and sedative properties of midazolam and α 2 -agonists have now been defined more precisely. Both classes of drugs have their unique profile, and there is no reason to condemn one or the other. Midazolam is an excellent anxiolytic, whereas dexmedetomidine is superior in the postoperative period and for sedation during diagnostic imaging.A total intravenous technique with propofol is often considered to be the standard for the prevention of emergence agitation; but alternatives do exist, such as a co-medication with dexmedetomidine or opioids. In clinical reality, a multimodal approach may often be advisable.The theoretical basis for propofol dosing has recently been adapted. In contrast to previous beliefs, the context-sensitive half-life of propofol seems to be quite short beyond the first year of life., Summary: Midazolam and dexmedetomidine are not interchangeable; each compound has its pros and cons. As an anxiolytic drug, midazolam indisputably deserves its place, whereas dexmedetomidine is a better sedative and particularly beneficial in the postoperative period. New data will allow more precise age-adapted dosing of propofol., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Anxiolytics are a class of drugs that include benzodiazepine receptor agonists and serotonin 1A receptor partial agonists. Although benzodiazepine receptor agonists have anxiolytic, sedative-hypnotic, muscle relaxant, and anticonvulsant effects, their use should be carefully monitored due to their potential for paradoxical reactions, withdrawal symptoms, and dependence. On the other hand, serotonin 1A receptor partial agonists have a slower onset, and their use also presents challenges. In clinical practice, having a thorough understanding of the various types of anxiolytics and their unique features is crucial.

Background: Although alprazolam is approved only for use in panic disorder and generalized anxiety disorder, it is used for numerous other conditions, not only by psychiatrists but also by medical professionals in general. This commentary critically analyzes the use of alprazolam., Methods: A narrative review approach was adopted, using relevant articles and textbooks, to compile pertinent literature for the aforementioned topic., Results: Among all its adverse reactions, the most bothersome concern about the use of alprazolam is its potential for abuse and dependence. This can be attributed to certain unique pharmacokinetic and pharmacodynamic properties of this benzodiazepine. Also, the withdrawal triggered by use of alprazolam is challenging to treat. Alternate pharmacological and non-pharmacological strategies for use in anxiety and insomnia are available, which might be safer than alprazolam. Also, policy changes can serve as an answer to curb alprazolam abuse to some extent. Alprazolam might still be a good choice for individuals who do not have a history of abuse of other substances, with adequate psychoeducation and close monitoring of their usage pattern., Conclusion: There is a need to reconsider the need for long-term use of benzodiazepines in general, and alprazolam in particular. However, they still might be an appropriate choice in individuals where abuse and dependence are less likely., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To investigate the short- and long-term risk of psychotropic medication use in parents who lose a child to cancer diagnosed in adolescence., Methods: This is a Swedish nationwide register-based study including 184 bereaved mothers and 184 bereaved fathers of 184 children diagnosed with cancer in adolescence. Logistic regression analyses, adjusted for sociodemographic characteristics and history of mental health problems, were performed to estimate risk of a prescription of psychotropic medication (anxiolytics, hypnotics/sedatives, antidepressants) in cancer-bereaved parents from 1 year before to 5 years after the child's death, with a general population sample of non-bereaved parents (n = 3291) as referents., Results: At the year of the child's death, 28%-36% of mothers and 11%-20% of fathers had a prescription of anxiolytics, hypnotics/sedatives or antidepressants. The corresponding percentages for non-bereaved mothers and fathers were 7%-12% and 4%-7%, respectively. Compared to non-bereaved mothers, bereaved mothers showed higher odds of prescriptions from 1 year before up to four (anxiolytics) and 5 years (hypnotics/sedatives and antidepressants) after the child's death. Bereaved fathers showed higher odds than non-bereaved fathers of prescriptions from 1 year before up to the year of (anxiolytics and hypnotics/sedatives) and 1 year after (antidepressants) the child's death. No differences in odds between bereaved and non-bereaved fathers were found at 2 years after the child's death. Being unmarried, born outside Sweden, and having a history of mental health problems were associated with higher odds of prescribed medications., Conclusions: Indicative of mental health problems of clinical importance, cancer-bereaved parents had a higher prevalence of use of psychotropic medication. A decrease in medication use was evident with time, but still at 5 years after the child's death mothers displayed a higher use while fathers showed no difference to non-bereaved fathers after 2 years., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Anxiety and epilepsy affect millions of people worldwide, and the treatment of these pathologies involves the use of Benzodiazepines, drugs that have serious adverse effects such as dependence and sedation, so the discovery of new anxiolytic and antiepileptic drugs are necessary. Many routes for synthesizing ibuprofen derivatives have been developed, and these derivatives have shown promising pharmacological effects. Therefore, this study aims to evaluate its anxiolytic and anticonvulsant effect against the adult Zebrafish animal model of Ibuprofen (IBUACT) and its interaction with the GABAergic receptor through in silico studies. The light/dark preference test (Scototaxis test) was used to evaluate the anxiolytic behavior of adult Zebrafish acutely treated with IBUACT and Diazepam, and their anticonvulsant effects were investigated through the pentylenetetrazol (PTZ)-induced seizure model. Animals treated with IBUACT showed anxiolytic behavior similar to Diazepam, and pretreatment with flumazenil reversed this behavior. PTZ-induced seizures were delayed by IBUACT in all three stages and were shown to bind strongly in the Diazepam region of GABA A . In addition, this work presents evidence of new pharmacological applications of ibuprofen derivative in pathologies of the central nervous system (CNS), opening the horizon for new studies.Communicated by Ramaswamy H. Sarma.

Background: In France, despite the known risks, the use of benzodiazepines and related (BZD) is excessive, particularly in older populations. Over the age of 70, 1 person in 2 uses BZD on a long-term basis (more than 3 years), whereas it is recommended not to exceed 12 weeks. To compensate for the numerous undesirable effects and to maintain a positive benefit-risk balance, these treatments must be very effective and improve significantly the quality of life., Aims: This study aims to determine whether the efficacy of BZD outweighs their adverse effects in older population., Methods: In a population of 109 patients with cognitive impairment and hospitalized in Saint-Quentin (France), we recorded the use of BZD and medical background. Neuropsychological and geriatric assessments allowed cognitive and thymic evaluation., Results: In our cohort of 109 patients, 50% of the subjects were BZD + and 78% were women. Patients in the BZD + group were no longer anxious but had poorer cognitive and executive performance than controls., Discussion: Long-term treatment of anxiety in patients aged 75 and over with BZD appears to be effective. The deleterious impact of BZD on cognition has been demonstrated., Conclusions: These results tend to consider non-medicinal therapies as serious alternatives to BZD for treating anxiety in the older population., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: Opioid use disorder (OUD) is a major public health crisis worldwide. Patients with OUD inevitably experience withdrawal symptoms when they attempt to taper down on their current opioid use, abstain completely from opioids, or attempt to transition to certain medications for opioid use disorder. Acute opioid withdrawal can be debilitating and include a range of symptoms such as anxiety, pain, insomnia, and gastrointestinal symptoms. Whereas acute opioid withdrawal only lasts for 1-2 weeks, protracted withdrawal symptoms can persist for months after the cessation of opioids. Insufficient management of opioid withdrawal often leads to devastating results including treatment failure, relapse, and overdose. Thus, there is a critical need for cost-effective, nonopioid medications, with minimal side effects to help in the medical management of opioid withdrawal syndrome. We discuss the potential consideration of cannabidiol (CBD), a nonintoxicating component of the cannabis plant, as an adjunctive treatment in managing the opioid withdrawal syndrome. Materials and Methods: A review of the literature was performed using keywords related to CBD and opioid withdrawal syndrome in PubMed and Google Scholar. A total of 144 abstracts were identified, and 41 articles were selected where CBD had been evaluated in clinical studies relevant to opioid withdrawal. Results: CBD has been reported to have several therapeutic properties including anxiolytic, antidepressant, anti-inflammatory, anti-emetic, analgesic, as well as reduction of cue-induced craving for opioids, all of which are highly relevant to opioid withdrawal syndrome. In addition, CBD has been shown in several clinical trials to be a well-tolerated with no significant adverse effects, even when co-administered with a potent opioid agonist. Conclusions: Growing evidence suggests that CBD could potentially be added to the standard opioid detoxification regimen to mitigate acute or protracted opioid withdrawal-related symptoms. However, most existing findings are either based on preclinical studies and/or small clinical trials. Well-designed, prospective, randomized-controlled studies evaluating the effect of CBD on managing opioid withdrawal symptoms are warranted.

Purpose: Despite the notable increase on the prescription of antidepressants and anxiolytics during pregnancy, recommendation on maintaining the treatment during prenatal period is still controversial. We aimed to separately assess the role of effects of the antidepressants and anxiolytic and the underlying illness, controlled by potential confounding associated with miscarriage onset., Methods: We used data from a validated pregnant cohort aged 15-49 years from 2002 to 2016 using BIFAP database. All confirmed miscarriages were used to perform a nested control analysis using conditional logistic regression. Women were classified according to use of each drug of interest into four mutually exclusive groups: nonusers, users only during prepregnancy, continuers, and initiators during first trimester. Adjusted odds ratios (aORs) for major confounders during pregnancy such as number of visits to primary care practitioners visits, obesity, smoking, HTA, diabetes with 95% confidence intervals were calculated., Results: Compared with nonusers, antidepressants continuers had the highest increased risk of miscarriage aOR (95%) of 1.29 (1.13-1.46), being continuers of paroxetine and fluoxetine the antidepressants with the strongest association. Likewise, continuers of anxiolytics and initiators showed an increased risk of 1.19 (1.04-1.37) and 1.30 (1.13-1.50). When separating the effect between the condition itself or the treatment, women exposed during first trimester, regardless treatment duration and/or the underlying illness, had the highest risk 1.27 (1.08-1.51) for antidepressants and 1.25 (1.13-1.39) for anxiolytics., Conclusions: Our analysis showed an association between prenatal exposure to antidepressants and anxiolytics and miscarriage onset after controlling by potential confounding adjusting for confounders and the underlying illness. This association was not supported for hypnotic medications. Further studies are warranted to evaluate the risk of miscarriage among subpopulation of pregnant women requiring these medications., (© 2022 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Objective: To examine associations of antidepressant, anxiolytic and hypnotic use amongst older women (≥65 years) with incident Parkinson's Disease (PD), using data from Women's Health Initiative linked to Medicare claims., Methods: PD was defined using self-report, first diagnosis, medications and/or death certificates and psychotropic medications were ascertained at baseline and 3-year follow-up. Cox regression models were constructed to calculate adjusted hazard ratios (aHR) with 95% confidence intervals (CI), controlling for socio-demographic, lifestyle and health characteristics, overall and amongst women diagnosed with depression, anxiety and/or sleep disorders (DASD)., Results: A total of 53,996 WHI participants (1,756 PD cases)-including 27,631 women diagnosed with DASD (1,137 PD cases)-were followed up for ~14 years. Use of hypnotics was not significantly associated with PD risk (aHR = 0.98, 95% CI: 0.82, 1.16), whereas PD risk was increased amongst users of antidepressants (aHR = 1.75, 95% CI: 1.56, 1.96) and anxiolytics (aHR = 1.48, 95% CI: 1.25, 1.73). Compared to non-users of psychotropic medications, those who used 1 type had ~50% higher PD risk, whereas those who used ≥2 types had ~150% higher PD risk. Women who experienced transitions in psychotropic medication use ('use to non-use' or 'non-use to use') between baseline and 3-year follow-up had higher PD risk than those who did not. We obtained similar results with propensity scoring and amongst DASD-diagnosed women., Interpretation: The use of antidepressants, anxiolytics or multiple psychotropic medication types and transitions in psychotropic medication use was associated with increased PD risk, whereas the use of hypnotics was not associated with PD risk amongst older women., (© 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Despite the known safety risks of long-term use of sedative-hypnotic/anxiolytic medications, there has been limited guidance for the safe and effective use of their chronic use in a primary care clinic setting. Understanding the characteristics of patients who receive sedative-hypnotic/anxiolytic medication and the clinical documentation process in primary care is the first step towards understanding the nature of the problem and will help inform future strategies for clinical research and practice., Objectives: Characterize patients who received a sedative-hypnotic/anxiolytic prescription in primary care, and (2) gain an understanding of the clinical documentation of sedative-hypnotic/anxiolytic indication and monitoring in electronic medical records (EMR)., Methods: A random selection of patients who received a prescription for a benzodiazepine or Z-drug hypnotic between January 2014 and August 2016 from four primary care clinics in Winnipeg were included. Data was collected retrospectively using the EMR (Accuro®). Patient variables recorded included sex, age, comorbidities, medications, smoking status, and alcohol status. Treatment variables included drug type, indication, pattern of use, dose, adverse events, psychosocial intervention, tapering attempts, social support, life stressor, and monitoring parameters for sedative-hypnotic use. Demographic and clinical characteristics were described using descriptive statistics., Results: Records from a sample of 200 primary care patients prescribed sedative-hypnotic/anxiolytics were analyzed (mean age 55.8 years old, 61.5% ≥ 65 years old, 61.0% female). Long-term chronic use (≥ 1 year) of a sedative-hypnotic/anxiolytic agent was observed in 29.5% of the sample. Zopiclone (30.7%) and lorazepam (28.7%) were the most common agents prescribed. Only 9.5% of patients had documentation of a past tapering attempt of their sedative-hypnotic/anxiolytic. The most common indications for sedative-hypnotic/anxiolytic use recorded were anxiety (33.0%) and sleep (18.0%), but indication was undetermined for 57.0% of patients. Depression (33.5%) and falls (18.5%) were reported by patients after the initiation of these agents., Conclusions: A higher proportion of females and users 65 years and older received a prescription for a sedative-hypnotic/anxiolytic, consistent with previous studies on sedative-hypnotic use. We found inconsistencies in the documentation surrounding sedative-hypnotic/anxiolytic use. The indication for their use was unclear in a large number of patients. These findings will help us understand the state of the problem in primary care and inform future strategies for clinical research., (© 2022. The Author(s).)

Background: Anxiety disorder is a common psychiatric illness. Medicinal herbs have become a field of interest in the treatment of anxiety. This study aimed to evaluate and compare the efficacy and acceptability of all possible medicinal herbs for the treatment of anxiety., Methods: A Bayesian network meta-analysis was conducted for adults with diagnosed or subthreshold anxiety in randomized controlled trials identified in PubMed, EMBASE, the Cochrane Library, and Web of Science, searched between Jan 1, 1987, and Dec 31, 2021. The outcomes included efficacy (measured by endpoint Hamilton Anxiety Scale [HAMA] Scores) and acceptability (discontinuation by ineffectiveness, worsening of the symptoms, or adverse events)., Results: A total of 29 trials were reviewed, comparing 12 medicinal herbs. Silexan (mean difference [MD]: -3.84, 95% credible interval [CrI]: -6.31 to -1.34) displayed a significant effect on anxiety, and possibly benefitted the treatment of depression (standard mean difference [SMD]: -0.37, 95% confidence interval [CI]: -0.53 to -0.20) and insomnia (SMD: -0.48, 95% CI: -0.76 to -0.21). Kava was found to be an effective anxiolytic (MD: -2.46, 95% CrI: -4.47 to -0.32) but possibly ineffective in patients with generalized anxiety disorder (MD: -0.17, 95% CrI: -2.55 to -1.97). Ginkgo biloba (MD: -4.63, 95% CrI: -9.01 to -0.23) and Withania somnifera (MD: -4.90, 95% CrI: -9.70 to -0.17) were efficacious, as measured by HAMA scores but the trials were limited by their small sample sizes. Galphimia glauca (MD: -1.23, 95% CrI: -4.68 to 2.23) and Manasamitravn Vataka (MD: -1.35, 95% CrI: -7.39 to 4.68) exhibited the same anxiolytic effect as standard treatments, but both were absent from trials that were rated low risk, highlighting that confidence in their ability to provide an anxiolytic effect requires additional study. Conversely, although Passionflower (MD: -4.20, 95% CrI: -8.82 to 0.16) and Saffron (MD: -2.71, 95% CrI: -6.06 to 0.57) did not reduce HAMA scores significantly in the summary network, both were worthy of further study because of support from separate networks. There was insufficient evidence to confirm the effectiveness of Valerian (MD: 0.95, 95% CrI: -6.57 to 8.42) in standard-controlled estimation or the ineffectiveness of Chamomile (MD: 0.54, 95% CrI: -5.13 to 6.25) compared with a placebo for anxiety. Gamisoyo-san (MD: -0.98, 95% CrI: -6.48 to 4.54) and L-theanine (MD: -0.49, 95% CrI: -6.54 to 5.57) did not outperform a placebo for the treatment of anxiety in terms of statistical certainty. All medicinal herbs were well-tolerated and exhibited a good safety profile compared with control groups. When all herbs were compared, there was no statistical evidence to suggest any comparison significantly reduced HAMA scores except Ginkgo biloba vs Kava (MD: -4.41, 95% CrI: -8.32 to -0.35), although Ginkgo biloba was ranked as worst due to its poor tolerability., Conclusion: Medicinal herbs may be promising for the treatment of anxiety. However, these results should be considered preliminary because of the unconvincing sample sizes, together with the potential effectiveness of placebos., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background and Objectives: Warnings have been published regarding an increased risk of severe respiratory depression in patients receiving gabapentinoids either alone or in combination with opioids and/or anxiolytics/hypnotics, especially in individuals with a respiratory risk factor. The aim is to report the prevalence of the use of gabapentinoids alone and associated with central nervous system depressant drugs, and possible associated risk factors for respiratory depression, in order to identify the most fragile population and establish intervention strategies., Methods: We performed a cross-sectional study using computerized prescription records from the northern area of Barcelona at Catalan Institute of Health for 363,007 inhabitants registered during 2021. Patients aged ≥ 18 years with one or more gabapentinoid prescription were included. Age, gender, polypharmacy, adjusted morbidity groups, quantity of chronic diseases, and the number of consultations per year were independent variables. Four age categories were defined (18-64 years, then 64-74, 75-84, and those aged 85 years or older). Descriptive and inferential statistics were employed. Level of statistical significance was 5% (p ≤ 0.05). For the analysis, the SPSS program (version 22) was employed., Results: Of the study sample, 9218 were prescribed gabapentidoids. Overall prevalence of use was 3.0% (women 3.6%, men 2.4%). On the whole, women used more drugs than men. In contrast to their younger counterparts, consumption increased 2.6 times, 3.8 times, and 4.0 times in the 65-74 age group, 75-84 age group, and those aged ≥ 85 years, respectively. Mean age was 65.59 (±15.80) years. Polypharmacy (5-9 drugs) was present in 41.7% of the patients and extreme polypharmacy (≥ 10 drugs) was present in 39.3% of the patients. Regarding renal function, 2396 patients (25.9%) had glomerular filtration that required dose adjustment (76.1% with gabapentin and 23.8% with pregabalin). In 141 patients (5.9%), a total daily dose higher than that authorized (109 with gabapentin, 29 with pregabalin) had been prescribed. The prescription of gabapentinoids combined with opioids and/or anxiolytics/hypnotics was significantly associated with (i) polypharmacy (5-9 drugs, OR: 3.42 [95% CI 3.00-3.88]; ≥ 10 drugs, OR 8.72 [95% CI 7.42-10.25]); (ii) quantity of chronic diseases, OR: 1.14 (95% CI 1.11-1.17); (iii) augmented number of consultations/year, OR: 1.01 (95% CI 1.00-1.01); (iv) female gender, OR: <  1 for men, OR: 0.66 (95% CI 0.60-0.73); (v) being elderly: 65-74 years, OR: 0.71 (95% CI 0.62-0.81); 75-84 years, OR: 0.62 (95% CI 0.54-0.71); ≥85 years, OR: 0.68 (95% CI 0.58-0.81); and (vi) adjusted morbidity groups, OR: 0.90 (95% CI 0.88-0.92), (p <  0.0001)., Conclusion: Exposure to gabapentinoids occurs in a non-negligible percentage of the population. Greater numbers of combinations of gabapentinoids and opioids and/or anxiolytics/hypnotics were associated with polypharmacy, quantity of chronic diseases, and augmented number of consultations, but not with male gender, older age, and adjusted morbidity groups., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Oral benzodiazepines (BZDs) are useful tools for periprocedural anxiolysis. The United States Food and Drug Administration (FDA) recently issued a black-box warning of their risks of abuse and dependence. We performed a systematic review evaluating the safety and efficacy of oral BZDs for periprocedural anxiolysis in outpatient dermatologic, plastic surgery, dental, and ophthalmologic procedures performed under local anesthesia., Methods: A systematic review of 5 databases was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Oral benzodiazepine safety and efficacy data were extracted from eligible articles., Results: A total of 43 articles and 4,060 subjects were included. Oral BZDs consistently imparted a positive anxiolytic effect and demonstrated superior or equivalent scores in patient satisfaction, surgeon satisfaction, pain, and anxiety to comparator groups in most studies. Thirty-five subjects experienced transient hypoxia, and 2 experienced transient hypertension. A total of 195 mild, self-limited adverse effects were reported. None of the studies addressed the risks of abuse and dependence in this clinical setting., Conclusion: Short-term use of oral BZDs for periprocedural anxiolysis seems to be safe and effective. The 2020 FDA black-box warning should not deter their appropriate use in dermatologic surgery and other low-risk outpatient procedures., (Copyright © 2022 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Benzodiazepines continue to be prescribed widely in the management of patients with insomnia or anxiety disorders, despite the availability and acceptability of alternative pharmacological and psychological treatments. Many patients will experience adverse effects during treatment and considerable distress when the dosage is reduced and stopped. Management of benzodiazepine withdrawal includes measures to prevent the development of dependence, careful attention to underlying medical conditions, medication consolidation and gradual dosage reduction, accompanying psychological interventions, occasional prescription of concomitant medication, and relapse prevention with on-going support to address psychosocial stressors. There are needs for easier patient access to services with refined expertise and for further research to optimise strategies for preventing dependence and facilitating withdrawal., (© 2021 Society for the Study of Addiction.)

Background: Monocarboxylate transporter 8 (MCT8) is the first thyroid hormone transporter that has been linked to a human disease. Besides genetic alterations other factors might impair MCT8 activity., Aim: This study aimed at investigating whether some common drugs having a structural similarity with TH and/or whose treatment is associated with thyroid function test abnormalities, or which behave as antagonists of TH action can inhibit MCT8-mediated T 3 transport., Methods: [ 125 I]T 3 uptake and efflux were measured in COS-7 cells transiently transfected with hMCT8 before and after exposure to increasing concentrations of hydrocortisone, dexamethasone, prednisone, prednisolone, amiodarone, desethylamiodarone, dronedarone, buspirone, carbamazepine, valproic acid, and L-carnitine. The mode of inhibition was also determined., Results: Dexamethasone significantly inhibited T 3 uptake at 10 μM; hydrocortisone reduced T 3 uptake only at high concentrations, i.e. at 500 and 1000 μM; prednisone and prednisolone were devoid of inhibitory potential. Amiodarone caused a reduction of T 3 uptake by MCT8 only at the highest concentrations used (44% at 50 μM and 68% at 100 μM), and this effect was weaker than that produced by desethylamiodarone and dronedarone; buspirone resulted a potent inhibitor, reducing T 3 uptake at 0.1-10 μM. L-Carnitine inhibited T 3 uptake only at 500 mM and 1 M. Kinetic experiments revealed a noncompetitive mode of inhibition for all compounds. All drugs inhibiting T 3 uptake did not affect T 3 release., Conclusion: This study shows a novel effect of some common drugs, which is inhibition of T 3 transport mediated by MCT8. Specifically, dexamethasone, buspirone, desethylamiodarone, and dronedarone behave as potent inhibitors of MCT8., (© 2021. Italian Society of Endocrinology (SIE).)

Combretaceae are reported in the literature for presenting neuroprotective and anxiolytic effects in animal models. Combretum lanceolatum Pohl. has few scientific reports on its pharmacological effects. The aim of this study was to evaluate the anxiolytic and anticonvulsant effects of the ethanol extract from the leaves of C. lanceolatum Pohl. (EtFoCl) and its possible mechanism of GABAergic action in adult zebrafish. EtFoCl was subjected to determination of the total phenol concentration, identification of phytochemical flavonoids by HPLC and in vitro antioxidant activity test, open field test and 96-hour acute toxicity in zebrafish. Anxiolytic doses were tested for pentylenetetrazole-induced seizures in adult zebrafish. To study the mechanisms of action, molecular docking simulations were performed between the main phytochemicals and the GABAA receptor (anxiolytic activity) and carbonic anhydrase II (anticonvulsant). The non-toxic doses that caused motor impairment were assessed in acute and chronic anxiety using the light and dark test. EtFoCl had altered the animals' locomotion, presenting an effect similar to the anxiolytic and anticonvulsant. These effects were prevented with flumazenil (GABAA antagonist). The phytochemicals homoorientin and quercetin-3-O-galactoside coupling in a region close to that of the inhibitor diazepam (GABAA receptor). Regarding the anticonvulsant mechanism, Homoorientina and Isovitexina were identified as the most favorable for the complex form with the carbonic anhydrase enzyme. C. lanceolatum has pharmacological potential for the treatment of acute and chronic anxiety and seizures, which can be partially explained by an interaction with the GABAA receptor.Communicated by Ramaswamy H. Sarma.

Objective: Determination of the dose-dependent effect of the Teraligen for various nosological forms of disorders in psychiatric practice and general medicine., Material and Methods: Analysis of 98 publications included in the database of the RISC (2012-2021) with the identification of disorders (according to ICD-10) in which Teraligen is prescribed or can be used (in adults and children from the age of 7)., Results: Despite a rather long and successful history use, research work on the study drug Teraligen continues. Currently Teraligen is widely and actively used by doctors of various specialties in the psychiatry, neurology, pediatrics, gerontology, internal medicine, gastroenterology, gynecology, cardiology, endocrinology and other disciplines. The drug is presented in several release forms: Teraligen 5 mg tablets; Teraligen retard 20 mg; Teraligen solution for intravenous injections. Teraligen is characterized by the following psychotropic effects: anxiolytic (++ - a distinct, moderately pronounced effect); sedative (++); hypnotic (++); antidepressant (+ - the effect is distinct, but expressed slightly and does not determine the drug main prescriptions spectrum); antipsychotic (± - the effect is weakly expressed and clinically insignificant when using conventional (5-80 mg/day) drug dosages)., Conclusion: According to the authors, the main effect of the «small» neuroleptic/antipsychotic Alimemazine (Teraligen ) is primarily aimed at pathological anxiety and affective instability. Its use is possible in various age groups, as it has a fairly high safety. In addition, like other «small» neuroleptics/antipsychotics with a predominantly sedative effect, the drug can be used to correct neuroleptics-prolongs side effects with dominant manifestations in the form of anxiety, irritability and insomnia.

Background: Agitation is common in people with dementia and negatively affects the quality of life of both people with dementia and carers. Non-drug patient-centred care is the first-line treatment, but there is a need for other treatment when this care is not effective. Current evidence is sparse on safer and effective alternatives to antipsychotics. We assessed the efficacy and safety of mirtazapine, an antidepressant prescribed for agitation in dementia., Methods: This parallel-group, double-blind, placebo-controlled trial-the Study of Mirtazapine for Agitated Behaviours in Dementia trial (SYMBAD)-was done in 26 UK centres. Participants had probable or possible Alzheimer's disease, agitation unresponsive to non-drug treatment, and a Cohen-Mansfield Agitation Inventory (CMAI) score of 45 or more. They were randomly assigned (1:1) to receive either mirtazapine (titrated to 45 mg) or placebo. The primary outcome was reduction in CMAI score at 12 weeks. This trial is registered with ClinicalTrials.gov, NCT03031184, and ISRCTN17411897., Findings: Between Jan 26, 2017, and March 6, 2020, 204 participants were recruited and randomised. Mean CMAI scores at 12 weeks were not significantly different between participants receiving mirtazapine and participants receiving placebo (adjusted mean difference -1·74, 95% CI -7·17 to 3·69; p=0·53). The number of controls with adverse events (65 [64%] of 102 controls) was similar to that in the mirtazapine group (67 [66%] of 102 participants receiving mirtazapine). However, there were more deaths in the mirtazapine group (n=7) by week 16 than in the control group (n=1), with post-hoc analysis suggesting this difference was of marginal statistical significance (p=0·065)., Interpretation: This trial found no benefit of mirtazapine compared with placebo, and we observed a potentially higher mortality with use of mirtazapine. The data from this study do not support using mirtazapine as a treatment for agitation in dementia., Funding: UK National Institute for Health Research Health Technology Assessment Programme., Competing Interests: Declaration of interests SB reports personal fees and non-financial support from Lilly; personal fees from Boehringer-Ingelheim, Axovant, Lundbeck, and Nutricia; and honoraria from the Hamad Medical Service for lectures and talks; outside the submitted work. He is a Trustee of the Alzheimer's Society and has research grants from UK National Institute for Health Research (NIHR), Economic and Social Research Council, and Engineering and Physical Sciences Research Council. AB reports being National Clinical Director for Dementia at NHS England and receiving professional fees from NHS England, personal fees from International Journal of Geriatric Psychiatry, personal fees from lectures and talks and from medico-legal reports and the Driver and Vehicle Licensing Authority, outside the submitted work. CB reports grants and personal fees from Acadia, Lundbeck; personal fees from Roche, Otsuka, Novartis, Eli Lilly, Suven, Sunovion, ADDEX, and Exciva; personal fees and travel expenses from Synexus, Novo Nordisk; and travel expenses from Biogen; outside the submitted work. PB reports work as a paid consultant for TauRx Therapeutics outside the submitted work. RH reports grant support from NIHR and being a Trustee of Alzheimer's Research UK. JO reports personal fees from TauRX Therapeutics, Axon, GE Healthcare, Roche, and Eisai; non-financial support from Alliance Medical; and grants from Merck; outside the submitted work. NT reports grant support from Avenir Pharma and NIHR Applied Research Collaborations and Comprehensive Research Network leadership roles. AJT reports grants from the NIHR Health Technology Assessment Programme, during the conduct of the study. All other authors declare no competing interests other than NIHR funding for investigator time on this grant., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: To assess the efficacy and safety of topiramate in treating binge eating disorder (BED), using a systematic review and meta-analysis of the available randomized clinical trials (RCTs)., Methods: The RCTs assessing topiramate vs placebo with or without adjunctive psychotherapy in BED were reviewed using a systematic search in the PubMed, Web of Science, PsycINFO, Cochrane Database of Systematic Review, and ClinicalTrials.gov search Websites, from inception to November 2019. Main outcomes were the changes in binge frequency, quality of life, and weight, respectively. Effect estimates were pooled using random-effect models and presented as risk ratios (RRs) or mean differences (MDs) and their 95% confidence interval (95% CI). Data extraction was performed by two independent reviewers., Results: Three studies were eligible for inclusion, involving 528 BED patients. Topiramate was found to be significantly more efficacious than placebo in reducing: (a) the number of binge episodes per week (MD = -1.31; 95% CI = -2.58 to -0.03; I2 = 94%); (b) the number of binge days per week (MD = -0.98; 95% CI = -1.80 to -0.16; I2 = 94%); and (c) weight (MD = -4.91 kg; 95% CI = -6.42 to -3.41; I2 = 10%). However, participants in the topiramate groups withdrew significantly more frequently for safety reasons, relative to placebo participants (RR = 1.90; 95% CI = 1.13-3.18, I2 = 0%)., Conclusions: Preliminary findings support a possible efficacy of topiramate for the treatment of BED, even if safety concerns could limit the practical use of this treatment in BED subjects.

Long-term usage of benzodiazepines for anxiety and sleeping disorders results in a decline in effectiveness and an increase in the risk of dependence and side-effects over time. For this reason, in 2009, benzodiazepines for anxiety and sleeping disorders were disinvested (i.e. reimbursement was discontinued) in the Netherlands. Several factors contributed to disinvestment: the broad support from involved actors for disinvestment, the possibility to keep reimbursing benzodiazepines for patients groups for whom long-term use is indicated, patient groups that were not well organized, and the fact that long-term benzodiazepine use for anxiety and sleeping disorders is not medically necessary as well as ineffective. In the first year following disinvestment, the usage of benzodiazepines decreased with 15%. In subsequent years, usage stabilized, after which it decreased again.

Background: Cannabidiol (CBD), a major nonintoxicating constituent of cannabis, exhibits anxiolytic properties in preclinical and human studies and is of interest as a novel intervention for treating anxiety disorders. Existing first-line pharmacotherapies for these disorders include selective serotonin reuptake inhibitor and other antidepressants. Cannabidiol has well-described inhibitory action on cytochrome P450 (CYP450) drug-metabolizing enzymes and significant drug-drug interactions (DDIs) between CBD and various anticonvulsant medications (eg, clobazam) have been described in the treatment of epilepsy. Here, we examined the likelihood of DDIs when CBD is added to medications prescribed in the treatment of anxiety., Methods: The effect of CBD on CYP450-mediated metabolism of the commonly used antidepressants fluoxetine, sertraline, citalopram, and mirtazapine were examined in vitro. Cannabidiol-citalopram interactions were also examined in vivo in patients (n = 6) with anxiety disorders on stable treatment with citalopram or escitalopram who received ascending daily doses of adjunctive CBD (200-800 mg) over 12 weeks in a recent clinical trial., Results: Cannabidiol minimally affected the metabolism of sertraline, fluoxetine, and mirtazapine in vitro. However, CBD significantly inhibited CYP3A4 and CYP2C19-mediated metabolism of citalopram and its stereoisomer escitalopram at physiologically relevant concentrations, suggesting a possible in vivo DDI. In patients on citalopram or escitalopram, the addition of CBD significantly increased citalopram plasma concentrations, although it was uncertain whether this also increased selective serotonin reuptake inhibitor-mediated adverse events., Conclusions: Further pharmacokinetic examination of the interaction between CBD and citalopram/escitalopram is clearly warranted, and clinicians should be vigilant around the possibility of treatment-emergent adverse effects when CBD is introduced to patients taking these antidepressants., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Ayahuasca is a classic hallucinogen with anxiolytic and antidepressive properties. Anecdotal evidence also suggests that it improves performance (eg, singing, speech). This controlled trial assessed the effects of ayahuasca on speech performance and anxiety in individuals with social anxiety disorder., Methods: Seventeen volunteers with social anxiety disorder participated in a pilot, proof-of-concept, randomized, parallel-group trial. Self-perception of performance during a public-speaking test was assessed with the Self-statements During Public Speaking Scale primary outcome). Secondary outcomes included anxiety/subjective effects (Visual Analog Mood Scale; Bodily Symptoms Scale), recognition of emotions in facial expressions (REFE), tolerability measures (cardiovascular measures, self-reports), and brain-derived neurotrophic factor plasma levels. Effects on anxiety and REFE were assessed again 7, 14, and 21 days postdrug., Findings: Compared with placebo, ayahuasca significantly improved self-perception of speech performance (Self-statements During Public Speaking Scale) and increased somatic symptoms (Bodily Symptoms Scale). There was also a significant time × group interaction in the cognitive deterioration Visual Analog Mood Scale factor and a significant effect of time in the REFE task, especially in reaction time. Other measures were not significantly modified. Ayahuasca was well tolerated, producing mainly nausea, gastrointestinal discomfort, and vomiting., Conclusions: Ayahuasca improved self-perception of speech performance in socially anxious individuals. These effects occurred independent of task-related anxiety and REFE, suggesting that ayahuasca could specifically improve the cognitive aspect of speech performance. Further studies should try to unveil the mechanisms involved in the effects of ayahuasca and to better understand its effects on anxiety., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The postnatal period is a significant period of physical, physiological and psychological change for mothers, rendering them particularly vulnerable to changes in mood or disorders such as postnatal depression (PND). Previous interventions with foods high in flavonoids have demonstrated beneficial acute and chronic mood effects in healthy child, adolescent and adult populations. It is unclear whether mood effects persist in populations who are potentially at-risk of developing mood disorders, such as postnatal mothers. This exploratory study investigated the effects of a 2-week daily dietary flavonoid intervention on mood (PANAS-NOW), anxiety (STAI), depressive symptoms (PHQ-8) and perceived quality of life (WHOQOL-BREF) in forty-one new mothers in the 0-12-month postnatal period, before and after flavonoid intervention. Mothers either added high flavonoid foods to their daily diet, or did not include additions following a randomised, between-groups, controlled design. Significant effects were observed in the flavonoid group with mothers reporting lower state anxiety and higher perceived quality of physical health at the 2-week timepoint. These findings suggest that regular dietary consumption of flavonoids may benefit mothers' anxiety and perceived quality of life in the postnatal period. Replication of these results may indicate the potential for dietary flavonoids to promote healthy mood regulation in mothers or prevent the onset or severity of symptoms in postnatal psychological disorders, both of which would be beneficial for women's health services and public mental health.

Background: Anxiety, obsessive-compulsive, and stress-related disorders frequently co-occur, and patients often present symptoms of several domains. Treatment involves the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), but data on comparative efficacy and acceptability are lacking. We aimed to compare the efficacy of SSRIs, SNRIs, and placebo in multiple symptom domains in patients with these diagnoses over the lifespan through a 3-level network meta-analysis., Methods and Findings: We searched for published and unpublished randomized controlled trials that aimed to assess the efficacy of SSRIs or SNRIs in participants (adults and children) with diagnosis of any anxiety, obsessive-compulsive, or stress-related disorder in MEDLINE, PsycINFO, Embase, and Cochrane Library from inception to 23 April 2015, with an update on 11 November 2020. We supplemented electronic database searches with manual searches for published and unpublished randomized controlled trials registered in publicly accessible clinical trial registries and pharmaceutical companies' databases. No restriction was made regarding comorbidities with any other mental disorder, participants' age and sex, blinding of participants and researchers, date of publication, or study language. The primary outcome was the aggregate measure of internalizing symptoms of these disorders. Secondary outcomes included specific symptom domains and treatment discontinuation rate. We estimated standardized mean differences (SMDs) with 3-level network meta-analysis with random slopes by study for medication and assessment instrument. Risk of bias appraisal was performed using the Cochrane Collaboration's risk of bias tool. This study was registered in PROSPERO (CRD42017069090). We analyzed 469 outcome measures from 135 studies (n = 30,245). All medications were more effective than placebo for the aggregate measure of internalizing symptoms (SMD -0.56, 95% CI -0.62 to -0.51, p < 0.001), for all symptom domains, and in patients from all diagnostic categories. We also found significant results when restricting to the most used assessment instrument for each diagnosis; nevertheless, this restriction led to exclusion of 72.71% of outcome measures. Pairwise comparisons revealed only small differences between medications in efficacy and acceptability. Limitations include the moderate heterogeneity found in most outcomes and the moderate risk of bias identified in most of the trials., Conclusions: In this study, we observed that all SSRIs and SNRIs were effective for multiple symptom domains, and in patients from all included diagnostic categories. We found minimal differences between medications concerning efficacy and acceptability. This three-level network meta-analysis contributes to an ongoing discussion about the true benefit of antidepressants with robust evidence, considering the significantly larger quantity of data and higher statistical power when compared to previous studies. The 3-level approach allowed us to properly assess the efficacy of these medications on internalizing psychopathology, avoiding potential biases related to the exclusion of information due to distinct assessment instruments, and to explore the multilevel structure of transdiagnostic efficacy., Competing Interests: The authors have declared that no competing interests exist.

Ethnopharmacological Relevance: Cross-cultural comparison of plants used during lactation and the postpartum period offers insight into a largely overlooked area of ethnopharmacological research. Potential roles of phytochemicals in emerging models of interaction among immunity, inflammation, microbiome and nervous system effects on perinatal development have relevance for the life-long health of individuals and of populations in both traditional and contemporary contexts., Aim of the Study: Delineate and interpret patterns of traditional and contemporary global use of medicinal plants ingested by mothers during the postpartum period relative to phytochemical activity on immune development and gastrointestinal microbiome of breastfed infants, and on maternal health., Materials and Methods: Published reviews and surveys on galactagogues and postpartum recovery practices plus ethnobotanical studies from around the world were used to identify and rank plants, and ascertain regional use patterns. Scientific literature for 20 most-cited plants based on frequency of publication was assessed for antimicrobial, antioxidant, anti-inflammatory, immunomodulatory, antidepressant, analgesic, galactagogic and safety properties., Results: From compilation of 4418 use reports related to 1948 species, 105 plant taxa were recorded ≥7 times, with the most frequently cited species, Foeniculum vulgare, Trigonella foenum-graecum, Pimpinella anisum, Euphorbia hirta and Asparagus racemosus, 81, 64, 42, 40 and 38 times, respectively. Species and use vary globally, illustrated by the pattern of aromatic plants of culinary importance versus latex-producing plants utilized in North Africa/Middle East and Sub-Saharan Africa with opposing predominance. For 18/20 of the plants a risk/benefit perspective supports assessment that positive immunomodulation and related potential exceed any safety concerns. Published evidence does not support a lactation-enhancing effect for nearly all the most-cited plants while antidepressant data for the majority of plants are predominately limited to animal studies., Conclusions: Within a biocultural context traditional postpartum plant use serves adaptive functions for the mother-infant dyad and contributes phytochemicals absent in most contemporary diets and patterns of ingestion, with potential impacts on allergic, inflammatory and other conditions. Polyphenolics and other phytochemicals are widely immunologically active, present in breast milk and predominately non-toxic. Systematic analysis of phytochemicals in human milk, infant lumen and plasma, and immunomodulatory studies that differentiate maternal ingestion during lactation from pregnancy, are needed. Potential herb-drug interaction and other adverse effects should remain central to obstetric advising, but unless a plant is specifically shown as harmful, considering potential contributions to health of individuals and populations, blanket advisories against postpartum herbal use during lactation appear empirically unwarranted., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Cognitive reappraisal is a strategy for emotional regulation, important in the context of anxiety disorders. It is not known whether anxiolytic effects of benzodiazepines affect cognitive reappraisal., Aims: We aimed to investigate the effect of 25 mg oxazepam on cognitive reappraisal., Methods: In a preliminary investigation, 33 healthy male volunteers were randomised to oxazepam or placebo, and then underwent an experiment where they were asked to use cognitive reappraisal to upregulate or downregulate their emotional response to images with negative or neutral emotional valence. We recorded unpleasantness ratings, skin conductance, superciliary corrugator muscle activity, and heart rate. Participants completed rating scales measuring empathy (Interpersonal Reactivity Index, IRI), anxiety (State-Trait Anxiety Inventory, STAI), alexithymia (Toronto Alexithymia Scale-20, TAS-20), and psychopathy (Psychopathy Personality Inventory-Revised, PPI-R)., Results: Upregulation to negative-valence images in the cognitive reappraisal task caused increased unpleasantness ratings, corrugator activity, and heart rate compared to downregulation. Upregulation to both negative- and neutral-valence images caused increased skin conductance responses. Oxazepam caused lower unpleasantness ratings to negative-valence stimuli, but did not interact with reappraisal instruction on any outcome. Self-rated trait empathy was associated with stronger responses to negative-valence stimuli, whereas self-rated psychopathic traits were associated with weaker responses to negative-valence stimuli., Conclusions: While 25 mg oxazepam caused lower unpleasantness ratings in response to negative-valence images, we did not observe an effect of 25 mg oxazepam on cognitive reappraisal., Competing Interests: The authors have declared that no competing interests exist.

Ethnopharmacological Relevance: Kava (Piper methysticum G. Forst. f.) is by far the most important plant used in the islands of Melanesia, Polynesia and Micronesia for its relaxing effects. Kava drinking is a pillar of South Pacific societies and is also the foundation of their economies. Preparations of kava extract as herbal medicinal drugs were banned in Germany in 2002 and again in 2019, with dramatic consequences for the South Pacific economies. In 2002, the major regulatory argument for the ban of kava was safety issues. In 2019, the assessment report of the European Medicines Agency's Herbal Medicinal Product Committee (HMPC) justified a negative benefit-to-risk ratio by a supposed lack of efficacy of ethanolic extracts for an indication of which kava extract preparations never had an approval. In this HMPC report the efficacy in the approved indications 'nervous anxiety, tension and restlessness' was attributed to the extract branded as 'WS 1490', which was assumed to have been prepared with acetone as an extraction solvent. In addition to this change of indication and the attribution of efficacy to acetone kava extract alone, the German health authorities and the HMPC still refuse to discuss quality issues as a likely factor impacting drug safety. The first case reports of liver toxicity were observed with an acetone extract in a timely relationship with the introduction of 'two-day kava' instead of 'noble kava' as used in ethanolic kava extracts., Aim of the Study: The correlation between clinical benefits and the type of extract preparation was examined., Methods: In order to identify the types of kava material and extracts used in clinical trials, the respective publications were compared with regulatory databases and protocols of a German regulatory advisory board., Results and Conclusions: The comparison reveals inconsistencies in the regulatory decisions. In all studies with WS 1490, the evidence points to the use of an ethanolic extract. The efficacy of kava extract for the approved indication was clearly demonstrated. The HMPC report and the recent renewed German regulatory ban of kava therefore require major revision, which should include the impact of the use of "two-day kava" on drug safety. Such a revision could contribute to restoring the reputation of "noble kava" on the international markets., (Copyright © 2020 Elsevier B.V. All rights reserved.)

After a traumatic brain injury (TBI), many persons experience significant and debilitating problems with anxiety. The aim of this systematic review was to critically evaluate the evidence regarding efficacy of pharmacological interventions for anxiety after TBI. We reviewed studies published in English before July 2020 and included original research on pharmacological interventions for anxiety after TBI in adults ≥16 years of age. MEDLINE, PubMed, CINAHL, EMBASE, PsycINFO, and CENTRAL databases were searched, with additional searching of key journals, clinical trials registries, and international drug regulators. The primary outcomes of interest were reduction in symptoms of anxiety and occurrence of harms. The secondary outcomes of interest were changes in depression, cognition, quality of life, and participation. Data were summarized in a narrative synthesis, and evidence quality was assessed using the Cochrane Risk of Bias tool. Only a single non-peer-reviewed, randomized controlled trial of 19 male military service members with mild TBI met inclusion criteria. This study found no significant effect of citalopram on anxiety symptoms over a 12-week intervention. The trial was stopped early because of poor recruitment, and much of the study detail was not included in the report. The methodological quality of the study was difficult to assess because of the lack of detail. No recommendations could be drawn from this review. There is a critical need for adequately powered and controlled studies of pharmacological interventions for anxiety after TBI across all severities that examine side-effect profiles and consider issues of comorbidity and effects of long-term pharmacotherapy.

Background: Anxiolytics such as benzodiazepines are widely used in the treatment of anxiety disorders, although they are no longer recommended as first-line therapy for these conditions due to increased risk of dependence, as well as cognitive adverse effects, especially among the elderly. High prescribing rates of anxiolytics may be indicative of higher prevalence of anxiety-related phenomena in a given society, either in a form of an anxiety disorder or as pressure on physicians to keep prescribing them, against current guidelines., Subjects and Methods: We inspected prescribing rates of anxiolytics in 21 European countries and compared them with six dimensions of Hofstede's cross-cultural framework, namely uncertainty avoidance (UAI), power distance (PD), individualism (IDV), masculinity (MAS), long-term orientation (LTO) and indulgence (IND)., Results: According to our findings, anxiolytic prescribing patterns in selected European countries correlate positively with Hofstede's dimensions of UAI and PD and negatively with IDV., Conclusion: Differences in prescribing rates of anxiolytics and trends in their use may be affected by cross-cultural factors. More research is needed to shed light on these regional differences in anxiolytic prescribing.

Background/aim: The aim of this study is to evaluate the effects of preemptive oral pregabalin on hemodynamic response, anxiety, sedation, and recovery in patients who underwent endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) under sedation with intravenous ketamine-propofol combination., Materials and Methods: Sixty patients were included in this study, and patients were randomly divided into two equal groups to receive the placebo (Group 1) versus pregabalin 150 mg (Group 2) one hour prior to EBUS- TBNA procedure. Patients received 0.25 mg kg-1 ketamine and 0.25 mg kg-1 propofol mixture (ketofol) for sedation. Timing of the parameters was defined as follows; T0: in hospital ward before pregabalin or placebo administration, T1: premedication, T2: in operating room, T3: before the procedure, T4: initiation, T5: 3 min after induction, T6: 6 min after induction, T7: 9 min after induction, and T8: 12 min after induction. Hemodynamic parameters, severity of coughing, sedation and anxiety scores, and complications were recorded. The level of satisfaction of the bronchoscopist and the patients were evaluated at the end of the procedure., Results: The heart rate and mean arterial pressure were significantly higher in Group 1 (P = 0.008, P = 0.04). Total doses of anesthetics, recovery time, and desaturation rate were significantly higher in Group 1 (P = 0.014, P = 0.001, P = 0.045). In Group 2, SpO2 level was significantly higher at various time periods (T1; P = 0.025, T4; P =0.043, T6; P = 0.001, T7; P = 0.003, T8; P < 0.001). The severity of coughing was found significantly lower in Group 2 (T4; P = 0.011, T5; P = 0.01, T6; P = 0.02, T7; P = 0.03, T8; P < 0.01). Anxiety scores were significantly lower in Group 2 (P < 0.001)., Conclusion: Preemptive oral pregabalin, in addition to sedation with ketamine-propofol combination, was effective in providing limited hemodynamic response, restricted coughing reflex, and lower anxiety during EBUS-TBNA. Besides, with pregabalin usage, decreased anesthetics consumption, lower complication rate, and shorter recovery time might have contributed to safety of the procedure and comfort of the bronchoscopist., Competing Interests: All authors declare that they have no conflict of interest., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Background: The antibacterial effects of psychotropics may be part of their pharmacological effects when treating depression. However, limited studies have focused on gut microbiota in relation to prescribed medication., Method: We longitudinally investigated the relationship between patients' prescribed medications and intestinal bacterial diversity in a naturalistic treatment course for patients with major depressive disorders and anxiety disorders. Patients were recruited and their stool was collected at 3 time points during their usual psychiatric treatments. Gut microbiota were analyzed using 16S rRNA gene sequencing. We examined the impact of psychotropics (i.e., antidepressants, anxiolytics, antipsychotics) on their gut microbial diversity and functions., Results: We collected 246 stool samples from 40 patients. Despite no differences in microbial diversity between medication groups at the baseline, over the course of treatment, phylogenic diversity whole-tree diversity decreased in patients on antipsychotics compared with patients without (P = .027), and beta diversity followed this trend. Based on a fixed-effect model, antipsychotics predicted microbial diversity; the higher doses correlated with less diversity based on the Shannon index and phylogenic diversity whole tree (estimate = -0.00254, SE = 0.000595, P < .0001; estimate = -0.02644, SE = 0.00833, P = .002, respectively)., Conclusion: Antipsychotics may play a role in decreasing the alpha diversity of the gut microbiome among patients with depression and anxiety, and our results indicate a relationship with medication dosage. Future studies are warranted and should consider patients' types and doses of antipsychotics in order to further elucidate the mechanisms of gut-brain interactions in psychiatric disorders., (© The Author(s) 2020. Published by Oxford University Press on behalf of CINP.)