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Anxiety disorders are one of the most prevalent mental health conditions worldwide, imposing a significant burden on individuals affected by them and society in general. Current research endeavors aim to enhance the effectiveness of existing anxiolytic drugs and reduce their side effects through optimization or the development of new treatments. Several anxiolytic novel drugs have been produced as a result of discovery-focused research. However, many drug candidates that show promise in preclinical rodent model studies fail to offer any substantive clinical benefits to patients. This review provides an overview of the diagnosis and classification of anxiety disorders together with a systematic review of anxiolytic drugs with a focus on their targets, therapeutic applications, and side effects. It also provides a concise overview of the constraints and disadvantages associated with frequently administered anxiolytic drugs. Additionally, the study comprehensively reviews animal models used in anxiety studies and their associated molecular mechanisms, while also summarizing the brain circuitry related to anxiety. In conclusion, this article provides a valuable foundation for future anxiolytic drug discovery efforts., Competing Interests: Declaration of competing interest Regarding the competing interest statement, I stated, “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.” In the current stage, this study was supported by the Provincial Education Department Project (23NSFSC2480), the Research Fund for Inheritance and Innovation Development of CDUTCM (CCCXFH202204), the National Natural Science Foundation General Project (82074316) and the Research and Development Fund Project of the Institute of Basic Theory of Traditional Chinese Medicine, China Academy of Chinese Medical Sciences (KJX202404). The authors have participated sufficiently in the work to take public responsibility for all or part of the content., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Exposure to a range of stressful life events (SLE) is implicated in youth psychopathology. Previous studies point to a discrepancy between parents'/children's reports regarding stressful life events. No study systematically assessed the correlation between such discrepancies and psychopathology in depressed youth. This study was designed to assess parent-youth discrepancies regarding stressful life events and its association with severity of psychopathology at baseline and response to selective serotonin reuptake inhibitor (SSRI) treatment in depressed youth. Methods: Reports regarding stressful life events were assessed in children/adolescents suffering from depressive/anxiety disorders using the life events checklist (LEC), a self-report questionnaire measuring the impact of negative life events (NLE) and positive life events (PLE), as reported by the children and their parents. The severity of depression/anxiety disorders and response to antidepressant treatment were evaluated and correlated with both measures of LEC. Results: Participants were 96 parent-child dyads (39 boys, 57 girls) aged 6-18 years (mean = 13.90 years, SD = 2.41). Parents reported more NLE and higher severity of NLE events than their children (number of NLE: 7.51 ± 4.17 vs. 6.04 ± 5.32; Cumulative severity of NLE: 24.95 ± 14.83 vs. 17.24 ± 12.94). Discrepancy in PLE, but not NLE, was associated with more severe psychopathology and reduced response to treatment. Discussion: Discrepancy in informant reports regarding life events in depressed/anxious youth, especially regarding PLE, is associated with more severe psychopathology and reduced response to pharmacotherapy. It is essential to use multiple reporters in assessing stressful life events in children.

Background: Women with menopausal transition (MT) have an elevated risk of experiencing common mental health diagnoses (CMHD: depression or anxiety). There is no recent data comparing the rate, and treatment, of CMHD between men and women., Methods: In this population-based study, incidence rates (IR) per 100 person-years-at-risk (PYAR) for men and women ≥45 years registered with an UK primary care practice between 2010 and 2021 were estimated. Incidence rate ratios (IRR) with 95 % confidence intervals (CIs) of CMHD were estimated using men as a reference. We measured first prescriptions for psychotropic medications received within 12 months after CMHD. For selective serotonin reuptake inhibitors (SSRIs) /selective norepinephrine reuptake inhibitors (SNRIs), we measured the IR of prescribing per 100 PYAR, by 10-year bands. Proportion of SSRIs/SNRIs prescribing was estimated per 100 persons., Results: Rates of anxiety and depressive disorders were 1.68 and 1.69 per 100 PYAR in women aged 45-54 years-old compared to 0.91 and 1.20 per 100 PYAR in men, with IRR of 1.84 (95 % CI 1.72-1.97) and 1.44 (1.35-1.53) respectively. SSRIs/SNRIs were the most prescribed medication; in 2021, IRs for SSRIs/SNRIs were 13.4 per 100 PYAR in both sexes. In 2021, the proportion of SSRIs/SNRIs prescribing was 50.67 per 100 women and 41.91 per 100 men., Limitations: MT is assumed based on women's age as menopause onset is rarely recorded in primary care databases., Conclusions: Women ≥45 years experienced more CMHD compared to men, especially 45-54 years-olds, which coincides with MT. The proportion of SSRIs/SNRIs prescribing was higher in women., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dana Alsugeir reports financial support was provided by Saudi Arabian Cultural Bureau. If there are other authors, they 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 The Authors. Published by Elsevier B.V. All rights reserved.)

The gut microbiome is a vast, variable, and largely unexplored component of human biology that sits at the intersection of heritable and environmental factors, and represents a rich source of novel chemistry that is already known to be compatible with the human body. This alone would make it a promising place to search for new therapeutics, but recent work has also identified gut microbiome abnormalities in patients with a number of psychiatric disorders, including anxiety disorders-suggesting that not only treatments, but cures may lie therein. Here, we'll discuss two known "para-endogenous" anxiolytics-γ-hydroxybutyrate and the neurosteroid allopregnanolone-which have recently been discovered to be produced by the microbiome., (Copyright © 2024. Published by Elsevier Inc.)

This study aims to analyze changes in health-related quality of life (HRQoL) and safety in patients with generalized anxiety disorder (GAD) prescribed a homogenous selection of cannabis-based medicinal products (CBMPs). Patients prescribed Adven CBMPs (Curaleaf International, UK) for GAD were identified from the UK Medical Cannabis Registry. Primary outcomes were changes in patient-reported outcome measures (PROMs) from baseline up to 12 months, including GAD-7, Single-Item Sleep Quality Scale (SQS), and EQ-5D-5L. Adverse events were recorded using CTCAE version 4.0. A total of 120 patients were identified for inclusion, of which 38 (31.67%), 52 (43.33%), and 30 (25.00%) were prescribed oils, dried flower, and both formulations of CBMP. Associated improvements in GAD-7, SQS, and EQ-5D-5L at 1, 3, 6, and 12 months were observed compared to baseline ( P  < 0.010). There were 24 (20.00%) patients who reported 442 (368.33%) adverse events, most of which were mild (n = 184, 41.63%) and moderate (n = 197, 44.57%). This study reports an association between initiation of a homogeneous CBMP therapy and improvements in anxiety severity and HRQoL in individuals with GAD. Moreover, therapy was well-tolerated at 12 months follow-up. Further investigation through randomized controlled trials will ultimately be required to determine causation., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Between 2003 and 2018, incident prescriptions of beta-blockers for anxiety increased substantially, particularly for young adults. National Institute for Health and Care Excellence guidance for anxiety does not recommend beta-blockers, probably due to a lack of evidence to support such use. Recent reports have highlighted the potential risks of beta-blockers., Aim: To understand when and why GPs prescribe beta-blockers for people with anxiety., Design and Setting: In-depth interviews with 17 GPs in Bristol and the surrounding areas., Method: Interviews were held by telephone or video call. A topic guide was used to ensure consistency across interviews. Interviews were audio-recorded, transcribed verbatim, and analysed thematically., Results: Many GPs viewed beta-blockers as 'low risk', particularly for young adults. Some GPs viewed beta-blockers as an alternative to benzodiazepines, acting quickly and not leading to dependence. GPs reflected that some patients appeared to want an 'immediate fix' to their symptoms, which GPs thought beta-blockers could potentially offer. This is salient in light of substantial waiting lists for talking therapies and delays in antidepressants taking effect. GPs described how some patients seemed more willing to try beta-blockers than antidepressants, as patients did not perceive them as 'mental health drugs' and therefore viewed them as potentially more acceptable and less stigmatising. Further, GPs viewed beta-blockers as 'patient-led', with patients managing their own dose and frequency, without GP input., Conclusion: Many GPs believe that beta-blockers have a role to play in the management of anxiety. Given recent increases in the prescribing of these drugs in primary care, there is a need to assess their safety and effectiveness as a treatment for people with anxiety disorders., (© The Authors.)

Background: Incident benzodiazepine prescriptions in primary care for anxiety decreased between 2003 and 2018. However, from 2008, incident prescribing of benzodiazepines for anxiety increased among those aged 18-34 years. There are increasing concerns around prescribing of benzodiazepines. Further, although guidelines state benzodiazepines should only be prescribed short term, in 2017, 44% of incident prescriptions were prescribed for longer than the recommended duration of 2-4 weeks., Aim: To understand when and why GPs prescribe benzodiazepines for anxiety in young adults., Design and Setting: A qualitative study was undertaken using in-depth interviews with 17 GPs from 10 general practices in South West England., Method: Interviews were conducted by telephone or videocall. A topic guide was used to ensure consistency across interviews. Interviews were audio-recorded, transcribed verbatim, and data analysed using reflexive thematic analysis., Results: GPs described caution in prescribing benzodiazepines for anxiety in young adults, but thought they had an important role in acute situations. GPs described caution in prescribing duration, but some thought longer-term prescriptions could be appropriate. In light of these views, some GPs questioned whether primary care needs to revisit how clinicians are using benzodiazepines. GPs perceived that some young adults requested benzodiazepines and suggested this might be because they wanted quick symptom relief. GPs noted that refusing to prescribe felt uncomfortable and that the number of young adults presenting to general practice, already dependent on benzodiazepines, had increased., Conclusion: Patient-driven factors for prescribing benzodiazepines suggest there are current unmet treatment needs among young adults with anxiety. Given increases in prescribing in this age group, it may be timely to revisit the role of benzodiazepines in the management of people with anxiety in primary care., (© The Authors.)

Background: Generalized anxiety disorder (GAD) (Chittodvega) is one among many types of mental disorders explained in Ayurveda. It can be defined as a Chitta (mind) + Udvega (anxiety)= Chittodvega - Anxious status of a mind. Celastrus paniculatus also known as Jyotishmati stimulates and improves the digestive fire and metabolism at a cellular level ( Jatharagni and Majja dhatwagni). It can be correlated to GAD. GAD is characterized by feelings of threat, restlessness, irritability, sleep disturbance, and tension, and symptoms such as palpitations, dry mouth, and sweating. It affects women more frequently than men and prevalence rates are high in midlife (prevalence in females over age 35: 10%) and older subjects. In modern medicine the first-line psychological and pharmaceutical treatments are selective serotonin reuptake inhibitors (SSRIs) like sertraline (SNRIs)., Aim and Objectives: To evaluate the comparative efficacy of Jyotishmati versus sertraline in the management of Chittodvega., Methods: In this randomized active controlled double blind equivalence trial a total of 70 patients will be enrolled and divided into two equal groups. Patients between 20-50 years age of either gender having symptoms of Chittodvega and a Hamilton anxiety rating (HAM-A) scale score less than 24 (i.e., mild to moderate) will be selected for the study. In Group A, sertraline capsules 25 mg for first 7 days and then dose increased to 50 mg at bedtime for next 53 days and in Group B Jyotishmati Capsules 500 mg will be given twice a day after food with water for 60 days., Result and Observation: The patients will be assessed on the HAM-A scale, serum cortisol and WHO Quality of Life on day 0, 30, 60 and 90 and data will be analyzed using paired and unpaired t-tests for continuous variables and chi-square tests for categorical variables to evaluate whether treatments are equivalent., Trial Registration: CTRI No. REF/2023/07/069880 Date - 15/09/2023., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Gamne R et al.)

Background: Major depressive disorder (MDD) is a serious and disabling condition characterized by abnormal mood changes. Clinical guidelines for depression treatment recommend antidepressant medications, with benzodiazepines acting as short-term synergists. However, little is currently known about the prevalence and associated clinical risk factors of benzodiazepine use among Chinese patients with MDD. This study aimed to explore the prevalence and clinical risk factors associated with benzodiazepine use in this population., Methods: A total of 2742 patients with MDD (males/females = 816/1926, aged 14-60 years) participated in this cross-sectional observational study. General information and psychosis assessments were collected online. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), anxiety symptoms using the Generalized Anxiety Disorder-7 (GAD-7), and sleep problems and suicidal tendencies using the third and ninth items of the PHQ-9. Multivariable logistic regression analysis models were employed to identify factors associated with benzodiazepine use., Results: The prevalence of benzodiazepine use among patients with MDD was 42.9 %. Among these patients, 99.6 % used a single benzodiazepine, with oxazepam being the most frequently prescribed. Age, severity of sleep problems, depressive symptoms, and anxiety symptoms were significantly correlated with benzodiazepine use (all P < 0.001)., Limitations: The cross-sectional design of this study precludes establishing causal relationships., Conclusion: Our findings indicate a high prevalence of benzodiazepine use among Chinese patients with MDD. Factors such as severe depressive symptoms, anxiety symptoms, age, and sleep problems appear to be associated with benzodiazepine use. These results underscore the importance of vigilance regarding benzodiazepine use in patients with MDD., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts with any financial interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: People with mental health conditions were potentially more vulnerable than others to the neuropsychiatric effects of the COVID-19 pandemic and the global efforts taken to contain it. The aim of this multinational study was to examine the changes in psychotropic drug prescribing during the pandemic among people with depressive and anxiety disorders., Methods: This study included electronic medical records and claims data from nine databases in six countries (France, Germany, Italy, the UK, South Korea, and the USA) of patients with a diagnosis of depressive or anxiety disorders between 2016 and 2021. The outcomes were monthly prevalence rates of antidepressant, antipsychotic, and anxiolytic drug prescribing. The associations between the pandemic and psychotropic drug prescribing were examined with interrupted time series analyses for the total sample and stratified by sex and age group. People with lived experience were not involved in the research and writing process., Findings: Between Jan 1, 2016 and Dec 31, 2020, an average of 16 567 914 patients with depressive disorders (10 820 956 females [65·31%] and 5 746 958 males [34·69%]) and 15 988 451 patients with anxiety disorders (10 688 788 females [66·85%] and 5 299 663 males [33·15%]) were identified annually. Most patients with depressive disorders and anxiety disorders were aged 45-64 years. Ethnicity data were not available. Two distinct trends in prescribing rates were identified. The first pattern shows an initial surge at the start of the pandemic (eg, antipsychotics among patients with depressive disorders in MDCD&#95;US (rate ratio [RR] 1·077, 95% CI 1·055-1·100), followed by a gradual decline towards the counterfactual level (RR 0·990, 95% CI 0·988-0·992). The second pattern, observed in four databases for anxiolytics among patients with depressive disorders and two for antipsychotics among patients with anxiety disorders, shows an immediate increase (eg, antipsychotics among patients with anxiety disorders in IQVIA&#95;UK: RR 1·467, 95% CI 1·282-1·675) without a subsequent change in slope (RR 0·985, 95% CI 0·969-1·003). In MDCD&#95;US and IQVIA&#95;US, the anxiolytic prescribing rate continued to increase among patients younger than 25 years for both disorders., Interpretation: The study reveals persistently elevated rates of psychotropic drug prescriptions beyond the initial phase of the pandemic. These findings underscore the importance of enhanced mental health support and emphasise the need for regular review of psychotropic drug use among this patient group in the post-pandemic era., Funding: University Grants Committee, Research Grants Council, The Government of the Hong Kong Special Administrative Region., Competing Interests: Declaration of interests HL reports grants from Research Grants Council of Hong Kong, outside the submitted work. WCYL reports research grants from AIR@InnoHK administered by Innovation and Technology Commission, outside the submitted work. JH reports grants from UKRI, Consultancy Fees from Wellcome Trust and Juli Health, and patents pending and stock from Juli Health, outside the submitted work. COT reports stock or stock options and other financial or non-financial interests from Roche Pharmaceutical as an employee, outside the submitted work. XL reports grants from IQVIA, outside the submitted work. SF and DMK report stock or stock options and other financial or non-financial interests from Johnson and Johnson as employees, outside the submitted work. JL reports stock or stock options and other financial or non-financial interests from IQVIA as an employee, outside the submitted work. KKCM reports grants from the CW Maplethorpe Fellowship, National Institute of Health Research, UK, Hong Kong Research Grant Council, and the European Commission Horizon 2020 Framework, outside the submitted work. ICKW reports grants from Amgen, Bristol-Myers Squibb, Pfizer, Janssen, Bayer, GSK and Novartis, the Hong Kong RGC, and the Hong Kong Health and Medical Research Fund, National Institute for Health Research in England, European Commission, and National Health and Medical Research Council in Australia, consulting fees from IQVIA, payment for expert testimony and a role as an independent non-executive director of Jacobson Medical, Hong Kong, outside of the submitted work. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Cannabinoids, notably cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), have emerged as promising candidates for anxiety disorder treatment, supported by both preclinical and clinical evidence. CBD exhibits notable anxiolytic effects with a favourable safety profile, though concerns regarding mild side effects and drug interactions remain. Conversely, THC, the primary psychoactive compound, presents a range of side effects, underscoring the importance of careful dosage management and individualized treatment strategies. So far there are no FDA approved cannabinoid medications for anxiety. The review highlights challenges in cannabinoid research, including dosage variability, variable preclinical data, and limited long-term data. Despite these limitations, cannabinoids represent a promising avenue for anxiety management, with the potential for further optimization in formulation, dosing protocols, and consideration of interactions with conventional therapies. Addressing these challenges could pave the way for novel and personalized approaches to treating anxiety disorders using cannabinoid-based therapies., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Blinding is thought to minimise expectancy effects and biases in double-blind randomised-controlled trials (RCTs). However, whether blinding integrity should be assessed and reported remains debated. Furthermore, it is unknown whether blinding failure influences the outcome of RCTs in anxiety disorders. We carried out a systematic review to understand whether blinding integrity is assessed and reported in anxiolytic RCTs. A secondary aim was to explore whether blinding integrity is associated with treatment efficacy., Method: Our protocol was pre-registered (PROSPERO CRD42022328750). We searched electronic databases for placebo-controlled, randomised trials of medication in adults with generalised and social anxiety disorders, and in panic disorder, from 1980. We extracted data regarding blinding integrity and treatment efficacy. Risk of bias was assessed with the Cochrane risk of bias tool. Where possible, we subsequently calculated Bang's Blinding Index, and assessed the association between blinding integrity and treatment effect size., Results: Of the 247 RCTs that met inclusion criteria, we were able to obtain assessments of blinding integrity from nine (3.64%). Overall, blinding failed in five of these trials (55.56%), but blinding was intact in 80% of placebo arms. We found a significant association between reduced blinding integrity among assessors and increased treatment effect size (betas < -1.30, p's < 0.001), but this analysis involved only four studies of which two were outlying studies. In patients, we saw a non-significant trend where reduced blinding integrity in the placebo groups was associated with increased treatment efficacy, which was not present in active medication arms. [Correction added on 19 August 2024, after first online publication: Results of the RCTs and its assessment of blinding integrity have been updated.] CONCLUSION: Consistent with work in other psychiatric disorders, blinding integrity is rarely reported in anxiolytic RCTs. Where it is reported, blinding appears to often fail. We found signals that suggest unblinding of clinician assessors (driven by two studies with complete unblinding), and of patients in placebo arms, might be associated with larger treatment effect sizes. We recommend that data regarding blinding integrity, along with the reasons patients and assessors offer for their beliefs regarding group allocation, are systematically collected in RCTs of anxiolytic treatment., (© 2024 The Author(s). Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Anxiety disorders are prevalent chronic psychological disease with complex pathogenic mechanisms. Current anxiolytics have limited efficacy and numerous side effects in many anxiety patients, highlighting the urgent need for new therapies. Recent research has been focusing on nutritional supplements, particularly amino acids, as potential therapies for anxiety disorders. Among these, L-Cysteine plays a crucial role in various biological processes. L-Cysteine exhibits antioxidant properties that can enhance the antioxidant functions of the central nervous system (CNS). Furthermore, metabolites of L-cysteine, such as glutathione and hydrogen sulfide have been shown to alleviate anxiety through distinct molecular mechanisms. Long-term administration of L-Cysteine has anxiolytic, antidepressant, and memory-improving effects. L-Cysteine depletion can lead to increased oxidative stress in the brain. This review delves into the potential mechanisms of L-Cysteine and its main products, glutathione (GSH) and hydrogen sulfide (H2S) in the management of anxiety and related diseases., (Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)

Background: Anxiety and depression cause major detriment to the patient, family, and society - particularly in treatment-resistant (TR) cases, which are highly prevalent. TR prevalence may be due to current diagnoses being based not on biological measures but on symptom lists that suffer from clinical subjectivity, variation in symptom presentation, and comorbidity., Aims: Goal-conflict-specific rhythmicity (GCSR) measured using the Stop-Signal Task (SST) may provide the first neural biomarker for an anxiety process and disorder. This GCSR has been validated with selective drugs for anxiety. So, we proposed that GCSR could differ between TR and non-TR individuals and do so differently between those diagnoses normally sensitive to selective anxiolytics and those not., Methods: We recorded electroencephalograms (EEG) from 20 TR participants (4 GAD, 5 SAD and 11 MDD) and 24 non-TR participants (4 GAD, 5 SAD and 15 Comorbid GAD/MDD (GMD)) while they performed the SST., Results: There was significant positive GCSR in all groups except the GAD-TR group. GAD-TR lacked GCSR in the low-frequency range. However, TR had little effect in SAD or MDD/GMD populations with apparent increases not decreases., Conclusions: Overall, these results suggest that GAD may occur in two forms: one resulting from excessive GCSR and so being drug sensitive, and the other resulting from some other mechanism and so being TR. In SAD and MDD groups, heightened GCSR could be a consequence rather than the cause, driven by mechanisms that are normally more sensitive to non-selective panicolytic antidepressants., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: Dr Glue has a contract with Douglas Pharmaceuticals to develop novel ketamine formulations. No other authors have disclosures.

Abstract: Anxiety comorbidity in bipolar disorder (BD) is important and thus significantly affects the course of BD and its outcomes. The treatment of generalized anxiety disorder comorbid with BD involves certain challenges, as antidepressant medications, which are standard in the treatment of anxiety disorder, have the risk of shifting to manic episodes and rapid cycling. In this case report, the response to agomelatine treatment in generalized anxiety disorder comorbid with bipolar 1 disorder was evaluated., Competing Interests: Conflicts of Interest and Source of Funding: The authors have no conflicts of interest to declare., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Cannabidiol (CBD), as one of the phytocannabinoids, has a wide range of therapeutic properties for various neuropsychiatric disorders due to central nervous system effects. These therapeutic properties demonstrated by preclinical and clinical studies encompass more than just anticonvulsant, anti-arthritic, analgesic, anti-inflammatory, antioxidant, antitumor, antiemetic, antipsychotic and neuroprotective effects. It has been hypothesized that CBD holds potential in the treatment of various neuropsychiatric and anxiety disorders. Thus, PRISMA was used as a guide for our systematic review. Eight of the 1550 articles screened in June 2023 were eligible for meta-analysis. Based on the 316 participants included in these eight articles, this meta-analysis revealed a substantial significant impact of CBD on anxiety with a considerable effect size (Hedges' g = -0.92, 95% CI -1.80 to -0.04). In addition, this meta-analysis focuses on the efficacy of CBD in treating anxiety disorders such as generalized anxiety disorder (GAD), social anxiety disorder (SAD), and post-traumatic stress disorder (PTSD). However, caution should be exercised in interpreting our findings due to the limited size of the clinical sample, and additional trials ought to be carried out if deemed necessary., 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 article., (Copyright © 2024. Published by Elsevier B.V.)

Background: Anxiety disorders are a major public health burden with limited treatment options., Aims: We investigated the long-term safety and efficacy of lysergic acid diethylamide (LSD)-assisted therapy in patients with anxiety with or without life-threatening illness., Method: This study was an a priori -planned long-term follow-up of an investigator-initiated, two-centre trial that used a double-blind, placebo-controlled, two-period, random-order, crossover design with two sessions with either oral LSD (200 μg) or placebo per period. Participants ( n = 39) were followed up 1 year after the end-of-study visit to assess symptoms of anxiety, depression and long-term effects of psychedelics using Spielberger's State-Trait Anxiety Inventory-Global (STAI-G), the Beck Depression Inventory (BDI), the Persisting Effects Questionnaire and measures of personality traits using the NEO - Five-Factor Inventory., Results: Participants reported a sustained reduction of STAI-G scores compared with baseline (least square means (95% CI) = -21.6 (-32.7, -10.4), d = 1.04, P < 0.001, for those who received LSD in the first period (94 weeks after the last LSD treatment) and -16.5 (-26.2, -6.8), d = 1.02, P < 0.05, for those who received LSD in the second period (68 weeks after the last LSD treatment)). Similar effects were observed for comorbid depression with change from baseline BDI scores of -8.1 (-13.2, -3.1), d = 0.71, P < 0.01, and -8.9 (-12.9, -4.9), d = 1.21, P < 0.01, for the LSD-first and placebo-first groups, respectively. Personality trait neuroticism decreased ( P < 0.0001) and trait extraversion increased ( P < 0.01) compared with study inclusion. Individuals attributed positive long-term effects to the psychedelic experience., Conclusions: Patients reported sustained long-term effects of LSD-assisted therapy for anxiety.

Anxiety disorders are chronic, disabling psychiatric disorders, and there is a growing medical need for the development of novel pharmacotherapeutic agents showing improved efficacy and an improved side effect profile as compared with the currently prescribed anxiolytic drugs. In the course of the search for next-generation anxiolytics, neuropeptide receptors have garnered interest as potential therapeutic targets, underscored by pivotal roles in modulating stress responses and findings from animal studies using pharmacological tools. Among these neuropeptide receptors, the type 1 receptor for melanin-concentrating hormone (MCH1), which has been demonstrated to be involved in an array of physiological processes, including the regulation of stress responses and affective states, has gained attraction as a therapeutic target for drugs used in the treatment of psychiatric disorders, including anxiety disorders. To date, a plethora of MCH1 antagonists have been synthesized, and studies using MCH1 antagonists and genetically manipulated mice lacking MCH1 have revealed that the blockade of MCH1 produces anxiolytic-like effects across diverse rodent paradigms. In addition, MCH1 antagonists have been demonstrated to show a rapid onset of antidepressant-like effects; therefore, they may be effective for conditions commonly encountered in patients with anxiety disorders, which is an advantage for anxiolytic drugs. Notably, MCH1 antagonists have not manifested the undesirable side effects observed with the currently prescribed anxiolytics. All these preclinical findings testify to the potential of MCH1 antagonists as novel anxiolytics. Although there are still issues that need to be resolved prior to the initiation of clinical trials, such as elucidating the precise neuronal mechanisms underlying their anxiolytic effects and exploring pertinent biomarkers that can be used in clinical trials, MCH1 blockade appears to be an attractive way to tackle anxiety disorders., (Copyright © 2024 Elsevier Inc. All rights reserved.)

While vulvar lichen sclerosus (VLS) causes intense pruritus, associated risks of mood disorders and prescription patterns and impact of concurrent sexual dysfunction are unknown. We queried TriNetX Diamond Network between 2009 and 2022, conducting three comparisons after propensity-score matching for demographics and relevant comorbidities: (1) women with lichen sclerosus (LS) sparing the vulva vs. women with VLS; (2) VLS patients who received treatment within 6 months of diagnosis vs. patients who did not and (3) VLS patients with vs. without sexual dysfunction. Outcomes included new depressive episodes, anxiety disorder, major depressive disorder (MDD), and prescriptions of antidepressants or benzodiazepines. After matching, VLS was associated with increased depressive episode [risk ratio (RR) 1.39], anxiety disorder (RR 1.93), and MDD (RR 2.00) diagnoses compared to LS sparing the vulva. Next, VLS treatment was associated with decreased risk of depressive episode (RR 0.60) and anxiety disorder (RR 0.72). Finally, concurrent sexual dysfunction was associated with increased benzodiazepine (RR 3.50), vaginal estrogen (RR 6.20), antipruritic agents (RR 3.90), and topical anti-inflammatory (RR 2.61) prescriptions. In conclusion, vulvar involvement is associated with increased risk of antidepressant and benzodiazepine prescriptions, and diagnosis of depressive episode, anxiety disorder, or MDD., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: Recovery from a COVID-19 infection can lead to post-COVID-19 condition (PCC), which causes a multitude of debilitating symptoms that negatively affect an individual's health-related quality of life, including depressive and anxiety symptoms. We aim to examine the mediatory effects of anxiety on depressive symptoms in persons with PCC receiving vortioxetine., Methods: We performed a post-hoc analysis of a randomized, double-blinded, placebo-controlled clinical trial investigating vortioxetine treatment on cognitive functioning in persons with PCC. Anxiety and depressive symptoms were measured by the 7-Item Generalized Anxiety Disorder (GAD-7) Scale and the 16-Item Quick Inventory of Depressive Symptomatology (QIDS-SR-16), respectively., Results: Based on data of 147 participants, GAD-7 scores were significantly positively associated with QIDS-SR-16 scores (β=0.038, 95 % CI [0.029,0.047], p < 0.001). After adjusting for covariates, a significant group (χ 2 =176.786, p < 0.001), time (χ 2 =8.914, p = 0.003), and treatment x time x GAD-7 score interaction (χ 2 =236.483, p < 0.001) effect was observed. Vortioxetine-treated participants had a significant difference in overall change in depressive symptoms (mean difference=-3.15, SEM=0.642, 95 % CI [-4.40,-1.89], p < 0.001)., Conclusion: Anxiety symptoms were significantly associated with depressive symptoms in persons with PCC. Antidepressant efficacy on ameliorating depressive symptoms is dependent on improving anxiety symptoms, underscoring significant implications in improving treatment efficacy and patient quality of life., Competing Interests: Declaration of competing interest Dr. Roger S. McIntyre has received research grant support from CIHR, GACD, National Natural Science Foundation of China (NSFC), and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. Dr. Roger McIntyre is a CEO of Braxia Scientific Corp. Dr. Taeho Greg Rhee was supported in part by the National Institute on Aging (NIA) (#R21AG070666; R21AG078972), National Institute of Mental Health (#R21MH117438), National Institute on Drug Abuse (#R21DA057540) and Institute for Collaboration on Health, Intervention, and Policy (InCHIP) of the University of Connecticut. Dr. Rhee serves as a review committee member for Patient-Centered Outcomes Research Institute (PCORI) and Substance Abuse and Mental Health Services Administration (SAMHSA) and has received honoraria payments from PCORI and SAMHSA. Dr. Rhee has also served as a stakeholder/consultant for PCORI and received consulting fees from PCORI. Dr. Rhee serves as an advisory committee member for International Alliance of Mental Health Research Funders (IAMHRF). Dr. Rhee is currently a co-Editor-in-Chief of Mental Health Science and has received honorarium payments annually from the publisher, John Wiley & Sons, Inc. Dr. Roger Ho has received funding from the National University of Singapore iHeathtech Other Operating Expenses (A-0001415-09-00)., (Copyright © 2024 Elsevier B.V. All rights reserved.)

For more than 20 years, the mainstay of pharmacologic treatment for depression and anxiety disorders has been serotonin reuptake inhibitors and selective serotonin and norepinephrine reuptake inhibitors. There are newer medications, many with novel mechanisms of action, that have come to market; however, first-line treatments remain the same. There are now more robust data on the use of various augmentation agents in the treatment of major depressive disorder providing better recommendations for use by the primary care provider. Data to support the use of psychedelic-assisted psychotherapy in the treatment of mood and anxiety disorders are not robust enough to recommend generalized use at this time., Competing Interests: Disclosure Neither Dr J. Markman nor Dr H. Combs have any financial conflicts of interest or funding sources to declare., (Published by Elsevier Inc.)

Background : Understanding how development influences medication and placebo responses in anxiety disorders could inform treatment decisions, including age-specific first- versus second-line psychopharmacological interventions. Objective : To meta-analytically compare the trajectory of selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and placebo response in youth and adults with anxiety disorders. Methods : Weekly symptom severity data were extracted from prospective, randomized, parallel-group, placebo-controlled trials of SSRIs and SNRIs in children, adolescents, and adults with anxiety disorders (generalized, separation, and social anxiety disorders as well as panic disorder). Treatment response was modeled for the standardized change in continuous measures of anxiety using a Bayesian hierarchical model. Change in symptom severity was evaluated as a function of time, and post hoc analyses were conducted to determine the sensitivity of these results across sample heterogeneity and alternative functional forms. Results : Data were included from 11 trials of youth (SSRI, κ = 7; SNRI, κ = 4) and 71 studies of adults (SSRI, κ = 46; SNRI, κ = 25). In total, 1067 youth participated in SSRI trials and 1024 in SNRI trials. In total, 10,826 adults participated in SSRI trials (placebo, n = 5367; SSRI n = 5,459) and 6232 in SNRI trials (placebo, n = 3,128; SNRI n = 3,094). A logarithmic model best described the response. Placebo response was similar in youth and adults (mean difference = -1.98 ± 6.21, 95% credible interval [CrI]: -10.2 to 14.2, p = 0.750), and statistically significant improvement from baseline emerged by week 2 in both adults (mean difference: -18.34 + 1.017, 95% CrI: -20.3 to 16.3, p < 0.001) and youth (mean difference: -23.74 + 3.736, 95% CrI: -31.1 to -16.4, p < 0.001). SSRIs produced similar improvements for youth and adults ( p = 0.129), but SNRIs produced slower improvement in youth than adults ( p = 0.018). Conclusions : Antidepressant-related improvement occurs early in youth and adults with anxiety disorders. SSRI response is similar in adults and youth; however, SNRIs produce greater responses in adults than youth, potentially representing a developmental effect.

Most cases of anxiety are currently treated with either benzodiazepines or serotonin reuptake inhibitors. These drugs carry with them risks for a multitude of side effects, and patient compliance suffers for this reason. There is thus a need for novel anxiolytics, and among the most compelling prospects in this vein is the study of the TAARs. The anxiolytic potential of ulotaront, a full agonist at the human TAAR1, is currently being investigated in patients with generalized anxiety disorder. Irrespective of whether this compound succeeds in clinical trials, a growing body of preclinical literature underscores the relevance of modulating the TAARs in anxiety. Multiple behavioral paradigms show anxiolytic-like effects in rodents, possibly due to increased neurogenesis and plasticity, in addition to a panoply of interactions between the TAARs and other systems. Crucially, multiple lines of evidence suggest that the TAARs, particularly TAAR1, TAAR2, and TAAR5, are expressed in the extended amygdala and hippocampus. These regions are central in the actuation of anxiety, and are particularly susceptible to neurogenic and neuroplastic effects which the TAARs are now known to regulate. The TAARs also regulate the dopamine and serotonin systems, both of which are implicated in anxiety. Ligands of the TAARs may thus constitute a new class of anxiolytics., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Beta-blocker prescriptions for patients with anxiety increased substantially between 2003 and 2018, yet there is no clinical guidance concerning their use. A previous review of propranolol - a beta-blocker - in the treatment of anxiety concluded there was insufficient evidence to support its use. Additional data have been published in the eight years since that review including some evidence for other beta-blockers. We aimed to synthesise all available data on the effectiveness of beta-blockers in the treatment of anxiety disorders in adults., Methods: We searched Medline, Embase, PsycINFO, Web of Science, and Trial Registries (September 2023), including randomised controlled trials (RCT), non-randomised control group comparative studies and cross-over trials reporting self- or clinician-reported anxiety symptoms. Study quality was assessed using Cochrane's Risk of Bias tool, with meta-analyses conducted by comparator group using random-effects models., Results: Searches produced 3068 records, with 10 studies included, of which five were included in meta-analyses (n = 179). There was no evidence for a beneficial effect of beta-blockers compared with either placebo or benzodiazepines in patients with social phobia or panic disorder with/without agoraphobia (p-value for all meta-analyses ≥0.54)., Limitations: Many of the included studies had small sample sizes, missing data and high or unclear risk of bias., Conclusion: Beta-blockers are increasingly prescribed for anxiety, yet there is a lack of robust evidence of effectiveness. There is a need to understand when and why practitioners are using these drugs, and to undertake a large RCT to provide definitive evidence of whether beta-blockers are an effective and safe treatment for anxiety., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Importance: Currently, 30-50 % of individuals with depression and 40 % with anxiety-collectively referred to as common mental disorders (CMDs), exhibit inadequate responses to antidepressant treatments., Objective: To assess the effectiveness and safety of drug-metabolizing enzyme pharmacogenetic variation informed treatment (PGxIT) versus usual antidepressant treatment (UT) in patients with CMDs., Data Sources: A literature search was conducted in the MEDLINE, Scopus, and Cochrane Library databases from inception until January 30, 2024., Study Selection: Studies were selected based on CMD diagnoses, reporting on the genetic variations of drug-metabolizing enzyme (DME) genes in relation to antidepressants, involving PGxIT and UT groups with human subjects, and published in English., Data Extraction and Synthesis: Data extraction and quality assessment were performed independently by two authors. A pooled risk ratio (RR) with 95 % CI was estimated using both random and fixed-effect models, and heterogeneity was assessed using Cochran's Q test and the I 2 statistic. The publication bias of eligible studies was assessed using post hoc Doi plots and the LFK index., Results: This systematic review included 18 studies (n = 7021). The PGxIT demonstrated greater efficacy in the remission of symptoms of depressive disorder at 8 weeks (RR 1.523 [95 % CI: 1.255-1.843]; I 2  = 48 %) and 12 weeks (RR 1.631 [95 % CI: 1.001-2.657]; I 2  = 86 %; p < 0.01), and symptoms of anxiety disorder compared to UT. Additionally, the risk of adverse drug events (ADEs) was significantly lower in the PGxIT group (RR = 0.65 [95 % CI: 0.52-0.82]; I 2  = 0 %) than in the UT group. The certainty of evidence for both outcomes was moderate., Conclusions and Relevance: This systematic review and meta-analysis suggest that pharmacogenetically guided antidepressant treatment, based on genetic variation in drug-metabolizing enzymes, is associated with superior efficacy in the remission of symptoms for patients with depressive disorders and a reduction in ADEs compared to usual treatment and the findings of the systematic review for remission in anxiety disorders indicate that, PGx guided treatment is also associated with increased remission of symptoms in anxiety disorders compared to usual treatment., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Anxiety disorders are common in children and adolescents, with many youths experiencing functional impairment in multiple domains because of these conditions. Biologic and cognitive-behavioral models provide a basis for the development and maintenance of these disorders. Cognitive behavioral therapy (CBT) with exposures and selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors are empirically supported treatments for childhood anxiety disorders. Exposures are a key component of CBT treatment and a case vignette demonstrates how to tailor exposures to the unique fears of the child., Competing Interests: Disclosure J.T. Stiede and K.H. Mangen have no disclosures to report. E.A. Storch reports receiving research funding to his institution from the REAM Foundation, United States, International OCD Foundation, United States, and NIH, United States. He was a consultant for Brainsway and Biohaven Pharmaceuticals in the past 12 months. He owns stock less than $5000 in NView. He receives book royalties from Elsevier, Wiley, Oxford, American Psychological Association, Guildford, Springer, and Jessica Kingsley., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Anxiety disorders are the most common psychiatric illness and include disorders such as generalized anxiety disorder (GAD), panic disorder (PD), and social anxiety disorder (SAD). Psychotherapy and pharmacotherapy are both effective treatments for anxiety disorders, with efficacy between 60% and 85%. Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors are first-line pharmacologic treatment for GAD, PD, and SAD. Recommendations for treating pediatric and geriatric populations vary slightly, but first-line treatments remain the same. Recent advancements in the treatment of anxiety disorders are limited although research has discovered novel pathways, which may lead to additional treatment options in the future., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Anxiety and depression are common comorbidities in idiopathic pulmonary fibrosis (IPF) that impair health-related quality of life. However, there is a lack of studies focusing on the mental disorder of IPF after antifibrotic treatment and their related predictive factors., Methods: Patients with an initial diagnosis of IPF were enrolled. Data on demographics, lung function, Generalized Anxiety Disorder-7 (GAD-7) Scale, Patient Health Questionnaire 9 (PHQ-9), Patient Health Questionnaire-15 (PHQ-15), and St. George's Respiratory Questionnaire total score(SGRQ-T) were collected. Changes in anxiety, depression, somatic symptoms, and quality of life scores before and after nintedanib treatment were compared, and the related predictive factors were analyzed., Results: A total of 56 patients with a first diagnosis of IPF were enrolled, with 42 and 35 patients suffering from anxiety and depression, respectively. The GAD-7, PHQ-9, PHQ-15, and SGRQ scores were higher in the anxiety and depression groups. SGRQ total score (SGRQ-T) [OR = 1.075, 95%CI= (1.011, 1.142)] was an independent predictor of IPF combined with anxiety ( p  < 0.05); SGRQ-T [OR = 1.080, 95%CI= (1.001, 1.167)] was also an independent predictor of IPF combined with depression ( p  < 0.05). After treatment, GAD-7, PHQ-9, PHQ-15, and SGRQ scores decreased ( p  < 0.05). ΔSGRQ-T significantly affected ΔGAD-7 (β = 0.376, p  = 0.009) and ΔPHQ-9 (β = 0.329, p  = 0.022)., Conclusion: Anxiety and depression in IPF patients are closely related to somatic symptoms, pulmonary function, and quality of life. The SGRQ-T score is of great value for assessing anxiety and depression in patients with IPF. Short-term treatment with nintedanib antifibrotic therapy can alleviate anxiety and depression in IPF patients.

The medicinal properties of resveratrol have garnered increasing attention from researchers. Extensive data have been accumulated on its use in treating cardiovascular diseases, immune system disorders, cancer, neurological diseases, and behavioral disorders. The protective mechanisms of resveratrol, particularly in anxiety-related stress disorders, have been well documented. However, less attention has been given to the side effects of resveratrol. This review explores not only the mechanisms underlying the anxiolytic effects of resveratrol but also the mechanisms that may lead to increased anxiety following resveratrol treatment. Understanding these mechanisms is crucial for enhancing the efficacy of resveratrol in managing anxiety disorders associated with stress and PTSD.

Abstract: Previous studies have found that anxiety disorders may increase the incidence of atrial fibrillation (AF). More and more studies have shown that α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are involved in the occurrence and development of cardiovascular diseases. However, the role of AMPARs in AF associated with anxiety disorder remains unclear. The aim of this study was to investigate the effect of AMPARs on AF susceptibility in rats with anxiety disorder and its possible mechanism. The anxiety disorder rat model was established by unpredictable empty bottle stimulation and was treated with AMPARs agonist and antagonist. Our results showed that AMPARs antagonist treatment significantly reduced sympathetic activity, improved heart rate variability, shortened action potential duration, prolonged effective refractory period, reduced AF induction rate, and improved cardiac electrical remodeling and the expression of inflammatory factors. In addition, inhibition of AMPARs reduced the phosphorylation of IκBα and p65. Our experimental results suggest that inhibition of AMPARs can reduce autonomic remodeling, improve atrial electrical remodeling, and suppress myocardial inflammation, which provides a potential therapeutic strategy for the treatment of AF associated with anxiety disorder., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Anxiety disorders constitute a spectrum of psychological conditions affecting millions of individuals worldwide, imposing a significant health burden. Historically, the development of anxiolytic medications has been largely focused on neurotransmitter function and modulation. However, in recent years, neurolipids emerged as a prime target for understanding psychiatric pathogenesis and developing novel medications. Neurolipids influence various neural activities such as neurotransmission and cellular functioning, as well as maintaining cell membrane integrity. Therefore, this review aims to elucidate the alterations in neurolipids associated with an anxious mental state and explore their potential as targets of novel anxiolytic medications. Existing evidence tentatively associates dysregulated neurolipid levels with the etiopathology of anxiety disorders. Notably, preclinical investigations suggest that several neurolipids, including endocannabinoids and polyunsaturated fatty acids, may hold promise as potential pharmacological targets. Overall, the current literature tentatively suggests the involvement of lipids in the pathogenesis of anxiety disorders, hinting at potential prospects for future pharmacological interventions., Competing Interests: Disclosure statement During the preparation of this work, the authors used ChatGPT to refine the flow and structure of some sentences. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: I declare grants or research support for the National Pregnancy Registry of Psychiatric Medications from Alkermes, Dr Reddy's Laboratories, Eisai, Otsuka America Pharmaceutical, Supernus Pharmaceuticals, and Teva Pharmaceutical Industries; and acting as a consultant for Up-to-Date.

Psychiatric disorders cause long-lasting disabilities across different age groups. While various medications are available for mental disorders, some patients do not fully benefit from them or experience treatment resistance. The pathogenesis of psychiatric disorders involves multiple mechanisms, including an increase in the inflammatory response. Targeting inflammatory mechanisms has shown promise as a therapeutic approach for these disorders. Curcumin, known for its anti-inflammatory properties and potential neuroprotective effects, has been the subject of studies investigating its potential as a treatment option for psychiatric disorders. This review comprehensively examines the potential therapeutic role of curcumin and its nanoformulations in psychiatric conditions, including major depressive disorder (MDD), bipolar disorder, schizophrenia, and anxiety disorders. There is lack of robust clinical trials across all the studied psychiatric disorders, particularly bipolar disorder and schizophrenia. More studies have focused on MDD. Studies on depression indicate that curcumin may be effective as an antidepressant agent, either alone or as an adjunct therapy. However, inconsistencies exist among study findings, highlighting the need for further research with improved blinding, optimized dosages, and treatment durations. Limited evidence supports the use of curcumin for bipolar disorder, making its therapeutic application challenging. Well-designed clinical trials are warranted to explore its potential therapeutic benefits. Exploring various formulations and delivery strategies, such as utilizing liposomes and nanoparticles, presents intriguing avenues for future research. More extensive clinical trials are needed to assess the efficacy of curcumin as a standalone or adjunctive treatment for psychiatric disorders, focusing on optimal dosages, formulations, and treatment durations., (© 2024 John Wiley & Sons Ltd.)

Background and Aim: Curcumin is a polyphenolic natural compound that has been used to treat various ailments such as symptoms of anxiety. However, the findings of studies regarding the anti-anxiety properties of curcumin are controversial. This review aims to evaluate if there are clinical benefits of curcumin in patients with symptoms of anxiety., Methods: PubMed, Embase, Web of Science, and the Cochrane Library were retrieved to collect randomized controlled trials (RCTs) from the database inception to August 16, 2023. The random-effects model was used to estimate the standard mean difference (SMD)., Results: A total of eight RCTs involving 567 participants were included in the analysis. A pooled analysis showed a significant effect of curcumin on anxiety symptoms (SMD: -1.56; 95% CI: -2.48, -0.64, p < 0.001; I 2  = 95.6%, p-heterogeneity< 0.001)., Conclusion: Present meta-analysis demonstrated that curcumin intake might contribute to alleviation of anxiety disorder. Due to the limited number of studies included, it is necessary to conduct more high-quality studies to confirm the clinical efficacy of curcumin., Competing Interests: Declaration of competing interest None., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Obesity impacts mental health greatly. Psychological factors may influence the effectiveness of its treatment. This study aimed to compare symptoms of generalised anxiety disorder and depression among adult women across different weight categories. The study sample comprised 1105 adult women. The computer-assisted web interview (CAWI) utilising the seven-item Generalised Anxiety Disorders Scale (GAD-7) and the nine-item Patient Health Questionnaire (PHQ-9) was used. Both GAD-7 and PHQ-9 scores correlated positively with BMI (r = 0.121, p < 0.001 and r = 0.173, p < 0.001, respectively) and negatively with age (r = -0.106, p < 0.001 and r = -0.103, p < 0.001, respectively). Patients undergoing treatment with semaglutide scored lower for both anxiety symptoms (8.71 ± 6.16, p = 0.013) and depression symptoms (9.76 ± 6.37, p = 0.013). Women who underwent bariatric surgery screened less frequently for anxiety (8.03 ± 6.27, p = 0.002) but not for depression. An interdisciplinary approach involving mental health professionals within the therapeutic team can comprehensively address factors contributing to obesity development and treatment outcomes. Further investigation of semaglutide's use is needed due to the promising evidence suggesting a positive effect on decreasing the severity of depression and anxiety symptoms to assess the direct or indirect character of this influence.

Chaihu-jia-Longgu-Muli decoction (CLMD) has been proven clinically effective in treating vertigo with anxiety disorder. However, the mechanism is not clear. This study aimed to explore the mechanism of CLMD in treating vertigo with anxiety disorder based on ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry (UPLC-Q-TOF/MS) and network pharmacology. UPLC-Q-TOF/MS was performed to identify the compounds in blood and the targets of compounds of CLMD in vertigo and anxiety were searched using databases. A protein-protein interaction network was built to screen the core targets. The core targets were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. In addition, the vertigo with anxiety rat model was used to verify the results. A total of 22 compounds were absorbed into the blood. Eighty-one potential targets associated with CLMD for vertigo with anxiety disorder were identified through network pharmacological analysis. Subsequently, GO and KEGG analysis showed that CLMD treatment for vertigo with anxiety disorder is associated with neurotransmitter levels and other pertinent physiological processes. The results of the animal experiments showed that CLMD decreased the levels of serotonin, norepinephrine and dopamine, alleviating the symptoms of vertigo and anxiety disorder in model rats. The study revealed CLMD could alleviate vertigo and anxiety symptoms through reducing the levels of neurotransmitters., (© 2024 John Wiley & Sons Ltd.)

Positive leadership behaviours at work are associated with worker well-being and performance. However there is less knowledge about whether exposure to low levels of positive leadership behaviours increase workers' risk of clinical mental disorders. We investigated whether low levels of positive leadership behaviours are prospectively associated with risk of treatment for depressive and anxiety disorders. In a cohort study, we linked survey data from 59,743 respondents from the Work Environment and Health in Denmark survey with national health register data. Leadership behaviours were measured with an eight-item scale. Treatment was defined as redeemed prescription for antidepressants or anxiolytics or hospital treatment for depression or anxiety. Using Cox proportional hazard regression, adjusting for demographic variables, job type and sector, adverse life events and childhood adversities, we estimated the association between leadership behaviours at baseline and risk of treatment during follow-up. We identified 999 cases of depression and anxiety treatment during follow-up. Compared to high levels of leadership behaviours, exposure to medium low and low levels were associated with an increased risk of treatment after adjustment for covariates. The results suggest that low levels of positive leadership behaviours are associated with an increased risk of treatment for depressive or anxiety disorders., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

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: Benzodiazepines and antidepressants are effective agents for the treatment of generalized anxiety disorder (GAD), with the HAM-A frequently used as a primary outcome measure. The GAD literature is inconsistent regarding which medications are more effective for somatic versus psychic symptoms of GAD, and treatment guidelines do not advocate for prescribing based on subtype. This meta-analysis aimed to determine whether benzodiazepines and antidepressants have a differential impact on the somatic versus psychic subscales of the HAM-A in GAD., Methods: An electronic search was undertaken for randomized controlled trials of either benzodiazepines or antidepressants for GAD that reported treatment response using the HAM-A subscales. Data were extracted by independent reviewers. A random effects assessment of weighted mean difference with 95% confidence intervals and subgroup difference was applied. All analysis was done on SPSS 26. An assessment of bias, and of quality of evidence was performed., Results: 24 randomized controlled trials met the inclusion criteria: 18 antidepressant trials, 5 benzodiazepine trials and 1 of both. 14 studies were assessed as having between some and high risk of bias, while 10 were assessed as having low risk of bias. Benzodiazepines (WMD of 1.81 [CI 1.03, 2.58]) were significantly more effective than antidepressants (WMD of 0.83 [CI 0.64, 1.02]) for reducing somatic symptoms of GAD (Chi 2  = 5.81, p = 0.02), and were also more effective (WMD of 2.46 [CI 1.83, 3.09]) in reducing psychic symptoms than antidepressants (WMD of 1.83 [CI 1.55, 2.10]), although this comparison did not reach statistical significance (Chi 2  = 3.31, p = 0.07)., Conclusion: The finding that benzodiazepines were significantly more effective than antidepressants for somatic symptoms needs to be weighed up against potential benefits of antidepressants over benzodiazepines. It may be useful for future treatment guidelines for GAD to explicitly consider symptom subtype., (Copyright © 2024. Published by Elsevier Inc.)

Anxiety disorders in children and adolescents often present in primary care, and many clinicians will need to guide families on treatment. The purpose of this article is to give a brief overview of assessment and treatment principles for clinicians in primary care. Anxiety and its expression are heavily influenced by children's developmental progression and capabilities. Anxiety disorders have multiple underlying etiologies including temperament, environmental exposure to stressors, and childhood trauma. All anxiety disorders are strengthened by an operant process known as escape conditioning. The most effective treatments for child and adolescent anxiety begin with behavioral-based interventions including exposure with response prevention (ERP) and cognitive behavioral therapy (CBT). Medication can be effective in combination with CBT and ERP, or as a standalone treatment when behavioral interventions are not available. Selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors have been evaluated by randomized clinical trials for the treatment of childhood anxiety, but most are not approved by the Food and Drug Administration. When anxiety is severe and functional impairment is high, referral for psychiatric care and multimodal treatment reduces the likelihood of poor outcomes.

Background/objectives: There is uncertainty about the optimum dose of omega-3 fatty acids for anxiety symptoms. We aimed to find the dose-dependent effect of omega-3 supplementation on anxiety symptoms., Methods: We systematically reviewed PubMed, Scopus, and Web of Science until December 2022 to find randomized trials that assessed the effects of omega-3 fatty acids supplementation on anxiety symptoms in adults. Investigators performed the literature search and screened the titles/abstracts and full-texts and between-reviewer agreement was assessed as Cohen's kappa coefficient. We conducted a random-effects dose-response meta-analysis to estimate standardized mean differences (SMD) and 95% confidence intervals (CIs) and assessed the certainty of evidence using the GRADE framework., Results: A total of 23 trials with 2189 participants were included. Each 1 gram per day supplementation with omega-3 fatty acids resulted in a moderate decrease in anxiety symptoms (SMD: -0.70, 95%CI: -1.17, -0.22; GRADE = low). The non-linear dose-response analysis indicated the greatest improvement at 2 g/d (SMD: -0.93, 95%CI: -1.85, -0.01), and that supplementation in a dose lower than 2 g/d did not affect anxiety symptoms. Omega-3 fatty acids did not increase adverse events (odds ratio: 1.20, 95%CI: 0.89, 1.61; GRADE = moderate)., Conclusions: The present dose-response meta-analysis suggested evidence of very low certainty that supplementation with omega-3 fatty acids may significantly improve anxiety symptoms, with the greatest improvements at 2 g/d. More trials with better methodological quality are needed to reach more robust evidence., Protocol Registration: PROSPERO (CRD42022309636)., (© 2024. The Author(s).)

Over the past decade, the idea of targeting the endocannabinoid system to treat anxiety disorders has received increasing attention. Previous studies focused more on developing cannabinoid receptor agonists or supplementing exogenous cannabinoids, which are prone to various adverse effects due to their strong pharmacological activity and poor receptor selectivity, limiting their application in clinical research. Endocannabinoid hydrolase inhibitors are considered to be the most promising development strategies for the treatment of anxiety disorders. More recent efforts have emphasized that inhibition of two major endogenous cannabinoid hydrolases, monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), indirectly activates cannabinoid receptors by increasing endogenous cannabinoid levels in the synaptic gap, circumventing receptor desensitization resulting from direct enhancement of endogenous cannabinoid signaling. In this review, we comprehensively summarize the anxiolytic effects of MAGL and FAAH inhibitors and their potential pharmacological mechanisms, highlight reported novel inhibitors or natural products, and provide an outlook on future directions in this field., Competing Interests: The authors declare no conflicts of interest in this work., (© 2024 Zhao et al.)

Successful therapy of mental disorders is very important in view of the high level of suffering of those affected. Since established pharmaceutical and psychotherapeutic approaches do not lead to the desired improvement in all cases, complementary or alternative treatment methods are intensively researched. Psilocybin-assisted psychotherapy seems particularly promising, and has been approved in the USA for larger clinical trials. Psilocybin belongs to the group of psychedelics and influences psychological experiences. In assisted therapy, psilocybin is administered in controlled doses under medical supervision to patients with different mental disorders. In the studies conducted so far, longer-term positive effects could be shown after just one or a few doses. In order to provide a better understanding of the potential therapeutic mechanisms, this article will first describe neurobiological and psychological effects of psilocybin. To better assess the potential of psilocybin-assisted psychotherapy for various disorders, clinical studies conducted so far with patients administered psilocybin are reviewed., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: How the trajectory of response to medication (and placebo response) varies among selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), benzodiazepines and across anxiety disorders is unknown., Methods: We performed a meta-analysis using weekly symptom severity data from randomized, parallel-group, placebo-controlled trials of SSRIs, SNRIs, and benzodiazepines in adults with anxiety disorders. Response was modeled for the standardized change in anxiety using Bayesian hierarchical models., Results: Across 122 trials (N=15,760), SSRIs, SNRIs, and benzodiazepines produced significant improvement in anxiety compared to placebo. Benzodiazepines produced faster improvement by the first week of treatment ( p  < 0.001). By week 8, the response for benzodiazepines and SSRIs ( p  = 0.103) and SNRIs ( p  = 0.911) did not differ nor did SSRIs and SNRIs differ ( p  = 0.057), although for patients with generalized anxiety disorder (GAD), the benzodiazepines produced greater improvement than SNRIs at week 8 (difference - 12.42, CrI: -25.05 to -0.78, p  = 0.037). Medication response was similar across anxiety disorders except for benzodiazepines, which produced greater improvement over the first 4 weeks compared to SSRIs and SNRIs in panic disorder. For SSRIs and SNRIs, women improved more than men, and for benzodiazepines, older patients improved more compared to younger patients. Finally, placebo response plateaued by week 4 of treatment, and, at week 8, social anxiety disorder trials had lower placebo response compared to other anxiety disorders., Conclusions: Benzodiazepines show early improvement compared to SSRIs and SNRIs. However, by week 8, all treatments yield similar results. Patient characteristics influence the improvement trajectory and magnitude, suggesting potential for personalized medication selection.

Background: Understanding the impact of CYP2D6 metabolism on paroxetine, a widely used antidepressant, is essential for precision dosing., Methods: We conducted an 8-week, multi-center, single-drug, 2-week wash period prospective cohort study in 921 Chinese Han patients with depressive or anxiety disorders (ChiCTR2000038462). We performed CYP2D6 genotyping (single nucleotide variant and copy number variant) to derive the CYP2D6 activity score and evaluated paroxetine treatment outcomes including steady-state concentration, treatment efficacy, and adverse reaction. CYP2D6 metabolizer status was categorized into poor metabolizers (PMs), intermediate metabolizers (IMs), extensive metabolizers (EMs), and ultrarapid metabolizers (UMs). The influence of CYP2D6 metabolic phenotype on paroxetine treatment outcomes was examined using multiple regression analysis and cross-ethnic meta-analysis. The therapeutic reference range of paroxetine was estimated by receiver operating characteristic (ROC) analyses., Findings: After adjusting for demographic factors, the steady-state concentrations of paroxetine in PMs, IMs, and UMs were 2.50, 1.12, and 0.39 times that of EMs, with PM and UM effects being statistically significant (multiple linear regression, P = 0.03 and P = 0.04). Sex and ethnicity influenced the comparison between IMs and EMs. Moreover, poor efficacy of paroxetine was associated with UM, and a higher risk of developing adverse reactions was associated with lower CYP2D6 activity score. Lastly, cross-ethnic meta-analysis suggested dose adjustments for PMs, IMs, EMs, and UMs in the East Asian population to be 35%, 40%, 143%, and 241% of the manufacturer's recommended dose, and 62%, 68%, 131%, and 159% in the non-East Asian population., Interpretation: Our findings advocate for precision dosing based on the CYP2D6 metabolic phenotype, with sex and ethnicity being crucial considerations in this approach., Funding: National Natural Science Foundation of China; Academy of Medical Sciences Research Unit., Competing Interests: Declaration of interests The PMEDA consortium is funded by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2021-I2M-C&T-B-099) and “the Fundamental Research Funds for the Central Universities” (Peking University Medicine Fund for world's leading discipline or discipline cluster development, BMU2022DJXK007). WY, YL, Yu S, JG, ZK, and YZ disclose that there is a planned and pending patent related to a device for predicting the treatment outcome of paroxetine, which is relevant to the content of this manuscript. Other authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)