Treatment of Anxiety Disorders in Primary Care: What Nurse Practitioners Need to Know.

Anxiety disorders are the most common mental illnesses and frequently co-occur with other mental and somatic symptoms or disorders. Primary care nurse practitioners (NPs) are key in reducing the treatment gap through early identification, treatment, and/or referral to behavioral health providers. Confronting primary care NPs are problems with time constraints, multiple comorbidities, and limited mental health training, particularly in relation to the differences in pharmacokinetic and pharmacodynamic actions of first-line anxiety disorder medications across age groups. The current article provides a brief summary of evidence-based treatment focusing on pharmacotherapy for anxiety disorders in the primary care setting. [Journal of Psychosocial Nursing and Mental Health Services, 62(5), 7-10.].

Toxicity of benzodiazepines in the treatment of insomnia disorders in older adults: a systematic literature review.

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.

Anxiolytic effects of Enterococcus faecalis 2001 on a mouse model of colitis.

Ulcerative colitis (UC) is a refractory inflammatory bowel disease, which is known to cause psychiatric disorders such as anxiety and depression at a high rate in addition to peripheral inflammatory symptoms. However, the pathogenesis of these psychiatric disorders remains mostly unknown. While prior research revealed that the Enterococcus faecalis 2001 (EF-2001) suppressed UC-like symptoms and accompanying depressive-like behaviors, observed in a UC model using dextran sulfate sodium (DSS), whether it has an anxiolytic effect remains unclear. Therefore, we examined whether EF-2001 attenuates DSS-induced anxiety-like behaviors. Treatment with 2% DSS for seven days induced UC-like symptoms and anxiety-like behavior through the hole-board test, increased serum lipopolysaccharide (LPS) and corticosterone concentration, and p-glucocorticoid receptor (GR) in the prefrontal cortex (PFC), and decreased N-methyl-D-aspartate receptor subunit (NR) 2A and NR2B expression levels in the PFC. Interestingly, these changes were reversed by EF-2001 administration. Further, EF-2001 administration enhanced CAMKII/CREB/BDNF-Drebrin pathways in the PFC of DSS-treated mice, and labeling of p-GR, p-CAMKII, and p-CREB showed colocalization with neurons. EF-2001 attenuated anxiety-like behavior by reducing serum LPS and corticosterone levels linked to the improvement of UC symptoms and by facilitating the CAMKII/CREB/BDNF-Drebrin pathways in the PFC. Our findings suggest a close relationship between UC and anxiety.

Management of physical and psychological trauma resulting from motor vehicle crashes in Australian general practice: a mixed-methods approach.

BACKGROUND: In Australia, motor vehicle crashes (MVC)-related health data are available from insurance claims and hospitals but not from primary care settings. This study aimed to identify the frequency of MVC-related consultations in Australian general practices, explore the pharmacological management of health conditions related to those crashes, and investigate general practitioners' (GPs) perceived barriers and enablers in managing these patients. METHODS: Mixed-methods study. The quantitative component explored annual MVC-related consultation rates over seven years, the frequency of chronic pain, depression, anxiety or sleep issues after MVC, and management with opioids, antidepressants, anxiolytics or sedatives in a sample of 1,438,864 patients aged 16 + years attending 402 Australian general practices (MedicineInsight). Subsequently, we used content analysis of 81 GPs' qualitative responses to an online survey that included some of our quantitative findings to explore their experiences and attitudes to managing patients after MVC. RESULTS: MVC-related consultation rates remained stable between 2012 and 2018 at around 9.0 per 10,000 consultations. In 2017/2018 compared to their peers, those experiencing a MVC had a higher frequency of chronic pain (48% vs. 26%), depression/anxiety (20% vs. 13%) and sleep issues (7% vs. 4%). In general, medications were prescribed more after MVC. Opioid prescribing was much higher among patients after MVC than their peers, whether they consulted for chronic pain (23.8% 95%CI 21.6;26.0 vs. 15.2%, 95%CI 14.5;15.8 in 2017/2018, respectively) or not (15.8%, 95%CI 13.9;17.6 vs. 6.7%, 95% CI 6.4;7.0 in 2017/2018). Qualitative analyses identified a lack of guidelines, local referral pathways and decision frameworks as critical barriers for GPs to manage patients after MVC. GPs also expressed interest in having better access to management tools for specific MVC-related consequences (e.g., whiplash/seatbelt injuries, acute/chronic pain management, mental health issues). CONCLUSION: Chronic pain, mental health issues and the prescription of opioids were more frequent among patients experiencing MVC. This reinforces the relevance of appropriate management to limit the physical and psychological impact of MVC. GPs identified a lack of available resources (e.g. education, checklists and management support tools) for managing MVC-related consequences, and the need for local referral pathways and specific guidelines to escalate treatments.

Utilization of antidepressants, anxiolytics, and hypnotics during the COVID-19 pandemic.

Since the onset of the COVID-19 pandemic, there have been concerns over the mental health impact of COVID-19. This is a review of the utilization of antidepressants, anxiolytics, and hypnotics since the COVID-19 pandemic was declared on March the 11th 2020. A number of reports so far have been based on large prescription databases for administrative use at the national or regional level, but mainly in high-income countries. We found studies reporting increased prescription rates of antidepressants, anxiolytics, and hypnotics during March 2020, which has been interpreted as hoarding of such medications. In the following months, most studies of antidepressant prescription rates did not display a clear pattern of change compared with prepandemic trends. In later phases of the pandemic small increases in utilization of antidepressants, with higher than predicted prescription rates, have been the most consistent finding, especially in youth. In most high-income countries, there were increasing trends in utilization of antidepressants also before 2020, which needs to be considered when estimating utilization during the pandemic, whereas for anxiolytics and hypnotics, the prepandemic patterns of prescriptions were more varying. Overall, after March 2020 we could not find any distinct changes in the utilization of anxiolytics and hypnotics during the COVID-19 pandemic. Most studies did not contain information about the prevalence of indicated psychiatric disorders in the studied populations. More studies are needed about the long-term effects of COVID-19, particularly regarding utilization of antidepressants. Research relating antidepressant utilization with the prevalence of major depression and anxiety disorders would promote a better understanding of how well antidepressant prescription rates reflect the needs of the population.

Psychotropic Medication Prescribing for Children and Adolescents After the Onset of the COVID-19 Pandemic.

Importance: Numerous studies have provided evidence for the negative associations of the COVID-19 pandemic with mental health, but data on the use of psychotropic medication in children and adolescents after the onset of the COVID-19 pandemic are lacking. Objective: To assess the rates and trends of psychotropic medication prescribing before and over the 2 years after the onset of the COVID-19 pandemic in children and adolescents in France. Design, Setting, and Participants: This cross-sectional study used nationwide interrupted time-series analysis of outpatient drug dispensing data from the IQVIA X-ponent database. All 8 839 143 psychotropic medication prescriptions dispensed to children (6 to 11 years of age) and adolescents (12 to 17 years of age) between January 2016 and May 2022 in France were retrieved and analyzed. Exposure: Onset of COVID-19 pandemic. Main outcomes and Measures: Monthly rates of psychotropic medication prescriptions per 1000 children and adolescents were analyzed using a quasi-Poisson regression before and after the pandemic onset (March 2020), and percentage changes in rates and trends were assessed. After the pandemic onset, rate ratios (RRs) were calculated between estimated and expected monthly prescription rates. Analyses were stratified by psychotropic medication class (antipsychotic, anxiolytic, hypnotic and sedative, antidepressant, and psychostimulant) and age group (children, adolescents). Results: In total, 8 839 143 psychotropic medication prescriptions were analyzed, 5 884 819 [66.6%] for adolescents and 2 954 324 [33.4%] for children. In January 2016, the estimated rate of monthly psychotropic medication prescriptions was 9.9 per 1000 children and adolescents, with the prepandemic rate increasing by 0.4% per month (95% CI, 0.3%-0.4%). In March 2020, the monthly prescription rate dropped by 11.5% (95% CI, -17.7% to -4.9%). During the 2 years following the pandemic onset, the trend changed significantly, and the prescription rate increased by 1.3% per month (95% CI, 1.2%-1.5%), reaching 16.1 per 1000 children and adolescents in May 2022. Monthly rates of psychotropic medication prescriptions exceeded the expected rates by 11% (RR, 1.11 [95% CI, 1.08-1.14]). Increases in prescribing trends were observed for all psychotropic medication classes after the pandemic onset but were substantial for anxiolytics, hypnotics and sedatives, and antidepressants. Prescription rates rose above those expected for all psychotropic medication classes except psychostimulants (RR, 1.12 [95% CI, 1.09-1.15] in adolescents and 1.06 [95% CI, 1.05-1.07] in children for antipsychotics; RR, 1.30 [95% CI, 1.25-1.35] in adolescents and 1.11 [95% CI, 1.09-1.12] in children for anxiolytics; RR, 2.50 [95% CI, 2.23-2.77] in adolescents and 1.40 [95% CI, 1.30-1.50] in children for hypnotics and sedatives; RR, 1.38 [95% CI, 1.29-1.47] in adolescents and 1.23 [95% CI, 1.20-1.25] in children for antidepressants; and RR, 0.97 [95% CI, 0.95-0.98] in adolescents and 1.02 [95% CI, 1.00-1.04] in children for psychostimulants). Changes were more pronounced among adolescents than children. Conclusions and Relevance: These findings suggest that prescribing of psychotropic medications for children and adolescents in France significantly and persistently increased after the COVID-19 pandemic onset. Future research should identify underlying determinants to improve psychological trajectories in young people.

Ecocebo: How the interaction between environment and drug effects may improve pharmacotherapy outcomes.

This narrative review describes the research on the effects of the association between environmental context and medications, suggesting the benefit of specific design interventions in adjunction to pharmacotherapy. The literature on Evidence-Based Design (EBD) studies and Neuro-Architecture show how contact with light, nature, and specific physical features of urban and interior architecture may enhance the effects of analgesic, anxiolytics, and antidepressant drugs. This interaction mirrors those already known between psychedelics, drugs of abuse, and setting. Considering that the physical feature of space is a component of the complex placebo configuration, the aim is to highlight those elements of built or natural space that may help to improve drug response in terms of efficacy, tolerability, safety, and compliance. Ecocebo, the integration of design approaches such as EBD and Neuro-Architecture may thus contribute to a more efficient, cost-sensitive, and sustainable pharmacotherapy.

Additive anxiolytic-like effect of citicoline and ACPA in the non-acute restraint stress (NARS) and acute restraint stress (ARS) mice.

The cannabinoid system plays a key role in stress-related emotional symptoms such as anxiety. Citicoline is a supplemental substance with neuroprotective properties that alleviates anxiety-related behaviors. There is a relation between the actions of cannabinoids and cholinergic systems. So, we decided to evaluate the effects of intracerebroventricular (i.c.v.) infusion of cannabinoid CB1 receptor agents on citicoline-produced response to anxiety-like behaviors in the non-acute restraint stress (NARS) and acute restraint stress (ARS) mice. For i.c.v. microinjection of drugs, a guide cannula was inserted in the left lateral ventricle. ARS was induced by movement restraint for 4 h. Anxiety-related behaviors were assessed using an elevated plus maze (EPM). The results showed that induction of ARS for 4 h decreased the percentage of time spent in the open arms (%OAT) and the percentage of entries to the open arms (%OAE) without affecting locomotor activity, showing anxiogenic-like behaviors. i.c.v. infusion of ACPA (1 µg/mouse) induced an anxiolytic-like effect due to the enhancement of %OAT in the NARS and ARS mice. Nonetheless, i.c.v. microinjection of AM251 (1 µg/mouse) decreased %OAT in the NARS and ARS mice which suggested an anxiogenic-like response. Intraperitoneal (i.p.) administration of citicoline (80 mg/kg) induced an anxiolytic-like effect by the augmentation of %OAT in the ARS mice. Furthermore, when ACPA and citicoline were co-administrated, ACPA potentiated the anxiolytic-like effect induced by citicoline in the NARS and ARS mice. On the other hand, when AM251 and the citicoline were co-injected, AM251 reversed the anxiolytic-like response induced by the citicoline in the NARS and ARS mice. The results of this research exhibited an additive effect between citicoline and ACPA on the induction of anxiolytic-like response in the NARS and ARS mice. Our results indicated an interaction between citicoline and cannabinoid CB1 receptor drugs on the control of anxiety-like behaviors in the NARS and ARS mice.

Baseline symptom severity and efficacy of Silexan in patients with anxiety disorders: A symptom-based, patient-level analysis of randomized, placebo-controlled trials.

The influence of baseline severity on the efficacy of Silexan, a proprietary essential oil from Lavandula angustifolia, in anxiety disorders has not been investigated in a pooled dataset. We report on an individual patient data analysis of all five double-blind, randomized, placebo-controlled trials with Silexan in anxiety disorders. Eligible participants received Silexan 80 mg/d or placebo for 10 weeks. Analyses were based on the Hamilton Anxiety Rating Scale (HAMA), its psychic and somatic anxiety subscores, and the Clinical Global Impressions (CGI) scale. To correlate baseline severity with outcome, patients were segregated into mild, moderate, and severe cases. Altogether 1,172 patients (Silexan, n = 587; placebo, n = 585) were analyzed. For the HAMA total score, we found a significant association between the score at baseline and the treatment effect of Silexan versus placebo at week 10 (p < 0.001). HAMA items from the somatic domain scored lower at baseline and showed less improvement than items from the psychic domain, particularly in patients with mild or moderate baseline symptoms. For CGI item 2 (global improvement), significant efficacy favoring Silexan were observed in mild, moderate, and severe baseline symptom severity. Although significant improvements were found for all subsets, the more severe the initial symptoms, the greater the treatment effects documented by the HAMA. Overall this analysis confirms that Silexan is an effective treatment option in early or mild stages of anxiety disorder. Given its favorable safety profile, Silexan can thus fill a therapeutic gap in the treatment of (subsyndromal) anxiety disorders.

[Treatment resistance in anxiety disorders-Definition and treatment options]. / Therapieresistenz bei Angsterkrankungen ­ Definition und Behandlungsoptionen.

Treatment resistance in anxiety disorders represents a clinical challenge, contributes to the chronicity of the diseases as well as sequential comorbidities, and is associated with a significant individual and socioeconomic burden. This narrative review presents the operational definition of treatment resistance in anxiety disorders according to international consensus criteria (< 50% reduction in the Hamilton Anxiety Scale, HAM­A, score or < 50% reduction in the Beck Anxiety Inventory, BAI, score or a clinical global impression-improvement, CGI­I, score > 2). At least two unsuccessful guideline-based treatment attempts with pharmacological monotherapy or at least one unsuccessful treatment attempt with adequately delivered cognitive behavioral therapy are required. Pharmacotherapeutically, after excluding pseudo-resistance, switching the medication within one class or to another class and augmentation strategies with other antidepressants (mirtazapine, agomelatine), antipsychotics (quetiapine) or anticonvulsants (valproate) are recommended. Psychotherapeutically, third-wave therapies, psychodynamic therapy, systemic therapy and physical exercise can be considered for therapy resistance. In cases of no response to psychotherapy or pharmacotherapy, the respective other form of therapy or a combination of both should be offered. Compounds targeting the glutamatergic and endocannabinoid systems as well as neuropeptides are being tested as potential innovative pharmaceuticals for treatment-resistant anxiety disorders. There is an urgent need for further research to identify predictive markers and mechanisms as well as to develop innovative pharmacological and psychotherapeutic interventions for treatment-resistant anxiety disorders.

Comparison of perception of stress and consumption of anxiolytics in hospital and out-hospital conditions: a cross-sectional study.

Background: The workplace is a place where medical workers are exposed to extreme stress, particularly during medical emergencies or events of epidemic or pandemic proportions. Anxiolytic therapy is often used to overcome professional challenges. Deepening knowledge about the prevalence of the use of anxiolytics and the perception of stress among medical workers enables the timely recognition of problems and the preparation of measures to improve the working conditions and quality of life of medical workers. The study's primary objective was to investigate whether there were differences in the usage of anxiolytics among healthcare professionals in and out of the hospital. In addition to the main objective, there are other objectives that have been established: To examine whether there are statistically justified differences in stress perceptions between hospital and outpatient healthcare professionals; 2. To examine the stress factors in the workplace in both hospital and outpatient settings. To compare the frequency of taking anxiolytics with respect to various variables (age, seniority, occupation and level of education); 4. determines the impact of working conditions on stress perception and life satisfaction in healthcare professionals. The design of research: Cross-sectional research. Materials and methods: The research involved 159 healthcare professionals in Slavonski Brod: 96 employees of the General Hospital "Dr. Josip Bencevic" and 63 employees of the Health Center and the Institute for Emergency Medicine of Brodsko-Posavina County. Respondents were able to participate in the study by filling out questionnaires online. The questionnaire was designed to be voluntary and anonymous and contained 53 questions. Results: Statistically significant differences were shown in the perception of stress, which is greater in hospital staff, than in the difference between stressors in the workplace, where hospital staff showed higher values in all categories, but three factors are more significant differences: "Organization of the workplace and financial issues," "Conflicts and communication at work" and "Professional and intellectual requirements." There are significant differences in the frequency of using anxiolytics with the assistance of a psychiatrist. Working conditions have a much greater impact on the perception of stress and life satisfaction in hospital staff, while in hospital staff only a weak link between the perception of stress and life satisfaction is expressed. Anxiolytics are consumed by 27.10% of hospital workers and 23.80% of outside-the-hospital workers. Conclusion: The consumption of anxiolytic drugs by healthcare professionals in hospital and outpatient conditions does not make a significant difference, but they do have statistically significant differences in their perception of stress.

Nitric Oxide (NO) Synthase Inhibitors: Potential Candidates for the Treatment of Anxiety Disorders?

Close to 19% of the world population suffers from anxiety. Current medications for this chronic mental disorder have improved treatment over the last half century or more, but the newer anxiolytics have proved disappointing, and enormous challenges remain. Nitric oxide (NO), an intra- and inter-cellular messenger in the brain, is involved in the pathogenesis of anxiety. In particular, excessive NO production might contribute to its pathology. This implies that it might be useful to reduce nitrergic activity; therefore, molecules aiming to downregulate NO production such as NO synthase inhibitors (NOSIs) might be candidates. Here, it was intended to critically review advances in research on these emerging molecules for the treatment of anxiety disorders. Current assessment indicates that, although NOSIs are implicated in anxiety, their potential anti-anxiety action remains to be established.

New users of anxiolytics and sedatives in Sweden-Drug type, doses, prescribers' characteristics, and psychiatric comorbidity in more than 750,000 patients.

OBJECTIVES: Anxiety and sleep disorders are common in the population and anxiolytics and sedatives are widely used. Our aim was to describe the drug utilization of new users of anxiolytics and sedatives in adults including type of drug, doses, prescribers' characteristics, and psychiatric comorbidity. METHODS: A register-based cohort study of new users (18-64 years) of anxiolytics and sedatives in 2015-2019, free of any such drug 5 years prior to inclusion. The individuals were linked to national registers on dispensed drugs and recorded diagnoses. RESULTS: In total, 764,432 new users of anxiolytics and sedatives were identified, which corresponds to an incidence of 26/1000 inhabitants and year. The proportion of new users of benzodiazepines (including both anxiolytics and sedatives) decreased, whereas the proportion of sedative antihistamines and melatonin increased. The most common drug dispensed was hydroxizin (33%) followed by benzodiazepine related drugs (zopiclone and zolpidem; 20%), propiomazine (14%) and benzodiazepines (13%). The majority (68%) of the prescriptions were from primary care. Most new users were prescribed 1-30DDDs and 52% among women and 49% among men were dispensed their drug only once during the first year. Half of the new users had a previous comorbid psychiatric disorder. CONCLUSIONS: The findings are well reflecting the recommendations in national guidelines.

Prescriptions of antidepressants and anxiolytics in France 2012-2022 and changes with the COVID-19 pandemic: interrupted time series analysis.

BACKGROUND: Depression and anxiety have increased in prevalence since the start of the COVID-19 pandemic. OBJECTIVE: To evaluate the consumption of antidepressants and anxiolytics from 2012 to 2022 and the pandemic's potential impact in France. METHODS: We conducted an interrupted time series analysis of routine drug sales data (Medic'AM) from all French outpatient pharmacies from 2012 to 2022. We investigated trends in defined daily doses of antidepressants and anxiolytics sold per 1000 inhabitants (DDD/TID) and related expenditures before and after pandemic onset and in relation with stringency of pandemic mitigation measures. Analyses were performed descriptively and using segmented linear regression, autoregressive and autoregressive integrated moving average models. FINDINGS: From 2012 to 2019, overall monthly antidepressant sales increased (+0.02 DDD/TID) while monthly anxiolytic sales decreased (-0.07 DDD/TID). With pandemic onset, there was a relevant and persisting trend increase (+0.20 DDD/TID per month) for antidepressant sales overall, with an estimated excess of 112.6 DDD/TID sold from May 2020 until December 2022. Anxiolytic sales were elevated from February 2020 throughout the pandemic but returned to expected levels by December 2022, with an estimated excess of 33.8 DDD/TID. There was no evident association between stringency and antidepressant or anxiolytic sales. CONCLUSIONS: This study showed a protracted trend increase in the consumption of antidepressants since pandemic onset, while increases in anxiolytic consumption were temporary. CLINICAL IMPLICATIONS: We provide evidence that the COVID-19 pandemic may have had long-lasting consequences on the prevalence and treatment of depression and anxiety disorders, requiring further actions by researchers and policy-makers to address this potential public mental health crisis.

Bark extract of Chaetocarpus castanocarpus (Roxb.) exhibits potent sedative, anxiolytic, and antidepressant effects through an in vivo approach in Swiss albino mice.

OBJECTIVE: Standard phytochemical investigations were performed to identify the secondary metabolites in the methanol extract of Chaetocarpus castanocarpus bark (MECC) and investigate the neuropharmacological potential of MECC in Swiss albino mice. MATERIALS AND METHODS: Swiss albino mice were used in the forced swimming test (FST) and tail suspension test (TST) to evaluate the antidepressant effect of MECC. Also, the hole board test (HBT) and elevated plus maze (EPM) were conducted to examine anxiolytic activities. In contrast, the open field test (OFT) and hole cross test (HCT) were employed to evaluate sleeping disorders. RESULTS: Alkaloids, glycosides, flavonoids, terpenoids, coumarins, and tannins are only a few secondary metabolites identified in MECC by qualitative and quantitative phytochemical investigations. The oral administration of MECC considerably shortened the immobility duration during FST and TST. Encouraging dose-dependent anxiolytic effects were also observed in all relevant experiments compared to the control. Additionally, during the OFT and HCT assessment, a noteworthy decline in the locomotor activities of the experimental animals was observed. CONCLUSIONS: The results of this investigation suggest that the Chaetocarpus castanocarpus bark is a possible source of therapeutic candidates for treating neurological disorders.

Gepirone-the latest antidepressant on market state-of-the-art or run-of-the-mill?

Gepirone was recently launched and FDA-approved for MDD. It belongs to azapirones group of psychotropics that is in popular use in Japan and China. Here, author wraps up current knowledge on gepirone contrasted with the older and cheaper anxiolytic buspirone.

Sedative drug prescription patterns in Danish adults from 2002 through 2021. A register-based cohort study.

OBJECTIVE: Pharmacological treatment strategies for insomnia seem to vary, and there is lack of knowledge about how sedative drugs are used in a real-world setting. We investigated changes in sedative drug prescription patterns in Danish adults who initiated treatment between 2002 and 2016. METHODS: All adults with a first-time purchase of a sedative drug registered in the Danish National Prescription Register from 2002 through 2016 were followed for five years between 2002 and 2021 for subsequent prescriptions of sedative drugs, death, or emigration. Sedative drugs were classified into anxiolytic benzodiazepines (N05BA), hypnotic benzodiazepines (N05CD), Z-drugs (N05CF), melatonin (N05CH01), promethazine (R06AD), and low-dose quetiapine (N05AH04). Analyses were stratified on time: 2002-2006, 2007-2011, and 2012-2016. RESULTS: A total of 842,880 individuals purchased their first sedative drug between 2002 and 2016. Most of them (40.0%) initiated treatment between 2002 and 2006, whereas 29.2% initiated treatment in 2012-2016. In 2002-2006, anxiolytic benzodiazepines (46.4%), Z-drugs (42.8%), and hypnotic benzodiazepines (5.4%) were the most common first treatment. This pattern changed over time with a gradual increase in the use of melatonin, promethazine, and low-dose quetiapine, which in 2011-2016 accounted for 27% of all first treatments. During the five years from first prescription, around 27% shifted to a different sedative drug. This percentage increased slightly over time, but over time the first shift to another drug class was most often to a Z-drug or anxiolytic benzodiazepine. Few individuals (5.8%) had more than one shift and the third choice seemed randomly distributed across all other drug classes. CONCLUSION: Sedative drug prescriptions are distributed on different drug classes, with Z-drugs and anxiolytic benzodiazepines as the most frequent first treatment, and second choice in case of shift.

Prolame produces anxiolytic- and antidepressant-like effects in middle-aged female rats with less uterotrophic effects than 17ß-estradiol.

Estrogen hormone replacement therapy (EHRT), improving women's life quality at menopause, reduces anxiety and depression symptoms associated with ovarian hormonal decline. However, its potential adverse effects, like thromboembolism and cancer risk, limit its use. Prolame is a synthetic 17ß-amino estrogen with antithrombotic actions that exerts anxiolytic- and antidepressant-like effects on young adult ovariectomized female rats. It is unknown if prolame's effects may be observed in age and endocrine conditions emulating menopause. This study aimed to identify the antidepressant- and anxiolytic-like effects of prolame and E2 (used as a reference estrogen treatment) in middle-aged female rats coursing with irregular cycles, in two different conditions: ovariectomized or gonadally intact. Results were compared with those from young adult ovariectomized rats. Prolame (60 or 120 µg/kg), 17ß-estradiol (E2, 40 or 80 µg/kg), or vehicle were chronically administered, and their effects were evaluated in the elevated plus-maze, defensive burying behavior test, open field test, and forced swimming test. Uterotrophic actions were estimated by uterine weight related to body weight. Prolame and E2 produced robust anxiolytic- and antidepressant-like effects in young adult ovariectomized rats, but these effects were absent in gonadally intact middle-aged rats. Interestingly, only prolame induced anxiolytic- and antidepressant-like effects in middle-aged ovariectomized rats. Uterotrophic effects of prolame were weaker than E2 effects, notably in middle-aged females. Altogether, present data support the notion that prolame has the potential to be considered an EHRT with relevant psychoactive actions and with apparently lower adverse-side effects, especially in middle-aged populations.

Anxiolytic-like effects of YL-IPA08, a potent ligand for the translocator protein (18 kDa) via regulating the synaptic plasticity in hippocampus.

TSPO, translocator protein (18 kDa) ligands have demonstrated consistent antidepression and anxiolytic effects in several preclinical studies. This study aimed to examine whether YL-IPA08[N-ethyl-N-(2-pyridinylmethyl)-2-(3,4-ichlorophenyl) -7-methylimidazo [1,2-a] pyridine-3-acetamide hydrochloride], a potent and selective TSPO ligand synthesized by our institute, could alleviate anxiety-related behaviors induced by electric shock (ES) and investigate its underlying mechanism. As expected, we showed that chronic treatment with YL-IPA08 significantly reversed anxiety-related behaviors induced by electrical stimulation (0.5 mA, 12 times, duration 1s, interval 10s) exposure. Using the analysis of RNA-sequencing (RNA-seq) technology, it was found that the differential genes associated with the anxiolytic effect of YL-IPA08 were mainly related to synaptic plasticity. Furthermore, YL-IPA08 restored the decreased levels of brain-derived neurotrophic factor (BDNF), synapse-related protein (e.g. synapsin-1 and post-synaptic density95, PSD95), and the number of doublecortin (DCX) + neurons in the hippocampus of post-ES mice. In addition, YL-IPA08 also enhanced the dendritic complexity and dendritic spine density of hippocampal dentate gyrus (DG) granule neurons. Meanwhile, the induction of long-term potentiation (LTP) was significantly enhanced by YL-IPA08. In summary, the findings from the current study showed that YL-IPA08 exerted a clear anxiolytic effect, which might be partially mediated by promoting hippocampal neuroplasticity.