Health Disparities and Comparison of Psychiatric Medication Use before and after the COVID-19 Pandemic Lockdown among General Practitioner Practices in the North East of England.

BACKGROUND: Psychiatric medications play a vital role in the management of mental health disorders. However, the COVID-19 pandemic and subsequent lockdown limited access to primary care services, leading to an increase in remote assessment and treatment options to maintain social distancing. This study aimed to investigate the impact of the COVID-19 pandemic lockdown on the use of psychiatric medication in primary care settings. METHODS: We conducted a retrospective claims-based analysis of anonymized monthly aggregate practice-level data on anxiolytics and hypnotics use from 322 general practitioner (GP) practices in the North East of England, where health disparities are known to be higher. Participants were all residents who took anxiolytics and hypnotics from primary care facilities for two financial years, from 2019/20 to 2020/21. The primary outcome was the volume of Anxiolytics and Hypnotics used as the standardized, average daily quantities (ADQs) per 1000 patients. Based on the OpenPrescribing database, a random-effect model was applied to quantify the change in the level and trend of anxiolytics and hypnotics use after the UK national lockdown in March 2020. Practice characteristics extracted from the Fingertips data were assessed for their association with a reduction in medication use following the lockdown. RESULTS: This study in the North East of England found that GP practices in higher health disparate regions had a lower workload than those in less health disparate areas, potentially due to disparities in healthcare utilization and socioeconomic status. Patients in the region reported higher levels of satisfaction with healthcare services compared to the England average, but there were differences between patients living in higher versus less health disparate areas. The study highlights the need for targeted interventions to address health disparities, particularly in higher health disparate areas. The study also found that psychiatric medication use was significantly more common in residents living in higher health disparate areas. Daily anxiolytics and hypnotics use decreased by 14 items per 1000 patients between the financial years 2019/20 and 2020/21. A further nine items per 1000 decreased for higher health disparate areas during the UK national lockdown. CONCLUSIONS: People during the COVID-19 lockdown were associated with an increased risk of unmet psychiatric medication demand, especially for higher health disparate areas that had low-socioeconomic status.

Adherence to Psychotropic Medication Before and During COVID-19: A Population-Wide Retrospective Observational Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic and associated public health measures have shifted the way people access health care. We aimed to study the effects of the COVID-19 pandemic on psychotropic medication adherence. METHODS: A retrospective cohort study using administrative data from the Manitoba Centre for Health Policy Manitoba Population Research Data Repository was conducted. Outpatients who received at least 1 prescription for an antidepressant, antipsychotic, anxiolytic/sedative-hypnotic, cannabinoid, lithium, or stimulants from 2015 to 2020 in Manitoba, Canada, were included. Adherence was measured using the proportion of individuals with a mean possession ratio of ≥0.8 over each quarter. Each quarter of 2020 after COVID-19-related health measures were implemented was compared with the expected trend using autoregression models for time series data plus indicator variables. Odds ratio of drug discontinuation among those previously adherent in 2020 was compared with each respective quarter of 2019. RESULTS: There were 1,394,885 individuals in the study population in the first quarter of 2020 (mean [SD] age, 38.9 [23.4] years; 50.3% female), with 36.1% having a psychiatric diagnosis in the preceding 5 years. Compared with the expected trend, increases in the proportions of individuals adherent to antidepressants and stimulants were observed in the fourth quarter (October-December) of 2020 (both P < 0.001). Increases in the proportions of individuals with anxiolytic and cannabinoid adherence were observed in the third quarter (July-September) of 2020 (both P < 0.05), whereas a decrease was seen with stimulants in the same quarter ( P < 0.0001). No significant changes were observed for antipsychotics. All drug classes except lithium had decreases in drug discontinuation in previously adherent patients during the pandemic compared with 2019. CONCLUSIONS: Improved adherence to most psychotropic medications in the 9 months after public health restrictions were enacted was observed. Patients who were already adherent to their psychotropic medications were less likely to discontinue them during the pandemic.

Anxiolytic-like Effects and Quantitative EEG Profile of Palmitone Induces Responses Like Buspirone Rather Than Diazepam as Clinical Drugs.

Anxiety is a mental disorder with a growing worldwide incidence due to the SARS-CoV-2 virus pandemic. Pharmacological therapy includes drugs such as benzodiazepines (BDZs) or azapirones like buspirone (BUSP) or analogs, which unfortunately produce severe adverse effects or no immediate response, respectively. Medicinal plants or their bioactive metabolites are a shared global alternative to treat anxiety. Palmitone is one active compound isolated from Annona species due to its tranquilizing activity. However, its influence on neural activity and possible mechanism of action are unknown. In this study, an electroencephalographic (EEG) spectral power analysis was used to corroborate its depressant activity in comparison with the anxiolytic-like effects of reference drugs such as diazepam (DZP, 1 mg/kg) and BUSP (4 mg/kg) or 8-OH-DPAT (1 mg/kg), alone or in the presence of the GABAA (picrotoxin, PTX, 1 mg/kg) or serotonin 5-HT1A receptor antagonists (WAY100634, WAY, 1 mg/kg). The anxiolytic-like activity was assayed using the behavioral response of mice employing open-field, hole-board, and plus-maze tests. EEG activity was registered in both the frontal and parietal cortex, performing a 10 min baseline and 30 min recording after the treatments. As a result, anxiety-like behavior was significantly decreased in mice administered with palmitone, DZP, BUSP, or 8-OH-DPAT. The effect of palmitone was equivalent to that produced by 5-HT1A receptor agonists but 50% less effective than DZP. The presence of PTX and WAY prevented the anxiolytic-like response of DZP and 8-OH-DPAT, respectively. Whereas only the antagonist of the 5-HT1A receptor (WAY) inhibited the palmitone effects. Palmitone and BUSP exhibited similar changes in the relative power bands after the spectral power analysis. This response was different to the changes induced by DZP. In conclusion, brain electrical activity was associated with the anxiolytic-like effects of palmitone implying a serotoninergic rather than a GABAergic mechanism of action.

Prescription of anxiolytics, sedatives, hypnotics and antidepressants in outpatient, universal care during the COVID-19 pandemic in Portugal: a nationwide, interrupted time-series approach.

BACKGROUND: The COVID-19 pandemic has had a significant impact on the population's mental health. However, its impact on the consumption of anxiolytics, sedatives, hypnotics and antidepressants remains to be evaluated. Hence, this article aims to assess the prescription trends of these drugs in Portugal, from January 2018 to March 2021, while critically examining whether the COVID-19 pandemic had an impact on these prescription trends or not. METHODS: A nationwide interrupted time-series analysis of the prescription data of anxiolytics, sedatives, hypnotics and antidepressants in outpatient setting of the public health sector was conducted. The data encompassed the defined daily dose per month, age range and sex and were analysed following a segmented regression approach. RESULTS: The pandemic preceded an immediate reduction in the prescription of anxiolytics, sedatives and hypnotics for children and adolescents. However, an increasing trend throughout the pandemic has been noted in the prescription of these drugs, especially among adults aged 65 years or above. A drop in antidepressant prescription was observed as an immediate effect of the pandemic among male and female adolescents and elderly women. From March 2020 to March 2021, a decreasing prescription trend has been noted among men. CONCLUSIONS: When analysing specific genders and age ranges, differences can be noted, in terms of both immediate impact and prescribing trends throughout 1 year of the COVID-19 pandemic. The impact of the pandemic on mental health and its association with the consumption trends of psychoactive drugs, and with the access to mental health treatments, should be further assessed.

The anxiolytic and circadian regulatory effect of agarwood water extract and its effects on the next generation; zebrafish modelling.

Anxiety is one of the most common psychiatric symptoms worldwide. Studies show that there is an increase of >25 % in the prevalence of anxiety with the onset of the COVID-19 pandemic process. Due to the various side effects of drugs used in the treatment of anxiety, interest in natural therapeutic alternatives has increased. Agarwood is a plant used as a natural therapeutic due to its sedative effect as well as many effects such as antioxidant and antibacterial. Although there are many studies with agarwood, comprehensive behavioral studies, including the next generation, are limited. In present study, zebrafish fed with diets containing 10-100 ppm water extract of Agarwood (AWE) for 3 and 8 weeks were exposed to predator stress using Oscar fish in order to test the potential anxiolytic effect of AWE. At the end of the period, zebrafish exposed to predator stress were subjected to anxiety and circadian tests. Histopathological evaluation and immunofluorescent analyzes of BDNF and 5HT4-R proteins were performed in the brains of zebrafish. The effects on the next generation were examined by taking offspring from zebrafish. According to the results, it was observed that AWE had a healing effect on anxiety-like behaviors and on the disrupted circadian rhythm triggered by the predatory stress it applied, especially in the 8 weeks 100 ppm group. Interestingly, it was also found to be effective in offspring of zebrafish fed diets with AWE.

Current Insights on Bioactive Molecules, Antioxidant, Anti-Inflammatory, and Other Pharmacological Activities of Cinnamomum camphora Linn.

C. camphora is a renowned traditional Unani medicinal herb and belongs to the family Lauraceae. It has therapeutic applications in various ailments and prophylactic properties to prevent flu-like epidemic symptoms and COVID-19. This comprehensive appraisal is to familiarize the reader with the traditional, broad applications of camphor both in Unani and modern medicine and its effects on bioactive molecules. Electronic databases such as Web of Science, PubMed, Google Scholar, Scopus, and Research Gate were searched for bioactive molecules, and preclinical/clinical research and including 59 research and review papers up to 2022 were retrieved. Additionally, 21 classical Unani and English herbal pharmacopeia books with ethnomedicinal properties and therapeutic applications were explored. Oxidative stress significantly impacts aging, obesity, diabetes mellitus, depression, and neurodegenerative diseases. The polyphenolic bioactive compounds such as linalool, borneol, and nerolidol of C. camphora have antioxidant activity and have the potential to remove free radicals. Its other major bioactive molecules are camphor, cineole, limelol, safrole, limonene, alpha-pinene, and cineole with anti-inflammatory, antibacterial, anxiolytic, analgesic, immunomodulatory, antihyperlipidemic, and many other pharmacological properties have been established in vitro or in vivo preclinical research. Natural bioactive molecules and their mechanisms of action and applications in diseases have been highlighted, with future prospects, gaps, and priorities that need to be addressed.

Trends in incident diagnoses and drug prescriptions for anxiety and depression during the COVID-19 pandemic: an 18-month follow-up study based on the UK Biobank.

Serious concerns have been raised about the negative effects of the COVID-19 pandemic on population psychological well-being. However, limited data exist on the long-term effects of the pandemic on incident psychiatric morbidities among individuals with varying exposure to the pandemic. Leveraging prospective data from the community-based UK Biobank cohort, we included 308,400 participants free of diagnosis of anxiety or depression, as well as 213,757 participants free of anxiolytics or antidepressants prescriptions, to explore the trends in incident diagnoses and drug prescriptions for anxiety and depression from 16 March 2020 to 31 August 2021, compared to the pre-pandemic period (i.e., 1 January 2017 to 31 December 2019) and across populations with different exposure statuses (i.e., not tested for COVID-19, tested negative and tested positive). The age- and sex-standardized incidence ratios (SIRs) were calculated by month which indicated an increase in incident diagnoses of anxiety or depression among individuals who were tested for COVID-19 (tested negative: SIR 3.05 [95% confidence interval 2.88-3.22]; tested positive: 2.03 [1.76-2.34]), especially during the first six months of the pandemic (i.e., March-September 2020). Similar increases were also observed for incident prescriptions of anxiolytics or antidepressants (tested negative: 1.56 [1.47-1.67]; tested positive: 1.41 [1.22-1.62]). In contrast, individuals not tested for COVID-19 had consistently lower incidence rates of both diagnoses of anxiety or depression (0.70 [0.67-0.72]) and prescriptions of respective psychotropic medications (0.70 [0.68-0.72]) during the pandemic period. These data suggest a distinct rise in health care needs for anxiety and depression among individuals tested for COVID-19, regardless of the test result, in contrast to a reduction in health care consumption for these disorders among individuals not tested for and, presumably, not directly exposed to the disease.

Trends in psychotropic drug consumption among French military personnel during the COVID-19 epidemic.

BACKGROUND: The coronavirus disease (COVID-19) pandemic may have had significant mental health consequences for military personnel, which is a population already exposed to psychological stress. To assess the potential impact of the COVID-19 pandemic, we analyzed the dispensing of three classes of psychotropic drugs (anxiolytics, hypnotics, and antidepressants) among French military personnel. METHODS: A retrospective analysis was conducted using the individualized medico-administrative data of persons insured by the National Military Social Security Fund from the National Health Data System. All active French military personnel aged 18-64 who received outpatient care and to whom drugs were dispensed between January 1, 2019, and April 30, 2021, were included from the French national health database. Rate ratios of dispensed anxiolytics, hypnotics and antidepressants (based on drug reimbursement) were estimated from negative binomial regressions before and after the start of the COVID-19 pandemic. RESULTS: Three hundred eighty-one thousand seven hundred eleven individuals were included. Overall, 45,148 military personnel were reimbursed for anxiolytics, 10,637 for hypnotics, and 4328 for antidepressants. Drugs were dispensed at a higher rate in 2020 and 2021 than in 2019. There was a notable peak at the beginning of the first lockdown followed by a decrease limited to the duration of the first lockdown. During the first lockdown only, there were temporary phenomena including a brief increase in drug dispensing during the first week followed by a decrease during the rest of lockdown, possibly corresponding to a stocking-up effect. For the study period overall, while there was a significant downward trend in psychotropic drug dispensing before the occurrence of COVID-19 (p < 0.001), the pandemic period was associated with an increase in dispensed anxiolytics (rate ratio, 1.03; 95% CI, 1.02-1.04, p < 0.05), hypnotics (rate ratio, 1.13; 95% CI, 1.11-1.16, p < 0.001) and antidepressants (rate ratio, 1.12; 95% CI, 1.10-1.13, p < 0.001) in the military population. CONCLUSIONS: The COVID-19 pandemic has probably had a significant impact on the mental health of French military personnel, as suggested by the trends in dispensed psychotropic drugs. The implementation of mental health prevention measures should be investigated for this population.

Prevalence of Gabapentinoids and Central Nervous System Depressant Drugs, and Their Association with Risk Factors for Respiratory Depression in Primary Care Patients.

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

[Effectiveness of the anxiolytic Anvifen in the treatment of post-COVID brain fog]. / Effektivnost' preparata Anvifen pri lechenii patsientov s sindromom postkovidnogo «tumana v golove¼.

OBJECTIVE: To determine the significance of anxiety disorder and comorbid disorders in patients with post-covid brain fog, to determine the effectiveness of the GABAergic nootropic drug with an anxiolytic effect - Anvifen. MATERIAL AND METHODS: 92 post-COVID-19 patients with no organic brain damage who complain of brain fog 12 weeks after the onset of COVID-19 symptoms. Group 1 (n=40; 43.4±4.5 years) were treated at home; group 2 (n=32; 44.9±5.5 years) were treated in a hospital without oxygen support; group 3 (n=20; 45.1±4.8 years) were treated in a hospital with oxygen support. Assessment scales: Hospital Anxiety and Depression Scale (HADS), Montreal Cognitive Assessment Scale (MoCA); Trail Making Test part B (TMT-B); a scoring questionnaire for the subjective characteristics of sleep; Fatigue Assessment Scale (FAS), 36-Item Short Form Survey (SF-36). According to the indicated scales, no statistically significant differences were found between the groups, therefore, the data of all patients were combined into one group, the indicators were compared before and after treatment (Anvifen 500 mg three times a day for 21 days). RESULTS: Results before/after treatment: HADS anxiety 10.5 [8.5;12]/7 [5;8] (p=0.000025); HADS depression 5 [4; 7] / 4 [4; 6] (p=0.00003); MoCA 22 [21; 22] / 25 [24; 26] (p=0.00001); TMT-B 281 [279; 290] sec / 231 [220; 236] sec (p=0.00001); FAS 27 [23; 31] / 20 [23; 31] (p=0.00001); questionnaire for scoring the subjective characteristics of sleep 15 [15; 16] / 25 [25; 26] (p=0.00001); SF-36 Physical Health 43.8 [42.3; 47.4] / 53.8 [52.3; 20] (p=0.00001); SF-36 Mental Health 34 [32.5; 35] / 47 [45.5; 48] (p=0.00001). CONCLUSION: The authors conclude that anxiety disorder and asthenia play an important role in the pathogenesis of post-COVID brain fog syndrome. Anvifen effectiveness is considered from the point of view of the participation of GABAergic structures in the pathogenesis of the phenomenon under study.

Anxiolytic effect of Anthemis nobilis L. (roman chamomile) and Citrus reticulata Blanco (tangerine) essential oils using the light-dark test in zebrafish (Danio rerio).

ETHNOPHARMACOLOGICAL RELEVANCE: The anxiety disorders are the most prevalent mental health condition, and anxiety is considered the sixth cause of disability surpassing diabetes mellitus, chronic obstructive pulmonary disease, and osteoarthritis. Besides, the COVID-19 pandemic provided an increase in the number of psychiatric diseases diagnosis in all social layers around the world. About 55%-94% of patients diagnosed with anxiety disorders are treated with benzodiazepines, meanwhile benzodiazepines can promote several adverse effects. In this way, alternative therapies, such as essential oils may offer significant benefits in the treatment of patients with anxiety disorders. However, the anxiolytic effect of these essential oils must be proper evaluated appropriate as well as the suitable dosage and side effect need further research. AIM OF THE STUDY: The aim was to evaluate the anxiolytic effect of Roman chamomile (Anthemis nobilis L.) and tangerine (Citrus reticulata Blanco) essential oils using the light-dark test in adult zebrafish (Danio rerio). MATERIAL AND METHODS: Both essential oils were analyzed by GC-MS and the major compounds were identified. The anxiolytic effect was evaluated by light-dark test in adult zebrafish. RESULTS: The results showed that roman chamomile essential oil has anxiolytic effect in adult zebrafish, whereas tangerine essential oil tends to reduce anxiety The major compounds of tangerine essential oil were limonene and γ-terpinene, and the major compounds of roman chamomile were pentadecyl-3-methyl-2-butenoate, hexadecyl-3-methyl-2-butenoate, 1-piperidinol and trans-1-ethyl-3-methyl-cyclopentane. CONCLUSIONS: The present study demonstrated that this anxiolytic effect may be attributed to the synergistic effect of the compounds present in roman chamomile essential oil, particularly the major compounds. The roman chamomile essential oil at the highest concentration showed anxiolytic effect. The tangerine essential oil showed a tendency to reduce anxiety, but it was not statistically significative. In addition, roman chamomile and tangerine essential oils did not cause cause alteration in locomotion activity and exploratory ability of the fish.

Evaluation of Neurotropic Activity and Molecular Docking Study of New Derivatives of pyrano[4″,3″:4',5']pyrido[3',2':4,5]thieno[3,2-d]pyrimidines on the Basis of pyrano[3,4-c]pyridines.

BACKGROUND: Heterocyclic compounds and their fused analogs, which contain pharmacophore fragments such as pyridine, thiophene and pyrimidine rings, are of great interest due to their broad spectrum of biological activity. Chemical compounds containing two or more pharmacophore groups due to additional interactions with active receptor centers usually enhance biological activity and can even lead to a new type of activity. The search for new effective neurotropic drugs in the series of derivatives of heterocycles containing pharmacophore groups in organic, bioorganic and medical chemistry is a serious problem. METHODS: Modern methodology of drugs involves synthesis, physicochemical study, molecular modeling and selection of active compounds through virtual screening and experimental evaluation of the biological activity of new chimeric compounds with pharmacophore fragments. For the synthesis of new compounds, classical organic methods were used and developed. For the evaluation of neurotropic activity of new synthesized compounds, some biological methods were used according to indicators characterizing anticonvulsant, sedative and antianxiety activity as well as side effects. For docking analysis, various soft ware packages and methods were used. RESULTS: As a result of multistep reactions, 11 new, tri- and tetracyclic heterocyclic systems were obtained. The studied compounds exhibit protection against pentylenetetrazole (PTZ) seizures as well as some psychotropic effects. The biological assays evidenced that nine of the eleven studied compounds showed a high anticonvulsant activity by antagonism with pentylenetetrazole. The toxicity of the compounds is low, and they do not induce muscle relaxation in the studied doses. According to the study of psychotropic activity, it was found that the selected compounds have an activating behavior and anxiolytic effects on the "open field" and "elevated plus maze" (EPM) models. The data obtained indicate the anxiolytic (antianxiety) activity of the derivatives of tricyclic thieno[2,3-b]pyridines and tetracyclic pyridothieno[3,2-d]pyrimidin-8-ones, especially pronounced in compounds 3b-f and 4e. The studied compounds increase the latent time of first immobilization on the "forced swimming" (FS) model and exhibit antidepressant effects; compounds 3e and 3f especially exhibit these effects, similarly to diazepam. Docking studies revealed that compounds 3c and 4b bound tightly in the active site of γ-aminobutyric acid type A (GABAA) receptors with a value of the scoring function that estimates free energy of binding (∆G) at -10.0 ± 5 kcal/mol. Compound 4e showed the best affinity ((∆G) at -11.0 ± 0.54 kcal/mol) and seems to be an inhibitor of serotonin (SERT) transporter. Compounds 3c-f and 4e practically bound with the groove of T4L of 5HT_1A and blocked it completely, while the best affinity observed was in compound 3f ((∆G) at -9.3 ± 0.46 kcal/mol). CONCLUSIONS: The selected compounds have an anticonvulsant, activating behavior and anxiolytic effects and at the same time exhibit antidepressant effects.

Effects of the COVID-19 pandemic on clinically diagnosed psychiatric disorders in persons with type 2 diabetes.

AIMS: To examine whether the incidence rates of diagnosed depression, anxiety disorders and stress reactions, as well as prescription rates of antidepressants and anxiolytics were higher during the COVID-19 pandemic than before in persons with type 2 diabetes in Germany. Contrary to earlier studies, clinical diagnoses of psychiatric disorders (ICD classification) were used. METHODS: The German Disease Analyzer (DA) database is an outpatient database containing routine data on patients´ diseases and treatments provided by a representative panel of physician practices selected from across Germany. We assessed incidence rates of depressive disorders (ICD-10: F32, F33), anxiety disorders (F41) and stress reactions (F43) in quarters from January 2019 to March 2021 in 95,765 people with type 2 diabetes included in the DA in 2019 (mean age 68.9 years, 58% men). Prescription rates of antidepressants and anxiolytics in quarters from January 2020 to March 2021 were compared with prescription rates from 1 year earlier. RESULTS: During the study period, the incidence rate of newly diagnosed depressive disorders in persons with type 2 diabetes declined slightly, while the incidence rates of anxiety and stress disorders remained largely constant. The rates of new prescriptions for antidepressants and anxiolytics were lower in all quarters of 2020 and in the first quarter of 2021 than in the quarters 1 year earlier. Diabetes-related complications were more prevalent in persons with incident psychiatric disorders than in those without. CONCLUSIONS: No increase in the incidence rates of clinically diagnosed psychiatric disorders was observed during the COVID-19 pandemic in Germany in persons with type 2 diabetes.

Consumption of Psychiatric Drugs in Primary Care during the COVID-19 Pandemic.

BACKGROUND: The main objective of this research was to analyze whether there were changes in the use of antidepressants, anxiolytics, and hypnotic-sedative drugs, in the context of primary health care, during the COVID-19 pandemic compared to the pre-pandemic period. We further sought to study consumption in vulnerable population groups. METHODS: A cross-sectional observational study was performed in a primary health district of Spain. The data were obtained from the Andalusian Public Health System database, for the pre-COVID-19 period, from March 2019 to February 2020, and for the COVID-19 period, from March 2020 to February 2021. Univariant and bivariant analyses were performed. The effect size was measured using the Rosenthal test. RESULTS: While the total number of medical prescriptions decreased by 2.5% in the COVID-19 period, the prescriptions of psychiatric drugs increased by 6.1%. The increase in the dose consumption per 1000 inhabitants (DHD) was highest for anxiolytics (7.2%), followed by hypnotic-sedatives (5.6%) and antidepressants (3.7%). The consumption of antidepressants, anxiolytics, and sedative-hypnotic drugs was higher in women, older people, and rural areas and lower in areas with social transformation needs, with these differences being statistically significant. CONCLUSIONS: The consumption of psychiatric drugs has increased over the COVID-19 pandemic, especially in women, older people, and rural areas. Thus, we should reflect on the adequate use of these drugs.

Variations in COVID-19 vaccination uptake among people in receipt of psychotropic drugs: cross-sectional analysis of a national population-based prospective cohort.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has disproportionately affected people with mental health conditions. AIMS: We investigated the association between receiving psychotropic drugs, as an indicator of mental health conditions, and COVID-19 vaccine uptake. METHOD: We conducted a cross-sectional analysis of a prospective cohort of the Northern Ireland adult population using national linked primary care registration, vaccination, secondary care and pharmacy dispensing data. Univariable and multivariable logistic regression analyses investigated the association between anxiolytic, antidepressant, antipsychotic, and hypnotic use and COVID-19 vaccination status, accounting for age, gender, deprivation and comorbidities. Receiving any COVID-19 vaccine was the primary outcome. RESULTS: There were 1 433 814 individuals, of whom 1 166 917 received a COVID-19 vaccination. Psychotropic medications were dispensed to 267 049 people. In univariable analysis, people who received any psychotropic medication had greater odds of receiving COVID-19 vaccination: odds ratio (OR) = 1.42 (95% CI 1.41-1.44). However, after adjustment, psychotropic medication use was associated with reduced odds of vaccination (ORadj = 0.90, 95% CI 0.89-0.91). People who received anxiolytics (ORadj = 0.63, 95% CI 0.61-0.65), antipsychotics (ORadj = 0.75, 95% CI 0.73-0.78) and hypnotics (ORadj = 0.90, 95% CI 0.87-0.93) had reduced odds of being vaccinated. Antidepressant use was not associated with vaccination (ORadj = 1.02, 95% CI 1.00-1.03). CONCLUSIONS: We found significantly lower odds of vaccination in people who were receiving treatment with anxiolytic and antipsychotic medications. There is an urgent need for evidence-based, tailored vaccine support for people with mental health conditions.

Antidepressant- and anxiolytic-like activities of Rosmarinus officinalis extract in rodent models: Involvement of oxytocinergic system.

BACKGROUND: Oxytocin (OXT), a neuropeptide involved in mammal reproductive and prosocial behaviors, has been reported to interact with various stressor-provoked neurobiological changes, including neuroendocrine, neurotransmitter, and inflammatory processes. In view of disturbances in psychosocial relationships due to social isolation and physical distancing measures amid the COVID-19 pandemic, being one of the triggering factors for the recent rise in depression and anxiety, OXT is a potential candidate for a new antidepressant. METHODS: In this present study, we have aimed to investigate the effects of oral administration of Rosmarinus officinalis extract (RE), extracted from distillation residue of rosemary essential oil, on central OXT level in the context of other stress biomarkers and neurotransmitter levels in mice models. Tail suspension test (TST) and elevated plus maze test (EPMT) following LPS injection were employed to assess depressive- and anxiety-like behavior in mice, respectively. FINDINGS: Pretreatment with RE for seven days significantly improved behavior in TST and EPMT. Whole-genome microarray analysis reveals that RE significantly reversed TST stress-induced alterations in gene expressions related to oxytocinergic and neurotransmitter pathways and inflammatory processes. In both models, RE significantly increased central Oxt and Oxtr expressions, as well as OXT protein levels. RE also significantly attenuated stress-induced changes in serum corticosterone, brain and serum BDNF levels, and brain neurotransmitters levels in both models. INTERPRETATION: Altogether, our study is the first to report antidepressant- and anxiolytic-like activities of RE through modulating oxytocinergic system in mice brain and thus highlights the prospects of RE in the treatment of depressive disorders of psychosocial nature.

Efficacy and Safety of Cannabidiol Plus Standard Care vs Standard Care Alone for the Treatment of Emotional Exhaustion and Burnout Among Frontline Health Care Workers During the COVID-19 Pandemic: A Randomized Clinical Trial.

Importance: Frontline health care professionals who work with patients with COVID-19 have an increased incidence of burnout symptoms. Cannabidiol (CBD) has anxiolytic and antidepressant properties and may be capable of reducing emotional exhaustion and burnout symptoms. Objective: To investigate the safety and efficacy of CBD therapy for the reduction of emotional exhaustion and burnout symptoms among frontline health care professionals working with patients with COVID-19. Design, Setting, and Participants: This prospective open-label single-site randomized clinical trial used a 1:1 block randomization design to examine emotional exhaustion and burnout symptoms among frontline health care professionals (physicians, nurses, and physical therapists) working with patients with COVID-19 at the Ribeirão Preto Medical School University Hospital in São Paulo, Brazil. Participants were enrolled between June 12 and November 12, 2020. A total of 214 health care professionals were recruited and assessed for eligibility, and 120 participants were randomized in a 1:1 ratio by a researcher who was not directly involved with data collection. Interventions: Cannabidiol, 300 mg (150 mg twice per day), plus standard care or standard care alone for 28 days. Main Outcomes and Measures: The primary outcome was emotional exhaustion and burnout symptoms, which were assessed for 28 days using the emotional exhaustion subscale of the Brazilian version of the Maslach Burnout Inventory-Human Services Survey for Medical Personnel. Results: A total of 120 participants were randomized to receive either CBD, 300 mg, plus standard care (treatment arm; n = 61) or standard care alone (control arm; n = 59) for 28 days. Of those, 118 participants (59 participants in each arm; 79 women [66.9%]; mean age, 33.6 years [95% CI, 32.3-34.9 years]) received the intervention and were included in the efficacy analysis. In the treatment arm, scores on the emotional exhaustion subscale of the Maslach Burnout Inventory significantly decreased at day 14 (mean difference, 4.14 points; 95% CI, 1.47-6.80 points; partial eta squared [ηp2] = 0.08), day 21 (mean difference, 4.34 points; 95% CI, 0.94-7.73 points; ηp2 = 0.05), and day 28 (mean difference, 4.01 points; 95% CI, 0.43-7.59 points; ηp2 = 0.04). However, 5 participants, all of whom were in the treatment group, experienced serious adverse events: 4 cases of elevated liver enzymes (1 critical and 3 mild, with the mild elevations reported at the final 28-day assessment) and 1 case of severe pharmacodermia. In 2 of those cases (1 with critical elevation of liver enzymes and 1 with severe pharmacodermia), CBD therapy was discontinued, and the participants had a full recovery. Conclusions and Relevance: In this study, CBD therapy reduced symptoms of burnout and emotional exhaustion among health care professionals working with patients during the COVID-19 pandemic. However, it is necessary to balance the benefits of CBD therapy with potential undesired or adverse effects. Future double-blind placebo-controlled clinical trials are needed to confirm the present findings. Trial Registration: ClinicalTrials.gov Identifier: NCT04504877.

Trends in the Use of Anxiolytics in Castile and Leon, Spain, between 2015-2020: Evaluating the Impact of COVID-19.

Anxiolytics (N05B) are one of the most widely used pharmacological groups. This study aimed to analyze the progression of the consumption of anxiolytics (ATC classification: N05B) dispensed in pharmacies in Castile and Leon, Spain, from 2015 to 2020, with a special focus on the possible impact of COVID-19 on the use of these drugs. A quantitative-qualitative analysis of usage was carried out using the total number of packs and the packs per 1000 inhabitants. Overall, the use of anxiolytics grew by 14.41% during 2015-2020. The most commonly used drugs were the short-acting benzodiazepine derivatives lorazepam (whose use increased by 15.18%) and alprazolam (whose use increased by 21.40%), and the dispensing of the long-acting derivative diazepam increased the most, by 31.83%. Anxiolytics consumption increased significantly in 2020 and peaked in March. The pattern of use remained the same in 2020. The consumption of anxiolytics has continued to increase in Castile and Leon over the last six years. The COVID-19 pandemic situation affected the dispensing of these drugs, causing a sharp increase in prescriptions, especially during March, when the confinement of the population was initiated.

About anxiety levels and anti-anxiety drugs among quarantined undergraduate Jordanian students during COVID-19 pandemic.

OBJECTIVE: This study was conducted to study the anxiety scores among undergraduate university students in Jordan during COVID-19 pandemic and to assess the relationship between quarantine and shifting to distance learning resulted from the governmental strict isolation measures and severity of anxiety among students. METHODS: A cross-sectional design was conducted to meet the study objectives. A convenience sample of 736 undergraduate university students in Jordan was recruited, and anxiety was assessed using the Hamilton Anxiety Scale. RESULTS: The results indicated that anxiety score was 22.76 and 40.6% of the participant experienced moderate to severe anxiety, whereas 23.5% experienced mild to moderate anxiety and 35.9% experienced mild anxiety. Factors like suffering from chronic illnesses, having chronic medications, grade point average, shifting to distance learning, quarantine during the pandemic, study duties, the newly developed evaluation methods and the experience of students towards the use of anti-anxiety drugs and herbs had significantly increased the anxiety scores. CONCLUSION: Our findings indicate that quarantine and shifting to distance learning during COVID-19 pandemic have negatively affected the anxiety scores of the university students which should be taken in consideration by the policymakers in Jordan in order to support this vulnerable group.