Quality of life, pain and use of analgesic, anxiolytic and antidepressant medication, in people living in care homes.

BACKGROUND: People living in care homes often have problems with pain, anxiety and depression. Whether being on analgesia, anxiolytics or antidepressants has any bearing on pain severity and quality of life (QoL) in this population, requires further investigation. OBJECTIVES: (i) to examine the relationship between pain, anxiety and depression and medication use in care home residents and (ii) to compare those on medications to treat pain, anxiety and depression, and those who were not, and associations with pain severity and overall QoL. METHODS: This was a secondary analysis of a randomised controlled trial testing a falls prevention intervention in care homes. We recorded pain, anxiety and depression, QoL measurements and prescribed medication use. RESULTS: In 1589 participants, the mean age was 84.7 years (±9.3 SD), 32.2% were male and 67.3% had a diagnosis of dementia. 54.3% and 53.2% of participants had some level of pain and anxiety or depression respectively, regardless of prescribed medication use. There was a direct association between pain severity and being on any analgesia, opioid analgesia, and antidepressants, but no associations between pain severity and use of paracetamol and anxiolytics. QoL was best for residents with no pain and not on any analgesia, anxiolytics or antidepressants and worst for those with moderate-extreme pain and taking at least two of these classes of medications. CONCLUSION: Many care home residents live with pain, anxiety and depression. Addressing residents' pain may also increase their quality of life, but using medication alone to reach this goal may be inadequate.

Antidepressant-like and Beneficial Effects of a Neoponcirin-Beta-Cyclodextrin Inclusion Complex in Mice Exposed to Prolonged Stress.

Neoponcirin causes anxiolytic-like effects in mice when administered intraperitoneally but not orally. Neoponcirin is non-water-soluble and insoluble in solvents, and in medium acid, it isomerizes, reducing its bioavailability. To improve the pharmacological properties of neoponcirin, we formed a neoponcirin complex with beta-cyclodextrin (NEO/ßCD), which was characterized by FT-IR, UV-Vis, and NMR, and their solubility profile. We evaluated the antidepressant-like effects of NEO/ßCD acutely administered to mice orally in the behavioral paradigms, the tail suspension (TST) and the forced swimming (FST) tests. We also analyzed the benefits of repeated oral doses of NEO/ßCD on depression- and anxiety-like behaviors induced in mice by chronic unpredictable mild stress (CUMS), using the FST, hole board, and open field tests. We determined the stressed mice's expression of stress-related inflammatory cytokines (IL-1ß, IL-6, and TNFα) and corticosterone. Results showed that a single or chronic oral administration of NEO/ßCD caused a robust antidepressant-like effect without affecting the ambulatory activity. In mice under CUMS, NEO/ßCD also produced anxiolytic-like effects and avoided increased corticosterone and IL-1ß levels. The effects of the NEO/ßCD complex were robust in both the acute and the stress chronic models, improving brain neurochemistry and recovering immune responses previously affected by prolonged stress.

Dispensing patterns of antidepressant and antianxiety medications for psychiatric disorders after benign hysterectomy in reproductive-age women: Results from group-based trajectory modeling.

BACKGROUND: Women with gynecologic disorders requiring a hysterectomy often have co-existing psychiatric diagnoses. A change in the dispensing pattern of antidepressant (AD) and antianxiety (AA) medications around the time of hysterectomy may be due to improvement in gynecologic symptoms, such as pelvic pain and abnormal bleeding, or the emotional impact of the hysterectomy. Unfortunately, these dispensing patterns before and after hysterectomy are currently undescribed. OBJECTIVES: To model the dispensing patterns of AD and AA medications over time among women with psychiatric disorders before and after benign hysterectomy for endometriosis and uterine fibroids; and to characterize clusters of patients with various dispensing behaviors based on these patterns. DESIGN: Retrospective cohort study. METHODS: This is a study of women who underwent a benign hysterectomy using data from the Merative MarkertScan® Research Databases (Ann Arbor, MI, USA). Inclusion criteria were reproductive-aged women (18-50 years), diagnosis of at least one mood or anxiety disorder, and at least one dispensing of AD or AA medications. We measured monthly adherence and persistence of AD/AA medication use over 12 months after hysterectomy. Group-based-trajectory modeling (GBTM) was used to identify trajectory groups of monthly AD/AA medication dispensing over the study period. Multinomial logistic regression was used to identify factors independently associated with individual dispensing trajectory patterns. RESULTS: For a total of 11,607 patients, 6 dispensing trajectory groups were identified during the study period: continuously high (27.0%), continuously moderate (21.9%), continuously low (17.9%), low-to-high (10.0%), moderate-to-low (9.8%), and low-to-moderate (13.4%). Compared with the continuously high group, younger age, no history of a mood disorder, and uterine fibroids were clinical predictors of low dispensing. The discontinuation rate at 3 months after hysterectomy was higher at 88.6% in the continuously low group and at 66.5% in the continuously low-to-moderate group. CONCLUSIONS: This study demonstrates that GBTM identified six distinct trajectories of AD/AA medication dispensing in the perioperative period. Trajectory models could be used to identify specific dispensing patterns for targeting interventions.

Dispensing patterns of antidepressant and antianxiety medications for psychiatric disorders after benign hysterectomy in reproductive-aged women: Results from the group-based trajectory modelingWomen with gynecologic disorders often have coexisting psychiatric diagnoses. A change in the dispensing pattern of antidepressant and antianxiety medications may be due to improvement in gynecologic symptoms or the emotional impact of the hysterectomy. However, static measures, such as the proportion of days covered or medication possession ratio, may not adequately predict meaningful dispensing patterns. Using the group-based trajectory modeling, 6 distinct patterns of medication dispensing over the perioperative periods of women with benign hysterectomy are identified and therefore used to assess how certain clinical characteristics influence these dispensing patterns. This study concludes that trajectory modeling may be a more appropriate approach to investigating dispensing patterns among women with preexisting psychiatric conditions.

BEHAVIORAL AND NEUROCHEMICAL CHANGES DURING INTRANASAL ADMINISTRATION OF ALPHA-GLUTAMYL-TRYPTOPHAN AND CHELATE COMPLEX OF ZINC ARGINYL-GLYCINATE ON MONOAMINE SYSTEMS DYSFUNCTIONS KNOCK-OUT MODELS.

Monoamine neurotransmitter system dysfunctions lead to behavioral disorders, cognitive metabolic, and other pathological conditions. In this case, different amino acids are precursors of monoamines, while the parenteral path of monoamine administration has pharmacological restrictions. Therefore, intranasal administration one of the most promising methods of delivering an active substance is. The purpose of the work is to study the effect of intranasal administration of a chelate complex of zinc arginyl-glycinate and alpha-glutamyl-tryptophan dipeptide on behavioral and neurochemical changes in acute and chronic experiments. MATERIAL AND METHODS: The studies used outbred Wistar and DAT-KO rats, and inbred C57Bl6 and TAAR1-KO mice. Using intranasal administration of a chelate complex of zinc arginyl-glycinate and alpha-glutamyl-tryptophan dipeptide we tested methods for evaluating different behavioral indicators and the level of cerebral monoamines and their metabolites. RESULTS: An anxiolytic effect of zinc arginyl-glycinate and its combination with alpha-glutamyl-tryptophan was revealed. Both drugs have a physiological effect on the autonomic nervous system, but the determination of their operating mechanisms requires further research. CONCLUSION: Thus, these data indicate that intranasal delivery of the dipeptides is effective during acute and chronic intranasal administration in rodents, the latter showed a change in the anxiety indicator. Acute AG intranasal administration demonstrated signs of lower anxiety and depressive-like behavior in C57Bl6 mice. The acute intranasal administration of a chelate complex zinc arginyl-glycinate and combination with alpha-glutamyl-tryptophan in doses of 50-100 mg/kg of body weight may be used for pre-clinical studies as a new anxiolytic/antidepressant.

L-Cysteine: A promising nutritional supplement for alleviating anxiety disorders.

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.

The Antidepressant- and Anxiolytic-Like Effects of the Phosphodiesterase Type-5 Inhibitor Tadalafil are Associated with the Modulation of the Gut-Brain Axis During CNS Autoimmunity.

Multiple Sclerosis (MS) is a debilitating disease that severely affects the central nervous system (CNS). Apart from neurological symptoms, it is also characterized by neuropsychiatric comorbidities, such as anxiety and depression. Phosphodiesterase-5 inhibitors (PDE5Is) such as Sildenafil and Tadalafil have been shown to possess antidepressant-like effects, but the mechanisms underpinning such effects are not fully characterized. To address this question, we used the EAE model of MS, behavioral tests, immunofluorescence, immunohistochemistry, western blot, and 16 S rRNA sequencing. Here, we showed that depressive-like behavior in Experimental Autoimmune Encephalomyelitis (EAE) mice is due to neuroinflammation, reduced synaptic plasticity, dysfunction in glutamatergic neurotransmission, glucocorticoid receptor (GR) resistance, increased blood-brain barrier (BBB) permeability, and immune cell infiltration to the CNS, as well as inflammation, increased intestinal permeability, and immune cell infiltration in the distal colon. Furthermore, 16 S rRNA sequencing revealed that behavioral dysfunction in EAE mice is associated with changes in the gut microbiota, such as an increased abundance of Firmicutes and Saccharibacteria and a reduction in Proteobacteria, Parabacteroides, and Desulfovibrio. Moreover, we detected an increased abundance of Erysipelotrichaceae and Desulfovibrionaceae and a reduced abundance of Lactobacillus johnsonii. Surprisingly, we showed that Tadalafil likely exerts antidepressant-like effects by targeting all aforementioned disease aspects. In conclusion, our work demonstrated that anxiety- and depressive-like behavior in EAE is associated with a plethora of neuroimmune and gut microbiota-mediated mechanisms and that Tadalafil exerts antidepressant-like effects probably by targeting these mechanisms. Harnessing the knowledge of these mechanisms of action of Tadalafil is important to pave the way for future clinical trials with depressed patients.

Intranasal midazolam for procedural distress in children in the emergency department: a systematic review and meta-analysis.

OBJECTIVES: Intranasal (IN) midazolam is the most common anxiolytic for children in the emergency department (ED), but evidence of benefit is conflicting. We synthesized the evidence on IN midazolam for procedural distress in children undergoing ED painful procedures. METHODS: We included trials involving painful ED procedures in children 0-18 years involving IN midazolam. Primary outcome was procedural distress. We summarized results using Tricco et al.'s classification of "neutral" (p ≥ 0.05), "favorable," and "unfavorable" (p < 0.05), supporting IN midazolam or comparator, respectively, or "indeterminate" (unable to judge). Where possible, we pooled results using meta-analysis. Methodologic quality of evidence was evaluated using Cochrane Collaboration's risk of bias tool and GRADE system. RESULTS: We included 41 trials (n = 2973 participants). Thirty trials involved intravenous insertion. IN midazolam was superior to placebo (RR = 7.2; 95% CI: 3.43, 15.25; 3 trials; I2 = 0%). However, 56-90% of the IN midazolam group resisted the procedure. Focusing on the three trials that used validated measures, IN midazolam was "neutral" versus IN ketamine and either "neutral" or "unfavorable" versus IN dexmedetomidine. There was no difference in the proportion of children with a satisfactory distress score between IN midazolam and oral midazolam (RR = 1.1; 95% CI: 0.74, 1.73; 2 trials; I2 = 53%), IN ketamine (RR = 1.1; 95% CI: 0.91, 1.25; 6 trials; I2 = 0%), or IN dexmedetomidine (RR = 0.4; 95% CI: 0.17, 1.05; 3 trials; I2 = 84%). Ten trials involved laceration repair. IN midazolam was "favorable" versus placebo; however, both groups scored in the anxious range. There was no difference in distress between IN midazolam and oral midazolam (SMD = 0.01; 95% CI:-0.32, 0.34; 2 trials; I2 = 0%) (Fig. 3E) [64,65]. Using validated instruments, IN midazolam was "unfavorable" versus IN dexmedetomidine but "favorable" versus oral diazepam and placebo. CONCLUSIONS: There is limited methodologically rigorous evidence that IN midazolam is better than placebo for IV insertion and laceration repair. At the doses studied, preliminary evidence suggests that IN dexmedetomidine may be superior to IN midazolam for both IV insertion and laceration repair.

ABSTRAIT: OBJECTIFS: Le midazolam intranasal (IN) est l'anxiolytique le plus courant chez les enfants du service des urgences (DE), mais les preuves des avantages sont contradictoires. Nous avons synthétisé les preuves sur l'IN midazolam pour la détresse procédurale chez les enfants subissant des procédures douloureuses d'urgence. MéTHODES: Nous avons inclus des essais impliquant des procédures douloureuses d'urgence chez les enfants de 0 à 18 ans impliquant IN midazolam. Le résultat principal était la détresse procédurale. Nous avons résumé les résultats en utilisant la classification de Tricco et coll. de « neutre ¼ (p 0,05), « favorable ¼, « défavorable ¼ (p < 0,05), à l'appui du midazolam IN ou du comparateur, respectivement, ou « indéterminé ¼ (incapable de juger). Dans la mesure du possible, nous avons regroupé les résultats en utilisant la méta-analyse. La qualité méthodologique des preuves a été évaluée à l'aide de l'outil de risque de biais de Cochrane Collaboration et du système GRADE. RéSULTATS: Nous avons inclus 41 essais (n = 2973 participants). Trente essais portaient sur l'insertion intraveineuse. L'IN midazolam était supérieur au placebo (RR = 7,2; IC à 95 % : 3,43,15,25; 3 essais; I2 = 0 %). Cependant, 56 à 90 % du groupe IN midazolam a résisté à la procédure. En se concentrant sur les trois essais qui ont utilisé des mesures validées, IN midazolam était « neutre ¼ par rapport à IN kétamine et « neutre ¼ ou « défavorable ¼ par rapport à IN dexmedetomidine. Il n'y avait pas de différence dans la proportion d'enfants ayant un score de détresse satisfaisant entre IN midazolam et midazolam oral (RR = 1,1; IC à 95 % : 0,74,1,73; 2 essais; I2 = 53 %), IN kétamine (RR = 1,1; IC à 95 % : 0,91,1,25; 6 essais; I2 = 0 %) ou IN dexmedetomidine (RR = 0,4; IC à 95 % : 0,17,1,05; 3 essais; I2 = 84 %). Dix essais portaient sur la réparation de la lacération. L'IN midazolam était « favorable ¼ par rapport au placebo, mais les deux groupes ont obtenu des résultats dans la fourchette de l'anxiété. Il n'y avait pas de différence de détresse entre le midazolam IN et le midazolam oral (SMD = 0,01; IC à 95 %:-0,32,0,34; 2 essais; I2 = 0 %) (figure 3E)64,65. À l'aide d'instruments validés, l'IN midazolam était « défavorable ¼ par rapport à l'IN dexmedetomidine, mais « favorable ¼ par rapport au diazépam oral et au placebo. CONCLUSION: Il y a peu de preuves méthodologiques rigoureuses que l'IN midazolam est meilleur que le placebo pour l'insertion IV et la réparation de lacération. Aux doses étudiées, des preuves préliminaires suggèrent que l'IN dexmedetomidine peut être supérieure à l'IN midazolam pour l'insertion IV et la réparation de lacération.

[A Case of Lung Cancer during Home Care with Suspected Chemical Coping].

An 81-year-old woman was prescribed hydromorphone for cancer pain and dyspnea. Owing to anxiety regarding worsening of symptoms, she began to use hydromorphone(10 to 12 times a day)even without symptoms. As chemical coping with opioid analgesics was suspected, the visiting nurse listened to the patient's perspective, and the patient was subsequently prescribed an anxiolytic(lorazepam)for insomnia and anxiety. Thereafter, the frequency of using hydromorphone hydrochloride tablets decreased.

[To study the effectiveness and impact on the quality of life of patients with subclinical and clinically pronounced anxiety disorder of a mobile application in combination with Adaptol therapy]. / Izuchenie effektivnosti i vliyaniya na kachestvo zhizni patsientov s subklinicheskim i klinicheski vyrazhennym trevozhnym rasstroistvom mobil'nogo prilozheniya v sochetanii s terapiei preparatom Adaptol.

OBJECTIVE: To study the effectiveness and the quality of life impact of the mobile application Zdorovye.ru in people with subclinical and clinical anxiety disorder (AD). MATERIAL AND METHODS: 200 patients with more than 7 points on the Hospital Anxiety and Depression Scale (HADS) were included. Participants were randomized into two groups: experimental one (EG, n=133) - to receive standard treatment with temgicoluril (Adaptol), 500 mg (Olainfarm JSC, Latvia) and the Zdorovye.ru application; control group (CG, n=52) - standard treatment with temgicoluril (Adaptol). RESULTS: There were a significant decrease in the HADS-A score, PSS-10 score and an increase in the visual analog scale EQ-5D score in both groups after 3 months of treatment (p<0.001). Clinical improvement was noticeable after 1.5 months in EG group: a decrease in HADS-A scores (p=0.001) and in tension and stress on PSS-10 subscales (p<0.001) were noted. This effect was not observed in the CG. After 3 months, all participants noted an improvement in quality of life (p<0.001), without a statistically significant difference between groups (p=0.233). The application left a positive impression on users and doctors - most respondents rated it as useful and clear. CONCLUSION: Taking temgicoluril (Adaptol) for 3 months led to symptoms decrease and the quality of life and well-being improvement in patients with AD. Using the mobile application Zdorovye.ru in conjunction with drug therapy made it possible to achieve a clinical effect earlier, in 1.5 months.

[Efficacy and safety of Aviandr in the treatment of anxiety in patients with adjustment disorders after COVID-19]. / Effektivnost' i bezopasnost' novogo preparata Aviandr v lechenii trevogi u patsientov s rasstroistvom adaptatsii posle perenesennoi ostroi koronovirusnoi infektsii.

OBJECTIVE: To investigate the efficacy and safety of Aviandr in the treatment of anxiety in patients with adjustment disorders after COVID-19. MATERIAL AND METHODS: A multicenter prospective open-label study included 109 patients of both sexes aged 18 to 65 years (70 women, 39 men, average age - 41.4±13.18 years) with a leading complaint of anxiety (Hamilton scale score, HAM-A ≥18 - ≤24), which arose after acute coronavirus infections. Clinical manifestations had to meet the diagnostic criteria F43.2 ICD-10. The drug Aviander was prescribed 20 mg 2 times a day for 4 weeks. At the end of taking the drug, patients were monitored for another 1 week (a delayed follow-up visit). Psychopathological, statistical and parametric research methods were used using standardized HAM-A, Montgomery-Asberg scales (MADRS), visual analog asthenia scale (VASH-A), Sheehan Disability Scale (SDS), digital character substitution test (DSST), general clinical impression scale (CGI). RESULTS: Data from 109\110 patients were analyzed to evaluate efficacy\safety. Aviandr was administered 20 mg 2 times daily for 4 weeks. Patients were followed for 1 week (delayed follow-up visit) at the end of treatment. Reducing the intensity of anxiety on the HAM-A scale was - 14.2±4.92 or 69.4±22.66% by the end of treatment. The response rate to therapy (responders are patients with a decrease in the total score on the HAM-A ≥50%) was 83.49%. Remission was achieved (sum of HAM-A scores ≤7) by the end of treatment 68.81% of patients, and 79.8% of patients at the follow-up visit. Significant changes were obtained on the MADRS, VAS-A, SDS and DSST scales. According CGI 45.9% of patients had «much improved¼ and 43.1% of patients had «very much improved¼ by the end of treatment; 58.7% of patients had «much improved¼ and of 33.9% patients had «very much improved¼ at the follow-up visit. 38 adverse events were reported in 27 (24.55%) patients during the study. A definite association with study drug was reported between 5 mild adverse events in 4 (3.64%) patients. No subjects withdrew from the study due to an adverse event. Positive dynamics (reduction of anxiety symptoms, decrease in asthenia) persisted after discontinuation of the study drug. No cases of withdrawal syndrome were observed. CONCLUSION: According to the results of the study, the anxiolytic, antidepressant, antiasthenic and pro-cognitive effects of Aviandr were observed. An increase in the social activity of patients was observed.

The effects of remimazolam in combination with estazolam on postoperative hemodynamics and pain intensity in patients undergoing laparoscopic gastrointestinal surgery.

OBJECTIVE: This study aimed to investigate the effects of combining remimazolam with estazolam on hemodynamics and pain levels after laparoscopic gastrointestinal surgery. METHODS: A total of 184 patients who underwent laparoscopic gastrointestinal surgery were enrolled in this double-blind randomized controlled trial. The patients were divided into four groups: Study Group 1(Remimazolam), Study Group 2(Estazolam), Study Group 3(Remimazolam + Estazolam), and Control Group. Anesthesia induction included intravenous injection of remimazolam and estazolam in the study groups, while the control group received normal saline. Hemodynamic parameters, stress responses, anxiety levels, and pain intensity were assessed at various time points. RESULTS: The results showed that the combination of remimazolam and estazolam significantly improved hemodynamic parameters compared to the control group. Study Group 3 exhibited the lowest anxiety levels and stress responses among all groups. Furthermore, Study Group 3 had the lowest pain intensity scores at different postoperative time points. CONCLUSION: The combination of remimazolam and estazolam effectively stabilized hemodynamics, reduced anxiety levels, and alleviated pain intensity after laparoscopic gastrointestinal surgery. These findings suggest that this combination therapy has the potential to improve surgical outcomes and patient comfort.

The Identification of Potential Anti-Depression/Anxiety Drug Targets by Stress-Induced Rat Brain Regional Proteome and Network Analyses.

Depression and anxiety disorders are prevalent stress-related neuropsychiatric disorders and involve multiple molecular changes and dysfunctions across various brain regions. However, the specific and shared pathophysiological mechanisms occurring in these regions remain unclear. Previous research used a rat model of chronic mild stress (CMS) to segregate and identify depression-susceptible, anxiety-susceptible, and insusceptible groups; then the proteomes of six distinct brain regions (the hippocampus, prefrontal cortex, hypothalamus, pituitary, olfactory bulb, and striatum) were separately and quantitatively analyzed. To gain a comprehensive and systematic understanding of the molecular abnormalities, this study aimed to investigate and compare differential proteomics data from the six regions. Differentially expressed proteins (DEPs) were identified in between specific regions and across all regions and subjected to a series of bioinformatics analyses. Regional comparisons showed that stress-induced proteomic changes and corresponding gene ontology and pathway enrichments were largely distinct, attributable to differences in cell populations, protein compositions, and brain functions of these areas. Additionally, a notable degree of overlap in the significantly enriched terms was identified, potentially suggesting strong connections in the enrichment across different regions. Furthermore, intra-regional and inter-regional protein-protein interaction networks and drug-target-DEP networks were constructed. Integrated analysis of the three association networks in the six regions, along with the DisGeNET database, identified ten DEPs as potential targets for anti-depression/anxiety drugs. Collectively, these findings revealed commonalities and differences across different brain regions at the protein level induced by CMS, and identified several novel protein targets for the development of new therapeutics for depression and anxiety.

Daidzein, but not genistein, has anxiolytic-liked effect on intact male Wistar rats.

The phytoestrogens daidzein and genistein are ubiquitous in human food. This study aimed to elucidate their anxiety-liked effects, their effects on the reproductive organs, and the molecular mechanism behind any anxiety-liked effects in intact adult male Wistar rats. These phytoestrogens are of interest due to their posited health benefits, particularly for female, but with some effect on males as well. This study comprised two experiments: (1) Male Wistar rats received either a vehicle, daidzein, or genistein (0.25, 0.50, or 1.00 mg/kg) by subcutaneously injection for four weeks. They were then tested for anxiety-liked behaviors. Then, the brain monoamines in anxiolytic rats were determined; (2) The modulation of gamma aminobutyric acid receptors by phytoestrogens was further analyzed by administration of diazepam to phytoestrogen-treated rats before behavioral tests. In the first experiment, the biological parameters measured, including body weight, daily food intake and reproductive organ weights were unaffected by either genistein or daidzein. However, anxiolytic-like effect was observed in the low-dose daidzein (0.25 mg/kg) group. Higher doses of daidzein or genistein of all doses had no effect. Further, the low-dose daidzein did not alter brain monoamine levels. In the second experiment, the anxiolytic-like behavior of daidzein-treated rats receiving diazepam did not differ from that of the rats treated with just diazepam or just daidzein. In conclusion, 4-week exposure to daidzein or genistein had no negative effects on the reproductive organs, body weight, food intake, anxiogenic-like behavior, or monoaminergic and diazepam-modulated GABAergic neurotransmissions of intact male rats. However, beneficial anxiolytic-like effects were apparent after low-dose treatment with daidzein.

The relationship between blinding integrity and medication efficacy in randomised-controlled trials in patients with anxiety disorders: A systematic review and meta-analysis.

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.

Increased sexual function after intake of clomethiazole.

An octogenarian woman showed increased sexual function after replacing alprazolam with clomethiazole, a sedative-hypnotic drug commonly prescribed in French-speaking Switzerland for the treatment of anxiety and insomnia in elderly patients. The patient's sexual symptoms did not improve after resuming alprazolam, but disappeared after interrupting clomethiazole, and did not reappear when alprazolam was discontinued. Considering the chronology of the events, increased sexual function was likely a manifestation of the introduction of clomethiazole. However, because alprazolam was interrupted when clomethiazole was introduced, we cannot exclude an association between increased sexual function and alprazolam interruption.

Cannabidiol in anxiety disorders: Current and future perspectives.

Anxiety disorders are highly prevalent psychiatric disorders, characterized by a chronic course and often accompanied by comorbid symptoms that impair functionality and decrease quality of life. Despite advances in basic and clinical research in our understanding of these disorders, currently available pharmacological options are associated with limited clinical benefits and side effects that frequently lead to treatment discontinuation. Importantly, a significant number of patients do not achieve remission and live with lifelong residual symptoms that limit daily functioning. Since the 1970s, basic and clinical research on cannabidiol (CBD), a non-psychotomimetic compound found in the Cannabis sativa plant, has indicated relevant anxiolytic effects, garnering attention for its therapeutic potential as an option in anxiety disorder treatment. This chapter aims to review the history of these studies on the anxiolytic effects of CBD within the current understanding of anxiety disorders. It highlights the most compelling current evidence supporting its anxiolytic effects and explores future perspectives for its clinical use in anxiety disorders.

Temporal trends in medication and service use patterns for mental health issues among men with prostate cancer.

OBJECTIVE: Prostate cancer can significantly impact mental wellbeing, creating uncertainty and morbidity. This study described patterns of psychotropic medication and mental health service use, as a proxy measure for mental health problems, 5 years before and 5 years after prostate cancer diagnosis. METHODS: Population-based registry data were linked with Pharmaceutical Benefits Scheme and Medicare Benefits Schedule data for all prostate cancer patients diagnosed in South Australia between 2012 and 2020 (n = 13,693). We estimated the proportion and rates of psychotropic medication and mental health service use before and after diagnosis. Multivariable adjusted interrupted time series analyses (ITSA) were conducted to uncover temporal patterns. RESULTS: Fifteen percent of men commenced psychotropic medications and 6.4% sought out mental health services for the first time after diagnosis. Psychotropic medication use rose from 34.5% 5 years before to 40.3% 5 years after diagnosis, including an increase in use of antidepressants (from 20.7% to 26.0%) and anxiolytics (from 11.3% to 12.8%). Mental health service use increased from 10.2% to 12.1%, with the increase mostly being general practice mental health visits (from 7.8% to 10.6%). Multivariable ITSA indicated a significant rise in medication and service utilisation immediately before and in the first 2 years following prostate cancer diagnosis. CONCLUSION: There is a clear increase in psychotropic medication use and mental health service use around the time of prostate cancer diagnosis. Mental health outcomes of men with prostate cancer may be improved with early mental health screening, particularly during the diagnosis process, to enable early intervention.

The Study of Myo-Inositol's Anxiolytic Activity on Zebrafish (Danio rerio).

INTRODUCTION: Myo-inositol (MI) is the most abundant inositol found in nature. To date MI supplementation is reported to be effective in the treatment of polycystic ovary syndrome, it is also suggested to alleviate the symptoms of diabetes and neurodegenerative disorders, but to date no statistically significant effects of inositol on depressive and anxiety symptoms were proven. In the study of anxiolytic effects in zebrafish, we often use the thigmotaxis index measuring the ratio of the amount of time the animal spends near the walls compared to the entire arena. AIM: The objective of this paper was to examine the effect of MI on zebrafish embryos' locomotor activity, as well as its potential anxiolytic activity in zebrafish larvae. MATERIAL AND METHODS: In the first part of the experiment, the embryos were incubated with 5, 10, 20, and 40 mg/mL MI. 1-day post fertilization, embryo mobility was evaluated and burst activity was calculated. In the next part of the study, the behavior of 5-day-old larvae was tested. RESULTS: Tests on embryo movement showed an increase in burst activity in the MI group at concentrations of 40 mg/mL (p < 0.0001) and a slight decrease in the group at concentrations of 10 mg/mL (p < 0.05). MI in the light/dark challenge had no impact on the thigmotaxis index. CONCLUSIONS: MI was shown to not affect stress reduction in zebrafish larvae. Further research on the potential of MI and other stereoisomers is needed.

[Recognan (citicoline) in the correction of asthenic and anxiety-depressive disorders]. / Rekognan (tsitikolin) v korrektsii astenicheskikh i trevozhno-depressivnykh narushenii.

The article reflects the results of a number of studies that demonstrate the therapeutic effectiveness of Recognan (citicoline) in anxiety-depressive and asthenic disorders against the background of somatic and neurological diseases, in the correction of post-stroke depression. Recent experimental animal studies prove the effect of citicoline on anxiety and depression. In the complex effect, Recognan potentiates the main pharmacological effect of antidepressants and anxiolytics. In some studies, a dose-dependent change in animal behavior has been observed in response to the analgesic and antidepressant effects of citicoline. The effectiveness of citicoline in combination with transcranial direct current stimulation in the treatment of depression has been shown. The analysis of these research materials allows us to recommend Recognan in the complex therapy of asthenic and anxiety-depressive disorders in response to such pathological conditions as anxiety, asthenia, depression.

The effect of SSRIs on unconditioned anxiety: a systematic review and meta-analysis of animal studies.

RATIONALE: Selective serotonin reuptake inhibitors (SSRIs) are the first choice of treatment for anxiety-like disorders. However, which aspects of anxiety are affected by SSRIs is not yet fully understood. OBJECTIVE: We aimed to systematically review the effect of six clinically effective SSRIs on four aspects of unconditioned anxiety: approach-avoidance behaviour (elevated plus maze), repetitive behaviour (marble burying), distress behaviour (ultrasonic vocalization), and activation of the autonomous nervous system (stress-induced hyperthermia). METHODS: We identified publications by searching Medline and Embase databases and assessed the risk of bias. A random effects meta-analysis was performed and moderator effects were analysed with Bayesian penalized meta-regression. RESULTS: Our search yielded 105 elevated plus maze, 63 marble burying, 11 ultrasonic vocalization, and 7 stress-induced hyperthermia articles. Meta-analysis suggested that SSRIs reduce anxiety-like behaviour in the elevated plus maze, marble burying and ultrasonic vocalization test and that effects are moderated by pre-existing stress conditions (elevated plus maze) and dose dependency (marble burying) but not by duration of treatment or type of SSRI. The reporting quality was low, publication bias was likely, and heterogeneity was high. CONCLUSION: SSRIs seem to reduce a broad range of unconditioned anxiety-associated behaviours. These results should be interpreted with caution due to a high risk of bias, likely occurrence of publication bias, substantial heterogeneity and limited moderator data availability. Our review demonstrates the importance of including bias assessments when interpreting meta-analysis results. We further recommend improving the reporting quality, the conduct of animal research, and the publication of all results regardless of significance.