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BACKGROUND: There is growing evidence for the therapeutic effects of the psychedelic drug psilocybin for major depression. However, due to the lack of safety data on combining psilocybin with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) and concerns that there may be a negative interaction on efficacy, participants enrolling in psychedelic trials are usually required to discontinue SNRI/SNRIs prior to enrolling. AIMS: Using data from a recent clinical trial examining the comparative efficacy the psychedelic drug psilocybin (P) combined with approximately 20 h of psychological support to a 6-week (daily) course of the SSRI escitalopram plus matched psychological support for major depressive disorder, we explored the effects of discontinuing SSRI/SNRIs prior to study enrolment on study outcomes. METHODS: Exploratory post hoc analyses using linear mixed effects model were performed to investigate the discontinuation effect on various validated depression symptom severity scales and well-being. The impact of SSRI/SNRIs discontinuation on the acute psychedelic experience was also explored. RESULTS/OUTCOMES: In the psilocybin group, there was a reduced treatment effect on all outcome measures for SSRI/SNRIs discontinuers compared with unmedicated patients at trial entry. However, no effects of discontinuation on measures of the acute psychedelic experience were found. CONCLUSION: Discontinuation of SSRI/SNRIs before psilocybin might diminish response to treatment; however, as we did not test SSRI/SNRI continuation in our trial, we cannot infer such causation. Moreover, the exploratory nature of the analyses makes them hypothesis generating, and not confirmatory. A controlled trial of SSRI/SNRI discontinuation versus continuation prior to psilocybin is urgently required.

BackgroundLong COVID, also known as post-acute sequelae of COVID-19 (PASC), is a poorly understood condition with symptoms across a range of biological domains that often have debilitating consequences. Some have recently suggested that lingering SARS-CoV-2 virus particles in the gut may impede serotonin production and that low serotonin may drive many Long COVID symptoms across a range of biological systems. Therefore, selective serotonin reuptake inhibitors (SSRIs), which increase synaptic serotonin availability, may be used to prevent or treat Long COVID. SSRIs are commonly prescribed for depression, therefore restricting a study sample to only include patients with depression can reduce the concern of confounding by indication.MethodsIn an observational sample of electronic health records from patients in the National COVID Cohort Collaborative (N3C) with a COVID-19 diagnosis between September 1, 2021, and December 1, 2022, and a comorbid depressive disorder, the leading indication for SSRI use, we evaluated the relationship between SSRI use during acute COVID-19 and subsequent 12-month risk of Long COVID (defined by ICD-10 code U09.9). We defined SSRI use as a prescription for SSRI medication beginning at least 30 days before acute COVID-19 and not ending before SARS-CoV-2 infection. To minimize bias, we estimated relationships using nonparametric targeted maximum likelihood estimation to aggressively adjust for high-dimensional covariates.ResultsWe analyzed a sample (n = 302,626) of patients with a diagnosis of a depressive condition before COVID-19 diagnosis, where 100,803 (33%) were using an SSRI. We found that SSRI users had a significantly lower risk of Long COVID compared to nonusers (adjusted causal relative risk 0.92, 95% CI (0.86, 0.99)) and we found a similar relationship comparing new SSRI users (first SSRI prescription 1 to 4 months before acute COVID-19 with no prior history of SSRI use) to nonusers (adjusted causal relative risk 0.89, 95% CI (0.80, 0.98)).ConclusionsThese findings suggest that SSRI use during acute COVID-19 may be protective against Long COVID, supporting the hypothesis that serotonin may be a key mechanistic biomarker of Long COVID.

Depressive disorders are leading contributors to the global mental health-related burden, and they represent a challenge for real-world clinicians, due to the low rates of remission despite the high availability of treatments. Often, depression shows in the context of multiple chronic comorbidities, thus requiring precise and accurate management of pharmacological treatments to avoid interactions and side effects. These criticalities call for the need for new strategies of treatment, which may include new insights into the pharmacological properties of currently available antidepressant drugs, to enhance their efficacy in the different contexts in which depression may arise. Trazodone is the prototype serotonin antagonist/reuptake inhibitor antidepressant (SARI). Due to the malleability granted by its multiple formulations, trazodone is frequently used to treat depression, both as an add-on to other antidepressants and as a monotherapy, with satisfying results. Moreover, its tolerability makes it one of the most prescribed antidepressants in patients with poly-treated comorbid medical illnesses, especially in the elderly. Herein, a case series is presented regarding the use of trazodone in patients with complex comorbid diagnoses or distressing side effects. Each of the three cases has been discussed in three specific Round Tables, involving expert clinicians in the fields of Psychiatry, Neurology, General Practice, and Geriatrics using the Nominal Group Technique. The ideas collected have been used to integrate the cases and the discussion with the intent of facilitating accessibility to the widest audience of physicians and clinical workers in different clinical practice contexts. The final aim of this paper is to promote an increasingly personalized use of trazodone in realworld patients with depression. [ABSTRACT FROM AUTHOR]

The present study aimed to assess the antidepressant profile of fluoxetine in the rats exhibiting lorazepam-induced abusive effects in place preference paradigm. Lorazepam, a benzodiazepine is commonly utilized for treating anxiety, panic attacks, status epilepticus, depressive disorders and sedation. Despite its therapeutic benefits, repeated lorazepam administration can lead to dependence, possibly involving heightened dopaminergic neurotransmission. Additionally, an important role is played by serotonergic system in anxiety and addiction pathophysiology and treatment. The study aimed to examine fluoxetine's impact on lorazepam-induced addiction, as fluoxetine, a selective serotonin reuptake inhibitor, enhances 5-HT availability by inhibiting its reuptake in neurons. Behavioral parameters, including growth rate, food intake, behaviors in forced swim test, open field, light dark box test, Skinner’s box and conditioned place preference, were monitored in rats subjected to oral lorazepam (2 mg/kg) and fluoxetine (1mg/kg) administration. Neurochemical analysis suggests that fluoxetine enhances serotonin levels, which counteracts the dopamine-driven addictive effects of lorazepam within the caudate and nucleus accumbens. This supports the notion that serotonin-dopamine interplay facilitates mitigate dependency by stabilizing the reward pathways following lorazepam administration. [ABSTRACT FROM AUTHOR]

Abstract Background Long COVID, also known as post-acute sequelae of COVID-19 (PASC), is a poorly understood condition with symptoms across a range of biological domains that often have debilitating consequences. Some have recently suggested that lingering SARS-CoV-2 virus particles in the gut may impede serotonin production and that low serotonin may drive many Long COVID symptoms across a range of biological systems. Therefore, selective serotonin reuptake inhibitors (SSRIs), which increase synaptic serotonin availability, may be used to prevent or treat Long COVID. SSRIs are commonly prescribed for depression, therefore restricting a study sample to only include patients with depression can reduce the concern of confounding by indication. Methods In an observational sample of electronic health records from patients in the National COVID Cohort Collaborative (N3C) with a COVID-19 diagnosis between September 1, 2021, and December 1, 2022, and a comorbid depressive disorder, the leading indication for SSRI use, we evaluated the relationship between SSRI use during acute COVID-19 and subsequent 12-month risk of Long COVID (defined by ICD-10 code U09.9). We defined SSRI use as a prescription for SSRI medication beginning at least 30 days before acute COVID-19 and not ending before SARS-CoV-2 infection. To minimize bias, we estimated relationships using nonparametric targeted maximum likelihood estimation to aggressively adjust for high-dimensional covariates. Results We analyzed a sample (n = 302,626) of patients with a diagnosis of a depressive condition before COVID-19 diagnosis, where 100,803 (33%) were using an SSRI. We found that SSRI users had a significantly lower risk of Long COVID compared to nonusers (adjusted causal relative risk 0.92, 95% CI (0.86, 0.99)) and we found a similar relationship comparing new SSRI users (first SSRI prescription 1 to 4 months before acute COVID-19 with no prior history of SSRI use) to nonusers (adjusted causal relative risk 0.89, 95% CI (0.80, 0.98)). Conclusions These findings suggest that SSRI use during acute COVID-19 may be protective against Long COVID, supporting the hypothesis that serotonin may be a key mechanistic biomarker of Long COVID.

Post-traumatic stress disorder (PTSD) is a mental health disorder, manifesting in people who have endured traumatic events like violence, war, natural disasters, accidents, or other life-threatening situations. Essentially, PTSD is a chronic and debilitating disorder, significantly impacting mental health and psychosocial well-being, necessitating the exploration of novel treatment approaches. Although conventional therapies like psychotherapy and antidepressants have demonstrated efficacy for certain individuals, their effectiveness is limited for some and minimal for others. Consequently, researchers and clinicians are investigating alternative therapeutic methods for these conditions. Among these emerging treatments, cannabidiol (CBD) has shown promising results. Nevertheless, early studies suggest that CBD might yield positive outcomes in mitigating symptoms related to both depression and PTSD.

Objective: The use of selective serotonin reuptake inhibitors (SSRIs) is common among hemodialysis patients who receive treatment for depression. However, studies on the efficacy of SSRIs in patients on chronic hemodialysis are few and have led to conflicting results. The present systematic review aims to evaluate, in randomized, controlled studies (RCSs), the efficacy of SSRI administration in reducing symptoms of depression in patients on chronic hemodialysis when compared with placebo or psychological interventions. Method: Research was run on December 2023 in the following databases: Ovid MEDLINE (1985 to present); Ovid EMBASE (1985 to present); Cochrane Library (Wiley); and PubMed (1985 to present). The primary outcome was the frequency and severity of the symptoms of depression assessed through the Beck Depression Inventory (BDI) or the Hamilton Depression Rating Scale (HAMD). The secondary outcome was the prevalence of adverse events. Results: Seven studies totaling 433 patients were included. The number of patients in each individual study ranged from 13 to 120. The length of studies ranged from 8 weeks to 6 months. Heterogeneous data precluded informative meta-analysis. Three studies compared sertraline with a placebo. Of these, two demonstrated that sertraline was better than the placebo in reducing the symptoms of depression while one showed no statistically significant differences between sertraline and the placebo. One study, comparing fluoxetine with a placebo showed that the symptoms of depression did not differ significantly at 8 weeks. In another study, escitalopram administration led to a significantly greater reduction in the Hamilton Depression Rating Scale score compared to a placebo, as well as in the Hamilton Anxiety Rating Scale score. In one study, citalopram and psychological interventions were both effective in reducing the symptoms of depression and anxiety and, in another study, sertraline was modestly more effective than CBT at 12 weeks in reducing the symptoms of depression. Conclusions: SSRIs may be effective in reducing the symptoms of depression in patients on chronic hemodialysis. SSRI administration, at the dosage used in the studies included in the present systematic review, seems safe in most hemodialysis patients. However, the paucity of studies and the limited number of patients included in the trials may suggest that further randomized, controlled studies are needed to determine if SSRIs may be used routinely in daily clinical practice in such a population. [ABSTRACT FROM AUTHOR]

Abstract Dystonia is characterized by sustained or intermittent involuntary muscle contractions. Psychiatric symptoms are essential non‐motor features of dystonia, and higher risks of depressive and anxiety disorders have been reported. The precedence of psychiatric to motor symptoms in some patients and the dopaminergic and serotonergic system involvement in both the motor and psychiatric aspects suggest these psychiatric disorders may be intrinsic to the neurobiology of dystonia. Nevertheless, psychiatric comorbidities are often construed as secondary reactions to motor disabilities and the negative bio‐psycho‐social impacts of dystonia, leading to underdiagnosis and undertreatment. Research on antidepressant use in dystonia is scarce, especially in children and adolescents. This report presents a 17‐year‐old female with dystonia comorbid with depression with psychotic features, whose motor symptoms improved but psychiatric symptoms persisted with dopaminergic pharmacotherapy. Sertraline was finally added 5 years after the onset and successfully managed her psychotic depression without worsening motor symptoms. Early detection, prompt diagnosis, and timely holistic treatment with dopaminergic agents, antidepressants, and psychosocial interventions are critical for the mental health of dystonia patients.

Abstract Introduction Pharmacotherapy such as selective serotonin reuptake inhibitors (SSRIs) or serotonin‐noradrenaline reuptake inhibitors is recommended for the treatment of anxiety disorders. Although there are patients with persisted symptoms of anxiety disorders who are treated with monotherapy of benzodiazepine anxiolytics without SSRIs, the characteristics of these patients are unclear. In the present study, we investigated the characteristics of patients with persisted symptoms of anxiety disorder without SSRI prescription. Methods From a prescription dataset covering 2018 and 2020, the prescriptions of 243 patients with anxiety disorder were analyzed. Patients were classified into two groups: SSRI non‐prescription and prescription groups. Results The SSRI non‐prescription group had a higher ratio of females than did the SSRI prescription group (60.1% vs. 44.6%, respectively, p = 3.12 × 10−2), but statistically not significant after the Bonferroni correction. No significant differences in age, body mass index, or duration of outpatient visits were found between groups. Among the independent variables, sex (female) was the only variable identified that predicted SSRI non‐prescription. Conclusion The present study showed that among patients with anxiety disorders, sex (female) was the only variable that predicted SSRI non‐prescription.

Premenstrual syndrome (PMS) is a common disorder affecting women of reproductive age, with an estimated global prevalence of 47.8%, with severe symptoms occurring in 3-8%, significantly affecting daily functioning. GABA conductance and changes in neurosteroid levels, particularly allopregnanolone, are suspected to play a substantial role in the disorder's etiology. In this paper, we provide an overview of recent reports on the etiology and recognized therapeutic approaches, encompassing both pharmacological and non-pharmacological interventions. Our examination includes studies on SSRIs, hormonal agents, neurosteroids, supplementation, and therapeutic roles. We aim to determine the most favorable treatment regimen by comparing medication effects and alternative methods. The treatment of PMS is crucial for enhancing the quality of life for affected women. Medications used in PMS treatment should be individually selected to achieve the best therapeutic effect, considering the clinical situation of the patients. [ABSTRACT FROM AUTHOR]

Background Major depressive disorder (MDD) is commonly treated with selective serotonin reuptake inhibitors (SSRIs). SSRIs inhibit the serotonin transporter (5-HTT), but the downstream antidepressant mechanism of action of these drugs is poorly understood. The serotonin 1B (5-HT1B) receptor is functionally linked to 5-HTT and 5-HT1B receptor binding and 5-HT1B receptor mRNA is reduced in the raphe nuclei after SSRI administration in primates and rodents, respectively. The effect of SSRI treatment on 5-HT1B receptor binding in patients with MDD has not been examined previously. This positron emission tomography (PET) study aimed to quantify brain 5-HT1B receptor binding changes in vivo after SSRI treatment for MDD in relation to treatment effect. Methods Eight unmedicated patients with moderate to severe MDD underwent PET with the 5-HT1B receptor radioligand [11C]AZ10419369 before and after 3 to 4 weeks of treatment with the SSRI escitalopram 10 mg daily. Depression severity was assessed at time of PET and after 6 to 7 weeks of treatment with the Montgomery-Åsberg Depression Rating Scale. Results We observed a significant reduction in [11C]AZ10419369 binding in a dorsal brainstem (DBS) region containing the median and dorsal raphe nuclei after escitalopram treatment (P  = .036). Change in DBS [11C]AZ10419369 binding correlated with Montgomery-Åsberg Depression Rating Scale reduction after 3-4 (r = 0.78, P  = .021) and 6-7 (r = 0.94, P  < .001) weeks' treatment. Conclusions Our findings align with the previously reported reduction of 5-HT1B receptor binding in the raphe nuclei after SSRI administration and support future studies testing change in DBS 5-HT1B receptor binding as an SSRI treatment response marker. [ABSTRACT FROM AUTHOR]

Introduction: Patients' adherence to antidepressants is generally reported to be poor. This study examined whether users of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) enhance medication adherence following access to a mobile application (app) tailored for this patient group. The study addresses the implementation phase of medication adherence. Methods: The study was a single group pre-post intervention design. Data were collected using the validated OsloMet Adherence-to-medication Survey tool (OMAS-37) before and after app access. Pre-app access survey (Survey 1) was conducted via social media and online newspapers, encompassing 445 SSRI/SNRI users aged 18 years and above. Post-app access survey (Survey 2) was sent to 103 SSRI/SNRI users from Survey 1. Wilcoxon Signed Rank Test compared preand post-intervention adherence measurements. Pearson's chi-square tests and Fisher's exact tests compared study population categories. Results: Forty-two SSRI/SNRI users, median age 26 (IQR 17), 93% identifying as female, used the app while using the same antidepressant during the 2-month period between gaining access to the app and Survey 2. There was a statistically significant reduction in non-adherence score post-app access (z = 3.57, n = 42, p < 0.001) with medium effect size (r = 0.39), indicating enhanced adherence. Total non-adherence score decreased by 39% from pre-to post-access, and there was a 12% decrease in users scoring equivalent with poor adherence (score <2) post-access. Twenty-nine of 37 non-adherence causes improved, with three showing statistical significance. Of 42 responders, 50% (n = 21) indicated using the app one to two times, while 50% (n = 21) more than three times. Approximately 69% (n = 28) found it useful, and 43% (n = 18) felt safer in their use of antidepressants after access to the app. No significant preference was observed for the app over alternative sources of information. Discussion: Enhanced medication adherence was observed among antidepressant users following access to the tailored app. Further studies are warranted to evaluate the app applicability to a broader range of antidepressants users or other patient groups, encompassing those in the initiation phase of medication adherence. The app is intended as an easily accessible supplement to the information and advice provided by prescribing physicians and dispensing pharmacists. [ABSTRACT FROM AUTHOR]

Depression is a common mental illness. However, its current treatments, like selective serotonin reuptake inhibitors (SSRIs) and micro-dosing ketamine, are extremely variable between patients and not well understood. Three neurotransmitters: serotonin, histamine, and glutamate, have been proposed to be key mediators of depression. This review focuses on analytical methods to quantify these neurotransmitters to better understand neurological mechanisms of depression and how they are altered during treatment. To quantitatively measure serotonin and histamine, electrochemical techniques such as chronoamperometry and fast-scan cyclic voltammetry (FSCV) have been improved to study how specific molecular targets, like transporters and receptors, change with antidepressants and inflammation. Specifically, these studies show that different SSRIs have unique effects on serotonin reuptake and release. Histamine is normally elevated during stress, and a new inflammation hypothesis of depression links histamine and cytokine release. Electrochemical measurements revealed that stress increases histamine, decreases serotonin, and leads to changes in cytokines, like interleukin-6. Biosensors can also measure non-electroactive neurotransmitters, including glutamate and cytokines. In particular, new genetic sensors have shown how glutamate changes with chronic stress, as well as with ketamine treatment. These techniques have been used to characterize how ketamine changes glutamate and serotonin, and to understand how it is different from SSRIs. This review briefly outlines how these electrochemical techniques work, but primarily highlights how they have been used to understand the mechanisms of depression. Future studies should explore multiplexing techniques and personalized medicine using biomarkers in order to investigate multi-analyte changes to antidepressants. [ABSTRACT FROM AUTHOR]

Adolescent major depressive disorder (MDD) is associated with altered restingstate connectivity between the default mode network (DMN) and the salience network (SN), which are involved in self-referential processing and detecting and filtering salient stimuli, respectively. Using spectral dynamical causal modelling, we investigated the effective connectivity and input sensitivity between key nodes of these networks in 30 adolescents with MDD and 32 healthy controls while undergoing resting-state fMRI. We found that the DMN received weaker inhibition from the SN and that the medial prefrontal cortex and the anterior cingulate cortex showed reduced self-inhibition in MDD, making them more prone to external influences. Moreover, we found that selective serotonin reuptake inhibitor (SSRI) intake was associated with decreased and increased self-inhibition of the SN and DMN, respectively, in patients. Our findings suggest that adolescent MDD is characterized by a hierarchical imbalance between the DMN and the SN, which could affect the integration of emotional and self-related information. We propose that SSRIs may help restore network function by modulating excitatory/inhibitory balance in the DMN and the SN. Our study highlights the potential of prefrontal-amygdala interactions as a biomarker and a therapeutic target for adolescent depression. [ABSTRACT FROM AUTHOR]

Introduction: Individuals with depression who do not respond to two or more courses of serotonergic antidepressants tend to have greater deficits in reward processing and greater internalizing symptoms, yet there is no validated self-report method to determine the likelihood of treatment resistance based on these symptom dimensions. Methods: This online case-control study leverages machine learning techniques to identify differences in self-reported anhedonia and internalizing symptom profiles of antidepressant non-responders compared to responders and healthy controls, as an initial proof-of-concept for relating these indicators to medication responsiveness. Random forest classifiers were used to identify a subset from a set of 24 reward predictors that distinguished among serotonergic medication resistant, non-resistant, and non-depressed individuals recruited online (N = 393). Feature selection was implemented to refine model prediction and improve interpretability. Results: Accuracies for full predictor models ranged from .54 to .71, while feature selected models retained 3-5 predictors and generated accuracies of .42 to .70. Several models performed significantly above chance. Sensitivity for non- responders was greatest after feature selection when compared to only responders, reaching .82 with 3 predictors. The predictors retained from feature selection were then explored using factor analysis at the item level and cluster analysis of the full data to determine empirically driven data structures. Discussion: Non-responders displayed 3 distinct symptom profiles along internalizing dimensions of anxiety, anhedonia, motivation, and cognitive function. Results should be replicated in a prospective cohort sample for predictive validity; however, this study demonstrates validity for using a limited anhedonia and internalizing self-report instrument for distinguishing between antidepressant resistant and responsive depression profiles. [ABSTRACT FROM AUTHOR]

Background Depression and treatment with antidepressant medication is common in patients with malignant glioma. However, the extent to which antidepressants may affect the disease is not fully understood. Therefore, the purpose of the present study was to investigate possible associations between treatment with antidepressant medication and survival in glioma patients. Methods We performed a registry-based cohort study including 1231 patients with malignant glioma (WHO grades 2, 3, and 4) having undergone surgery, and 6400 matched controls without glioma. All data were extracted from the RISK North database, which contains information from multiple national population-based registries in Sweden. Results Treatment with antidepressants is more common in patients with malignant glioma (27%), compared to controls (16%), P  < .001. Treatment with antidepressants after surgery for glioma was significantly associated with poorer survival. These effects were observed both for selective serotonin reuptake inhibitors (SSRIs) and non-SSRIs. In grade 4 glioma, SSRI treatment was associated with a hazard ratio (HR) of 3.32 (95% CI 2.69–4.10, P  < .001), and non-SSRI treatment a HR of 3.54 (95% CI 2.52–4.99, P  < .001), compared to glioma patients without antidepressants. In grade 2-3 glioma, the HR for SSRI treatment was 3.26 (95% CI 2.19–4.85, P  < .001), and for non-SSRI treatment was 7.71 (95% CI 4.22–14.12, P  < .001). Conclusions Our results demonstrate a negative association between antidepressant medication and survival in glioma. Further research will be needed to clarify causation. [ABSTRACT FROM AUTHOR]

Antidepressants (ADs) are among the most commonly prescribed drugs worldwide. Persons with mental illness taking ADs commonly report sexual dysfunction (SD) related to treatment. A brief discussion on the neurobiology of sexual functioning and mechanism of treatment-emergent SD (TESD) was performed. The incidence of prevalence of TESD in various studies has been reviewed. TESD impacts patients as it frequently leads to nonadherence, while psychiatrists have challenges in proceeding forward with treatment in such patients. Assessment of patients with suspected TESD is described with a focus on practical tips for clinicians. Five strategies (watchful waiting, drug holiday, downward titration, switching, and add-on therapy) to manage TESD have been extensively discussed with evidence in the literature. Each strategy comes with its own bag of advantages and drawbacks, which have been pointed out for simplicity. A detailed discussion on individual pharmacological strategies is given, and options for non-pharmacological management that can be tried are enlisted. Common clinical case scenarios have been discussed to incorporate the implementation of this literature [ABSTRACT FROM AUTHOR]

Dystonia is characterized by sustained or intermittent involuntary muscle contractions. Psychiatric symptoms are essential non‐motor features of dystonia, and higher risks of depressive and anxiety disorders have been reported. The precedence of psychiatric to motor symptoms in some patients and the dopaminergic and serotonergic system involvement in both the motor and psychiatric aspects suggest these psychiatric disorders may be intrinsic to the neurobiology of dystonia. Nevertheless, psychiatric comorbidities are often construed as secondary reactions to motor disabilities and the negative bio‐psycho‐social impacts of dystonia, leading to underdiagnosis and undertreatment. Research on antidepressant use in dystonia is scarce, especially in children and adolescents. This report presents a 17‐year‐old female with dystonia comorbid with depression with psychotic features, whose motor symptoms improved but psychiatric symptoms persisted with dopaminergic pharmacotherapy. Sertraline was finally added 5 years after the onset and successfully managed her psychotic depression without worsening motor symptoms. Early detection, prompt diagnosis, and timely holistic treatment with dopaminergic agents, antidepressants, and psychosocial interventions are critical for the mental health of dystonia patients. [ABSTRACT FROM AUTHOR]

Introduction: Pharmacotherapy such as selective serotonin reuptake inhibitors (SSRIs) or serotonin‐noradrenaline reuptake inhibitors is recommended for the treatment of anxiety disorders. Although there are patients with persisted symptoms of anxiety disorders who are treated with monotherapy of benzodiazepine anxiolytics without SSRIs, the characteristics of these patients are unclear. In the present study, we investigated the characteristics of patients with persisted symptoms of anxiety disorder without SSRI prescription. Methods: From a prescription dataset covering 2018 and 2020, the prescriptions of 243 patients with anxiety disorder were analyzed. Patients were classified into two groups: SSRI non‐prescription and prescription groups. Results: The SSRI non‐prescription group had a higher ratio of females than did the SSRI prescription group (60.1% vs. 44.6%, respectively, p = 3.12 × 10−2), but statistically not significant after the Bonferroni correction. No significant differences in age, body mass index, or duration of outpatient visits were found between groups. Among the independent variables, sex (female) was the only variable identified that predicted SSRI non‐prescription. Conclusion: The present study showed that among patients with anxiety disorders, sex (female) was the only variable that predicted SSRI non‐prescription. [ABSTRACT FROM AUTHOR]

Depressive disorders are leading contributors to the global mental health-related burden, and they represent a challenge for real-world clinicians, due to the low rates of remission despite the high availability of treatments. Often, depression shows in the context of multiple chronic comorbidities, thus requiring precise and accurate management of pharmacological treatments to avoid interactions and side effects. These criticalities call for the need for new strategies of treatment, which may include new insights into the pharmacological properties of currently available antidepressant drugs, to enhance their efficacy in the different contexts in which depression may arise. Trazodone is the prototype serotonin antagonist/reuptake inhibitor antidepressant (SARI). Due to the malleability granted by its multiple formulations, trazodone is frequently used to treat depression, both as an add-on to other antidepressants and as a monotherapy, with satisfying results. Moreover, its tolerability makes it one of the most prescribed antidepressants in patients with poly-treated comorbid medical illnesses, especially in the elderly. Herein, a case series is presented regarding the use of trazodone in patients with complex comorbid diagnoses or distressing side effects. Each of the three cases has been discussed in three specific Round Tables, involving expert clinicians in the fields of Psychiatry, Neurology, General Practice, and Geriatrics using the Nominal Group Technique. The ideas collected have been used to integrate the cases and the discussion with the intent of facilitating accessibility to the widest audience of physicians and clinical workers in different clinical practice contexts. The final aim of this paper is to promote an increasingly personalized use of trazodone in real-world patients with depression.

Objective: Serotonin reuptake inhibitors cause weight gain, leading to drug discontinuation, relapse, and worsening of symptoms. This study aims to investigates the effect of metformin on weight loss, anthropometric indicators and laboratory assessments in patients of Rasht city. Methods: This clinical trial study with parallel-group design was organized based on 60 patients in treatment group (undergoing metformin) and 60 patients in control group (undergoing routine treatment) in Shafa hospital during July 2019 to January 2020. First, we determined the overweight patients. After that, a psychiatric assistant randomly divides them into two groups, intervention and control. Both groups of patients will be explained in terms of how they were studied and whether or not they received metformin. In order to statistical analysis of collected data, we applied the Mann-Whitney U test and repeated measures ANOVA. For conducting all analysis, the IBM SPSS Statistics 28 software was used. Results: The mean BMI and abdominal circumference decreased significantly in the intervention group. The wrist circumference in the intervention group decreased over time, but this difference was not statistically significant. There was no statistically significant difference between the average changes of the mean values of the laboratory assessment among the group. Conclusion: Weight gain can cause problems related to compliance with treatment and anxiety and depression. On the other hand, in our study, metformin was not superior to lifestyle improvements and practicing preventive methods for weight control. Further research on SSRIs and monitoring of anthropometric indices is recommended.

BackgroundAmong the renewed applications of psychedelic medicines in psychiatry, 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for posttraumatic stress disorder (PTSD) has demonstrated the most promise in early small-scale studies. Recent exploratory analyses from prior clinical trials of MDMA-assisted therapy for PTSD have suggested that recent use of selective serotonin reuptake inhibitors (SSRIs)-the only medication class with United States Food and Drug Administration (FDA) approval to treat PTSD-can significantly dampen the efficacy of this novel therapy. Although psychedelic medicines are not yet FDA approved, MDMA is very likely to be the first to achieve FDA approval-perhaps within the next 2 years. Given this timeline, the field would benefit from more knowledge about potential interactions between this novel therapy and our current treatments.MethodsThis brief report reviews selected literature in the basic and clinical neurosciences relevant to the interaction of SSRIs and MDMA.FindingsThe possibility that SSRI use could dampen future responses to MDMA-assisted therapy for PTSD raises many important questions about the biological mechanisms as well as ethical implications around the most appropriate way to counsel patients. In this brief report, we compare the evidence for SSRIs and MDMA-assisted therapy in the treatment of PTSD and discuss what is known about the neurobiological interactions between these 2 medicines.ConclusionsThere is strong neurobiological plausibility for the hypothesis that chronic SSRI use dampens response to MDMA-assisted therapy, although current knowledge in the field is limited and primarily relates to acute pharmacodynamic interactions. Our commentary highlights the urgent need for future work dedicated to addressing this important clinical topic.

Background: Fluvoxamine (FVX) has been proposed as a potential treatment for severe COVID-19 by the σ-1 receptor agonist, which can reduce cytokine production. However, the efficacy of FVX remains controversial. Methods: A historical retrospective cohort study was conducted in mild to moderate COVID-19 patients, 2:1 ratio of standard of care (SOC) and FVX treatments to assess the effectiveness of FVX in preventing deterioration by the fifth day of treatment. Results: Of 752 eligible patients, 234 received FVX while 518 received SOC, and there was no significant difference in the effectiveness of FVX and SOC in preventing clinical deterioration. On the fifth day after treatment, 86.1 % of patients in the FVX-treated group did not experience clinical deterioration compared to 78.7 % in the SOC group. Notably, the FVX group had higher rates of pneumonia development and hospitalization, requiring more oxygen supplementation while showing less reduction in viral shedding than the SOC group. However, no difference in mechanical ventilation use, ICU admission, and survival was observed. Conclusion: Fluvoxamine treatment is failed to demonstrate effectiveness in preventing deterioration in mild to moderate COVID-19 and may lead to a higher incidence of pneumonia, hospitalization, and oxygen supplementation, necessitating careful consideration before prescribing the drug for COVID-19.

Background: Treatment of depressive episodes in young patients is challenging owing to several reasons such as poor diagnostic stability and atypical presentation. Evidence regarding treating such patients with antidepressants such as selective serotonin reuptake inhibitor (SSRI) is not clear. Methods: Fifty patients aged 10-24 years diagnosed with depressive episodes and drug-free for at least 3 months were rated on Beck's Depression Inventory (BDI), The Mood Disorder Questionnaire (MDQ), and Beck Scale for Suicidal Ideation (BSS). The scores of BSS and BDI were compared across four timeframes (weeks 0, 2, 4, and 6) for MDQ-positive and negative patients by using the generalized estimating equations model. Results: Patients who were MDQ-positive (11 patients) tended to score higher on BDI (at weeks 2 and 4) and BSS (at weeks 2, 4, and 6) as compared to MDQ-negative patients (39 patients). After being started on SSRI, MDQ-positive patients showed a poorer response as compared to the other group. The small sample size and short follow-up duration were the major limitations. Conclusions: Close clinical monitoring with regular follow-up during antidepressant initiation is recommended to reduce the risk of suicidality. [ABSTRACT FROM AUTHOR]

We present the case of a 42-year-old female whose escitalopram use potentially contributed to a diagnosis of collagenous colitis. The patient presented with significant watery, nonbloody diarrhea, abdominal cramping and pain, and weight loss. Established risk factors of microscopic colitis in this patient include a history of smoking and female gender. The patient underwent a colonoscopy, which confirmed histological changes consistent with collagenous colitis. Prescribed therapy included oral budesonide and omeprazole, continued for eight and twelve weeks, respectively. Escitalopram was continued, with a discussion regarding changing to an alternative therapy. Based on the patient's history of escitalopram use, this case suggests a relationship between escitalopram and microscopic colitis. Though case reports of patients diagnosed with microscopic colitis after antidepressant use are published, this case appears to be the only report of collagenous colitis without macroscopic complications following escitalopram use. This case adds further support in that antidepressants may contribute to microscopic colitis. Despite an undefined frequency of association, healthcare providers who prescribe antidepressants should be cognizant of the theorized association and understand risk factors, screening, and treatment approaches. [ABSTRACT FROM AUTHOR]

Introduction: Depression is strongly associated with Alzheimer's disease (AD). Antidepressants are commonly used in patients before and after their diagnosis of AD. To date, the relationship between antidepressants and AD remains unclear. Methods: In our study, we administered sertraline or paroxetine to wild type (WT) and APPswe/PSEN1dE9 (APP/PSEN1) transgenic mouse models for up to 12 months. We quantified the drug concentrations using LC-MS/MS analysis and measured serum serotonin level using an ELISA assay. Additionally, we evaluated the amyloid burdens through thioflavin-S and Congo red stainings, and recognition memory using the novel object recognition test. Results: Our findings revealed that mice treated with paroxetine exhibited a significantly higher level of weight gain compared to the control group and increased mortality in APP/PSEN1 mice. After 12 months of antidepressant treatment, the sertraline level was measured at 289.8 ng/g for cerebellum, while the paroxetine level was 792.9 ng/g for cerebellum. Sertraline significantly increased thioflavin-S and Congo red depositions, along with gliosis, in both isocortex and hippocampus of APP/PSEN1 mice compared to the control group. Both antidepressants also led to a decreased recognition index in APP/PSEN1 mice. Conclusion: These findings suggest a potential role of sertraline in AD pathogenesis, emphasizing the need to reassess the use of these antidepressants in patients with AD. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has impacted many aspects of everyday life, including the (mental) healthcare system. An increase in depression and anxiety symptoms has been reported worldwide, and is particularly pronounced in females and young people. We aimed to evaluate changes in prescription rates for psychopharmacological medication, which is often used to treat depression and anxiety. Method: Based on data from the Austrian public health insurance institutions, we conducted an interrupted time series analysis of antidepressants and antipsychotics, comparing prescription rate developments before and throughout the COVID-19 pandemic (2013 to 2021), with a special focus on adolescents (10–19 years) in comparison to the general population. Data were based on all public prescriptions in the outpatient sector nationwide. Age- and sex-stratified time-series models were fitted to the pre-COVID period (first quarter (Q1) of 2013 to second quarter (Q2) of 2020). These were used to generate forecasts for the period from the third quarter (Q3) of 2020 to the fourth quarter (Q4) of 2021, which were subsequently compared to observed developments in order to assess significant deviations from the forecasted development paths. Results: For the majority of the evaluated period, we found a significant excess of antidepressant prescriptions among both male and female adolescents (10–14 and 15–19 years) compared to the forecasted development path, while the general population was mostly within 97.5% confidence intervals of the forecasts. Regarding antipsychotics, the interrupted time series analysis revealed a significant excess in the group of female adolescents in almost all quarters, which was especially pronounced in the 15–19 age group. Prescription rates of antipsychotics in the general population only showed a significant excess in two quarters. Conclusion: Increased rates of adolescents receiving psychopharmacological treatment echo the epidemiological trends of an increase in depression and anxiety symptoms reported in the literature. This increase is especially pronounced in female adolescents. [ABSTRACT FROM AUTHOR]

Aim and Objectives: This study examined SSRI-related adverse drug reactions (ADRs), medication adherence, commonly prescribed SSRIs, and gender and age distribution in patients with depression at three tertiary care hospitals in Kerala, India. Materials and Methods: The prospective observational study was conducted in the psychiatry departments of Al Azhar Medical College Hospital in Thodupuzha, Mount Zion Medical College Hospital in Adoor and Christuraj Hospital in Kottarakara. A predefined WHO form was used to evaluate ADRs. A study-specific data collection form was used to record demographics, clinical details, and prescribed drugs following a unified research protocol. In addition, the WHO causality scale, the Naranjo Probability scale, Hartwig's severity assessment scale, and the Modified Shumock and Thornton Preventability Scale were also used to evaluate ADRs. Results: Among the 230 patients (female, 56.52%; depression prevalence age 21-40, 57.83%) who took SSRI, 26.87% reported ADRs. Depressive mood disorder was the most prevalent diagnosis, affecting 47% of patients, followed by generalized anxiety disorder (17.3%). Escitalopram (60.43%) was the most prescribed SSRI for depression, followed by fluvoxamine (21.74%). ADRs were predominantly observed in the cardiovascular, neurological, and gastrointestinal systems. Nausea was the most common ADR (25.77%), followed by insomnia (22.68%), lethargy (16.49%), and headache (11.3%).43% of the ADRs were 'probable causality.' Among all the ADRs, 54% were preventable. 64% of the ADRs were mild in their severity. Escitalopram, the most prescribed medication, was the primary cause of ADRs, with fatigue being particularly prevalent. Non-adherence to SSRIs was common, especially with escitalopram, often due to missed doses. Conclusion: This study shows the prevalence of depressive mood disorders in the population examined. SSRIs like escitalopram and fluvoxamine often cause insomnia and nausea when prescribed for depression. Clinical pharmacists are crucial to patient counselling and education. Targeted strategies are needed to reduce antidepressant nonadherence due to multiple factors. Given the dangers of untreated depression, such as suicide, public health requires effective depression management. [ABSTRACT FROM AUTHOR]

Postpartum depression affects many individuals after parturition, and selective serotonin reuptake inhibitors (SSRIs) are often used as the first-line treatment; however, both SSRIs and lactation are independently associated with bone loss due to the role of serotonin in bone remodeling. Previously, we have established that administration of the SSRI fluoxetine during the peripartal period results in alterations in long-term skeletal characteristics. In the present study, we treated mice with either a low or high dose of fluoxetine during lactation to determine the consequences of the perturbation of serotonin signaling during this time period on the dam skeleton. We found that lactational fluoxetine exposure affected both cortical and trabecular parameters, altered gene expression and circulating markers of bone turnover, and affected mammary gland characteristics, and that these effects were more pronounced in the dams that were exposed to the low dose of fluoxetine in comparison to the high dose. Fluoxetine treatment during the postpartum period in rodents had short term effects on bone that were largely resolved 3 months post-weaning. Despite the overall lack of long-term insult to bone, the alterations in serotonin-driven lactational bone remodeling raises the question of whether fluoxetine is a safe option for the treatment of postpartum depression. [ABSTRACT FROM AUTHOR]

Psychedelics could have revolutionary potential in psychiatry, although, until recently, the pharmacodynamic properties of such compounds have not seemed to differ much from those of serotonin, whose levels are raised by Serotonin Reuptake Inhibitors (SSRI). The cardinal point is that serotonergic compounds, such as antidepressive drugs, do not have the potential to induce long-lasting neuroplasticity as psychedelics do. Therefore, the biological underpinnings of the peculiar effect of such compounds had not been fully understood until new astonishing molecular findings came out this year to shed new light on them. Specifically, the phenomena of neuroplasticity are triggered by the stimulation of a peculiar type of receptors: the intracellular 5-HT2A receptors. Interestingly, psychedelics can reach this pool of intracellular receptors due to their lipophilic properties, as they can cross the lipophilic neuronal membrane while serotonin cannot. The importance of such a discovery should not be underestimated as the specific mechanisms involved have not yet been elucidated and a better understanding of them could pave the way to the development of new drugs (and/or new tailored therapeutic strategies) able to sustain neuroplasticity while minimizing side effects. [ABSTRACT FROM AUTHOR]

Fluvoxamine (FVX) has been proposed as a potential treatment for severe COVID-19 by the σ-1 receptor agonist, which can reduce cytokine production. However, the efficacy of FVX remains controversial. A historical retrospective cohort study was conducted in mild to moderate COVID-19 patients, 2:1 ratio of standard of care (SOC) and FVX treatments to assess the effectiveness of FVX in preventing deterioration by the fifth day of treatment. Of 752 eligible patients, 234 received FVX while 518 received SOC, and there was no significant difference in the effectiveness of FVX and SOC in preventing clinical deterioration. On the fifth day after treatment, 86.1 % of patients in the FVX-treated group did not experience clinical deterioration compared to 78.7 % in the SOC group. Notably, the FVX group had higher rates of pneumonia development and hospitalization, requiring more oxygen supplementation while showing less reduction in viral shedding than the SOC group. However, no difference in mechanical ventilation use, ICU admission, and survival was observed. Fluvoxamine treatment is failed to demonstrate effectiveness in preventing deterioration in mild to moderate COVID-19 and may lead to a higher incidence of pneumonia, hospitalization, and oxygen supplementation, necessitating careful consideration before prescribing the drug for COVID-19. [ABSTRACT FROM AUTHOR]

Background—Various antidepressant agents are metabolized by the CYP2C19 enzyme, including Citalopram and Escitalopram. Variation in CYP2C19 expression might give rise to different plasma concentrations of the active metabolites, potentially affecting both drugs' efficacy and tolerability. Aim—The aim of this study was to evaluate differences in the Escitalopram and Citalopram efficacy and tolerability between different CYP2C19 genotype-based metabolizing categories in outpatients suffering from major depressive disorder (MDD). Methods—In a retrospective, longitudinal cohort study of electronic medical-record data, 283 patients with MDD who were prescribed Escitalopram or Citalopram with the available CYP2C19-genotyping test were enrolled. The primary efficacy end point was adverse drug reactions recorded in the medical files. A proportional-odds, multilevel-regression model for longitudinal ordinal data was used to estimate the relation between the CYP2C19 genotype and adverse drug reactions, adjusting for potential confounding variables and other explanatory variables. Latent-class analysis (LCA) was utilized to detect the presence of clinically significant subgroups and their relation to an individual's metabolizing status for CYP2D6/CYP2C19. Results—With poor CYP2C19 metabolizers as a reference, for each unit difference in the activity score of the CYP2C19 phenotype, the odds ratio for drug intolerability was lowered by 0.73 (95% credible intervals: 0.56–0.89), adjusting for significant covariates. In addition, applying LCA, we identified two qualitatively different subgroups: the first group (61.85%) exhibited multiple side effects, low compliance, and frequent treatment changes, whereas the second group (38.15%) demonstrated fewer side effects, good adherence, and fewer treatment changes. The CYP2C19 phenotype was substantially associated with the group membership. Conclusions—We found a positive association between the CYP2C19 activity scores, as inferred from the genotype, and both the efficacy of and tolerability to both Es/Citalopram. LCA enabled valuable insights into the underlying structure of the population; the CYP2C19 phenotype has a predictive value that discriminates between low-adherence, low-drug-tolerance, and low-response patients and high-adherence, high-drug-tolerance, and high-response patients. Personalized medicine based on CYP2C19 genotyping could evolve as a promising new avenue towards mitigating Escitalopram and Citalopram therapy and the associated side effects and enhancing treatment success. [ABSTRACT FROM AUTHOR]

Premenstrual syndrome (PMS) is a common disorder affecting women of reproductive age, with an estimated global prevalence of 47.8%, with severe symptoms occurring in 3-8%, significantly affecting daily functioning. GABA conductance and changes in neurosteroid levels, particularly allopregnanolone, are suspected to play a substantial role in the disorder’s etiology. In this paper, we provide an overview of recent reports on the etiology and recognized therapeutic approaches, encompassing both pharmacological and non-pharmacological interventions. Our examination includes studies on SSRIs, hormonal agents, neurosteroids, supplementation, and therapeutic roles. We aim to determine the most favorable treatment regimen by comparing medication effects and alternative methods. The treatment of PMS is crucial for enhancing the quality of life for affected women. Medications used in PMS treatment should be individually selected to achieve the best therapeutic effect, considering the clinical situation of the patients.

Introduction:Patients’ adherence to antidepressants is generally reported to be poor. This study examined whether users of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) enhance medication adherence following access to a mobile application (app) tailored for this patient group. The study addresses the implementation phase of medication adherence.Methods:The study was a single group pre-post intervention design. Data were collected using the validated OsloMet Adherence-to-medication Survey tool (OMAS-37) before and after app access. Pre-app access survey (Survey 1) was conducted via social media and online newspapers, encompassing 445 SSRI/SNRI users aged 18 years and above. Post-app access survey (Survey 2) was sent to 103 SSRI/SNRI users from Survey 1. Wilcoxon Signed Rank Test compared pre- and post-intervention adherence measurements. Pearson’s chi-square tests and Fisher’s exact tests compared study population categories.Results:Forty-two SSRI/SNRI users, median age 26 (IQR 17), 93% identifying as female, used the app while using the same antidepressant during the 2-month period between gaining access to the app and Survey 2. There was a statistically significant reduction in non-adherence score post-app access (z = 3.57, n = 42, p < 0.001) with medium effect size (r = 0.39), indicating enhanced adherence. Total non-adherence score decreased by 39% from pre-to post-access, and there was a 12% decrease in users scoring equivalent with poor adherence (score

Adolescent major depressive disorder (MDD) is associated with altered resting-state connectivity between the default mode network (DMN) and the salience network (SN), which are involved in self-referential processing and detecting and filtering salient stimuli, respectively. Using spectral dynamical causal modelling, we investigated the effective connectivity and input sensitivity between key nodes of these networks in 30 adolescents with MDD and 32 healthy controls while undergoing resting-state fMRI. We found that the DMN received weaker inhibition from the SN and that the medial prefrontal cortex and the anterior cingulate cortex showed reduced self-inhibition in MDD, making them more prone to external influences. Moreover, we found that selective serotonin reuptake inhibitor (SSRI) intake was associated with decreased and increased self-inhibition of the SN and DMN, respectively, in patients. Our findings suggest that adolescent MDD is characterized by a hierarchical imbalance between the DMN and the SN, which could affect the integration of emotional and self-related information. We propose that SSRIs may help restore network function by modulating excitatory/inhibitory balance in the DMN and the SN. Our study highlights the potential of prefrontal-amygdala interactions as a biomarker and a therapeutic target for adolescent depression.

Abstract Background We present a case report on the efficacy of the short‐term application of vortioxetine in managing winter depression in patients with seasonal bipolar disorder (BP). Standard treatment strategies for BP may not adequately address seasonal depressive symptoms during winter in patients with seasonal BP patterns. Depressive symptoms during winter may be linked to seasonal changes in serotonin transporter binding, such as a decrease in synaptic serotonin levels, necessitating alternative approaches. Although antidepressants, including vortioxetine, are effective in treating seasonal monopolar depression, their efficacy and safety in treating depression in patients with seasonal BP patterns remain unclear. Case Presentation This case report focuses on a 44‐year‐old male patient diagnosed with seasonal BP who had recurrent depressive episodes, specifically during winter. Notably, the patient had a significant decrease in recurrent episodes after short‐term seasonal vortioxetine use without inducing mania or rapid cycling. Conclusion Our study highlights the potential effectiveness of a seasonal, short‐term treatment strategy with antidepressants, including vortioxetine, for winter depression in individuals with BP.

Rapid neutrophil recruitment to sites of inflammation is crucial for innate immune responses. Here, we reveal that the G-protein-coupled receptor GPR35 is upregulated in activated neutrophils, and it promotes their migration. GPR35-deficient neutrophils are less recruited from blood vessels into inflamed tissue, and the mice are less efficient in clearing peritoneal bacteria. Using a bioassay, we find that serum and activated platelet supernatant stimulate GPR35, and we identify the platelet-derived serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) as a GPR35 ligand. GPR35 function in neutrophil recruitment is strongly dependent on platelets, with the receptor promoting transmigration across platelet-coated endothelium. Mast cells also attract GPR35+ cells via 5-HIAA. Mice deficient in 5-HIAA show a loss of GPR35-mediated neutrophil recruitment to inflamed tissue. These findings identify 5-HIAA as a GPR35 ligand and neutrophil chemoattractant and establish a role for platelet- and mast cell-produced 5-HIAA in cell recruitment to the sites of inflammation and bacterial clearance.

Abstract Background Factors influencing antidepressant treatment discontinuation are poorly understood. In the present study, we aimed to estimate the prevalence of antidepressant treatment discontinuation and identify demographic characteristics, psychiatric comorbidities, and specific side effects associated with treatment discontinuation. Methods We leveraged data from the Australian Genetics of Depression Study (AGDS; N = 20,941) to perform a retrospective cohort study on antidepressant treatment discontinuation. Participants were eligible if they were over 18 years of age, had taken antidepressants in the past 4 years, and provided informed consent. Results Among the ten antidepressants studied, the highest discontinuation rates were observed for Mirtazapine (57.3%) and Amitriptyline (51.6%). Discontinuation rates were comparable across sexes except for Mirtazapine, for which women were more likely to discontinue. The two most common side effects, reduced sexual function and weight gain, were not associated with increased odds of treatment discontinuation. Anxiety, agitation, suicidal thoughts, vomiting, and rashes were associated with higher odds for treatment discontinuation, as were lifetime diagnoses of PTSD, ADHD, and a higher neuroticism score. Educational attainment showed a negative (protective) association with discontinuation across medications. Conclusions Our study suggests that not all side effects contribute equally to discontinuation. Common side effects such as reduced sexual function and weight gain may not necessarily increase the risk of treatment discontinuation. Side effects linked to discontinuation can be divided into two groups, psychopathology related and allergy/intolerance.

Abstract Background Antidepressant discontinuation is associated with a broad range of adverse effects. Debilitating discontinuation symptoms can impede the discontinuation process and contribute to unnecessary long-term use of antidepressants. Antidepressant trials reveal large placebo effects, indicating a potential use of open-label placebo (OLP) treatment to facilitate the discontinuation process. We aim to determine the effect of OLP treatment in reducing antidepressant discontinuation symptoms using a series of N-of-1 trials. Methods A series of randomized, single-blinded N-of-1 trials will be conducted in 20 patients with fully remitted DSM-V major depressive disorder, experiencing moderate to severe discontinuation symptoms following antidepressant discontinuation. Each N-of-1 trial consists of two cycles, each comprising two-week alternating periods of OLP treatment and of no treatment in a random order, for a total of eight weeks. Our primary outcome will be self-reported discontinuation symptoms rated twice daily via the smartphone application ‘StudyU’. Secondary outcomes include expectations about discontinuation symptoms and (depressed) mood. Statistical analyses will be based on a Bayesian multi-level random effects model, reporting posterior estimates of the overall and individual treatment effects. Discussion Results of this trial will provide insight into the clinical application of OLP in treating antidepressant discontinuation symptoms, potentially offering a new cost-effective therapeutic tool. This trial will also determine the feasibility and applicability of a series of N-of-1 trials in a clinical discontinuation trial. Trial registration ClinicalTrials.gov: NCT05051995, first registered September 20, 2021.

Objectives: Fluvoxamine (FVX) is an antidepressant proposed to its immunomodulatory effects in preventing deterioration in mild and moderate COVID-19. Methods: An open-label, 1:1 randomized controlled trial was assigned either combination therapy 50 mg twice daily of FVX for 10 days and favipiravir (FPV) or FPV alone to assess the efficacy in preventing disease progression in mild to moderate COVID-19 on the 5th day. Results: In total, 134 patients with mild COVID-19 received FPV and 132 received FVX/FPV, 31 patients with moderate COVID-19 received FPV/dexamethasone (FPV/Dex), and 30 received FVX/FPV/Dex. The intention-to-treat (ITT) analysis showed no difference of no clinical deterioration on the 5th day in both mild COVID-19 (100% in FPV vs 97% in FVX/FPV) and moderate COVID-19 (83.9% in FPV/Dex vs 86.7% in FVX/FPV/Dex). However, there was a low rate of oxygen supplemental, hospitalization, or intensive care in both groups and zero death in all groups. No significant difference in oxygen supplemental, hospitalization, radiological, virological, or biochemical outcomes, and the immunomodulatory effect was observed between the group. Conclusion: The combined fluvoxamine treatment did not add benefit in preventing deterioration in patients with mild to moderate COVID-19 without the immunomodulatory effect observed, although it demonstrated low hospitalization rates, oxygen supplemental, intensive care needed, and zero mortality. Trial Registration: Thai clinical trials registry (TCTR) no. 20210615002.

Abstract Background Currently, the main pharmaceutical intervention for COVID-19 is vaccination. While antidepressant (AD) drugs have shown some efficacy in treatment of symptomatic COVID-19, their preventative potential remains largely unexplored. Analysis of association between prescription of ADs and COVID-19 incidence in the population would be beneficial for assessing the utility of ADs in COVID-19 prevention. Methods Retrospective study of association between AD prescription and COVID-19 diagnosis was performed in a cohort of community-dwelling adult mental health outpatients during the 1st wave of COVID-19 pandemic in the UK. Clinical record interactive search (CRIS) was performed for mentions of ADs within 3 months preceding admission to inpatient care of the South London and Maudsley (SLaM) NHS Foundation Trust. Incidence of positive COVID-19 tests upon admission and during inpatient treatment was the primary outcome measure. Results AD mention was associated with approximately 40% lower incidence of positive COVID-19 test results when adjusted for socioeconomic parameters and physical health. This association was also observed for prescription of ADs of the selective serotonin reuptake inhibitor (SSRI) class. Conclusions This preliminary study suggests that ADs, and SSRIs in particular, may be of benefit for preventing COVID-19 infection spread in the community. The key limitations of the study are its retrospective nature and the focus on a mental health patient cohort. A more definitive assessment of AD and SSRI preventative potential warrants prospective studies in the wider demographic.

Autism spectrum disorder is an increasingly diagnosed disorder among children, yet its pathogenesis is still unknown. Possible causes are sought in genetic mutations, cellular processes occurring in the nervous system during development and external factors affecting the fetus during the prenatal period. In recent years, there have been an increasing number of reports linking the occurrence of the spectrum to antidepressant medications, especially from the SSRI group, taken by pregnant women for depressive disorders, which occur in up to a dozen percent of women in this group. The involvement of serotonin in the development of the nervous system during the fetal period is taken as the reason for this phenomenon. To date, no clear consensus has been reached on this issue, and many distractors in the research are highlighted, such as the effect of maternal depression on fetal development, among others. There is no doubt that further research is needed to better assess the risk of ASD associated with SSRI use and dosage during pregnancy

Background: Factors influencing antidepressant treatment discontinuation are poorly understood. In the present study, we aimed to estimate the prevalence of antidepressant treatment discontinuation and identify demographic characteristics, psychiatric comorbidities, and specific side effects associated with treatment discontinuation. Methods: We leveraged data from the Australian Genetics of Depression Study (AGDS; N = 20,941) to perform a retrospective cohort study on antidepressant treatment discontinuation. Participants were eligible if they were over 18 years of age, had taken antidepressants in the past 4 years, and provided informed consent. Results: Among the ten antidepressants studied, the highest discontinuation rates were observed for Mirtazapine (57.3%) and Amitriptyline (51.6%). Discontinuation rates were comparable across sexes except for Mirtazapine, for which women were more likely to discontinue. The two most common side effects, reduced sexual function and weight gain, were not associated with increased odds of treatment discontinuation. Anxiety, agitation, suicidal thoughts, vomiting, and rashes were associated with higher odds for treatment discontinuation, as were lifetime diagnoses of PTSD, ADHD, and a higher neuroticism score. Educational attainment showed a negative (protective) association with discontinuation across medications. Conclusions: Our study suggests that not all side effects contribute equally to discontinuation. Common side effects such as reduced sexual function and weight gain may not necessarily increase the risk of treatment discontinuation. Side effects linked to discontinuation can be divided into two groups, psychopathology related and allergy/intolerance. [ABSTRACT FROM AUTHOR]

Background: Antidepressant discontinuation is associated with a broad range of adverse effects. Debilitating discontinuation symptoms can impede the discontinuation process and contribute to unnecessary long-term use of antidepressants. Antidepressant trials reveal large placebo effects, indicating a potential use of open-label placebo (OLP) treatment to facilitate the discontinuation process. We aim to determine the effect of OLP treatment in reducing antidepressant discontinuation symptoms using a series of N-of-1 trials. Methods: A series of randomized, single-blinded N-of-1 trials will be conducted in 20 patients with fully remitted DSM-V major depressive disorder, experiencing moderate to severe discontinuation symptoms following antidepressant discontinuation. Each N-of-1 trial consists of two cycles, each comprising two-week alternating periods of OLP treatment and of no treatment in a random order, for a total of eight weeks. Our primary outcome will be self-reported discontinuation symptoms rated twice daily via the smartphone application ‘StudyU’. Secondary outcomes include expectations about discontinuation symptoms and (depressed) mood. Statistical analyses will be based on a Bayesian multi-level random effects model, reporting posterior estimates of the overall and individual treatment effects. Discussion: Results of this trial will provide insight into the clinical application of OLP in treating antidepressant discontinuation symptoms, potentially offering a new cost-effective therapeutic tool. This trial will also determine the feasibility and applicability of a series of N-of-1 trials in a clinical discontinuation trial. Trial registration: ClinicalTrials.gov: NCT05051995, first registered September 20, 2021. [ABSTRACT FROM AUTHOR]

The peripartal period is marked by alterations in calcium metabolism to accommodate for embryonic skeletal mineralization and support bone development of offspring in early life, and serotonin plays a critical role in modulating peripartal bone remodeling. Selective serotonin reuptake inhibitors (SSRIs) are commonly used as first‐line treatment for psychiatric illness during pregnancy and the postpartum period and considered safe for maternal use during this time frame. In order to evaluate the effect of peripartal alterations of the serotonergic system on maternal skeletal physiology, we treated dams with the SSRI fluoxetine during gestation only, lactation only, or during the entire peripartal period. Overall, we found a low dose of fluoxetine during gestation only had minimal impacts on maternal bone at weaning, but there were implications on maternal skeleton at weaning when dams were exposed during lactation only or during the entire peripartal period. We found that these effects were differential between female mice dosed lactationally or peripartally, and there were also impacts on maternal mammary gland at weaning in both of these groups. Though SSRIs are largely considered safe maternally during the peripartal period, this study raises the question whether safety of SSRIs, specifically fluoxetine, during the peripartal period should be reevaluated. [ABSTRACT FROM AUTHOR]

Lifelong premature ejaculation (PE) in men lacks an adequate on-demand pharmacological treatment. Although selective serotonin reuptake inhibitors (SSRIs) are used for PE they only work after chronic treatment, or if used ondemand, less adequately than chronic SSRI treatment. It has been shown that the addition of a behaviorally silent 5-HT1A-receptor antagonist to an SSRI can generate acute inhibitory effects on male rat sexual behavior. Atlas987 is a selective 5-HT1A-receptor antagonist with equal potency to displace agonist and antagonist binding to pre- and post-synaptic 5-HT1A receptors in rat and human brain. To investigate whether Atlas987 together with the SSRI paroxetine, a combination called Enduro, induces acute inhibitory effects on male rat sexual behavior, we tested Enduro in Wistar rats in a dose-dependent manner. We first tested the 5-HT1A receptor antagonist Atlas987 in 8-OH-DPAT induced serotonergic behavior in rats. Second, we tested Enduro in a dose-dependent manner in male sexual behavior. Third, we tested the effective time window of Enduro's action, and lastly, we measured the plasma levels of Atlas987 and paroxetine over an 8-h period. Results showed that Enduro acutely and dose-dependently reduced the number of ejaculations and increased the ejaculation latencies. The behavioral pattern induced reflected a specific effect on sexual behavior excluding nonspecific effects like sedation or sensoric-motoric disturbances. The time-window of activity of Enduro showed that this sexual inhibitory activity was at least found in a 1-4 h' time window after administration. Plasma levels showed that in this time frame both Atlas987 and paroxetine are present. In conclusion, in rats, Enduro is successful in acutely inhibiting sexual behavior. These results may be therapeutically attractive as "on demand" treatment for life-long premature ejaculation in men. [ABSTRACT FROM AUTHOR]

• Adding 50 mg of fluvoxamine twice daily to favipiravir provides no benefit. • Fluvoxamine is ineffective in preventing severe COVID-19. • No anti-inflammatory effect or improved radiologic outcome was seen with fluvoxamine. • Cytokine changes are similar in fluvoxamine and non-fluvoxamine treatments. • The study found no immunomodulatory effect of fluvoxamine. Fluvoxamine (FVX) is an antidepressant proposed to its immunomodulatory effects in preventing deterioration in mild and moderate COVID-19. An open-label, 1:1 randomized controlled trial was assigned either combination therapy 50 mg twice daily of FVX for 10 days and favipiravir (FPV) or FPV alone to assess the efficacy in preventing disease progression in mild to moderate COVID-19 on the 5th day. In total, 134 patients with mild COVID-19 received FPV and 132 received FVX/FPV, 31 patients with moderate COVID-19 received FPV/dexamethasone (FPV/Dex), and 30 received FVX/FPV/Dex. The intention-to-treat (ITT) analysis showed no difference of no clinical deterioration on the 5th day in both mild COVID-19 (100% in FPV vs 97% in FVX/FPV) and moderate COVID-19 (83.9% in FPV/Dex vs 86.7% in FVX/FPV/Dex). However, there was a low rate of oxygen supplemental, hospitalization, or intensive care in both groups and zero death in all groups. No significant difference in oxygen supplemental, hospitalization, radiological, virological, or biochemical outcomes, and the immunomodulatory effect was observed between the group. The combined fluvoxamine treatment did not add benefit in preventing deterioration in patients with mild to moderate COVID-19 without the immunomodulatory effect observed, although it demonstrated low hospitalization rates, oxygen supplemental, intensive care needed, and zero mortality. Thai clinical trials registry (TCTR) no. 20210615002. [ABSTRACT FROM AUTHOR]

Background A prominent finding in major depressive disorder (MDD) is distorted stress hormone dynamics, which is regulated by serotonergic brain signaling. An interesting feature of the cerebral serotonin system is the serotonin 4 receptor (5-HT4R), which is lower in depressed relative to healthy individuals and also has been highlighted as a promising novel antidepressant target. Here, we test the novel hypothesis that brain 5-HT4R availability in untreated patients with MDD is correlated with cortisol dynamics, indexed by the cortisol awakening response (CAR). Further, we evaluate if CAR changes with antidepressant treatment, including a selective serotonin reuptake inhibitor, and if pretreatment CAR can predict treatment outcome. Methods Sixty-six patients (76% women) with a moderate to severe depressive episode underwent positron emission tomography imaging with [11C]SB207145 for quantification of brain 5-HT4R binding using BPND as outcome. Serial home sampling of saliva in the first hour from awakening was performed to assess CAR before and after 8 weeks of antidepressant treatment. Treatment outcome was measured by change in Hamilton Depression Rating Scale 6 items. Results In the unmedicated depressed state, prefrontal and anterior cingulate cortices 5-HT4R binding was positively associated with CAR. CAR remained unaltered after 8 weeks of antidepressant treatment, and pretreatment CAR did not significantly predict treatment outcome. Conclusions Our findings highlight a link between serotonergic disturbances in MDD and cortisol dynamics, which likely is involved in disease and treatment mechanisms. Further, our data support 5-HT4R agonism as a promising precision target in patients with MDD and disturbed stress hormone dynamics. [ABSTRACT FROM AUTHOR]

Abstract Background Depressive symptoms are the most common neuropsychiatric symptoms in patients with Alzheimer’s disease (AD). However, despite being common, no definite consensus recommendations exist for the management of depression in AD. Objective To assess the effects of selective serotonin reuptake inhibitors (SSRIs) on the alleviation of depressive symptoms in patients with AD. Material and methods Medline, Scopus, Web of Science, Google Scholar, and PsychINFO were electronically searched from inception until October 2022. Response to therapy and mean depression scores between the treatment (or before) and placebo (or after) groups were the primary outcomes. For depression scores, the standard mean deviation and accompanying 95% confidence interval were determined. The risk of bias was determined using the funnel plot, trim and fill, Egger’s and Begg’s analyses. Results SSRIs attenuated depressive symptoms in patients with AD (0.905 SMD, 95%CI, 0.689 to 1.121, p