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Purpose: Pharmacodynamic drug-drug interactions (PD DDIs) may influence the safety of non-vitamin K antagonist oral anticoagulants (NOACs), but the extent to which PD DDIs increase bleeding risks, remains unclear. Therefore, the impact of PD DDIs on bleeding outcomes in NOAC-treated patients with atrial fibrillation (AF) was investigated. Methods: Using Belgian nationwide data, NOAC-treated AF patients were included between 2013–2019. Concomitant use of PD interacting drugs when initiating NOAC treatment was identified. Results: Among 193,072 patients, PD DDIs were identified in 114,122 (59.1%) subjects. After multivariable adjustment, concomitant use of PD interacting drugs was associated with significantly higher risks of major or clinically-relevant non-major bleeding (adjusted hazard ratio (aHR) 1.19, 95% confidence interval (CI) (1.13–1.24)), gastrointestinal (aHR 1.12, 95%CI (1.03–1.22)), urogenital (aHR 1.21, 95%CI (1.09–1.35)) and other bleeding (aHR 1.28, 95%CI (1.20–1.36)), compared to NOAC-treated AF patients without PD interacting drug use. Increased bleeding risks were most pronounced with P2Y12 inhibitors (aHR 1.62, 95%CI (1.48–1.77)) and corticosteroids (aHR 1.53, 95%CI (1.42–1.66)), followed by selective serotonin or serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI, aHR 1.26, 95%CI (1.17–1.35)), low-dose aspirin (aHR 1.14, 95%CI (1.08–1.20)) and non-steroidal anti-inflammatory drugs (NSAID, aHR 1.10, 95%CI (1.01–1.21)). Significantly higher intracranial bleeding risks in NOAC users were observed with SSRI/SNRIs (aHR 1.50, 95%CI (1.25–1.81)) and corticosteroids (aHR 1.49, 95%CI (1.21–1.84)). Conclusion: Concomitant use of PD interacting drugs, especially P2Y12 inhibitors and corticosteroids, was associated with higher major, gastrointestinal, urogenital, and other bleeding risks in NOAC-treated AF patients. Remarkably, higher intracranial bleeding risks were observed with SSRI/SNRIs and corticosteroids. [ABSTRACT FROM AUTHOR]

Psycho-dermatology is an evolving speciality of psychosomatic medicine where psychological factors play a role in initiating and/or exacerbating the dermatological conditions. Dermatologists should be well versed with the basic pharmacotherapy of psycho-cutaneous disorders and work in close liaison with the psychiatrists when it comes to the holistic management of the same. The review has been divided into two parts, with part 1 consisting of anti-depressants and mood stabilisers and part 2 consisting of anti-psychotics, anxiolytics, and sedative-hypnotic agents used in psycho-dermatology. This comprehensive review focusses on the various psychotropic drugs which are of paramount significance to the dermatologists. The knowledge of these drugs will lead to the pertinent treatment of the psychiatric dermatoses, which has been a less explored territory in the arena of dermatology. Within the realm of psycho-dermatology, a diverse array of anti-depressants is utilised to address psychiatric dermatoses. These include selective serotonin reuptake inhibitors like citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline, alongside selective serotonin norepinephrine reuptake inhibitors such as venlafaxine, desvenlafaxine, and duloxetine. Additionally, norepinephrine dopamine reuptake inhibitors like bupropion; tricyclic antidepressants including doxepin, amitriptyline, imipramine, and clomipramine; and tetracyclic antidepressants like mirtazapine are commonly employed. Supplementary medications like anti-convulsants (e.g., gabapentin and pregabalin) further enrich the therapeutic landscape in psycho-dermatology. The approach to treatment in psycho-dermatology is meticulous, starting with a precise psychiatric diagnosis and followed by tailored drug interventions. Factors such as individual response, side-effect profiles, potential drug interactions, and concurrent medical conditions guide the selection and titration of medications. Typically, treatment initiates at conservative doses, with adjustments made based on patient progress and tolerability. This comprehensive review not only illuminates the psycho-cutaneous indications of these medications including in patients with co-morbidties but also underscores the imperative of vigilant monitoring for adverse effects and its management. This systematic review aimed to evaluate the use of psychotropic medications, including antidepressants and mood stabilizers, in dermatology. A comprehensive search of PubMed Central was conducted for studies published between 1986 and 2023, focusing on meta-analyses, reviews, and systematic reviews. After screening 2287 records, 26 studies met the inclusion criteria. The findings underscore the potential role of psychotropic drugs in managing dermatological conditions, highlighting the need for further research to strengthen the evidence base in psycho-dermatology. [ABSTRACT FROM AUTHOR]

Converging evidence suggests electroencephalography (EEG) methods may elucidate alterations in global structural and functional connectivity that underlie the pathophysiology of depressive disorders. Extant literature suggests SSRIs and SNRIs may broadly induce alterations to EEG-measured neural activity. Herein, this systematic review comprehensively evaluates changes to EEG spectral signatures associated with vortioxetine and each FDA-approved agent within the SSRI and SNRI class. We conducted a systematic review of studies investigating changes to EEG spectral signatures associated with SSRI, SNRI, and/or vortioxetine treatment in persons with MDD. Database search occurred from database inception to May 3, 2024. Our search yielded 15 studies investigating overall spectral signature changes associated with SSRI- and/or SNRI-treatment. The existing literature presents with mixed findings. Notwithstanding, we did observe a pattern in which the SSRI and SNRI agents reproducibly affect EEG spectral signatures. We observed overlapping yet distinct spectral patterns for each agent within- and between-drug classes of SSRIs and SNRIs. Changes in resting/wake EEG were also observed. The findings from our systematic review are mixed. Heterogeneity exists with sample size, composition, dosing of antidepressants, duration of antidepressant exposure, as well as the type of EEG devices used. Our findings provide support to the notion that although SSRIs, SNRIs and vortioxetine block reuptake of the serotonin transporter; they are different in their profile of pharmacology as evidenced by differential EEG signatures. EEG changes associated with SSRIs, SNRIs and vortioxetine are also highly replicated findings across mixed studies and populations. • The existing literature presents with mixed findings. • SSRI and SNRI agents reproducibly affect EEG spectral signatures. • Changes in resting/wake EEG were also observed post-treatment. [ABSTRACT FROM AUTHOR]

Highlights: Amygdala is proposed as site of action for serotonin drugs ameliorating anxiety. Contrary to this, intra-amygdala infusion of SSRIs did not affect social behavior. Similarly, 5-HT1A, 5-HT2A, and 5-HT3 agonism/antagonism in amygdala had no effect. Thus, serotonin effects on social behavior are likely not modulated by amygdala. Serotonin signaling plays critical roles in social and emotional behaviors. Likewise, decades of research demonstrate that the amygdala is a prime modulator of social behavior. Permanent excitotoxic lesions and transient amygdala inactivation consistently increase social behaviors in non-human primates. In rodents, acute systemic administration of drugs that increase serotonin signaling is associated with decreased social interactions. However, in primates, the direct involvement of serotonin signaling in the amygdala, particularly in affiliative social interaction, remains unexplored. Here, we examined the effects of serotonin manipulations within the amygdala on social behavior in eight pairs of familiar male macaques. We microinfused drugs targeting the serotonin system into either the basolateral (BLA) or central (CeA) amygdala and measured changes in social behavior. Surprisingly, the results demonstrated no significant differences in social behavior following the infusion of a selective serotonin reuptake inhibitor, 5-HT1A agonist or antagonist, 5-HT2A agonist or antagonist, or 5-HT3 agonist or antagonist into either the BLA or CeA. These findings suggest that serotonin signaling in the amygdala does not directly contribute to the regulation of social behavior between familiar conspecifics. Future research should explore alternative mechanisms and potential interactions with other brain regions to gain a comprehensive understanding of the complex neural circuitry governing social behavior. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic pneumonias denote a rare condition, wherein infiltrating eosinophilic granulocytes accumulate within the lung parenchyma. Although eosinophilic pneumonias may be idiopathic, they are also associated with secondary causes. More than 110 medications have been linked to eosinophilic pneumonia, including several antidepressants. This review presents an analysis of case reports of eosinophilic pneumonia correlated to antidepressants. Objectives: The objectives of this study are to provide a contemporary overview of the literature delineating eosinophilic pneumonia as a potential sequela of antidepressant medication treatment, and to discuss possible pathogenetic mechanisms linking antidepressants to eosinophilic pneumonia. Methods and Data Selection: A literature search was performed in PubMed and Scopus databases from 1963 to October 2024. The search strategy used the terms "eosinophilic pneumonia AND antidepressants". Sources included in this review were screened for relevance, focusing on references discussing eosinophilic pneumonia associated with any class of antidepressants. Case reports meeting the diagnostic criteria for acute eosinophilic pneumonia (AEP) or chronic eosinophilic pneumonia (CEP) were included in the review. Clinical, epidemiological, laboratory, radiology and bronchoscopy data, implicated antidepressant and dosage, and therapeutic interventions were reported. Results: This study found that various types of antidepressants are associated with AEP and CEP. The clinical presentation ranges from mild symptoms to respiratory failure and intubation. Outcomes were favorable in most cases, with complete remission achieved after discontinuation of the causative drug and, in severe cases, a short course of corticosteroids. Conclusions: Although a rare cause, antidepressants may lead to eosinophilic pneumonia, and should be considered in the differential diagnosis of unexplained pulmonary infiltrates. Clinical suspicion must be aroused, as early recognition would prevent unnecessary work-up and navigation of the diagnosis. [ABSTRACT FROM AUTHOR]

Background: Multidrug-resistant bacteria cause over 700,000 deaths annually, a figure projected to reach 10 million by 2050. Among these bacteria, the ESKAPEE group is notable for its multiple resistance mechanisms. Given the high costs of developing new antimicrobials and the rapid emergence of resistance, drug repositioning offers a promising alternative. Results: This study evaluates the antibacterial activity of sertraline and paroxetine. When tested against clinical and reference strains from the ESKAPEE group, sertraline exhibited minimum inhibitory concentration (MIC) values between 15 and 126 μg/mL, while the MIC values for paroxetine ranged from 60 to 250 μg/mL. Both drugs effectively eradicated bacterial populations within 2 to 24 h and caused morphological changes, such as protrusions and cellular fragmentation, as shown by electron scanning microscopy. Regarding their mechanisms of action as antibacterials, for the first time, increased membrane permeability was detected, as evidenced by heightened dye absorption, along with the increased presence of total proteins and dsDNA in the extracellular medium of Escherichia coli ATCC2 25922 and Staphylococcus aureus ATCC 25923, and oxidative stress was also detected in bacteria treated with sertraline and paroxetine, with reduced efficiency observed in the presence of antioxidants and higher levels of oxygen-reactive species evidenced by their reaction with 6-carboxy-2′,7′-dichlorodihydrofluorescein diacetate. The drugs also inhibited bacterial efflux pumps, increasing ethidium bromide accumulation and enhancing tetracycline activity in resistant strains. Conclusions: These findings indicate that sertraline and paroxetine could serve as alternative treatments against multidrug-resistant bacteria, as well as efflux pump inhibitors (EPIs), and they support further development of antimicrobial agents based on these compounds. [ABSTRACT FROM AUTHOR]

Introduction: Increasingly, pharmacogenetic testing helps providers with medication selection based upon patient-specific DNA results. While several government-funded organizations work towards consensus and standardization for testing and interpretation, compliance to these best practices remains inconsistent. Pharmacogenetic testing companies often develop proprietary practices for interpreting and reporting, which can lead to incongruency of reported results among companies and potential discrepancies in interpretation. Methods: To identify the differences of commercial pharmacogenetic testing vendors' interpretation of genotype-to-phenotype translations and medication recommendations from the Clinical Pharmacogenetic Implementation Consortium (CPIC) guidelines, a retrospective manual chart review was completed in a large rural healthcare system that utilizes two institution-approved pharmacogenetic vendors. One hundred patients were evaluated: 50 who completed testing through Company A and 50 who completed testing through Company B. Genes of interest for genotype-to-phenotype translation included CYP2B6 , CYP2C19 , and CYP2D6. Comparison of medication recommendations for drug-gene pairs sertraline (CYP2B6 and/or CYP2C19) , escitalopram (CYP2C19), and paroxetine (CYP2D6) were compared with recommendations from CPIC, with consideration of the CPIC Serotonin Reuptake Inhibitor Antidepressants (SSRI) guideline 2023 update. This was accomplished via a novel binning process to enable comparison of company-provided binned medication recommendations with CPIC guideline recommendations. Briefly, the binning system included three categorizations based upon the relevant CPIC guideline recommendations–no action needed (green), recommend monitoring (yellow) and therapeutic intervention or alternative recommended (red). Results: There were 32/250 (12.8%) genotype-to-phenotype translation discrepancies from CPIC guidelines, all from Company A. Of 266 evaluated binned medication recommendations, there were 114 (42.9%) discrepancies between the pharmacogenetic testing companies (Company A: 93 discrepancies, Company B: 21 discrepancies) and CPIC's guideline based upon comparison with the novel binning system. Discussion: Significant differences were observed between testing companies' interpretations and recommendations, which is concerning as these discrepancies could lead to providers making medication decisions that are not supported by CPIC's clinical practice guidelines. This may result in suboptimal outcomes for patients, leading to patient and provider dissatisfaction and erosion of trust with pharmacogenetic testing. A proposed resolution for the discrepancies in company-to-company interpretation is adherence to the CPIC guidelines and transparency in interpretation practices. [ABSTRACT FROM AUTHOR]

Background: Antidepressants such as SSRIs and SNRIs are widely prescribed; however, significant concerns exist regarding psychiatric adverse drug reactions (ADRs), particularly suicidal ideation, suicide attempts, and completed suicides. This study analyzes pharmacovigilance (PhV) data from the EudraVigilance database to assess the frequency of psychiatric ADRs, including suicide-related events, associated with six commonly used antidepressants. Another aim of the study is to evaluate the utility of pharmacovigilance data in providing insights into real-world risks associated with medications, highlighting the importance of improving the ADR reporting system and ensuring the completeness and reliability of ADR reports. Methods: Data from December 2001 to September 2024 were analyzed for duloxetine, citalopram, escitalopram, fluoxetine, venlafaxine, and sertraline. Reports were categorized by age, gender, and source, focusing on psychiatric ADRs and suicide-related events, including completed suicides and suicide attempts. Results: Psychiatric ADRs accounted for a substantial portion of total reported ADRs for the studied antidepressants, ranging from 33.9% to 38.2%. Venlafaxine had the highest count of psychiatric ADRs (13,134 cases), with duloxetine showing the highest relative percentage (38.2%). Completed suicides were most frequent with venlafaxine (1635 cases), while the highest percentage relative to total ADRs was observed for fluoxetine and citalopram (6%). ADRs occurred more frequently in women, particularly for duloxetine (67%) and sertraline (61.3%), and suicide attempts were prevalent in patients aged 18–64, with notable incidence in the 0–17 age group. Conclusions: This study highlights the significant patterns, risks, and underreporting of psychiatric ADRs associated with commonly prescribed antidepressants. Using EudraVigilance data and a worst-case scenario approach, it reveals the extent of suicide-related ADRs, age and gender disparities, and the impact of incomplete reporting on risk assessment. [ABSTRACT FROM AUTHOR]

Background/Objectives: Depression and anxiety are the two most common mental health disorders that can affect the well-being of the entire body. Multiple studies confirm that they can threaten the musculoskeletal system and the effects of orthopedic treatment as well. In turn, orthopedic disorders may worsen the symptoms of depression and anxiety. The study is aimed at assessing the incidence of depressive and anxiety disorders in orthopedic patients of our department and what are the characteristics of orthopedic patients regarding depressive disorders. Methods: After obtaining personal consent for trial, 336 patients undergoing elective orthopedic surgery over a 12-month period were evaluated. Preoperatively, patients completed surveys containing questions from the PHQ-9 and GAD-7 forms. The pain was assessed with the VAS scale of 0–10 points and the information on the current psychiatric treatment was acquired. Patients were divided into subgroupsand statistical analysis was performed. Results: The incidence of moderate depression and generalized anxiety symptoms in orthopedic patients was 12.2% and 11.3%, respectively (several times higher than in the general population). In the group most at risk of depression, i.e., women over 40 and with foot and ankle diseases, the incidence of treated depression was 36%. In foot and ankle patients, prevalence for depression was more than three times higher (OR = 3.24, 95% CI 1.542–7.24) compared to the reference group. Conclusions: The problem of depression and generalized anxiety in orthopedic patients is clearly more common than in the general population. In our study, patients with foot and ankle disorders are the most vulnerable to depression. [ABSTRACT FROM AUTHOR]

Background: Several studies provide clear evidence that exposure to various infections during pregnancy are linked with an increased risk for schizophrenia. In preclinical studies, administration of polyinosinic‐polycytidylic acid (Poly I:C) in pregnant rodents can induce maternal immune activation leading to impairments in brain function in the offspring. Objectives: The aim of this study was to investigate the effect of vortioxetine, a multimodal selective serotonin reuptake inhibitor (SSRI), in the pathophysiology of Poly I:C‐induced schizophrenia‐like model in rats. Methods: For this purpose, Poly I:C (8 mg/kg, ip) was injected into pregnant animals 14 days after mating, and tail blood was taken for determination of IL‐6 levels after 2 h. At postnatal days 83–86, behavioral tests were performed. Results: Our results revealed that Poly I:C caused impairments in prepulse inhibition, novel object recognition, social interaction, and open‐field tests. Chronic administration of vortioxetine (2.5, 5, and 10 mg/kg, ip, postnatal days 69–83) caused significant improvements in these deficits. Conclusion: Overall, our findings indicate that vortioxetine may provide new therapeutic approaches for the treatment of schizophrenia. We think that increased serotonergic activity in frontal brain regions may provide the ameliorative effect of vortioxetine, especially on negative and cognitive symptoms. Therefore, it will be useful to determine the efficacy of vortioxetine with combined drugs with further studies. [ABSTRACT FROM AUTHOR]

Objective(s): Acute lung injury (ALI) is characterized by severe hypoxia and alveolar damage, often caused by oxidative stress, endoplasmic reticulum stress (ERS), and apoptosis. Fluvoxamine (FLV), an antidepressant, has tissue-protective properties through various intracellular mechanisms. This study investigates the anti-inflammatory effects of FLV used as an antidepressant in a lipopolysaccharide (LPS)-induced ALI model. Materials and Methods: Thirty-two female Wistar Albino rats aged 14-16 weeks and weighing 300-350 g, with 8 animals in each group, were divided into four groups: control, LPS, LPS+FLV, and FLV. After LPS administration, rats were euthanized, and histopathological analysis, immunohistochemistry for tumor necrosis factor-a (TNF-a) and caspase-3 (Cas-3), ELISA for oxidative stress markers, and PCR for CHOP, Cas-12, and Cas-9 gene expressions were conducted. Results: In the LPS group, lung tissue damage, increased inflammatory cell infiltration, increased Cas-3 and TNF-a expressions, increased oxidative stress markers, and increased CHOP, Cas-9, and Cas-12 mRNA expressions were observed compared to the control group. FLV treatment in the LPS+FLV group significantly reversed these effects in the LPS group. Conclusion: FLV exhibits protective effects against ALI by mitigating inflammation, ERS, and apoptosis via the CHOP/Cas-9/Cas-12 pathway. Further studies are needed to explore additional pathways and potential clinical applications of FLV. [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.

Lipid storage myopathies are considered inborn errors of metabolism affecting the fatty acid metabolism and leading to accumulation of lipid droplets in the cytoplasm of muscle fibers. Specific diagnosis is based on investigation of organic aids in urine, acylcarnitines in blood and genetic testing. An acquired lipid storage myopathy in patients treated with the antidepressant drug sertraline, a serotonin reuptake inhibitor, has recently emerged as a new tentative differential diagnosis. We analyzed the muscle biopsy tissue in a group of 11 adult patients with muscle weakness and lipid storage myopathy which developed at a time when they were on sertraline treatment. This group comprise most patients with lipid storage myopathies in western Sweden during the recent nine-year period. By enzyme histochemistry, electron microscopy, quantitative proteomics, immunofluorescence of the respiratory chain subunits, western blot and genetic analyses we demonstrate that muscle tissue in this group of patients exhibit a characteristic morphological and proteomic profile. The patients also showed an acylcarnitine profile in blood suggestive of multiple acyl-coenzyme A dehydrogenase deficiency, but no genetic explanation was found by whole genome or exome sequencing. By proteomic analysis the muscle tissue revealed a profound loss of Complex I subunits from the respiratory chain and to some extent also deficiency of Complex II and IV. Most other components of the respiratory chain as well as the fatty acid oxidation and citric acid cycle were upregulated in accordance with the massive mitochondrial proliferation. The respiratory chain deficiency was verified by immunofluorescence analysis, western blot analysis and enzyme histochemistry. The typical ultrastructural changes of the mitochondria included pleomorphism, dark matrix and frequent round osmiophilic inclusions. Our results show that lipid storage myopathy associated with sertraline treatment is a mitochondrial disorder with respiratory chain deficiency and is an important differential diagnosis with characteristic features. [ABSTRACT FROM AUTHOR]

Borderline personality disorder (BPD) is a severe mental illness, with high rates of co-morbid depression and suicidality. Despite the importance of optimizing treatment in BPD, little is known about how neural processes relate to individual treatment response. This study examines how baseline regional brain blood oxygen level dependent (BOLD) activation during a functional magnetic resonance imaging (fMRI) task of emotion regulation is related to treatment response following a six-month randomized clinical trial of Dialectical Behavior Therapy (DBT) or Selective Serotonin Reuptake Inhibitor (SSRI) treatment. Unmedicated females with BPD (N = 37), with recent suicidal behavior or self-injury, underwent an fMRI task in which negative personal memories were presented and they were asked to distance (i.e., downregulate their emotional response) or immerse (i.e., experience emotions freely). Patients were then randomized to DBT (N = 16) or SSRI (N = 21) treatment, with baseline and post-treatment depression and BPD severity assessed. BOLD activity in prefrontal cortex, anterior cingulate, and insula was associated with distancing. Baseline BOLD during distancing in dorsolateral, ventrolateral, and orbital prefrontal cortex (dlPFC, vlPFC, OFC) differentially predicted depression response across treatment groups, with higher activity predicting better response in the SSRI group, and lower activity predicting better response in the DBT group. All female samples. Findings indicate that greater prefrontal engagement during emotion regulation may predict more antidepressant benefit from SSRIs, whereas lower engagement may predict better response to DBT. These results suggest different mechanisms of action for SSRI and DBT treatment, and this may allow fMRI to guide individualized treatment selection. • Borderline personality disorder (BPD) is associated with high rates of depression. • Neural processes may offer insight into predicting antidepressant response. • Prefrontal engagement differentially predicted response to SSRI and DBT treatment. • Examining prefrontal activity may allow for more individualized treatment in BPD. [ABSTRACT FROM AUTHOR]

Women with menopausal transition (MT) have an elevated risk of experiencing common mental health diagnoses (CMHD: depression or anxiety). There is no recent data comparing the rate, and treatment, of CMHD between men and women. In this population-based study, incidence rates (IR) per 100 person-years-at-risk (PYAR) for men and women ≥45 years registered with an UK primary care practice between 2010 and 2021 were estimated. Incidence rate ratios (IRR) with 95 % confidence intervals (CIs) of CMHD were estimated using men as a reference. We measured first prescriptions for psychotropic medications received within 12 months after CMHD. For selective serotonin reuptake inhibitors (SSRIs) /selective norepinephrine reuptake inhibitors (SNRIs), we measured the IR of prescribing per 100 PYAR, by 10-year bands. Proportion of SSRIs/SNRIs prescribing was estimated per 100 persons. Rates of anxiety and depressive disorders were 1.68 and 1.69 per 100 PYAR in women aged 45–54 years-old compared to 0.91 and 1.20 per 100 PYAR in men, with IRR of 1.84 (95 % CI 1.72–1.97) and 1.44 (1.35–1.53) respectively. SSRIs/SNRIs were the most prescribed medication; in 2021, IRs for SSRIs/SNRIs were 13.4 per 100 PYAR in both sexes. In 2021, the proportion of SSRIs/SNRIs prescribing was 50.67 per 100 women and 41.91 per 100 men. MT is assumed based on women's age as menopause onset is rarely recorded in primary care databases. Women ≥45 years experienced more CMHD compared to men, especially 45–54 years-olds, which coincides with MT. The proportion of SSRIs/SNRIs prescribing was higher in women. • Women experienced more common mental health diagnoses (CMHD) compared with men. • Women going through menopausal transition (45–54 years old) had higher rates of CMHD. • SSRIs/SNRIs were the most prescribed in men and women with CMHD. • Prevalence of SSRIs/SNRIs was higher in women with CMHD compared with men. [ABSTRACT FROM AUTHOR]

Background Despite the well-documented efficacy of antidepressant agents for the treatment of major depressive disorder (MDD), initial treatment nonresponse rates are high. Recent years have seen an increase in research into predictive biomarkers toward improving diagnosis and individualized treatment. Among those, epigenetic mechanisms such as DNA methylation constitute promising candidate markers in predicting antidepressant treatment response in MDD. The present study sought to address epigenome-wide DNA methylation as a predictor of antidepressant treatment response in the largest sample to date of patients with MDD. Methods Epigenome-wide DNA methylation was analyzed using the Infinium MethylationEPIC BeadChip in peripheral blood of n = 230 Caucasian patients with MDD receiving 6-week antidepressant treatment in a naturalistic in-patient setting as well as in a subsample of n = 107 patients primarily receiving continuous treatment with serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors. Treatment response was assessed by means of the Hamilton Depression Scale. Results No genome-wide significant hits were observed. Suggestive (P  < 1E-5) epigenome-wide evidence was discerned for altered DNA methylation at 6 CpG sites (LOC102724467 , LOC100506023 , RSPO2 , SAG , IL16 , PRKCI) to predict response to naturalistic antidepressant treatment. In patients treated with serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors, differential DNA methylation at 11 CpGs, for example, mapping to the TIMP2 , VDAC1 , or SORL1 genes, was suggestively associated with treatment response. Conclusions The present results provide preliminary evidence for altered DNA methylation patterns to be associated with antidepressant treatment response in MDD. Provided significant replication in independent and larger samples, the present findings might in the future aid in clinical decision-making toward more individualized and thus more efficacious treatments of MDD. [ABSTRACT FROM AUTHOR]

Psychedelic therapies are an emerging class of treatments in psychiatry with great potential, however relatively little is known about their interactions with other commonly used psychiatric medications. As psychedelic therapies become more widespread and move closer to the clinic, they likely will need to be integrated into existing treatment models which may include one or more traditional pharmacological therapies, meaning an awareness of potential drug-drug interactions will become vital. This commentary outlines some of the issues surrounding the study of drug-drug interactions of this type, provides a summary of some of the relevant key results to date, and charts a way forward which relies crucially on multimodal neuroimaging investigations. Studies in humans which combine Positron Emission Tomography (PET) and functional Magnetic Resonance Imaging (fMRI), plus ancillary measures, are likely to provide the most comprehensive assessment of drug-drug interactions involving psychedelics and the relevant effects at multiple levels of the drug response (molecular, functional, and clinical). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Antidepressants and menopause are risk factors which are independently associated with an increased risk of fractures. This review aims to investigate the risk of fragility fractures in women aged 40 and older and prescribed antidepressants. Methods: A literature search was conducted using PubMed, Ovid Embase, Ovid PsychINFO, Web of Science, and Scopus from inception to 1 June 2024. Relevant citations were identified and screened against our inclusion/exclusion criteria. The study population comprised women over 40 years. The risk of fragility fractures was compared between users and non-users of antidepressants. Risk of bias assessment was carried out using the ROBINS-I tool. A meta-analysis of cohort studies was performed to assess fracture risk associated with prescribing of any antidepressant agents, and SSRIs specifically. Results: Of the 3,676 articles retrieved, five observational studies were found eligible for inclusion (n = 1,240,354). In a meta-analysis of 4 studies, an increased risk of fractures in women was associated with the prescribing of antidepressants (HR = 1.62, 95% CI: 1.15–2.28; I2 = 96.50%) and SSRIs in particular (HR = 1.36, 95% CI: 1.20–1.55; I2 = 40.32%). Conclusions: Findings from this review suggest that prescribing of antidepressants is associated with an increased risk of fractures in women aged 40 and older. Substantial heterogeneity between studies may have affected the results of the meta-analysis. [ABSTRACT FROM AUTHOR]

Several magnetic resonance imaging (MRI) studies have reported that antidepressant medications are strongly linked to brain microstructural alterations. Notably, external capsule alterations have been reported to be a biological marker for therapeutic response. However, prior studies did not investigate whether a change in the neurite density or directional coherence of white matter (WM) fibers underlies the observed microstructural alterations. This MRI-based case–control study examined the relationship between patients' current use of antidepressant medications and advanced measurements of external capsule WM microstructure derived from multishell diffusion imaging using neurite orientation dispersion and density imaging (NODDI). The study compared a group of thirty-five participants who were taking antidepressant medications comprising selective serotonin reuptake inhibitors (SSRIs) (n = 25) and serotonin and norepinephrine reuptake inhibitors (SNRIs) with a control group of thirty-five individuals matched in terms of age, sex, race, and atherosclerotic cardiovascular risk factors. All participants were selected from the Dallas Heart Study phase 2, a multi-ethnic, population-based cohort study. A series of multiple linear regression analyses were conducted to predict microstructural characteristics of the bilateral external capsule using age, sex, and antidepressant medications as predictor variables. There was significantly reduced neurite density in the bilateral external capsules of patients taking SSRIs. Increased orientation dispersion in the external capsule was predominantly seen in patients taking SNRIs. Our findings suggest an association between specific external capsule microstructural changes and antidepressant medications, including reduced neurite density for SSRIs and increased orientation dispersion for SNRIs. [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 realworld patients with depression. [ABSTRACT FROM AUTHOR]

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

Treatment-resistant depression (TRD) is an epidemic with rising social, economic, and political costs. In a patient whose major depressive episode (MDE) persists through an adequate antidepressant trial, insurance companies often cover alternative treatments which may include repetitive transcranial magnetic stimulation (rTMS). RTMS is an FDA-cleared neuromodulation technique for TRD which is safe, efficacious, noninvasive, and well-tolerated. Recent developments in the optimization of rTMS algorithms and targeting have increased the efficacy of rTMS in treating depression, improved the clinical convenience of these treatments, and decreased the cost of a course of rTMS. In this opinion paper, we make a case for why conventional FDA-cleared rTMS should be considered as a first-line treatment for all adult MDEs. RTMS is compared to other first-line treatments including psychotherapy and SSRIs. These observations suggest that rTMS has similar efficacy, fewer side-effects, lower risk of serious adverse events, comparable compliance, the potential for more rapid relief, and cost-effectiveness. This suggestion, however, would be strengthened by further research with an emphasis on treatment-naive subjects in their first depressive episode, and trials directly contrasting rTMS with SSRIs or psychotherapy. [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]

Introduction and purpose: Pruritus is a subjective, unpleasant sensation that leads to scratching and significantly impacts the quality of life of patients. In pancreatic cancer, its etiology is multifactorial. It can result from various mechanisms, with a particular emphasis on cholestasis, which represents the most important and frequent cause of this symptom, as well as paraneoplastic processes, neuropathic mechanisms, or side effects of therapy. The aim of this study is to analyze the mechanisms responsible for pruritus in pancreatic cancer, discuss diagnostic challenges, and review the available therapeutic methods and challenges, including bile duct decompression, the use of autotaxin inhibitors, opioid receptor antagonists, and SSRI drugs. The article is based on an analysis of the available scientific literature and cited sources. Description of the state knowledge: Topics discussed include pathomechanisms of pruritus in pancreatic cancer include cholestatic, opioid-induced, paraneoplastic, neuropathic and pruritus caused by antineoplastic therapies. Another key topic is the diagnostic process for pruritus in pancreatic cancer patients, which involves laboratory and imaging studies, clinical dermatological assessment, and differential diagnosis. Lastly, a comprehensive therapeutic approach is addressed, consisting of causal treatment, pharmacological interventions, and supportive care.

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.

Background Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for depression and anxiety. However, little is known about how pharmacological action is related to cognitive and affective processes. Here, we examine whether specific reinforcement learning processes mediate the treatment effects of SSRIs. Methods The PANDA trial was a multicentre, double-blind, randomized clinical trial in UK primary care comparing the SSRI sertraline with placebo for depression and anxiety. Participants (N = 655) performed an affective Go/NoGo task three times during the trial and computational models were used to infer reinforcement learning processes. Results There was poor task performance: only 54% of the task runs were informative, with more informative task runs in the placebo than in the active group. There was no evidence for the preregistered hypothesis that Pavlovian inhibition was affected by sertraline. Exploratory analyses revealed that in the sertraline group, early increases in Pavlovian inhibition were associated with improvements in depression after 12 weeks. Furthermore, sertraline increased how fast participants learned from losses and faster learning from losses was associated with more severe generalized anxiety symptoms. Conclusions The study findings indicate a relationship between aversive reinforcement learning mechanisms and aspects of depression, anxiety, and SSRI treatment, but these relationships did not align with the initial hypotheses. Poor task performance limits the interpretability and likely generalizability of the findings, and highlights the critical importance of developing acceptable and reliable tasks for use in clinical studies. Funding This article presents research supported by NIHR Program Grants for Applied Research (RP-PG-0610-10048), the NIHR BRC, and UCL, with additional support from IMPRS COMP2PSYCH (JM, QH) and a Wellcome Trust grant (QH). [ABSTRACT FROM AUTHOR]

Background: Mental health diagnoses can co-occur with complex medical illness in pediatric patients. Pediatricians may not feel comfortable with managing psychopharmacology for patients and access to child psychiatrists can be limited. Palliative care (PC) providers follow patients with serious illness longitudinally to address burdensome symptoms that affect quality of life and may be responsible for evaluation and treatment of mental health concerns; however, education in managing psychologic distress for pediatric palliative care (PPC) providers is limited. Objective: This study seeks to describe the antidepressant prescribing practices of PPC providers and describe their level of training and comfort in assessing for anxiety and depression and prescribing psychotropic medications. Methods: An electronic survey approved by the American Academy of Hospice and Palliative Medicine was distributed nationally to PPC providers. Results: A total of 58 providers responded to the survey (response rate 12.3%). Most reported prescribing a variety of antidepressants (79%). Very few used formal assessment tools to screen for depression (7%) or anxiety (16%). Less than a third of providers consulted child psychiatry before prescribing antidepressants (29%). More than half of providers (54.5%) had no formal training in assessment and treatment of anxiety and depression in pediatric patients. Despite this, many providers (70%) reported feeling comfortable in prescribing antidepressants while also endorsing interest in more training for behavioral health evaluation and treatment (82.5%). Conclusions: Limited training in assessing mental health concerns, prescribing, and managing psychopharmacology suggests an opportunity for more targeted education for pediatric PC providers regarding antidepressant prescribing practices. [ABSTRACT FROM AUTHOR]

Microdosing ketamine is a novel antidepressant for treatment‐resistant depression. Traditional antidepressants, like selective serotonin reuptake inhibitors (SSRIs), inhibit serotonin reuptake, but it is not clear if ketamine shows a similar mechanism. Here, we tested the effects of feeding ketamine and SSRIs to Drosophila melanogaster larvae, which has a similar serotonin system to mammals and is a good model to track depressive behaviors, such as locomotion and feeding. Fast‐scan cyclic voltammetry (FSCV) was used to measure optogenetically stimulated serotonin changes, and locomotion tracking software and blue dye feeding to monitor behavior. We fed larvae various doses (1–100 mM) of antidepressants for 24 h and found that 1 mM ketamine did not affect serotonin, but increased locomotion and feeding. Low doses (≤10 mM) of escitalopram and fluoxetine inhibited dSERT and also increased feeding and locomotion behaviors. At 100 mM, ketamine inhibited dSERT and increased serotonin concentrations, but decreased locomotion and feeding because of its anesthetic properties. Since microdosing ketamine causes behavioral effects, we further investigated behavioral changes with a SERT16 mutant and low doses of other NMDA receptor antagonists and 5‐HT1A and 2 agonists. Feeding and locomotion changes were similar to ketamine in the mutant, and we found NMDA receptor antagonism increased feeding, while serotonin receptor agonism increased locomotion, which could explain these effects with ketamine. Ultimately, this work shows that Drosophila is a good model to discern antidepressant mechanisms, and that ketamine does not work on dSERT like SSRIs, but effects behavior with other mechanisms that should be investigated further. [ABSTRACT FROM AUTHOR]

Background: To investigate the association between pre-trial expectancy, suggestibility, and response to treatment in a trial of escitalopram and investigational drug, COMP360, psilocybin, in the treatment of major depressive disorder (ClinicalTrials.gov registration: NCT03429075). Methods: We used data (n = 55) from our recent double-blind, parallel-group, randomized head-to-head comparison trial of escitalopram and investigational drug, COMP360, psilocybin. Mixed linear models were used to investigate the association between pre-treatment efficacy-related expectations, as well as baseline trait suggestibility and absorption, and therapeutic response to both escitalopram and COMP360 psilocybin. Results: Patients had significantly higher expectancy for psilocybin relative to escitalopram; however, expectancy for escitalopram was associated with improved therapeutic outcomes to escitalopram, expectancy for psilocybin was not predictive of response to psilocybin. Separately, we found that pre-treatment trait suggestibility was associated with therapeutic response in the psilocybin arm, but not in the escitalopram arm. Conclusions: Overall, our results suggest that psychedelic therapy may be less vulnerable to expectancy biases than previously suspected. The relationship between baseline trait suggestibility and response to psilocybin therapy implies that highly suggestible individuals may be primed for response to this treatment. [ABSTRACT FROM AUTHOR]

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.

Background: Multidrug-resistant bacteria cause over 700,000 deaths annually, a figure projected to reach 10 million by 2050. Among these bacteria, the ESKAPEE group is notable for its multiple resistance mechanisms. Given the high costs of developing new antimicrobials and the rapid emergence of resistance, drug repositioning offers a promising alternative. Results: This study evaluates the antibacterial activity of sertraline and paroxetine. When tested against clinical and reference strains from the ESKAPEE group, sertraline exhibited minimum inhibitory concentration (MIC) values between 15 and 126 μg/mL, while the MIC values for paroxetine ranged from 60 to 250 μg/mL. Both drugs effectively eradicated bacterial populations within 2 to 24 h and caused morphological changes, such as protrusions and cellular fragmentation, as shown by electron scanning microscopy. Regarding their mechanisms of action as antibacterials, for the first time, increased membrane permeability was detected, as evidenced by heightened dye absorption, along with the increased presence of total proteins and dsDNA in the extracellular medium of Escherichia coli ATCC2 25922 and Staphylococcus aureus ATCC 25923, and oxidative stress was also detected in bacteria treated with sertraline and paroxetine, with reduced efficiency observed in the presence of antioxidants and higher levels of oxygen-reactive species evidenced by their reaction with 6-carboxy-2′,7′-dichlorodihydrofluorescein diacetate. The drugs also inhibited bacterial efflux pumps, increasing ethidium bromide accumulation and enhancing tetracycline activity in resistant strains. Conclusions: These findings indicate that sertraline and paroxetine could serve as alternative treatments against multidrug-resistant bacteria, as well as efflux pump inhibitors (EPIs), and they support further development of antimicrobial agents based on these compounds.

Background: Eosinophilic pneumonias denote a rare condition, wherein infiltrating eosinophilic granulocytes accumulate within the lung parenchyma. Although eosinophilic pneumonias may be idiopathic, they are also associated with secondary causes. More than 110 medications have been linked to eosinophilic pneumonia, including several antidepressants. This review presents an analysis of case reports of eosinophilic pneumonia correlated to antidepressants. Objectives: The objectives of this study are to provide a contemporary overview of the literature delineating eosinophilic pneumonia as a potential sequela of antidepressant medication treatment, and to discuss possible pathogenetic mechanisms linking antidepressants to eosinophilic pneumonia. Methods and Data Selection: A literature search was performed in PubMed and Scopus databases from 1963 to October 2024. The search strategy used the terms “eosinophilic pneumonia AND antidepressants”. Sources included in this review were screened for relevance, focusing on references discussing eosinophilic pneumonia associated with any class of antidepressants. Case reports meeting the diagnostic criteria for acute eosinophilic pneumonia (AEP) or chronic eosinophilic pneumonia (CEP) were included in the review. Clinical, epidemiological, laboratory, radiology and bronchoscopy data, implicated antidepressant and dosage, and therapeutic interventions were reported. Results: This study found that various types of antidepressants are associated with AEP and CEP. The clinical presentation ranges from mild symptoms to respiratory failure and intubation. Outcomes were favorable in most cases, with complete remission achieved after discontinuation of the causative drug and, in severe cases, a short course of corticosteroids. Conclusions: Although a rare cause, antidepressants may lead to eosinophilic pneumonia, and should be considered in the differential diagnosis of unexplained pulmonary infiltrates. Clinical suspicion must be aroused, as early recognition would prevent unnecessary work-up and navigation of the diagnosis.