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Purpose: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for psychiatric conditions. Previous studies have shown that SSRIs can increase bleeding risk by affecting platelet aggregation. However, their impact on perioperative outcomes in hip surgery remains uncertain. This case-control study examines the link between preoperative SSRI use and perioperative transfusion requirements in hip surgery patients. Methods: Data from the M161Ortho dataset of Pearl Diver patient records database were utilized. Patients who underwent hip joint surgery between 2010 and 2022 and had documented preoperative SSRI use within one month prior to surgery were included. Patients with coagulopathy disorders or coagulopathy medication use were excluded. Perioperative transfusion need was defined as receiving red blood cell or whole blood transfusions on the same date or within 10 days following the surgery. Results: A total of 75,374 patients with preoperative SSRI use were matched with an equal number of non-SSRI users. Preoperative SSRI use was associated with an increased risk of requiring perioperative transfusion (5.7% vs. 5.1%, P < 0.001). Subgroup analysis demonstrated increased transfusion risk in patients undergoing pinning (2.6% vs. 1.8%, P = 0.02), open reduction with internal fixation (ORIF) (8.9% vs. 8.2%, P = 0.007), and total hip arthroplasty (THA) (3.8% vs. 3.4%, P < 0.001), but no significant difference was observed in patients undergoing hemiarthroplasty. Conclusion: Clinicians should be aware of the potential risk of increased perioperative transfusion requirements in hip surgery patients using SSRIs, especially during pinning, ORIF, and THA procedures. It is essential to consider this when managing patients on SSRIs before hip surgery. [ABSTRACT FROM AUTHOR]

Objective: This study investigated prescribing patterns of two cohorts of patients treated with selective serotonin reuptake inhibitors (SSRI) in primary care in Wales (UK), to better understand drivers for increased usage. Methods: This e‐cohort study included patients receiving a first READ‐coded SSRI prescription in SAIL in either 2005 or 2015. Patients were followed up for 3 years from date of SSRI prescription. Influence of age and other demographic data on prescribing patterns, and details of mental health or medication reviews that took place were identified. Results: In total 67,006 patients were included across the two cohorts; 29,534 in 2005, and 37,472 in 2015. Citalopram was the most commonly prescribed SSRI in both cohorts. A READ‐coded diagnosis relating to SSRI treatment could not be identified in 24,797 patients. The percentage of patients continuing treatment for 3 years was 6.9% and 11.3% in 2005 and 2015, respectively. In total, 21,150 (72%) patients in the 2005 cohort and 23,947 (64%) in the 2015 cohort received at least one medication review during follow‐up. Conclusions: The proportion of patients continuing longer term treatment was small, whilst the number of recorded mental health and medication reviews offers some reassurance that prescribing remained appropriate. [ABSTRACT FROM AUTHOR]

Whether use of antidepressants is related to the risk of developing lower-grade (WHO grades 2-3) and higher-grade (WHO grade 4) glioma was investigated in this study. A registry-based case–control study was performed with 1283 glioma case patients and 6400 age-, sex-, and geographically matched control participants who were diagnosed in Sweden during 2009-2013. Conditional logistic regression was used to analyze whether selective serotonin reuptake inhibitors (SSRIs) or non-SSRIs were associated with the risk of developing lower- or higher-grade glioma in the study population. Our results show that use of antidepressant medication was not associated with the risk of developing glioma. We also performed a meta-analysis in which the data set from the present study was combined with results from 2 previous epidemiologic studies to answer the same questions. The meta-analysis showed a modest risk reduction of developing glioma in relation to antidepressant treatment (odds ratio = 0.90; 95% CI, 0.83-0.97) when all glioma subgroups and all forms of antidepressant medications were combined. In conclusion, it remains possible that antidepressants may have common monoaminergic mechanism(s) that reduce the risk of developing glioma. [ABSTRACT FROM AUTHOR]

A 31‐week fetus was diagnosed with premature ductal constriction due to maternal treatment with sertraline. An emergent Cesarean section was performed at 32 gestational weeks. The baby was born in a severely depressed condition, with supra‐systemic pulmonary hypertension, requiring intubation, mechanical ventilation, and milrinone infusion. The patient's condition improved rapidly, allowing weaning from the ventilator and the inodilator therapy. The baby was discharged home at 38 weeks postmenstrual age, in good general condition, without any signs of pulmonary hypertension, requiring no respiratory support. The echo examinations on the first and third months after birth were normal. [ABSTRACT FROM AUTHOR]

Abstract Background We explored if the administration of fluoxetine, recognized for its potential in adipocyte browning, entails a differential risk of coronary heart disease (CHD) in comparison to other SSRI medications. Methods Using the National Health Insurance Research Database of Taiwan from 2000 to 2013, we conducted a retrospective cohort study. The exposure cohort comprised individuals prescribed fluoxetine for over 90 days (n = 2,228). Conversely, those administered other SSRIs (excluding fluoxetine) for a duration surpassing 90 days were designated as the non-exposed cohort (n = 8,912). CHD incidence served as our primary outcome measure, and we employed Cox proportional hazards models to scrutinize the relationship between fluoxetine exposure and CHD development rates. Results Compared with the non-exposed cohort, the fluoxetine use had a significantly decreased 21% risk of developing CHD in the exposed cohort (adjusted hazard ratio: 0.79%, 95% confidence interval: 0.68–0.92). Noticeably, results indicated that there was an inverse association between the fluoxetine exposure and the risk of CHD, regardless of whether men, women or other age groups. Conclusion Our findings suggest that clinical use of fluoxetine was associated with a 21% reduced risk of CHD relative to other SSRI prescriptions.

Abstract Purpose Depression is prevalent in patients undergoing bariatric surgery (BSx). Long-term use of antidepressant is associated with weight gain, particularly the use of selective serotonin reuptake inhibitors (SSRIs). Little is known about whether different types of antidepressants affect the response to BSx. The purpose of this study was to determine the relationship between SSRI use and nutritional and biochemical measurements in those with obesity pre-/post-BSx. Methods This is a cross-sectional and prospective cohort study. Patients were enrolled pre-BSx and divided into 3 groups: SSRI, non-SSRI and no antidepressant. Nutritional, biochemical and pharmacological data were collected pre- and 6 months post-BSx. Results Pre-BSx, 77 patients were enrolled: 89.6% female, median age 45 years and body mass index (BMI) of 45.3 kg/m2. 14.3% were taking SSRIs and had a significantly higher BMI (52.1 kg/m2) compared to 62.3% in no antidepressant (46.0 kg/m2) and 23.4% in non-SSRI antidepressants (43.1 kg/m2). At 6 months post-BSx (n = 58), the SSRI group still had significantly higher BMI in comparison to the other two groups. No other significant differences found between groups. Conclusion Despite higher BMI, patients taking SSRI and undergoing BSx had similar responses, based on nutritional and biochemical parameters, to those on non-SSRI or no antidepressants. Level of evidence Level III: Evidence obtained from well-designed cohort or case–control analytic studies.

Background Delineation of changes in neural function associated with novel and established treatments for social anxiety disorder (SAD) can advance treatment development. We examined such changes following selective serotonin reuptake inhibitor (SSRI) and attention bias modification (ABM) variant – gaze-contingent music reward therapy (GC-MRT), a first-line and an emerging treatments for SAD. Methods Eighty-one patients with SAD were allocated to 12-week treatments of either SSRI or GC-MRT, or waitlist (n s = 22, 29, and 30, respectively). Baseline and post-treatment functional magnetic resonance imaging (fMRI) data were collected during a social-threat processing task, in which attention was directed toward and away from threat/neutral faces. Results Patients who received GC-MRT or SSRI showed greater clinical improvement relative to patients in waitlist. Compared to waitlist patients, treated patients showed greater activation increase in the right inferior frontal gyrus and anterior cingulate cortex when instructed to attend toward social threats and away from neutral stimuli. An additional anterior cingulate cortex cluster differentiated between the two active groups. Activation in this region increased in ABM and decreased in SSRI. In the ABM group, symptom change was positively correlated with neural activation change in the dorsolateral prefrontal cortex. Conclusions Brain function measures show both shared and treatment-specific changes following ABM and SSRI treatments for SAD, highlighting the multiple pathways through which the two treatments might work. Treatment-specific neural responses suggest that patients with SAD who do not fully benefit from SSRI or ABM may potentially benefit from the alternative treatment, or from a combination of the two. Trial Registration: ClinicalTrials.gov, Identifier: NCT03346239. https://clinicaltrials.gov/ct2/show/NCT03346239 [ABSTRACT FROM AUTHOR]

Aim: Selective serotonin reuptake inhibitors (SSRIs) are among the most important antidepressants. However, there is limited research on predicting the occurrence of treatment‐resistant depression (TRD) after 5 years. Examining the predictive effect of TRD occurrence using resting‐state fMRI in patients initiating SSRIs treatment at the onset of major depressive disorder (MDD) could potentially enhance TRD management. Methods: A total of 60 first‐episode drug‐naive MDD patients who met the criteria, along with 41 healthy controls of Han Chinese ethnicity, were recruited. All MDD patients received SSRIs as the initial treatment for relieving depressive symptoms. Resting‐state fMRI scans were conducted for all subjects. Follow‐up assessments were conducted over a period of five years, during which MDD patients were categorized into treatment‐resistant depression (TRD) and non‐treatment‐resistant depression (NRD) groups based on disease progression. Amplitude of low‐frequency fluctuations (ALFF), fractional amplitude of low‐frequency fluctuations (fALFF), and Regional Homogeneity (ReHo) values were calculated and compared among the three groups. Additionally, receiver operating characteristic (ROC) curves were employed to identify potential predictors. Results: After 5 years of follow‐up, it was found that 43 MDD patients were classified as NRD, while 17 were classified as TRD. In comparison to TRD, NRD exhibited decreased ALFF in the left middle cingulum gyrus (MCG.L) and in the right middle frontal gyrus (MFG.R), as well as decreased ReHo in MCG.L. Furthermore, NRD showed increased fALFF in the left precuneus (PCUN.L). The area under the curve (AUC) values were as follows: 0.724 (MCG.L by ALFF), 0.732 (MFG.R), 0.767 (PCUN.L), 0.774 (MCG.L by ReHo), 0.878 (combined), 0.547 (HAMD), and 0.408 (HAMA) respectively. Conclusion: The findings suggest that PCUN.L, MFG.R, MCG.L, and the combined measures may indicate the possibility of developing TRD after 5 years when SSRIs are used as the initial therapy for relieving depressive symptoms in MDD patients. [ABSTRACT FROM AUTHOR]

Introduction: Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) may cause withdrawal at dose decrease, discontinuation, or switch. Current diagnostic methods (e.g., DSM) do not take such phenomenon into account. Using a new nosographic classification of withdrawal syndromes due to SSRI/SNRI decrease or discontinuation [by Psychother Psychosom. 2015;84(2):63–71], we explored whether DSM is adequate to identify DSM disorders when withdrawal occurs. Methods: Seventy-five self-referred patients with a diagnosis of withdrawal syndrome due to discontinuation of SSRI/SNRI, diagnosed via the Diagnostic Clinical Interview for Drug Withdrawal 1 – New Symptoms of Selective Serotonin Reuptake Inhibitors or Serotonin-Norepinephrine Reuptake Inhibitors (DID-W1), and at least one DSM-5 diagnosis were analyzed. Results: In 58 cases (77.3%), the DSM-5 diagnosis of current mental disorder was not confirmed when the DID-W1 diagnosis of current withdrawal syndrome was established. In 13 cases (17.3%), the DSM-5 diagnosis of past mental disorder was not confirmed when criteria for DID-W1 diagnosis of lifetime withdrawal syndrome were met. In 3 patients (4%), the DSM-5 diagnoses of current and past mental disorders were not confirmed when the DID-W1 diagnoses of current and lifetime withdrawal syndromes were taken into account. The DSM-5 diagnoses most frequently mis-formulated were current panic disorder (50.7%, n = 38) and past major depressive episode (18.7%, n = 14). Conclusion: DSM needs to be complemented by clinimetric tools, such as the DID-W1, to detect withdrawal syndromes induced by SSRI/SNRI discontinuation, decrease, or switch, following long-term use. [ABSTRACT FROM AUTHOR]

This study evaluated the bioequivalence of the newly developed dapoxetine hydrochloride tablet relative to the marketed reference product by comparing their pharmacokinetic profiles under fasted and fed conditions. A total of 60 healthy Chinese male subjects participated in a single‐center, 2‐period, 2‐sequence, randomized, open‐label, self‐crossover study with a washout period of 14 days, 30 in the fasted group and 30 in the fed group. Following a single 30‐mg oral dose of the test or reference dapoxetine formulation, blood samples were collected before dosing to 72 hours after dosing. Liquid chromatography‐tandem mass spectrometry was performed to measure plasma concentration of dapoxetine and determine pharmacokinetic parameters through noncompartmental analysis. The vital signs and adverse events were also monitored during the study. The 90% confidence intervals of the geometric mean ratios for maximum plasma concentration, area under the plasma concentration‐time curve from time 0 to the last concentration time, and area under the plasma concentration‐time curve from time 0 extrapolated to infinity of the 2 dapoxetine formulations completely fell within the regulatory criteria for bioequivalence of 80%‐125%. In addition, both dapoxetine hydrochloride formulations were generally well tolerated. The generic dapoxetine hydrochloride tablet was bioequivalent to the marketed reference product in healthy Chinese men with no discernible safety differences. [ABSTRACT FROM AUTHOR]

Purpose: Depression is prevalent in patients undergoing bariatric surgery (BSx). Long-term use of antidepressant is associated with weight gain, particularly the use of selective serotonin reuptake inhibitors (SSRIs). Little is known about whether different types of antidepressants affect the response to BSx. The purpose of this study was to determine the relationship between SSRI use and nutritional and biochemical measurements in those with obesity pre-/post-BSx. Methods: This is a cross-sectional and prospective cohort study. Patients were enrolled pre-BSx and divided into 3 groups: SSRI, non-SSRI and no antidepressant. Nutritional, biochemical and pharmacological data were collected pre- and 6 months post-BSx. Results: Pre-BSx, 77 patients were enrolled: 89.6% female, median age 45 years and body mass index (BMI) of 45.3 kg/m2. 14.3% were taking SSRIs and had a significantly higher BMI (52.1 kg/m2) compared to 62.3% in no antidepressant (46.0 kg/m2) and 23.4% in non-SSRI antidepressants (43.1 kg/m2). At 6 months post-BSx (n = 58), the SSRI group still had significantly higher BMI in comparison to the other two groups. No other significant differences found between groups. Conclusion: Despite higher BMI, patients taking SSRI and undergoing BSx had similar responses, based on nutritional and biochemical parameters, to those on non-SSRI or no antidepressants. Level of evidence: Level III: Evidence obtained from well-designed cohort or case–control analytic studies. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to systematically review whether concurrent treatment with an SSRI and low‐dose ASA increases the risk of bleeding compared with treatment with an SSRI alone or ASA alone. Methods: Medline, Embase, the Cochrane Library, PsycINFO and Web of Science (from database inception to January 2023) were searched according to PICO: P = patients on treatment with an SSRI and/or low‐dose ASA; I = intervention: SSRI + ASA; C = comparison: ASA or SSRI alone; O = outcomes: bleeding/major bleeding. The included articles were assessed using checklists. Studies without major risk of bias formed the basis for the conclusions. Extracted data were pooled using random‐effects meta‐analyses. Certainty of evidence was assessed according to GRADE. Results: Twenty‐four studies met the PICO and were included. One randomized and six nonrandomized studies were assessed not to have major risk of bias. Regarding SSRI + ASA vs. ASA only, the pooled hazard ratio of three nonrandomized studies (n = 38 467) was 1.37 (95% confidence interval: 1.10; 1.70; I2 = 0%), and the pooled odds ratio of two nonrandomized studies (n = 28 296) was 0.95 (0.77; 1.19; I2 = 0%). Regarding SSRI + ASA vs. SSRI only, the randomized controlled trial (n = 1048) reported a hazard ratio of 1.82 (0.66; 5.02), the hazard ratio being 1.60 (1.24; 2.06) for ASA vs. placebo in patients without SSRI treatment; and one nonrandomized controlled study (n = 18 920) reported an incidence rate ratio of 1.03 (0.96; 1.12). Conclusions: The compiled evidence was too uncertain to support an interaction when an SSRI is added to low‐dose ASA. Low‐dose ASA added to an SSRI may imply an increased risk of bleeding primarily attributable to the initiation of ASA. [ABSTRACT FROM AUTHOR]

Objective: We evaluated the presence and impact of unblinding during the influential Treatment for Adolescents with Depression Study (ClinicalTrials.gov Identifier: NCT00006286). Method: Our analysis was part of a Restoring Invisible and Abandoned Trials reanalysis. Treatment for Adolescents with Depression Study trialled fluoxetine, placebo, cognitive behaviour therapy or their combination, in treating adolescents with major depressive disorder. We analysed the accuracy of guesses of fluoxetine or placebo allocation, and their effects on change in Children's Depression Rating Scale-Revised at 12 weeks. Results: Of 221 participants allocated to fluoxetine or placebo, 151 adolescents (68%) had their guess about pill-treatment-arm allocation recorded at week 6, and guesses were recorded for 154 independent evaluators, 159 parents and 164 pharmacotherapists. All of these groups guessed treatment allocation more accurately than would be expected by chance (60–66% accuracy; all p -values ⩽ 0.004). Guesses did not become more accurate between 6 and 12 weeks and were not predicted by adverse events, though event documentation was poor. Treatment guess had a substantial and statistically significant effect on outcome (Children's Depression Rating Scale-Revised change mean difference 9.12 [4.69; 13.55], β = 0.334, p < 0.001), but actual treatment arm did not (1.53 [−2.83; 5.89], β = 0.056, p = 0.489). Removing guess from the analysis increased the apparent effect of treatment arm, making it almost statistically significant at the conventional alpha-level of 0.05 (p = 0.06). Conclusions: For Treatment for Adolescents with Depression Study, treatment guesses strongly predicted outcomes and may have led to the exaggeration of drug effectiveness in the absence of actual effects. The integrity of double-blinding in trials should be routinely assessed and reported. [ABSTRACT FROM AUTHOR]

The mechanisms by which Psilocybin Therapy (PT) improves depression remain an important object of study, with scientists actively exploring acute psychological experiences and neurobiological processes as candidates. In a phase 2, double-blind, randomized, active comparator controlled trial involving patients with moderate-to-severe major depressive disorder, we investigated whether acute psychological experiences could meaningfully account for the unique efficacy of PT versus Escitalopram Treatment over a core 6-week trial period. An exploratory-factor-analysis-derived single-factor of depression was used as the outcome. Among a comprehensive set of acute experiences related to psilocybin, so-called "mystical experience" and "ego dissolution" were unique in mediating the effect of treatment condition on depressive response with high specificity. Higher reported levels of mystical experience, emotional breakthrough, and intense responses to music-listening were furthermore associated with greater antidepressant response. These results provide qualified support for the causal mechanistic role of acute psychological experiences in the treatment of depression via PT. [ABSTRACT FROM AUTHOR]

Abstract Vascular endothelial growth factor (VEGF) signaling is known to be involved in the antidepressant‐like effects of conventional antidepressants, such as desipramine (DMI), a tricyclic antidepressant, and fluoxetine (FLX), a selective serotonin reuptake inhibitor; however, the precise role of neuronal VEGF signaling in mediating these effects remains unclear. Using mice with excitatory neuron‐specific deletion of VEGF and its receptor, fetal liver kinase 1 (Flk‐1) in the forebrain, we examined the effects of forebrain excitatory neuron‐specific deletion of VEGF or Flk‐1 on the antidepressant‐like effects of repeated DMI and chronic FLX administration in the forced swim test (FST). Repeated intraperitoneal (i.p.) injections of DMI (10, 10, and 20 mg/kg at 24, 4, and 1 h before the FST, respectively) significantly decreased immobility in control mice; however, this effect was completely blocked in mice with neuron‐specific VEGF or Flk‐1 deletion. Although chronic treatment with FLX (18 mg/kg/day, i.p.) did not impact immobility in control mice 1 day after the 22nd injection, immobility was significantly reduced 1 day after the preswim and the 23rd FLX injection. However, in mice with neuron‐specific Flk‐1 deletion, chronic FLX treatment significantly increased immobility in the preswim and failed to produce antidepressant‐like effects. Collectively, these findings indicate that neuronal VEGF–Flk‐1 signaling contributes to the antidepressant‐like actions of conventional antidepressants.

Vascular endothelial growth factor (VEGF) signaling is known to be involved in the antidepressant‐like effects of conventional antidepressants, such as desipramine (DMI), a tricyclic antidepressant, and fluoxetine (FLX), a selective serotonin reuptake inhibitor; however, the precise role of neuronal VEGF signaling in mediating these effects remains unclear. Using mice with excitatory neuron‐specific deletion of VEGF and its receptor, fetal liver kinase 1 (Flk‐1) in the forebrain, we examined the effects of forebrain excitatory neuron‐specific deletion of VEGF or Flk‐1 on the antidepressant‐like effects of repeated DMI and chronic FLX administration in the forced swim test (FST). Repeated intraperitoneal (i.p.) injections of DMI (10, 10, and 20 mg/kg at 24, 4, and 1 h before the FST, respectively) significantly decreased immobility in control mice; however, this effect was completely blocked in mice with neuron‐specific VEGF or Flk‐1 deletion. Although chronic treatment with FLX (18 mg/kg/day, i.p.) did not impact immobility in control mice 1 day after the 22nd injection, immobility was significantly reduced 1 day after the preswim and the 23rd FLX injection. However, in mice with neuron‐specific Flk‐1 deletion, chronic FLX treatment significantly increased immobility in the preswim and failed to produce antidepressant‐like effects. Collectively, these findings indicate that neuronal VEGF–Flk‐1 signaling contributes to the antidepressant‐like actions of conventional antidepressants. [ABSTRACT FROM AUTHOR]

Background and Aims: Benzodiazepines (BZDs) carry a risk for drug overdose and are prescribed alone or simultaneously with selective‐serotonin reuptake inhibitors (SSRIs) for the treatment of anxiety and depression in young adults. We aimed to measure risks of drug overdose following BZD treatment initiation, and simultaneous BZD and SSRI initiation, compared with SSRI treatment alone in young adults with depression or anxiety. Design, Setting, Participants: The cohort study used administrative databases covering privately (MarketScan, 1/1/2009–12/31/2018) and publicly (Medicaid, 1/1/2015–12/31/2016) insured young adults (18–29 years) in the United States. Those with depression or anxiety diagnoses newly initiating BZD or SSRI treatment (without BZD or SSRI prescriptions in prior year) were included. Simultaneous "BZD + SSRI" initiation was defined as starting BZD and SSRI treatment on the same day. The cohorts included 604 664 privately insured young adults (BZD = 22%, BZD + SSRI = 10%, SSRI = 68%) and 110 493 publicly insured young adults (BZD = 23%, BZD + SSRI = 5%, SSRI = 72%). Measurements: Incident medically treated drug overdose events were identified from emergency department and inpatient encounters (ICD poisoning codes) within 6 months of treatment initiation. Crude and propensity‐score adjusted cumulative incidence and hazard ratios (HR) were estimated. Sub‐analyses evaluated drug overdose intent. Findings Adjusted HRs of drug overdose for BZD vs. SSRI treatment was 1.36 (95% confidence interval [CI]:1.23–1.51) in privately and 1.59 (95%CI:1.37–1.83) in publicly insured young adults. The adjusted HRs of drug overdose for BZD + SSRI treatment vs. SSRI treatment were 1.99 (95%CI:1.77–2.25) in privately and 1.98 (95%CI:1.47–2.68) in publicly insured young adults. Conclusions: Among young adults in the United States, initiating benzodiazepine treatment for anxiety and depression, alone or simultaneously with selective‐serotonin reuptake inhibitors (SSRI), appears to have an increased risk of medically treated drug overdose compared with SSRI treatment alone. These associations were observed in publicly and privately insured individuals. [ABSTRACT FROM AUTHOR]

Perinatal mood disorders are a tremendous burden to childbearing families and treatment with selective serotonin reuptake inhibitor (SSRI) antidepressants is increasingly common. Exposure to SSRIs may affect serotonin signaling and ultimately, microbes that live in the gut. Health of the gut microbiome during pregnancy, lactation, and early infancy is critical, yet there is limited evidence to describe the relationship between SSRI exposure and gut microbiome status in this population. The purpose of this Preferred Reporting Items for Systematic reviews and Meta‐Analyses (PRISMA)‐compliant scoping review is to assess evidence and describe key concepts regarding whether SSRI exposure affects the maternal and infant gut microbiome. Sources were collected from PubMed, Web of Science, and Scopus databases, and an additional gray literature search was performed. Our search criteria returned only three sources, two rodent models and one human subjects research study. Results suggest that fluoxetine (SSRI) exposure may affect maternal gut microbiome dynamics during pregnancy and lactation. There were no available sources to describe the relationship between perinatal SSRI exposure and the infant gut microbiome. There is a significant gap in the literature regarding whether SSRI antidepressants affect the maternal and infant gut microbiome. Future studies are required to better understand how SSRI antidepressant exposure affects perinatal health. [ABSTRACT FROM AUTHOR]

Background: Pulmonary hypertension (PH) often leads to right ventricle (RV) failure, a significant cause of morbidity and mortality. Despite advancements in PH management, progression to RV maladaptation and subsequent failure remain a clinical challenge. This study explored the effect of paroxetine, a selective serotonin reuptake inhibitor (SSRI), on RV function in a rat model of PH, hypothesizing that it improves RV function by inhibiting G protein-coupled receptor kinase 2 (GRK2) and altering myofilament protein phosphorylation. Methods: The Su5416/hypoxia (SuHx) rat model was used to induce PH. Rats were treated with paroxetine and compared to vehicle-treated and control groups. Parameters measured included RV morphology, systolic and diastolic function, myofilament protein phosphorylation, GRK2 activity, and sympathetic nervous system (SNS) markers. Results: Paroxetine treatment significantly improved RV systolic function, evidenced by increased stroke volume, cardiac output, and ejection fraction, without significantly affecting RV hypertrophy, myosin heavy chain/titin isoform switching, or fibrosis. Enhanced phosphorylation of titin and myosin light chain-2 was observed, correlating positively with improved systolic function. Contrary to the hypothesis, improvements occurred independently of GRK2 inhibition or SNS modulation, suggesting an alternate mechanism, potentially involving antioxidant properties of paroxetine. Conclusion: Paroxetine improves RV systolic function in PH rats, likely through mechanisms beyond GRK2 inhibition, possibly related to its antioxidant effects. This highlights the potential of paroxetine in managing RV dysfunction in PH, warranting further investigation into its detailed mechanisms of action and clinical applicability.

Introduction: Prior studies have identified SSRI use as a risk factor for certain adverse bleeding outcomes. However, the risk of significant bleeding from perioperative SSRI use after brain tumor resection remains largely undetermined. This study evaluates if patients taking SSRIs perioperatively have a higher risk of intracranial hemorrhage (ICH) following elective craniotomy for tumor resection. Methods: Researchers reviewed electronic medical records of patients age 18 and older, who received elective craniotomy for tumor resection between 2010 and 2019. Data collection included subject demographics and relevant medical history. We compared intracranial hemorrhage rates and risks between perioperative SSRI-use cohorts. Results: Of 1,061 patients, 796 (75%) did not use SSRIs perioperatively while 265 (25%) used SSRIs perioperatively. Among those using perioperative SSRIs, 8 patients (3.0%) experienced an ICH within 1 week and 11 patients (4.2%) had an ICH within 1 month. Similarly, for those who stopped SSRI use perioperatively, we found 31 patients (3.9%) experienced an ICH within 1 week and 40 patients (5.0%) had an ICH within 1 month. Using logistic regression analysis, the relative risk for perioperative SSRI-use and ICH was statistically non-significant at 0.692 (95% CI: 0.260 - 1.839, p = 0.460). Conclusions: Based on our results, perioperative SSRI use does not appear to result in an increased risk of bleeding within 1 week or month of craniotomy for tumor resection. These results remained consistent when controlled for several additional bleeding comorbidities and demographics between cohorts

Paroxetine is a commonly used drug in psychiatric settings for disorders such as major depressive disorder, obsessive-compulsive disorder, social anxiety disorder, generalized anxiety disorder, panic disorder, premenstrual dysphoric disorder, and posttraumatic stress disorder. However, this drug comes with its own series of adverse effects, including dry mouth, drowsiness, constipation, sexual side effects, etc. In our case study, we wish to highlight a case of depression who developed a rarely documented side effect of serial nightmares after prescribing paroxetine. On cross-tapering it with sertraline, her nightmares gradually resolved with no deterioration of depressive symptoms. By reporting this case, we wish to emphasize on this potential side effects of paroxetine which should be kept in mind while choosing this agent. Such reporting is important as this rare side effect could be confused with other clinical pictures, thereby affecting management. It also helps us enhance our knowledge of how selective serotonin reuptake inhibitors can lead to the development of nightmares.

Anhedonia is clinically defined as difficulty or inability to feel pleasure or to be motivated to perform activities that were previously pleasurable. Anhedonia is a core feature of depressive disorders but can be present in other conditions such as substance use and anxiety disorders. Herein we report the case of a 34-year-old female who developed marked anhedonia after left cortico-amygdalohippocampectomy. Despite optimal seizure control, the person struggled with anhedonia and other depressive symptoms. After ruling out medico-neurologic complications, she was prescribed with a selective serotonin reuptake inhibitor and cognitive-behavioral therapy. Anhedonia can be a challenging neuropsychiatric presentation that requires ruling out the effects of antiseizure medications, neurosurgery, and other drugs before prescribing antidepressants.

Objective: We conducted a meta-analysis to determine the effectiveness of selective serotonin reuptake inhibitors in improving motor outcomes after stroke. For accuracy, we only included studies in which selective serotonin reuptake inhibitors were administered to patients in the recovery phase after stroke (<6 mos after stroke). Design: Meta-analyses were conducted according to the tools used to measure motor function. We searched the SCOPUS, PubMed, Embase, and Cochrane Library databases for studies, which compared motor recovery in patients who receive selective serotonin reuptake inhibitor medication in the recovery phase after stroke with a control group that did not receive any selective serotonin reuptake inhibitor. Results: A total of 3715 publications were assessed, and nine studies met the study criteria. The group, which received selective serotonin reuptake inhibitors, showed improved Fugl-Meyer Motor Scale and Barthel index scores compared with the control group. However, there was no significant difference in the modified Rankin Scale scores between the selective serotonin reuptake inhibitor and control groups. The incidence of adverse effects after the administration of selective serotonin reuptake inhibitors did not differ from that in the control group. Conclusions: Our study showed that the use of selective serotonin reuptake inhibitor in the recovery phase of stroke improved motor function without significant increase in adverse effects. [ABSTRACT FROM AUTHOR]

This brief report describes the case of a 16-year-old girl who was commenced on sertraline for anxiety and depression, and subsequently developed severe and debilitating motor tics. Cessation of sertraline was associated with the resolution of tics; after this, paroxetine was trialled and well tolerated with good response of targeted symptoms and without re-emergence of tics. A narrative literature review yielded a retrospective observational study and eight single case reports on selective serotonin receptor inhibitor-induced motor tics (three in adolescents and five in adults). Tics are not commonly considered as a side-effect of SSRIs. This case report is novel is several aspects: the tics emergence was immediate whereas previous cases were delayed; the tics symptoms were measured and quantified by a validated scale; a dose-response relationship was observed; to our knowledge, our case was the first adolescent female reported; and finally, paroxetine was well-tolerated as a substitute, although it is unclear whether the observed tics-sparing effect is co-incidental, ideocratic or can be replicated. [ABSTRACT FROM AUTHOR]

Overview: Reproductive experience (pregnancy and motherhood) leads to long-term changes in the neurobiological and hormonal features of anxiety in rats and humans. The aim of this study was to examine whether reproductive experience alters the effects of two pharmacological treatments for anxiety, a benzodiazepine (diazepam) and a selective serotonin reuptake inhibitor (fluoxetine), on animal models of anxiety. Methods: In Experiment 1, virgin (n = 47) and age-matched mother (n = 50) rats at 1-month post-weaning were injected with diazepam (1.3 mg/kg or 1.7 mg/kg, i.p.) or vehicle, in the proestrus (high estradiol/progesterone/allopregnanolone) or metestrus (low estradiol/progesterone/allopregnanolone) phase of the estrous cycle 30 min prior to the elevated plus maze (EPM). In Experiment 2, virgin (n = 25) and mother rats (n = 20) were administered fluoxetine (10 mg/kg) or vehicle for 2 weeks prior to being tested on a Pavlovian fear conditioning and extinction protocol, and the EPM. Results: Replicating past research, in virgin rats, the low dose of diazepam produced anxiolytic-like effects in proestrus, but only the high dose was anxiolytic-like in metestrus. In contrast, in mother rats, both doses of diazepam were anxiolytic-like irrespective of estrous phase. Fluoxetine produced anxiogenic-like effects in virgin rats during fear extinction and the EPM, but had no behavioural effects in mothers. In contrast, fluoxetine increased plasma corticosterone levels measured 30-min post-EPM in mothers, but not virgin rats. Conclusions: Reproductive experience alters the dose responsivity and efficacy of common anti-anxiety medications in female rats. These findings highlight the importance of considering reproductive status in studies on anxiety and its treatment. [ABSTRACT FROM AUTHOR]

Introduction: Selective serotonin reuptake inhibitors (SSRIs) are the most often used medications to treat major depressive disorder (MDD). Despite their effectiveness in reducing depressive symptoms, several issues are associated with their use in MDD, such as limited improvement of anhedonia, emergence of emotional blunting, induction or exacerbation of insomnia, and sexual dysfunction. Due to its also devoid of the issues related to treatment noted with SSRIs. The aim of this 12-week non-inferiority naturalistic observation was to compare the effectiveness and tolerability of SSRIs and trazodone in extended release (XR) in MDD. Methods: A total of 186 subjects were recruited, of which 92 received trazodone XR and 94 received SSRIs. Patients were allocated to trazodone XR or SSRIs, according to the attending physician based on clinical evaluation. Assessments at baseline and weeks 2, 4, 8, and 12 were conducted to evaluate the severity of depression (Montgomery–Åsberg Depression Rating Scale, clinician- and patientrated Quick Inventory of Depressive Symptomatology—the primary endpoints of the study), anhedonia (the Snaith–Hamilton Pleasure Scale), anxiety (the Hamilton Anxiety Rating Scale), insomnia (the Athens Insomnia Scale), and therapeutic effectiveness (the Clinical Global Impression Scale). Results: After 12 weeks, trazodone XR was more effective than SSRIs in reducing the severity of depression, anxiety, and insomnia. There was a trend for higher effectiveness of in reduction of anhedonia, which became insignificant after controlling the results for the duration of previous psychiatric treatment as a covariate. The proportion of treatment-responsive subjects in the trazodone XR group compared to SSRIs was comparable or higher. The proportion of patients achieving remission was higher in the trazodone XR arm vs. the SSRI arm. Discussion: In summary, the results indicate that trazodone XR is effective in MDD in the “real-world” setting. Its potential superiority over SSRIs in addressing particular symptomatic dimensions should be verified in future studies. [ABSTRACT FROM AUTHOR]

Selective serotonin reuptake inhibitors (SSRIs) are commonly used to treat depression and anxiety. The purpose of this study was to assess in real time the effect of paroxetine, an SSRI, on newly formed bone volume (NFBV) in standardized calvarial defects (SCDs) in rats. Fourteen Wistar albino female rats with a mean age of 7.5 months and a mean weight of 275 g were used. The animals were randomly divided into 2 groups. The experimental group was given paroxetine 8 weeks before the surgical procedure and throughout the experiment, and the control group was given a placebo 8 weeks before the surgical procedure and throughout the experiment. In each group, 14 SCDs measuring 4.6 mm in diameter were created on the parietal bone. In both groups, a Bio-Oss + collagen membrane was placed. All defects showed primary closure. The volume of the newly formed bone (NFBV) was measured using in vivo micro–computed tomographic imaging. Measurements were taken at days 0, 14, 28, 42, and 56 after surgery using real-time assessment with micro–computed tomographic imaging. The mean NFBV was 17.12 ± 4.52 mm3 and 12.52 ± 4.78 mm3 for the control and experimental groups, respectively, at day 56. The differences between the 2 groups were statistically significant (P <.05) at all time intervals. Paroxetine intake significantly reduced the amount of regenerated NFBV and the rate of new bone formation. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) and circulating cell-free mitochondrial DNA (ccf-mtDNA) have attracted interest as biological markers of affective disorders. In response to stress, it is known that miRNAs in mitochondria diffuse out of the cytoplasm alongside mtDNA; however, this process has not yet been identified. We hypothesized that miRNAs derived from specific cell nuclei cause mitochondrial damage and mtDNA fragmentation under MDD-associated stress conditions. A comprehensive analysis of the plasma miRNA levels and quantification of the plasma ccf-mtDNA copy number were performed in 69 patients with depression to determine correlations and identify genes and pathways interacting with miRNAs. The patients were randomly assigned to receive either selective serotonin reuptake inhibitors (SSRI) or mirtazapine. Their therapeutic efficacy over four weeks was evaluated in relation to miRNAs correlated with ccf-mtDNA copy number. The expression levels of the five miRNAs showed a significant positive correlation with the ccf-mtDNA copy number after correcting for multiple testing. These miRNAs are involved in gene expression related to thyroid hormone synthesis, the Hippo signaling pathway, vasopressin-regulated water reabsorption, and lysine degradation. Of these five miRNAs, miR-6068 and miR-4708-3p were significantly associated with the SSRI and mirtazapine treatment outcomes, respectively. This study did not show comparison with a healthy group. The expression levels of specific miRNAs were associated with ccf-mtDNA copy number in untreated depressed patients; moreover, these miRNAs were linked to antidepressant treatment outcomes. These findings are expected to lead to the elucidation of new pathological mechanism of depression. • Five microRNAs were associated with mitochondrial DNA in patients with depression. • These miRNAs showed positive correlation. • These were associated with genes on pathways such as thyroid hormone synthesis. • miR-6068 and miR-4708-3p were associated with antidepressant treatment outcome. [ABSTRACT FROM AUTHOR]

Premenstrual symptoms are characterized by unpleasant psychophysical symptoms that appear during the luteal phase before menstruation and interfere with a woman's quality of life. Premenstrual syndrome (PMS) is a pathological condition with premenstrual symptoms, of which premenstrual dysphoric disorder (PMDD) is a particularly severe psychological symptom. This study aimed to examine the gender differences in the diagnosis and treatment of PMS and PMDD among obstetricians and gynecologists (OB/ GYNs) in Japan. Data were obtained from the survey conducted by the Japanese Society of Obstetrics and Gynecology. We used data from 1,257 of the 1,265 OB/GYNs who are engaged in PMS/PMDD practice and reported their gender. Multivariate regression analysis adjusted for propensity scores was performed. Female OB/GYNs were more frequently engaged in treating patients with PMS/PMDD than males [odds ratio (OR) 1.74; 95% confidence interval (CI) 1.36-2.21]. With regard to the diagnostic methods, more female OB/GYNs selected the two-cycle symptom diary than males (OR 2.88; 95% CI 1.80- 4.60). Regarding treatment, fewer female OB/GYNs selected selective serotonin reuptake inhibitors as their first-line drug (OR 0.39; 95% CI 0.17-0.89). Gender differences were found in the selection of PMS/ PMDD diagnosis and treatment methods among Japanese OB/GYNs. [ABSTRACT FROM AUTHOR]

Sertralin, antidepresan ve anksiyolitik özellikleri olan pek çok ruhsal bozukluğun tedavisinde kullanılabilen seçici serotonin geri alım inhibitörü (SSGI) grubundan bir antidepresandır. Sertraline bağlı nadir görülen yan etki kanama eğiliminin artmasıdır. Bu yazıda sertralin kullanımıyla başlayan ve ilacın kesilmesinin ardından kaybolan sertalin kullanımı ile ilişkili ekimoz olgusu sunulmuştur.

Biased memory processing contributes to the development and exacerbation of depression, and thus could represent a potential therapeutic target for stress-induced mental disorders. Synchronized spikes in hippocampal neurons, corresponding to sharp wave ripples (SWRs), may play a crucial role in memory reactivation. In this study, we showed that the frequency of SWRs increased in the ventral hippocampus, but not in the dorsal hippocampus, after stress exposure. Administration of the selective serotonin reuptake inhibitors (SSRIs) fluoxetine and fluvoxamine inhibited the generation of ventral hippocampal SWRs and reduced locomotor activity and local field potential power in the gamma bands. These results suggest that the antidepressant effects of SSRIs may be mediated by the suppression of ventral hippocampal SWRs.

Paroxetine is a commonly used drug in psychiatric settings for disorders such as major depressive disorder, obsessive-compulsive disorder, social anxiety disorder, generalized anxiety disorder, panic disorder, premenstrual dysphoric disorder, and posttraumatic stress disorder. However, this drug comes with its own series of adverse effects, including dry mouth, drowsiness, constipation, sexual side effects, etc. In our case study, we wish to highlight a case of depression who developed a rarely documented side effect of serial nightmares after prescribing paroxetine. On cross-tapering it with sertraline, her nightmares gradually resolved with no deterioration of depressive symptoms. By reporting this case, we wish to emphasize on this potential side effects of paroxetine which should be kept in mind while choosing this agent. Such reporting is important as this rare side effect could be confused with other clinical pictures, thereby affecting management. It also helps us enhance our knowledge of how selective serotonin reuptake inhibitors can lead to the development of nightmares. [ABSTRACT FROM AUTHOR]

Abstract Background Jitteriness/anxiety syndrome is a recognized adverse effect observed during the initiation or change of dose in antidepressant treatment. Managing patients who develop this syndrome remains a challenge. While escitalopram is a widely used antidepressant known to cause these symptoms, this report explores vortioxetine as a therapeutic alternative. Case Presentation Three distinct clinical scenarios were observed in patients who manifested jitteriness/anxiety syndrome while on escitalopram treatment for depression. Patient A was initiated on escitalopram and experienced an initial alleviation in depressive symptoms, but 3 months later displayed mood elevation, talkativeness, and increased activity, which disturbed his daily life. A transition to vortioxetine subsequently resolved the mood elevation. Patient B exhibited elevated mood, hyperactivity, irritability, and talkativeness just 6 days post‐initiation of treatment with escitalopram. After the discontinuation of escitalopram and unsuccessful trials with aripiprazole, lurasidone, and lamotrigine, her depressive mood intensified, culminating in suicidal ideation. Starting vortioxetine led to a consistent improvement of her symptoms, and she resumed work and was emotionally stable. Patient C was initially diagnosed with bipolar disorder and faced a relapse into depression despite undergoing various treatments. After 2 weeks on escitalopram, she exhibited irritability and self‐harm urges. Three months later, after being re‐diagnosed with depressive disorders with anxious distress, vortioxetine was administered, which significantly reduced her depressive symptoms and allowed her to continue her education. Conclusion Vortioxetine presents as a promising therapeutic alternative that is worth considering for patients with escitalopram‐induced jitteriness/anxiety syndrome.

Introduction: Selective serotonin reuptake inhibitors (SSRIs) are the most often used medications to treat major depressive disorder (MDD). Despite their effectiveness in reducing depressive symptoms, several issues are associated with their use in MDD, such as limited improvement of anhedonia, emergence of emotional blunting, induction or exacerbation of insomnia, and sexual dysfunction. Due to its also devoid of the issues related to treatment noted with SSRIs. The aim of this 12-week non-inferiority naturalistic observation was to compare the effectiveness and tolerability of SSRIs and trazodone in extended release (XR) in MDD.Methods: A total of 186 subjects were recruited, of which 92 received trazodone XR and 94 received SSRIs. Patients were allocated to trazodone XR or SSRIs, according to the attending physician based on clinical evaluation. Assessments at baseline and weeks 2, 4, 8, and 12 were conducted to evaluate the severity of depression (Montgomery–Åsberg Depression Rating Scale, clinician- and patient-rated Quick Inventory of Depressive Symptomatology—the primary endpoints of the study), anhedonia (the Snaith–Hamilton Pleasure Scale), anxiety (the Hamilton Anxiety Rating Scale), insomnia (the Athens Insomnia Scale), and therapeutic effectiveness (the Clinical Global Impression Scale).Results: After 12 weeks, trazodone XR was more effective than SSRIs in reducing the severity of depression, anxiety, and insomnia. There was a trend for higher effectiveness of in reduction of anhedonia, which became insignificant after controlling the results for the duration of previous psychiatric treatment as a covariate. The proportion of treatment-responsive subjects in the trazodone XR group compared to SSRIs was comparable or higher. The proportion of patients achieving remission was higher in the trazodone XR arm vs. the SSRI arm.Discussion: In summary, the results indicate that trazodone XR is effective in MDD in the “real-world” setting. Its potential superiority over SSRIs in addressing particular symptomatic dimensions should be verified in future studies.

Aim: This evidence-based case report aims to provide the latest evidence about the risk of gastrointesinal (GI) bleeding in selective serotonin reuptake inhibitor (SSRI) users with dyspepsia. Method: The literature search was conducted in four major electronic databases (PubMed, Cochrane, Scopus, ProQuest). The selected articles were sorted through screening abstract based on the inclusion and exclusion criteria. Critical appraisal was performed by using validated critical appraisal tool. Results: Of 247 records from extensive literature searching, three eligible studies (one randomized clinical trial and two cohort studies) were obtained to answer the clinical question. All studies showed SSRIs did not increase the risk of GI bleeding in patients with functional dyspepsia and peptic ulcer. However, the adverse event of SSRIs might be under-reported. Conclusion: According to the evidence, the risk of GI bleeding in SSRIs users with dyspepsia is still unclear. Larger size of sample of controlled trial study is recommended to be conducted to calculate the precise risk of GI bleeding in SSRI users with dyspepsia. [ABSTRACT FROM AUTHOR]

Individual treatment outcomes to antidepressants varies widely, yet the determinants to this difference remain elusive. MicroRNA (miRNA) gene expression regulation in major depressive disorder (MDD) has attracted interest as a biomarker. This 4-week randomized controlled trial examined changes in the plasma miRNAs that correlated with the treatment outcomes of mirtazapine (MIR) and selective serotonin reuptake inhibitor (SSRI) monotherapy. Pre- and post- treatment, we comprehensively analyzed the miRNA levels in MDD patients, and identified the gene pathways linked to these miRNAs in 46 patients. Overall, 141 miRNA levels significantly demonstrated correlations with treatment remission after 4 weeks of MIR, with miR-1237-5p showing the most robust and significant correlation after Bonferroni correction. These 141 miRNAs displayed a negative correlation with remission, indicating a decreasing trend. These miRNAs were associated with 15 pathways, including TGF-β and MAPK. Through database searches, the genes targeted by these miRNAs with the identified pathways were compared, and it was found that MAPK1, IGF1, IGF1R, and BRAF matched. Alterations in specific miRNAs levels before and after MIR treatment correlated with remission. The miRNAs mentioned in this study have not been previously reported. No other studies have investigated treatment with MIR. The identified miRNAs also correlated with depression-related genes and pathways. [ABSTRACT FROM AUTHOR]

Objective: Stress may have an important role in the origin and progress of depression and can impair metabolichomeostasis. The one-carbon cycle (1-CC) metabolism and amino acid (AA) profile are some of the consequencesrelated to stress. In this study, we investigated the Paroxetine treatment effect on the plasma metabolite alterationsinduced by forced swim stress-induced depression in mice.Materials and Methods: In this experimental study that was carried out in 2021, thirty male NMRI mice (6-8 weeksage, 30 ± 5 g) were divided into five groups: control, sham, paroxetine treatment only (7 mg/kg BW/day), depressioninduction, and Paroxetine+depression. Mice were subjected to a forced swim test (FST) to induce depression and thenwere treated with Paroxetine, for 35 consecutive days. The swimming and immobility times were recorded during theinterventions. Then, animals were sacrificed, plasma was prepared and the concentration of 1-CC factors and twentyAAs was measured by spectrophotometry and high-performance liquid chromatography system (HPLC) techniques.Data were analyzed by SPSS, using One-Way ANOVA and Pearson Correlation, and P

Abstract Aim Selective serotonin reuptake inhibitors (SSRIs) are used to treat major depressive disorder (MDD) and other psychiatric disorders (e.g., obsessive compulsive disorder, social anxiety disorder, and panic disorder). In MDD treatment, SSRIs do not show remission in approximately 30% of patients, indicating a need for a better treatment option. Forced swimming test (FST) is a behavioral assay to evaluate depression‐like behavior and antidepressant efficacy in rodents. In the present study, we evaluated the combination effect of brexpiprazole with SSRIs on FST in mice, in order to investigate their synergistic effect. Methods Brexpiprazole (0.003 mg/kg) was intraperitoneally injected to mice 15 min before testing. Escitalopram (10 mg/kg), fluoxetine (75 mg/kg), paroxetine (10 mg/kg), or sertraline (15 mg/kg) were orally administered to mice 60 min before testing. Then, the mice were placed in water and immobility time was measured. Data from animals treated with escitalopram, fluoxetine, paroxetine, and sertraline were pooled as SSRI‐treated group data. Results Combination treatment of brexpiprazole with SSRIs reduced immobility time in FST more than vehicle or each single treatment. A significant interaction effect was confirmed in the combination of brexpiprazole and SSRIs (p = 0.0411). Conclusion Efficacy of adjunctive brexpiprazole has already been demonstrated in clinical trials in MDD patients not adequately responding to antidepressants including escitalopram, fluoxetine, paroxetine, and sertraline. The synergistic antidepressant‐like effect of brexpiprazole with SSRIs found in this study supports the already known clinical findings.

Trichotillomania (TTM) is a less addressed cause of alopecia. Refusal to accept this condition as a psychiatric illness causes marked delay in seeking help. This article aims to evaluate the treatment response of TTM patients. This is a case series study on 5 patients (4 females, 1 male) of TTM, of whom 3 patients took treatment on an outpatient basis (obsessive-compulsive and related disorders clinic) and 2 patients at indoor (orange unit) at the Department of Psychiatry, Bangabandhu Sheikh Mujib Medical University, from January 2022 to July 2023. Out of 7 cases, 2 patients did not come after the 1st follow-up. Pharmacological management was chosen according to established guidelines. All patients were given basic psychoeducation and relevant psychological intervention. A total of 5 cases were described. The median time to receive effective psychiatric treatment is 8.6 years (4–15 years). The median time to respond after starting therapy is 6 weeks. All patients responded well to selective serotonin reuptake inhibitors. Augmentation with low-dose antipsychotics and the addition of specific pharmacologic agents have been shown to improve outcomes. Psychological management helped patients most in achieving long-term remission. Despite the prolonged treatment gap, patients of TTM showed marked improvement with combined pharmacological and psychological intervention in a short time. Further study involving a more significant number of cases is needed to support the findings.

Context Fluvoxamine may have a potential immune-regulatory action and a therapeutic role in severe acute respiratory syndrome-coronavirus (SARS-CoV-2) infection that may prevent progression and/or hospitalization. Aims Trial that compared fluvoxamine versus placebo in nonhospitalized adults with confirmed SARS-CoV-2 infection (mild and moderate coronavirus disease 2019 cases). Settings and design This is a double-blinded, randomized clinical trial. Patients and methods The study enrolled 162 cases with positive PCR assay for SARS-CoV-2 infection and who were symptomatic within 7 days of the first dose of study medication. Statistical analysis The demographic, clinical, and laboratory data gathered together will be tabulated and statistically analyzed. The statistical analysis of data was carried out using Excel and the SPSS programs statistical package for AQ8 Social Sciences, version 17. Quantitative data were described as median (minimum–maximum). An analysis of the data was carried out to test statistically significant differences between groups. Quantitative data were presented as mean±SD and the Student’s t test was used to compare between two groups. Results In all, 162 patients completed the study; 72 patients were of mild severity; 90 patients were moderate cases and each group was randomized to receive fluvoxamine or placebo besides standard care. In the mild group, no significant difference was recorded while slight significance exists in the moderate severity group. Conclusions Fluvoxamine may have an added value besides the current standard care in reducing the need for hospitalization in outpatient cases, especially pneumonic ones; however, more larger studies are needed.

Microscopic colitis is a common cause of chronic diarrhea, particularly in patients with autoimmune disorders. Colonic mucosa appears normal and only shows inflammation on histological examination. There are two histological variations of microscopic colitis. It has been associated with several drug classes, and certain drugs are associated with one variation or another. In this case report, we discuss the case of a patient who is on a drug not previously associated with her variation of microscopic colitis and who has an autoimmune condition whose relationship to microscopic colitis is not well studied. We aim to outline the potential triggers for the disease and to call for further studies regarding how certain drugs and/or autoimmune disorders trigger it in order to further our understanding and improve management.

Background: Migraine and depression have a bi-directional, positive association. The likelihood of these conditions being comorbidities is high, thus, the possibility of concomitant use of an antidepressant and a triptan is also increased. Case Presentation: We present a case of a 39-year-old female with a history of migraine with aura and depression who had brief episodes of exacerbated depressive symptoms following oral administration of sumatriptan 100 mg daily as needed while taking various selective serotonin reuptake inhibitor (SSRI) and serotonin and norepinephrine reuptake inhibitor (SNRI) medications on different occasions. The patient experienced 30-minute episodes of sweating and subjective increase in temperature approximately 2–3 hours after administration of sumatriptan 100 mg. This was followed by a transient exacerbation of sadness described by the patient as unhappiness, hopelessness, and tearfulness, which lasted 1 to 2 hours. To date, there are no other published case reports that have described this particular presentation. Several studies have reported possible serotonin syndrome as a result of the combination. Current evidence and known pharmacological actions of SSRIs/SNRIs and triptans are not well-defined enough to explain how one can experience episodic worsening depression. Conclusion: This case illustrates that clinicians should consider other potential adverse effects of the combined use of triptans and SSRIs/SNRIs beyond serotonin syndrome. [ABSTRACT FROM AUTHOR]

Objective: Cholinesterase inhibitors (CEIs) are prescribed for dementia to maintain or improve memory. Selective serotonin reuptake inhibitors (SSRIs) are also prescribed to manage psychiatric symptoms seen in dementia. What proportion of outpatients actually responds to these drugs is still unclear. Our objective was to investigate the responder rates of these medications in an outpatient setting using the electronic medical record (EMR). Methods: We used the Johns Hopkins EMR system to identify patients with dementia who were prescribed a CEI or SSRI for the first time between 2010 and 2021. Treatment effects were assessed through routinely documented clinical notes and free-text entries in which healthcare providers record clinical findings and impressions of patients. Responses were scored using a three-point Likert scale named the NOte-based evaluation method for Treatment Efficacy (NOTE) in addition to the Clinician's Interview-Based Impression of Change Plus caregiver input (CIBIC-plus), a seven-point Likert scale used in clinical trials. To validate NOTE, the relationships between NOTE and CIBIC-plus and between NOTE and change in MMSE (Mini-Mental State Examination) before and after medication were examined. Inter-rater reliability was evaluated using Krippendorff's alpha. The responder rates were calculated. Results: NOTE showed excellent inter-rater reliability and correlated well with CIBIC-plus and changes in MMSEs. Out of 115 CEI cases, 27.0% reported improvement and 34.8% reported stable symptoms in cognition; out of 225 SSRI cases, 69.3% reported an improvement in neuropsychiatric symptoms. Conclusion: NOTE showed high validity in measuring the pharmacotherapy effects based on unstructured clinical entries. Although our real-world observation included various types of dementia, the results were remarkably similar to what was reported in controlled clinical trials of Alzheimer's disease and its related neuropsychiatric symptoms. [ABSTRACT FROM AUTHOR]

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used over-the-counter medications that can increase the risk of gastrointestinal (GI) bleeding through antiplatelet effects and loss of GI protection. Selective serotonin reuptake inhibitors (SSRIs), commonly used for mental and behavioral health, are another group of medications that can cause platelet dysfunction. Previous literature has shown a possible increased risk of GI bleeding with concurrent use of SSRIs and NSAIDs. We performed a network meta-analysis comparing NSAIDs, SSRIs, and combined SSRI/NSAIDs to assess the risk of GI bleeding. Methods: The following databases were searched: MEDLINE, Embase, Web of Science Core Collection, SciELO, KCI, and Cochrane database. All comparative studies, i.e., case–control, cohort, and randomized controlled trials were included. Direct and network meta-analysis was conducted using DerSimonian–Laird approach and random effect. For binary outcomes, odds ratio (OR) with 95% confidence interval (CI) and p value were calculated. Results: After a comprehensive search through November 10th, 2021, 15 studies with 82,605 patients were identified. 11 studies reported higher rates of GI bleeds in SSRI/NSAID than SSRI users (36.9% vs 22.8%, OR 2.14, 95% CI 1.52–3.02, p < 0.001, I2 = 86.1%). 10 studies compared SSRI/NSAID to NSAID users with higher rates of bleeds in SSRI/NSAID group (40.9% vs 34.2%, OR 1.49, 95% CI 1.20–1.84, p < 0.001, I2 = 68.8%). The results were consistent using network meta-analysis as well. Conclusion: Given higher risk of bleeding with concurrent NSAIDs and SSRIs, prescribers should exercise caution when administering NSAIDs and SSRIs concurrently especially in patients with higher risks of GI bleeding. [ABSTRACT FROM AUTHOR]

The efficacy of selective serotonin reuptake inhibitors (SSRIs) in the treatment of acute COVID-19 is still under investigation, with conflicting results reported from randomized controlled trials (RCTs). Different dosing regimens may have contributed to the contradictory findings. To evaluate the efficacy and safety of SSRIs and the effect of different dosing regimens on the treatment of acute COVID-19. Seven databases were searched from January 2020 to December 2022. Trial registries, previous reviews, and preprint servers were hand-searched. RCTs and observational studies with no language restrictions. COVID-19 inpatients/outpatients. SSRIs prescribed after diagnosis were compared against a placebo or standard of care. Risk of bias was rated using the revised Cochrane Risk of Bias Tool for Randomized Trials version 2.0 and Risk of Bias in Non-Randomized Studies of Interventions. Outcomes were mortality, hospitalization, composite of hospitalization/emergency room visits, hypoxemia, requirement for supplemental oxygen, ventilator support, and serious adverse events. RCT data were pooled in random-effects meta-analyses. Observational findings were narratively described. Subgroup analyses were performed on the basis of SSRI dose, and sensitivity analyses were performed excluding studies with a high risk of bias. The Grading of Recommendations, Assessment, Development and Evaluations framework was used to assess the quality of evidence. Six RCTs (N = 4197) and five observational studies (N = 1156) were included. Meta-analyses associated fluvoxamine with reduced mortality (risk ratio, 0.72; 95% CI, 0.63–0.82) and hospitalization (risk ratio, 0.79; 95% CI, 0.64–0.99) on the basis of moderate quality of evidence. Medium-dose fluvoxamine (100 mg twice a day) was associated with reduced mortality, hospitalization, and composite of hospitalization/emergency room visits, but low-dose fluvoxamine (50 mg twice a day) was not. Fluvoxamine was not associated with increased serious adverse events. Observational studies support the use of fluvoxamine and highlight fluoxetine as a possible alternative to SSRIs for the treatment of COVID-19. Fluvoxamine remains a candidate pharmacotherapy for treating COVID-19 in outpatients. Medium-dose fluvoxamine may be preferable over low-dose fluvoxamine. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: Generalized anxiety disorder (GAD) in children and adolescents is associated with substantial morbidity and increases the risk of future psychopathology. However, relatively few psychopharmacologic studies have examined treatments for GAD in pediatric populations, especially in prepubertal youth. Methods: Children and adolescents aged 7–17 years of age with a primary diagnosis of GAD were treated with flexibly dosed escitalopram (10–20 mg daily, n = 138) or placebo (n = 137) for 8 weeks. Efficacy measures included the Pediatric Anxiety Rating Scale (PARS) for GAD, Clinical Global Impression of Severity (CGI-S) scale, Children's Global Assessment Scale (CGAS); safety measures included the Columbia-Suicide Severity Rating Scale (C-SSRS) as well as adverse events (AEs), vital signs, and electrocardiographic and laboratory monitoring. Results: Escitalopram was superior to placebo in reducing anxiety symptoms of GAD, as seen in the difference in mean change from baseline to week 8 on the PARS severity for GAD score (least squares mean difference = −1.42; p = 0.028). Functional improvement, as reflected by CGAS score, was numerically greater in escitalopram-treated patients compared with those receiving placebo (p = 0.286), and discontinuation owing to AEs did not differ between the two groups. Vital signs, weight, laboratory, and electrocardiographic results were consistent with previous pediatric studies of escitalopram. Conclusions: Escitalopram reduced anxiety symptoms and was well tolerated in pediatric patients with GAD. These findings confirm earlier reports of escitalopram efficacy in adolescents aged 12–17 years and extend the safety and tolerability data to children with GAD aged 7–11 years. ClinicalTrials.gov Identifier: NCT03924323. [ABSTRACT FROM AUTHOR]

Abstract Introduction Metacognitive beliefs about worry may trigger anxiety. However, the effect of generalized anxiety disorder (GAD) treatment on metacognition has not yet been investigated. Objectives To validate the Metacognitions Questionnaire (MCQ-30) in a Brazilian GAD sample and verify whether different interventions reduce metacognitive beliefs. Method We recruited 180 GAD individuals and randomized them to Body in Mind Training (BMT), Fluoxetine (FLX), or an active control group (Quality of Life [QoL]) for 8 weeks. The MCQ-30 was assessed for internal consistency, was evaluated with confirmatory and exploratory factor analyses, and was tested for convergent validity with the Penn State Worry Questionnaire (PSWQ). Generalized estimating equations (GEE) were employed to analyze differences after the interventions. Results The MCQ-30 demonstrated good internal consistency and acceptability; the original five-factor model was supported. There was a positive moderate correlation between MCQ-30 scores and worry. GEE showed a significant group x time interaction (p < 0.001). Both BMT (mean difference [MD] = -6.04, standard error [SE] = -2.39, p = 0.034) and FLX (MD = -5.78, SE = 1.91, p = 0.007) reduced MCQ-30 scores. FLX was superior to QoL, but not BMT, at weeks 5 and 8. There were no differences between BMT and QoL. Conclusion The Brazilian-Portuguese version of MCQ-30 showed good psychometric properties. Furthermore, the positive effect of FLX and BMT on metacognition suggests it may represent a potential therapeutic target.

Objective: Stress may have an important role in the origin and progress of depression and can impair metabolic homeostasis. The one-carbon cycle (1-CC) metabolism and amino acid (AA) profile are some of the consequences related to stress. In this study, we investigated the Paroxetine treatment effect on the plasma metabolite alterations induced by forced swim stress-induced depression in mice. Materials and Methods: In this experimental study that was carried out in 2021, thirty male NMRI mice (6-8 weeks age, 30 ± 5 g) were divided into five groups: control, sham, paroxetine treatment only (7 mg/kg BW/day), depression induction, and Paroxetine+depression. Mice were subjected to a forced swim test (FST) to induce depression and then were treated with Paroxetine, for 35 consecutive days. The swimming and immobility times were recorded during the interventions. Then, animals were sacrificed, plasma was prepared and the concentration of 1-CC factors and twenty AAs was measured by spectrophotometry and high-performance liquid chromatography system (HPLC) techniques. Data were analyzed by SPSS, using One-Way ANOVA and Pearson Correlation, and P<0.05 was considered significant. Results: Plasma concentrations of phenylalanine, glutamate, aspartate, arginine, ornithine, citrulline, threonine, histidine, and alanine were significantly reduced in the depression group in comparison with the control group. The Homocysteine (Hcy) plasma level was increased in the Paroxetine group which can be associated with hyperhomocysteinemia. Moreover, vitamin B12, phenylalanine, glutamate, ornithine, citrulline, and glycine plasma levels were significantly reduced in the depression group after Paroxetine treatment. Conclusion: This study has demonstrated an impairment in the plasma metabolites’ homeostasis in depression and normal conditions after Paroxetine treatment, although, further studies are required. [ABSTRACT FROM AUTHOR]