Selective Serotonin Reuptake Inhibitors Research Articles

8429 Serotonin Receptor Antagonist Alleviates Vascular Defects Produced by Selective Serotonin Reuptake Inhibitor Treatment During Gestation

Abstract Disclosure: L.P. Agnew: None. R. Domingues: None. A. Weichmann: None. L.L. Hernandez: None. Maternal mental health is critical for both mother and infant and often antidepressant therapy outweighs the potential risks of selective serotonin reuptake inhibitor (SSRI) treatment; however, SSRI use is associated with adverse neonatal outcomes. Preliminary work in our laboratory revealed placental apoptosis in pregnant dams treated with fluoxetine (FLX) and dams genetically deficient for the serotonin transporter gene. We hypothesize that SSRIs decrease placental blood flow, causing apoptosis and organ death via signaling through the serotonin 2A/2C receptors. Pregnant female C57BL6 mice were randomized to be treated daily, via I.P. injection, from E10-17.5 with saline (CON; n=6), 2 mg/kg FLX (n=5), or 2 mg/kg ketanserin plus 2 mg/kg FLX (n=5). On E17.5, using high-resolution ultrasound imaging, we identified the uterine artery, individual umbilical cords, and placental disc blood vessels. We calculated blood pressure, blood volume, blood flow rate, and heart rate in the uterine artery, umbilical cord, and placental disc. FLX (decreased blood volume in the uterine artery compared to ketanserin plus FLX (48.42 ± 18.26, 116.54 ± 45.25; p=0.0077), and decreased average (89.38 ± 31.50) and peak (130.36 ± 39.05) blood velocity in the uterine artery compared to ketanserin plus FLX average (162.76 ± 68.46; p=0.0322) and peak (236.77 ± 92.43; p=0.0242) blood velocity. FLX decreased average (0.04 + 0.02) and peak (0.07 ± 0.04) blood pressure in the uterine artery compared to ketanserin and FLX treated animals average (0.12 ± 0.10; p=0.0634) and peak (0.25 ± 0.19; p=0.0412) blood pressure. Ketanserin plus FLX (391 ± 38.29) decreased heart rate (BPM) in the placental disc compared to untreated controls (450.67 ± 26.08; p=0.0128). In the umbilical cord, ketanserin plus FLX (393 ± 28.25) decreased BPM compared to CON (450.17 ± 29.44; p=0.0078) and compared to FLX treatment alone (437.20 ± 17.28; p=0.0450). FLX treatment of dams during pregnancy reduces blood flow volume, heart rate, and blood flow velocity to the placenta via the uterine artery. The use of ketanserin, an inhibitor of serotonin receptor 2A/2C signaling, in combination with FLX, reduced the effects of FLX on the uterine artery. These data suggest that treatment with ketanserin could be utilized to alleviate the reproductive side effects of antidepressant usage for pregnant mothers while allowing the mother to remain on antidepressants. Future research should further investigate the effects of SSRI and ketanserin on blood flow to the fetus through the umbilical cord. Presentation: 6/2/2024

PET imaging identifies anti-inflammatory effects of fluoxetine and a correlation of glucose metabolism during epileptogenesis with chronic seizure frequency

The serotonergic system has shown to be altered during epileptogenesis and in chronic epilepsy, making selective serotonin reuptake inhibitors interesting candidates for antiepileptogenic therapy. In this study, we aimed to evaluate disease-modifying effects of fluoxetine during experimental epileptogenesis.Status epilepticus (SE) was induced by lithium-pilocarpine, and female rats were treated either with vehicle or fluoxetine over 15 days. Animals were subjected to 18F-FDG (7 days post-SE), 18F-GE180 (15 days post-SE) and 18F-flumazenil positron emission tomography (PET, 21 days post-SE). Uptake (18F-FDG), volume of distribution (18F-GE180) and binding potential (18F-flumazenil) were calculated. In addition, hyperexcitability testing and video-EEG monitoring were performed.Fluoxetine treatment did not alter brain glucose metabolism. 18F-GE180 PET indicated lower neuroinflammation in the hippocampus of treated animals (−22.6%, p = 0.042), but no differences were found in GABAA receptor density. Video-EEG monitoring did not reveal a treatment effect on seizure frequency. However, independently of the treatment, hippocampal FDG uptake 7 days after SE correlated with seizure frequency during the chronic phase (r = −0.58; p = 0.015).Fluoxetine treatment exerted anti-inflammatory effects in rats during epileptogenesis. However, this effect did not alter disease outcome. Importantly, FDG-PET in early epileptogenesis showed biomarker potential as higher glucose metabolism correlated to lower seizure frequency in the chronic phase.

Amygdala activity after subchronic escitalopram administration in healthy volunteers: A pharmaco-functional magnetic resonance imaging study.

Selective serotonin reuptake inhibitors (SSRIs) are used for the treatment of several conditions including anxiety disorders, but the basic neurobiology of serotonin function remains unclear. The amygdala and prefrontal cortex are strongly innervated by serotonergic projections and have been suggested to play an important role in anxiety expression. However, serotonergic function in behaviour and SSRI-mediated neurobiological changes remain incompletely understood. To investigate the neural correlates of subchronic antidepressant administration. We investigated whether the 2- to 3-week administration of a highly selective SSRI (escitalopram) would alter brain activation on a task robustly shown to recruit the bilateral amygdala and frontal cortices in a large healthy volunteer sample. Participants performed the task during a functional magnetic resonance imaging acquisition before (n = 96) and after subchronic escitalopram (n = 46, days of administration mean (SD) = 15.7 (2.70)) or placebo (n = 40 days of administration mean (SD) = 16.2 (2.90)) self-administration. Compared to placebo, we found an elevation in right amygdala activation to the task after escitalopram administration without significant changes in mood. This effect was not seen in the left amygdala, the dorsomedial region of interest, the subgenual anterior cingulate cortex or the right fusiform area. There were no significant changes in connectivity between the dorsomedial cortex and amygdala or the subgenual anterior cingulate cortex after escitalopram administration. To date, this most highly powered study of subchronic SSRI administration indicates that, contrary to effects often seen in patients with anxiety disorders, subchronic SSRI treatment may increase amygdala activation in healthy controls. This finding highlights important gaps in our understanding of the functional role of serotonin.

Post-COVID-19 condition-Clinical phenotyping in practice

The high number and clinical heterogeneity of neurological impairments in patients with apost-COVID-19 condition (PCC) poses achallenge for outpatient care. Our aim was to evaluate the applicability of the proposed subtypes according to the guidelines "Long/Post-COVID" (30 May 2024) and their phenotyping using clinical and neuropsychological findings from our post-COVID outpatient clinic. The evaluation was based on cross-sectional neurological and psychological test examinations of the patients, which were carried out using standardized questionnaires and test batteries. In addition, adetailed anamnesis of the current symptoms and aretrospective survey of the acute symptoms up to 4 weeks after the confirmed infection was conducted. The subtypes were classified according to the abovementioned guidelines based on the medical history and selected patient questionnaires, to which we added a5th subtype with reference to the previous guidelines "Long/Post-COVID" (as of 5 March 2023). Atotal of 157 patients were included between August 2020 and March 2022. The presentation was at a median of 9.4months (interquartile range, IQR = 5.3) after infection, with amean age of 49.9 years (IQR = 17.2) and more women (68%) presenting, with atotal hospitalization rate of 26%. Subtype1 (postintensive care syndrome) showed the highest proportion of men, highest body mass index (BMI) scores and the highest rates of subjective complaints of word-finding difficulties (70%). Subtype2 (secondary diseases) was dominated by cognitive impairment and had the highest depression scores. Subtype3 (fatigue and exercise-induced insufficiency) was the most common, had the most symptoms and most severe subjective fatigue and the largest proportion of women. Subtype4 (exacerbation) mainly showed affective symptoms. Subtype5 (complaints without relevance to everyday life) had the lowest scores for depression, fatigue and BMI. Neurological and psychological conditions were frequently pre-existing in all groups. The management of PCC can be improved at various levels. Astandardized subtype classification enables early individually tailored treatment concepts. Patients at risk should be identified at the primary care level and informed about risk factors and prevention strategies. Regular monitoring of cardiovascular risk factors and physical activity are essential for PCC treatment. In the case of cognitive deficits and concurrent affective symptoms, psychotherapeutic support and drug treatment with selective serotonin reuptake inhibitors (SSRI) should be provided at an early stage.

DNA methylation of serotonin genes as predictive biomarkers of antidepressant treatment response

Selective serotonin reuptake inhibitors (SSRI) are frequently ineffective in treating depressive episodes and biomarkers are needed to optimize antidepressant treatment outcomes. DNA methylation levels of serotonin transporter (SLC6A4) and tryptophan hydroxylase 2 genes (TPH2) have been suggested to predict antidepressant clinical outcomes but their applicability remains uncertain. In this study, we: 1) evaluated SLC6A4/TPH2 methylation biomarker potential for predicting clinical outcomes after escitalopram treatment; 2) evaluated whether changes in SLC6A4/TPH2 methylation are informative of treatment mechanisms. We used a cohort of 90 unmedicated patients with major depressive disorder that were part of a 12-week open-label longitudinal trial and compared our observations with previous findings. Depressive symptoms were measured at baseline and after 8 and 12 weeks of treatment using the Hamilton Depression Rating Scale (HAMD6/17). We found an association between baseline TPH2 methylation and both clinical response (β:3.43; p = 0.01; 95 % CI:[0.80; 6.06]) and change in depressive symptoms after 8 weeks (β:−45.44; p = 0.01; 95 %CI:[− −78.58; −12.30]). However, we found no evidence for predictive value of any gene (TPH2 AUC: 0.74 95 % CI:[0.42;0.79]; SLC6A4: AUC: 0.61; 95 % CI: [0.48–0.78]). Methylation levels changed at the trend level for CpG sites of SLC6A4 and TPH2 over the course of 12 weeks of treatment. In addition, similar to previous observations, we found a trend for an association between methylation of SLC6A4 CpG2 (chr17:30,236,083) and HAMD17 change after 12 weeks. Our findings suggest that although TPH2 and SLC6A4 methylation may be informative of antidepressant treatment outcome, they are unlikely to prove useful as clinical predictor tools.

Comparison of the Effect of Selective Serotonin and Norepinephrine Reuptake Inhibitors on Bone Mineral Density with Selective Serotonin Reuptake Inhibitors and Healthy Controls

Purpose: This study investigated the association between selective serotonin reuptake inhibitor (SSRI) and selective serotonin and norepinephrine reuptake inhibitor (SNRI) use and the risk of decreased bone mineral density in postmenopausal women.Methods: Sixty-three patients diagnosed with GAD (Generalized Anxiety Disorder) were treated with venlafaxine or duloxetine from the SNRI group, and sixty patients treated with SSRIs were enrolled. Social demographic features, the Hamilton Anxiety Scale (HAS) results, and the Hamilton Depression Scale (HDS) scores of all the patients were assessed. The BMD (bone mineral density) of the patients was measured by dual-energy X-ray absorptiometry (DXA) at the femoral and lumbar regions. The BMD of the patients was compared with that of 40 healthy controls.Results: Bone measurements in the SNRI and SSRI users were similar to those of the healthy controls. However, osteopenic values were observed in the SSRI users, while normal bone density was found in the SNRI users. Also, the bone mineral densities were compared between patients using duloxetine and venlafaxine with healthy controls, showing similar T-score and Z-score values with no significant differences compared to the control group. However, while the lumbar region T-scores of those using duloxetine were within normal values, they were within the osteopenia range of venlafaxine and healthy controls.Conclusion: SNRIs may have a lower risk of developing osteoporosis than SSRIs. Of the SNRIs, duloxetine appears to be safer than venlafaxine. Further randomized controlled studies are warranted to determine whether SNRI use is risky.

Nonvitamin K Anticoagulants: Risk of Bleeding When Interacting With Other Medications: A Cohort Study From Medicare.

Patients on nonvitamin K antagonist (NVKA) are usually taking other drugs. Potential interaction may increase the gastrointestinal (GI) bleeding risk associated with NVKA. Observational cohort study using Medicare data from 2017 to 2020. Participants receiving a NVKA were included. A concomitant overlapping period while on NVKA was assessed for nonsteroidal anti-inflammatory drugs (NSAIDS), selective serotonin reuptake inhibitors (SSRI), antiplatelets, glucocorticoids, aspirin and proton pump inhibitors (PPI). A logistic regression predicting either any bleeding or GI bleeding was conducted estimating the odds ratio (OR) and 95% confidence interval (CI). A total of 102 531 people on NVKA with mean age 77 years (SD = 9.8) and 55% females (N = 56 671) were included. Previous history of GI bleeding occurred in 2 908 (2.8%) participants, concomitant exposure to PPI occurred in 38 713 (38%), SSRI in 16 487 (16%), clopidogrel in 15 795 (15.4%), NSAIDs in 13 715 (13.4%) and glucocorticoids in 13 715 (13.4%). Risk for any bleeding was shown for clopidogrel (OR: 1.37, 95% CI: 1.30, 1.44), prasugrel/ticagrelor (OR: 1.36, 95% CI: 1.18, 1.58), glucocorticoids (OR: 1.26, 95% CI: 1.19, 1.34), and SSRIs (OR: 1.13, 95% CI: 1.07, 1.19). GI bleeding risk was shown for clopidogrel (OR: 1.44, 95% CI: 1.34, 1.55), prasugrel/ticagrelor (OR: 1.47, 95% CI: 1.20, 1.79), SSRIs (OR: 1.09, 95% CI: 1.01, 1.17) and glucocorticoids (OR: 1.33, 95% CI: 1.23, 1.44). PPI use was correlated with both NSAID (r = 0.07, p ≤ 0.0001) and SSRI use (r = 0.09, p ≤ 0.0001). NVKA concomitantly taken with antiplatelets, glucocorticoids, and SSRIs showed an increased risk for any bleeding and GI bleeding.

Effect of childhood trauma on cognitive function in individuals with major depressive disorder and healthy controls

BackgroundIndividuals with major depressive disorder (MDD) exhibit cognitive impairment, while childhood trauma (CT) is associated with an elevated risk of both MDD and cognitive dysfunction. The effect of CT on cognitive function in MDD patients and healthy controls (HCs) is unclear. MethodsMDD patients and HCs were enrolled between December 2013 and December 2016. The Childhood Trauma Questionnaire (CTQ) was used to assess CT. Depressive symptoms and cognitive function were assessed at baseline and after 8-week acute-phase treatment with selective serotonin reuptake inhibitors (SSRIs) in MDD patients. ResultsA total of 909 people were included in the analysis. The interaction between MDD and CT had a main effect on Digit Symbol-Coding Test (DSCT), Stroop Color Test (SCT), and Stroop Color-Word Test (SCWT) scores. The effect of CT on cognitive function disappeared after adjusting for MDD diagnosis and years of education. Neglect could predict poor performance on SCT and SCWT in the HC group. After acute-phase treatment with SSRIs, CT did not significantly predict changes in cognitive function or depressive symptoms. LimitationsThe CTQ assessment might cause recall bias, and the cross-sectional design could not establish the causal link between CT and cognitive function. ConclusionThe effect of CT on cognitive function was modulated by MDD diagnosis and years of education. CT did not predict changes in depressive symptoms or cognitive function after acute-phase treatment with SSRIs. The direct influence of CT on cognitive function in MDD patients may be over-estimated. Trial registrationClinicalTrials.gov: NCT02023567; registration date: December 2013.

A Proposed Algorithm for the Pharmacological Treatment of Generalized Anxiety Disorder in the Older Patient.

This is a new algorithm from the Psychopharmacology Algorithm Project at the Harvard South Shore Program, focused on generalized anxiety disorder (GAD) in older adults. Pertinent articles were identified and reviewed. Selective serotonin reuptake inhibitors (SSRIs) are considered to be first-line medications, with a preference for sertraline or escitalopram. If avoiding sexual side effects is a priority, buspirone is an option for the relatively healthy older adult. If response is inadequate, the second recommended trial is with a different SSRI or one of the serotonin-norepinephrine update inhibitors (SNRIs), venlafaxine or duloxetine. For a third medication trial, additional alternatives added to the previous options now include pregabalin/gabapentin, lavender oil, and agomelatine. If there is an unsatisfactory response to the third option chosen, quetiapine may be considered. We recommend caution with the following for acute treatment in this population: benzodiazepines and hydroxyzine. Other agents given low priority but having some supportive evidence were vilazodone, vortioxetine, mirtazapine, and cannabidiol. Acknowledging that the median age of onset of GAD is in early adulthood, many patients with GAD will have been started on benzodiazepines (or other medications that require caution in the elderly) for GAD at a younger age. These medications may be continued with regular observation to see if the potential harms are starting to exceed the benefits and a switch to other recommended agents may be justified.

The antidepressant, sertraline, impacts growth and reproduction in the benthic deposit feeder, Tubifex tubifex

Among emerging contaminants, pharmaceuticals are considered one of the most pertinent substances that may threaten aquatic ecosystems. Pharmaceuticals are designed to be directed at specific metabolic- and molecular pathways. Thus, they are assumed to be still biologically active when entering the ecosystem and may result in unpremeditated impacts on non-target organisms. One of the most widely used selective serotonin reuptake inhibitors, sertraline (an antidepressant), is regularly found in aquatic environments. However, knowledge about the effects, and in particular, of sediment-associated sertraline in benthic invertebrates is limited. We examined the impacts of chronic exposure (28 d) to sediment-associated sertraline (3.3, 33, 330 μg/g dw sed.) on survival, growth and reproduction in the deposit-feeding oligochaete, Tubifex tubifex. Sertraline significantly decreased T. tubifex survival and growth. Worms exposed to high sertraline concentrations (330 μg/g) had a lower growth rate and reproduction, as indicated by a significantly lower number of cumulated cocoons. Worms exposed to an environmentally relevant concentration (3.3 μg/g) decreased growth but maintained a reproduction rate similar to that of the control. The implications are that adult worms exposed to high sertraline concentrations presumably required more energy for maintenance and detoxification, thereby reducing available energy for reproduction and growth. This represents a trade-off between survival, reproduction and growth. In contrast, T. tubifex exposed to environmentally relevant concentrations allocated more energy to reproduction by slightly increasing the number of cocoons produced and reducing growth. However, the quantity and quality of offspring may be impacted as we observed fewer juveniles in the environmentally relevant treatment than in the control. Overall, the results indicate that sediment-associated sertraline is bioavailable and negatively impacts T. tubifex survival, growth, and reproduction even at environmentally relevant concentrations.

Serotonergic Antidepressants are Associated With Higher Rates of Hematoma After Anterior Cervical Spine Surgery: A Large Propensity-matched Cohort Analysis.

Large database propensity-matched retrospective cohort analysis. This study aimed to investigate the potential effects of serotonergic antidepressants on outcomes after anterior cervical spine surgery (ACSS). It was hypothesized that the perioperative use of serotonergic antidepressants would be associated with higher rates of hematoma formation and worse outcomes after ACSS. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) have been associated with worse outcomes after orthopaedic procedures. A retrospective cohort analysis was performed using TriNetX, an aggregated and de-identified electronic health record platform. Patients who underwent anterior cervical surgery were included via Current Procedural Terminology (CPT) codes and the International Classification of Disease (ICD-10) encounter diagnosis codes. Cohorts were 1:1 propensity matched across seven demographic and medical comorbidity parameters, and outcomes were compared. The incidence of adverse outcomes, as well as healthcare utilization, within 14 days, 30 days, 90 days and 2-years post-operatively was evaluated. Following propensity matching, each cohort consisted of 9,249 patients, for a total of 18,498 patients included in final statistical analysis. SSRI/SNRI's were associated with higher odds of hematoma formation within 7-days (0.69% vs. 0.46%, OR 1.5 [95% CI 1.02-2.2], P=0.04) and within 14-days postoperatively (0.81% vs. 0.52%, OR 1.6 [95% CI 1.1-2.3], P=0.01. Within 30- and 90-days, SSRI/SNRI's were associated with higher risk of emergency department utilization (30-day OR 1.30 [1.1-1.4]; 90-day OR 1.3 [1.2-1.4]) and irrigation & debridement (I&D) (30-day OR 1.9 [1.2-3.0]). SSRIs/SNRIs were also associated with significantly higher risk of I&D within 2-years (OR 1.3 [1.1-1.6]). The use of serotonergic antidepressants perioperatively was associated with higher odds and risk of numerous outcomes, including hematoma formation, emergency department utilization and the need for irrigation & debridement. Future prospective studies are required to confirm these results. III; retrospective cohort analysis.

Poor muscle health and cardiometabolic risks associated with antidepressant treatment.

This study aims to investigate whether antidepressant users display differences in fat distribution and muscle composition relative to non-users and to explore risk factors for developing cardiovascular disease (CVD) and type 2 diabetes. The study used quantitative adipose and muscle tissue measures derived from magnetic resonance imaging data from UK Biobank (N = 40,174). Fat distribution and muscle composition of selective serotonin reuptake inhibitor (SSRI) and tricyclic antidepressant (TCA) users were compared with sex-, age-, and BMI-matched control individuals. Cox regression models were used to test for increased risk of developing CVD and type 2 diabetes. SSRI users had more visceral fat, smaller muscle volume, and higher muscle fat infiltration compared with matched control individuals. Female users showed a larger increase in BMI over time compared with male users. However, male users displayed an unhealthier body composition profile. Male SSRI users also had an increased risk of developing CVD. Both male and female TCA users showed lower muscle volume and an increased risk of developing type 2 diabetes. Adverse changes in body composition of antidepressant users are not captured by tracking the body weight or the BMI of the patients. These changes may lead to a worsened cardiometabolic risk profile.

Incident Benzodiazepine and Z-Drug Use and Subsequent Risk of Serious Infections.

Animal studies have suggested a link between benzodiazepine and related Z-drug (BZDR) use and immune dysfunction. Corresponding evidence in humans is limited and focuses mainly on pneumonia. This study aimed to assess the association of incident BZDR use with subsequent development of serious infections. This Swedish register-based study included a population-based demographically matched cohort, a co-twin control cohort, and an active comparator cohort. Out of 7,362,979 individuals aged below 65 years who were BZDR naïve by 2007, 713,896 BZDR recipients with incident dispensation of any BZDRs between 2007 and 2019 were 1:1 matched to 713,896 nonrecipients from the general population; 9197 BZDR recipients were compared with their 9298 unexposed co-twins/co-multiples; and 434,900 BZDR recipients were compared with 428,074 incident selective serotonin reuptake inhibitor (SSRI) recipients. The outcomes were identified by the first inpatient or specialist outpatient diagnosis of serious infections in the National Patient Register, or death from any infections recorded as the underlying cause in the Cause of Death Register. Cox proportional hazards regression models were fitted and controlled for multiple confounders, including familial confounding and confounding by indication. To study a possible dose-response association, the cumulative dosage of BZDRs dispensed during the follow-up was estimated for each BZDR recipient and modeled as a time-varying exposure with dose categories in tertiles [≤ 20 defined daily doses (DDDs), > 20 DDDs ≤ 65, and > 65 DDDs). The risk of infections was assessed in BZDR recipients within each category of the cumulative BZDR dosage compared to their demographically matched nonrecipients. In the demographically matched cohort (average age at incident BZDR use 42.8 years, 56.9% female), the crude incidence rate of any serious infections in BZDR recipients and matched nonrecipients during 1-year follow-up was 4.18 [95% confidence intervals (CI) 4.13-4.23] and 1.86 (95% CI 1.83-1.89) per 100 person-years, respectively. After controlling for demographic, socioeconomic, clinical, and pharmacological confounders, BZDR use was associated with 83% relative increase in risk of any infections [hazard ratio (HR) 1.83, 95% CI 1.79-1.89]. The risk remained increased, although attenuated, in the co-twin cohort (HR 1.55, 95% CI 1.23-1.97) and active comparator cohort (HR 1.33, 95% CI 1.30-1.35). The observed risks were similar across different types of initial BZDRs and across individual BZDRs, and the risks increased with age at BZDR initiation. We also observed a dose-response association between cumulative BZDR dosage and risk of serious infections. BZDR initiation was associated with increased risks of serious infections,even when considering unmeasured familial confounding and confounding by indication. The exact pathways through which BZDRs may affect immune function, however, remain unclear. Further studies are needed to explore the neurobiological mechanisms underlying the association between BZDR use and serious infections, as it can lead to safer therapeutic strategies for patients requiring BZDR.

Association between psychopharmacotherapy and postpartum hemorrhage

BackgroundPrior studies evaluating the relationship between psychopharmacotherapy (PPT), and postpartum hemorrhage (PPH) have yielded inconsistent findings. Clarifying this potential relationship is important for effective counseling and risk stratification. ObjectivesOur primary objective was to evaluate the association between prenatal exposure to PPT (any drug class) and the occurrence of PPH requiring transfusion of packed red blood cells (PPH+pRBC) after systematically adjusting for known hemorrhage risk factors at the time of admission for delivery. Secondary objectives were to evaluate the association between individual PPT drug classes and PPH+pRBC, and the association between treatment intensity of mental health condition and PPH+pRBC. Finally, we evaluated the association between PPT and a broader definition of PPH that included deliveries requiring multiple uterotonic drugs. Study designThis is a retrospective cross-sectional study of all pregnancies delivered at 23 weeks of gestational age or greater at seven hospitals within a large academic health system in New York between January 2019 and December 2022. There were no exclusion criteria, as postpartum hemorrhage risk assessment is necessary for all patients admitted for delivery. We assessed exposure to prenatal PPT, including selective serotonin reuptake inhibitors (SSRIs: escitalopram, fluoxetine, sertraline), serotonin-norepinephrine reuptake inhibitors (SNRIs: duloxetine, venlafaxine), dopamine-norepinephrine reuptake inhibitors (DNRIs: buproprion), benzodiazepines (alprazolam, diazepam, lorazepam), and others (buspirone, trazodone, zolpidem). Multivariable logistic regression was performed to evaluate the relationship between PPT and PPH+pRBC, while systematically adjusting for known hemorrhage risk factors at the time of hospital admission. Similar regression analyses were performed to address the secondary objectives. ResultsA total of 107,425 deliveries were included. Non-Hispanic White patients constituted the largest race and ethnicity group (43.4%), followed by Hispanic patients (18.7%), Asian or Pacific Islander patients (13.2%), and non-Hispanic Black patients (12.3%). Prenatal exposure to PPT occurred in 3.6% of pregnancies (n=3,834). The overall rate of PPH+pRBC was 2.9% (n=3,162). PPH+pRBC occurred more frequently in pregnancies exposed to PPT than in pregnancies which were not exposed (5.5% vs. 2.8%, respectively; aOR 2.10, 95% CI: 1.79–2.44). SSRIs and benzodiazepine monotherapy were each associated with higher odds of PPH+pRBC than nonexposure. Compared to patients without a mental health condition, monotherapy was associated with nearly 2-fold increased odds and combination PPT was associated with nearly 4-fold greater odds of PPH+pRBC after adjustment for confounding variables (monotherapy: aOR 1.94, 95% CI: 1.64–2.28; combination PPT: aOR 3.96, 95% CI: 2.61–5.79). Patients with untreated mental health conditions (no PTT) had no increased odds of PPH+pRBC compared to those without mental health conditions. Finally, after adjusting for covariates, a positive association was found between PPT and PPH requiring pRBC transfusion and/or the use of two additional uterotonic agents beyond routine postpartum oxytocin (aOR 1.53, 95% CI: 1.35–1.73). ConclusionsPrenatal PPT exposure is associated with increased odds of clinically significant PPH+pRBC after adjusting for other hemorrhage risk factors. Combination PPT was associated with greater odds of PPH+pRBC than monotherapy.

An Update of Post-Stroke Depression and the Use of Selective Serotonin Reuptake Inhibitors in Post-Stroke Recovery

An Update of Post-Stroke Depression and the Use of Selective Serotonin Reuptake Inhibitors in Post-Stroke Recovery

Sexual dysfunctions (SD) and selective serotonin reuptake inhibitors (SSRIs): from preclinical studies to intervention strategies

In the light of existing literature, we reviewed the causes, management and potential therapeutic benefits of SSRI (Selective serotonin reuptake inhibitor) agents regarding sexual functions. (SSRIs) are the most commonly used medications for the treatment of depression, based on their effectiveness and safety profile. Sexual dysfunctions (SD) caused by SSRIs are one of the most important reasons for discontinuation of treatment in both genders. Knowing the intervention strategies in patients who develop SD is pivotal for the proper management of sexual side effects and the treatment adherence of patients. The effects of SSRIs on sexual functions can also be used to treat certain disorders. SSRIs have a high success rate in the treatment of premature ejaculation and their off-label use for this purpose is widely recognized.

Prevalence of Antidepressant Prescriptions for Community-Dwelling Adults Diagnosed with Depressive Disorder in the UK: A Systematic Review.

The UK National Institute for Health and Care Excellence (NICE) guidance for the treatment of depression is widely followed and has international influence. According to these guidelines, antidepressant medications are recommended for moderate to severe depression. Nonetheless, antidepressants are increasingly prescribed, including for cases of subthreshold and mild depression. This may indicate that a proportion of depressed patients uses pharmacological interventions with unclear evidence-base, though other factors such as physical and mental health comorbidities need to be accounted for. This study aims to investigate the prevalence and trends of antidepressant prescriptions among community-dwelling adults diagnosed with depression according to NICE recommendations. We conducted a systematic review of PsycInfo, PubMed/MEDLINE, and Scopus databases. Observational studies reporting on the prevalence of antidepressant treatments in UK adults diagnosed with depression were sought. Fifteen studies were included. The prevalence of antidepressants for depression treatment ranged from 30.8 to 95% and mainly concerned selective serotonin reuptake inhibitors (SSRIs) among classes of antidepressant drugs. Little information about depression severity as well as comorbid conditions was reported. High prevalence rates of antidepressant drug use highlight the widespread adoption of pharmacological interventions, while also raising concerns about compliance with NICE guidelines. Careful assessment of depressive illness severity and comorbidities is needed to ensure the delivery of adequate care to people with depression. Systematic Review Registration Number (PROSPERO) CRD42023448152.

Mastering Ejaculation Challenges Through Comprehensive Strategies: A Case Report

Background This case report explores the successful management of psychogenic anejaculation in a 31-year-old poultry farmer. Despite an 8-year history of anejaculation during intercourse, the patient achieved ejaculation during masturbation. Initial pharmacological intervention with duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, provided partial success. To address persisting challenges, dual sex therapy and sensate focus therapy were introduced, based on the work of Masters and Johnson. The integrated approach proved effective, leading to successful ejaculation and the conception of the patient's wife. This case emphasizes the necessity of a comprehensive approach to psychological anejaculation, combining pharmacological and psychotherapeutic interventions for successful outcomes.

Exploring The Relationship Between SSRIs, Falls, Fractures, And Bone Mineral Density In Older Irish Adults: Results From The TUDA Study

Abstract Background Selective Serotonin Reuptake Inhibitors (SSRIs) are associated with an increased risk of falls and fractures, though the results from studies are inconsistent. SSRIs may cause a decline in bone mineral density (BMD), but this remains unclear. We aimed to explore the relationship between SSRI use and falls, fractures and BMD in older Irish adults. Methods Study participants were from a cross-sectional study of adults aged >60 years; Trinity Ulster University Department of Agriculture (TUDA) study. Falls and falls resulting in fracture in the preceding year were self-reported so participants with an MMSE < 24 were excluded. The relationship between SSRIs and falls and falls with fractures was explored in multivariate logistic regression adjusting for relevant covariates and medications: loop and thiazide diuretics, alpha and beta blockers, calcium channel blockers, ACE-inhibitors, benzodiazepines, opioids. In a subgroup with no prior diagnosis of osteoporosis or on medications for same, the relationship with SSRI's and BMD (as assessed with DXA) was explored. Results There were 4521 participants, 67.6% female, mean age 73.3 ± 8.1 years, 9.4% (n=427) using SSRIs. SSRI use predicted an increased risk of falls in the last year both before and after multivariate adjustment (OR 1.71, 1.37-2.14, p<0.001). In participants with falls (n=1448), those who had a fall with fracture versus a fall with no fracture were no more likely to be using SSRIs. In a subsample, (n=2178) no relationship was found between SSRI use and BMD at the hip, neck of femur or spine. Conclusion SSRIs use was associated with a 71% increased risk of falls though did not predict BMD or fractures. However, duration of SSRI use was not known and there was no prospective follow up. It remains unclear whether increased fracture risk in SSRI users found elsewhere is explained solely by falls risk.

The Effectiveness of Ketamine Treatment on Depression

As the diagnosis rate of depression continues to rise, effective treatment options for this condition have become one of the most researched areas in the field. Earlier antidepressants were primarily developed based on mechanisms that involve regulating imbalanced neurotransmitters. For example, the widely known Selective Serotonin Reuptake Inhibitors (SSRIs) and various tricyclic antidepressants work by adjusting the concentration of different neurotransmitters, such as dopamine and norepinephrine, in the synaptic cleft to alleviate depressive symptoms. Additionally, many therapeutic approaches have been developed and applied based on the widely accepted hormone hypothesis and neurotrophic factor hypothesis. Ketamine, a drug traditionally used as an anesthetic, has recently been discovered to possess antidepressant properties. Its efficacy and underlying neuroscientific mechanisms are currently under investigation. Unlike earlier antidepressants, Ketamine produces significant antidepressant effects within a short time after administration. Multiple studies have suggested that Ketamine's rapid and effective therapeutic results may be based on entirely new antidepressant mechanisms and targets that have yet to be fully understood. This provides a new solution for the treatment of treatment-resistant depression and offers new hope to patients who have tried various treatments without success. In this literature review, Ketamine's therapeutic effects and its underlying mechanisms will be thoroughly examined. The content will be divided into three sections: significant antidepressant effects, underlying principles and mechanisms, and factors relevant to the improvement of Ketamine therapy.