Effects Of SSRIs Research Articles

(100) Urinary and Gynecologic Adverse Events Associated with Ssri Use

Abstract Introduction SSRIs are the most prescribed psychiatric drug in the United States, with approximately 40% of patients reporting side effects to their provider (1,2). It is accepted that side effects of SSRIs may include sexual dysfunction, including decreased libido and anorgasmia (3,4). However, the safety of SSRIs on the functions of the genitourinary and reproductive systems in real-world settings remains unclear. Objective The aim of this study was to identify urinary and gynecologic adverse events associated with SSRIs using data from the FDA Adverse Events Reporting System (FAERS). Secondarily, we identify variability of adverse events across individual SSRIs. Methods A specialized software to analyze adverse events, OpenVigil 2.1, was used to query the FAERS data. We defined 445 search terms related to genitourinary and reproductive system related events. We performed disproportionality analysis to identify associations between search terms and SSRIs as a class, then each SSRI (fluoxetine, sertraline, paroxetine, escitalopram, citalopram). Subgroup analysis was performed to stratify adverse events by age. Results Adverse events related to SSRI usage include a variety of genitourinary and reproductive system related side effects, not limited to sexual dysfunction. Gynecologic bleeding, urinary retention, hypersexuality emerged as surprisingly statistically significant signals across females. Statistically significant adverse events related to sexual dysfunction were present up to age 60, with the strongest signals found in the 40-59 years age group. Urinary symptoms were most prevalent in the 0-18 years and over 60 years age group. Of the SSRIs, citalopram had the strongest association with sexual disorders and dysfunction. Conclusions In this study, we offer the most granular side effect profile of SSRIs related to the urinary and reproductive systems to date. While the pathophysiology of each adverse event remains unclear, an understanding of potential risks of these drugs is valuable in the management of patients taking SSRIs, particularly in the event of rare side effects that are often not associated with SSRI use. These are important considerations for clinical practice as side effects of SSRIs can impact treatment compliance and patient quality of life.

Exploring the role of inflammation in major depressive disorder: beyond the monoamine hypothesis.

Major depressive disorder affects approximately 8.4% of the United States population. The World Health Organization estimates that 280 million adults worldwide are suffering from depression. They have estimated that by 2030 it will be the second most serious condition. Current treatment relies on the monoamine hypothesis, however, one-third of patients with MDD do not respond to monoamine-based antidepressants. For years, it was hypothesized that the primary pathway of MDD involved serotonin as the main neurotransmitter. The monoamine hypothesis, a widely accepted theory, sought to explain the biological basis of MDD as being caused by the depletion of monoamine neurotransmitters, namely norepinephrine and serotonin. This hypothesis regarding monoamines as the pathophysiological basis of MDD led to the design and widespread use of selective serotonin reuptake inhibitors. However, given that only one-third of patients improve with SSRI it is reasonable to infer that the pathway involved is more complex than once hypothesized and there are more neurotransmitters, receptors, and molecules involved. The monoamine hypothesis does not explain why there is a delay in the onset of effect and action of SSRIs. Several studies have demonstrated that chronic stress is a risk factor for the development of MDD. Thus the monoamine hypothesis alone is not enough to fully account for the pathophysiology of MDD highlighting the need for further research involving the pathways of MDD. In this paper, we review the role of inflammation and cytokines on MDD and discuss other pathways involved in the development and persistence of depressive symptoms.

Acute anxiogenic effects of escitalopram are associated with mild alterations in D-amphetamine-induced behavior and social approach evoked by playback of 50-kHz ultrasonic vocalizations in rats

Rats communicate through auditory signals in the ultrasonic range, so-called ultrasonic vocalizations (USV). Short, high-frequency 50-kHz USV are associated with positive affective states and are emitted in appetitive situations, often rewarding social interactions, such as rough-and-tumble play and mating. Exaggerated levels of 50-kHz USV emission can be observed in response to psychostimulants, most notably d-amphetamine (AMPH). There is robust evidence suggesting that 50-kHz USV serve as affiliative signals and help to maintain or re-establish social proximity. A key neurotransmitter involved in behavioral regulation is serotonin (5-hydroxytryptamine, 5-HT). This includes both, the regulation of anxiety-related behavior and ultrasonic communication. Here, we show that acute treatment with the selective 5-HT reuptake inhibitor (SSRI) escitalopram (ESC) leads to increased anxiety-related behavior in the elevated plus maze and tested whether such acute anxiogenic effects of ESC result in alterations in ultrasonic communication in sender and/or receiver. To this aim, we conducted a dose-response study in male rats and assessed AMPH-induced hyperactivity and 50-kHz ultrasonic calling in the sender and social approach behavior evoked by playback of pro-social 50-kHz USV in the receiver. Acute ESC treatment affected both, sender and receiver. This was reflected in a lack of AMPH-induced changes in acoustic features of 50-kHz USV and absence of social exploratory behavior evoked by 50-kHz USV playback, respectively. Albeit the SSRI effects were relatively mild, this supports the notion that the 5-HT system is involved in the regulation of a key aspect of the social behavior repertoire of rodents, namely socio-affective communication through 50-kHz USV.

Transcriptional changes in specific subsets of Drosophila neurons following inhibition of the serotonin transporter

The transcriptional effects of SSRIs and other serotonergic drugs remain unclear, in part due to the heterogeneity of postsynaptic cells, which may respond differently to changes in serotonergic signaling. Relatively simple model systems such as Drosophila afford more tractable microcircuits in which to investigate these changes in specific cell types. Here, we focus on the mushroom body, an insect brain structure heavily innervated by serotonin and comprised of multiple different but related subtypes of Kenyon cells. We use fluorescence-activated cell sorting of Kenyon cells, followed by either bulk or single-cell RNA sequencing to explore the transcriptomic response of these cells to SERT inhibition. We compared the effects of two different Drosophila Serotonin Transporter (dSERT) mutant alleles as well as feeding the SSRI citalopram to adult flies. We find that the genetic architecture associated with one of the mutants contributed to significant artefactual changes in expression. Comparison of differential expression caused by loss of SERT during development versus aged, adult flies, suggests that changes in serotonergic signaling may have relatively stronger effects during development, consistent with behavioral studies in mice. Overall, our experiments revealed limited transcriptomic changes in Kenyon cells, but suggest that different subtypes may respond differently to SERT loss-of-function. Further work exploring the effects of SERT loss-of-function in other circuits may be used help to elucidate how SSRIs differentially affect a variety of different neuronal subtypes both during development and in adults.

Different Effects of SSRIs, Bupropion, and Trazodone on Mitochondrial Functions and Monoamine Oxidase Isoform Activity.

Mitochondrial dysfunction is involved in the pathophysiology of psychiatric and neurodegenerative disorders and can be used as a modulator and/or predictor of treatment responsiveness. Understanding the mitochondrial effects of antidepressants is important to connect mitochondria with their therapeutic and/or adverse effects. Pig brain-isolated mitochondria were used to evaluate antidepressant-induced changes in the activity of electron transport chain (ETC) complexes, monoamine oxidase (MAO), mitochondrial respiratory rate, and ATP. Bupropion, escitalopram, fluvoxamine, sertraline, paroxetine, and trazodone were tested. All tested antidepressants showed significant inhibition of complex I and IV activities at high concentrations (50 and 100 µmol/L); complex II + III activity was reduced by all antidepressants except bupropion. Complex I-linked respiration was reduced by escitalopram >> trazodone >> sertraline. Complex II-linked respiration was reduced only by bupropion. Significant positive correlations were confirmed between complex I-linked respiration and the activities of individual ETC complexes. MAO activity was inhibited by all tested antidepressants, with SSRIs causing a greater effect than trazodone and bupropion. The results indicate a probable association between the adverse effects of high doses of antidepressants and drug-induced changes in the activity of ETC complexes and the respiratory rate of mitochondria. In contrast, MAO inhibition could be linked to the antidepressant, procognitive, and neuroprotective effects of the tested antidepressants.

Effect of Selective Serotonin Reuptake Inhibitors on Motor Recovery After Stroke: A Systematic Meta-analysis.

We conducted a meta-analysis to determine the effectiveness of SSRIs in improving motor outcomes after stroke. For accuracy, we only included studies in which SSRIs were administered to patients in the recovery phase after stroke (<6 months after stroke). 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 SSRI medication in the recovery phase after stroke with a control group that did not receive any SSRI. A total of 3,715 publications were assessed, and nine studies met the study criteria. The group which received SSRI showed improved Fugl-Meyer Motor Scale and Barthel index scores compared to the control group. However, there was no significant difference in the modified Rankin Scale scores between the SSRI and control groups. The incidence of adverse effects after the administration of SSRIs did not differ from that in the control group. Our study showed that the use of SSRI in the recovery phase of stroke improved motor function without significant increase in side effects.

Is the total score of the Hamilton Depression Rating Scale affected by side effects of SSRIs and SNRIs?

Abstract This talk will focus on the pitfalls of using multidimensional rating scales to measure the severity of depression – with particular emphasis on the Hamilton Depression Rating Scale (HDRS-17). First, the history behind the development of the HDRS-17 will be briefly covered. Second, it will be argued that the HDRS-17 measures symptoms that overlap with common antidepressant side effects (gastrointestinal dysfunction, sexual dysfunction, somatic anxiety and sleep disturbances), making it possible that side effects of antidepressant treatment are erroneously rated as symptoms of depression. The rest of the talk will focus on the results of a recent study (1) in which we used individual-level data from antidepressant treatment trials to assess whether side effect ratings co-vary with HDRS-17 ratings. Specifically, data from all HDRS-17-rated, industry-sponsored pre- and post-marketing trials (n = 4647) comparing the serotonin and noradrenaline reuptake inhibitor, duloxetine, to placebo and/or to a selective serotonin reuptake inhibitor were pooled. Severity was assessed for side effects related to sleep, somatic anxiety, gastrointestinal function, and sexual dysfunction. Analysis of covariance was used to assess the relation between these side effects and ratings of relevant HDRS-17-derived outcome parameters. Side effects related to sleep, somatic anxiety and sexual dysfunction significantly and exclusively associated with higher scores on HDRS-17 items measuring the corresponding domains. Side effects related to gastrointestinal function associated with higher HDRS-17 item scores on all assessed domains. Treatment outcome was significantly related to side effect severity when assessed using HDRS-17-sum (beta 0.32 (0.074), p &lt; 0.001), but not when the HDRS-6-sum-score (beta 0.035 (0.043), p = 0.415) or the depressed mood item (beta 0.007 (0.012), p = .527) were used as effect parameters. That some HDRS-17 items co-vary with common antidepressant side effects likely leads to an underestimation of antidepressant efficacy. Finally, based on data from a recent study (2), it will be argued that the Montgomery-Åsberg Depression Rating Scale is biased in the same direction as the HDRS-17 (underestimates antidepressant efficacy), albeit to a lesser extent.

Is the most really the best: a review for the most selective SSRI concept three decades later

IntroductionPharmaceutical slogans presuming a particular antidepressant molecule being the best solely based on a core concept could be proved “not accurate” especially following patients’ actual exposure to the antidepressant for longer than the usual six or twelve weeks’ trialsObjectivesReviewing the current situations of SSRI induced anhedonia recognition and its management. Distinguishing anhedonia as a core symptoms of depression from SSRI induced anhedonia and the combination of both.MethodsReview of literatures including theses related to the same topicResultsResearch suggests that, SSRIs might be more effective at treating some symptoms than others. More specifically, it has been suggested that, SSRIs might be more effective at improving symptoms such as low mood and anxiety but not anhedonia (Argyropoulos et al. psych.pharmaology, 2013; 27(10), 869-877). It has been proposed that, catecholaminergic antidepressants might be more effective treatments for anhedonia and emotional blunting in MDD than SSRIs (McCabe et al. Biological psychiatry, 2010; 67(5), 439–445. The primary effect of SSRIs is reduced processing of negative stimuli rather than increased positive stimuli. Emotional blunting is related to SSRI dose and possibly serotonergic effects on the frontal lobes and/or serotonergic modulation of midbrain dopaminergic systems projecting to the prefrontal cortex (PFC). By enhancing serotonergic transmission, SSRIs can activate the inhibitory Gamma Aminobutyric Acid (GABA) interneurons, thereby dampening the noradrenergic and dopaminergic input ( Blier. Int J Neuropsychopharmacol., 2014; 17:997–1008).Management of SSRI induced anhedonia includes lowering the current SSRI dose. Adding non SSRI antidepressant to the current SSRI dose or to a lowered SSRI dose. Gradual discontinuation of the SSRI and switching to another antidepressant with a different profile (SNRI) that might improve the patient’s emotional response (Koenigs. Behav Brain Res., 2009;201:239–43).Bupropion is an antidepressant with less possibility to give rise to emotional blunting. (Tomoko et al. Neuroscience Letters., 2021; 749, 135716. agomelatine(Thome et al. Journal of neural transmission., 2015; 122(1), 3-7.Vortioxetine and others (Bing et al. frontiers in psychiatry., Jan, 2019; 10-17. are of inrerest in this regard.Image 2:ConclusionsThe most selective SSRI concept assumes that most selective means less affinity to other receptors or secondary binding sites which might suggest less side effects and perhaps being the most efficacious. Not only serotonin but multiple neurotransmitters are in action at the downstream part of a cascade of events underpinning the etiology of MDD. MDD has heterogeneous etiology and this explains why patients respond differently. SSRI induced anhedonia could be tackled and we need to explore how many patients would benefit from that now and have not yet.Disclosure of InterestNone Declared

Effect of SSRI on C-Reactive Protein in Case of Depression

Introduction: Depression can present with several symptoms, such as loss of pleasure, feelings of guilt, low selfesteem, and disturbed sleep or appetite. In recent socio- economic scenario incidence &amp; prevalence of depressionis on increasing trend. SSRIs are the mainstay of treatment of depression.Objective: the anti-inflammatory role of escitalopram in freshly diagnosed depression case and also to find anycorrelation between depression &amp; inflammation.Material &amp; Methods: It was a cross-sectional analytical study conducted at College of Medicine and Sagore DuttaHospital by Department of Biochemistry in collaboration with Department of Psychiatry. 71 Patients attendingpsychiatric OPD who are newly diagnosed as Major depressive disorder (MDD) were selected. 73 Age and sexmatched healthy family members of the patients were taken as controls.Before starting treatment C reactive protein(CPR) &amp; Hamilton depression rating scale (HAMD) was assessed. After 12 weeks of treatment same parameterswere assessed again.Results: after 12 weeks of treatment mean CPR &amp; HAMD score is significantly reduced in case group as comparedto the baseline values respectively. The reduction of HAMD score is negatively correlated with the baseline CPR.Conclusion: Escitalopram significantly reduce the CPR value which may have a role in improvement of HAMDscore.

Effect of citalopram and sertraline on the expression of miRNA- 124, 132, and 16 and their protein targets in patients with depression.

This study aimed to evaluate the effect of SSRIs on the expression of miRNAs and their protein targets. In a 100 day open-label study of citalopram (n=25) and sertraline (n=25), levels of miRNA 16, 132, and 124 and glucocorticoid receptor (GR), Brain-derived neurotrophic factor (BDNF), and serotonin transporter (SERT) protein expression were measured by QRT-PCR and western blot in healthy control (n=20), patients with depression at the baseline, and same patients after 100 days of treatment. Expression levels of GR and BDNF proteins were lower in the depressed group before treatment as compared with the healthy group (P<0.0001). The SERT level was higher among the depressed group before treatment in comparison with the healthy group (P<0.0001). The level of GR and BDNF significantly increased, and SERT expression decreased after receiving sertraline (P<0.05). When the depressed group received citalopram, only SERT and GR were altered (P<0.05). Among the microRNAs' expression investigated, mir-124 and mir-132 were higher, and mir-16 was lower among the depressed compared with the healthy group (P<0.0001). Individuals receiving citalopram only showed an increase in the expression of mir-16 while administration of sertraline led to a significant increase in the expression of mir-16 and a decrease in mir-124 and mir-132 (P<0.05). This elucidated the relationship between antidepressant treatment and the expression of different microRNA that control gene expression in various pathways involved in depressed patients. Receiving SSRI can affect the level of these proteins and their relevant microRNAs.

Mutation of the Drosophila melanogaster serotonin transporter dSERT impacts sleep, courtship, and feeding behaviors.

The Serotonin Transporter (SERT) regulates extracellular serotonin levels and is the target of most current drugs used to treat depression. The mechanisms by which inhibition of SERT activity influences behavior are poorly understood. To address this question in the model organism Drosophila melanogaster, we developed new loss of function mutations in Drosophila SERT (dSERT). Previous studies in both flies and mammals have implicated serotonin as an important neuromodulator of sleep, and our newly generated dSERT mutants show an increase in total sleep and altered sleep architecture that is mimicked by feeding the SSRI citalopram. Differences in daytime versus nighttime sleep architecture as well as genetic rescue experiments unexpectedly suggest that distinct serotonergic circuits may modulate daytime versus nighttime sleep. dSERT mutants also show defects in copulation and food intake, akin to the clinical side effects of SSRIs and consistent with the pleomorphic influence of serotonin on the behavior of D. melanogaster. Starvation did not overcome the sleep drive in the mutants and in male dSERT mutants, the drive to mate also failed to overcome sleep drive. dSERT may be used to further explore the mechanisms by which serotonin regulates sleep and its interplay with other complex behaviors.

The effect of selective serotonin and norepinephrine reuptake inhibitors on clinical outcome of COVID-19 patients: A systematic review and meta-analysis.

Background and AimDue to the high social and economic burden and also mortality and morbidity caused by coronavirus disease 2019 (COVID‐19) in the past few years, researchers have aimed at finding solutions to suppressing the severity of infection. Recently, selective serotonin and serotonin‐norepinephrine reuptake inhibitors (SSRI/SNRI) have been investigated as an adjuvant treatment for COVID‐19. The aim of the current study was to investigate the impact of SSRI/SNRIs on outcomes of COVID‐19 patients.MethodsIn this systematic review and meta‐analysis, a comprehensive search strategy consisting of relevant words was performed by two researchers in PubMed, Scopus and EMBASE libraries. Studies reporting the effect of SSRI and/or SNRI use in COVID‐19 patients' outcome were included. Hospitalization, mortality, hospitalization event, and length of hospital stay were considered as main outcomes of this study. Analysis was carried out using Comprehensive Meta‐Analysis (CMA‐version 2) and final data were reported as odds ratio (OR) and 95% confidence interval (CI).ResultsOur search led to the final selection of 9 articles including 15,287 patients. The effect of fluvoxamine, fluoxetine, and the overall effect of SSRI/SNRI use on mortality of COVID‐19 patients were investigated in 3, 2, and 7 articles, respectively. The results of our analyses showed that these medications could significantly decrease mortality of COVID‐19 patients (OR and 95% [CI]: 0.595 [0.467–0.758], 0.620 [0.469–0.821], and 0.596 [0.437–0.813]). The effect of SSRI/SNRIs on hospitalization events of COVID‐19 patients was not significant (OR: 0.240% and 95% CI: 0.041–1.4). Also, length of hospital stay was longer in patients who administrated SSRIs.ConclusionAccording to this study's results, SSRI/SNRIs may be effective in reducing mortality of COVID‐19 patients, suggesting the superiority of fluvoxamine to fluoxetine. The safety profile and affordable cost of SSRI/SNRIs for a short‐term use may be other reasons to propose them as beneficial medications in preventing mortality in COVID‐19.

16.3 Do Genetic Variants Moderate Sexual and Skeletal Side Effects of SSRIs?

The objective is to examine whether genetic variants in serotonin pathway–related genes moderate the effects of SSRIs on bone mineral accrual and sexual functioning in older adolescents and young adults.

Serum amyloid P component (SAP) modulates antidepressant effects through promoting membrane insertion of the serotonin transporter.

Serum amyloid P component (SAP) is a universal constituent of human amyloid deposits including those in Alzheimer's disease. SAP has been observed to be elevated in patients with depression, and higher SAP levels are associated with better response to the antidepressant escitalopram. The mechanisms underlying these clinical observations remain unclear. We examined the effect of SAP on serotonin transporter (SERT) expression and localization using Western blot, confocal microscopy, and positron emission tomography with the radioligand [11C]DASB. We also investigated the effect of SAP on treatment response to escitalopram in mice with the forced swim test (FST), a classical behaviour paradigm to assess antidepressant effects. SAP reduced [11C]DASB binding as an index of SERT levels, consistent with Western blots showing decreased total SAP protein because of increased protein degradation. In conjunction with the global decrease in SERT levels, SAP also promotes VAMP-2 mediated SERT membrane insertion. SAP levels are correlated with behavioural despair and SSRI treatment response in mice with FST. In MDD patients, the SAP and membrane SERT levels are correlated with response to SSRI treatment. SAP has complex effects on SERT levels and localization, thereby modulating the effect of SSRIs, which could partially explain clinical variability in antidepressant treatment response. These results add to our understanding of the mechanism for antidepressant drug action, and with further work could be of clinical utility.

A Quality Improvement of the Identification of Obesity in Patients With Mental Health Morbidity and Referral to Weight Management Services

AimsA quality improvement project was undertaken to counteract obesity in patients with mental health morbidity. The exponential trend of increased antidepressant prescribing (SSRI, SNRI and anti-psychotic medication) has created a trend towards weight gain in patients. An audit of the Serious Mental Illness (SMI) register and depression registers was conducted in a population of 591 patients. Those patients identified as obese were offered referral to the local authority weight management services.MethodsPatients have a body weight and BMI calculation with their twice yearly mental health and medication review and those whose BMI met the obesity criteria were offered referral to the local authority for 12 weeks weight management services.ResultsOf the SMI and depression register 189 (32%) patients met the criteria for referral to the weight management program. Of these 154 (81%) patients accepted the local NHS weight management program, 35 (18%) of patients declined the NHS weight management program.ConclusionWeight gain is a known side effect of antidepressant medication SSRI and SNRIs and Anti psychotic medication resulting in increased risk of obesity and cardiovascular and metabolic disease. The QI program was undertaken to counteract these changes with referral to weight management services to address the weight gain the patients were experiencing.This quality improvement service was done to help patients across three surgeries lose weight in an effective and educational manner. We found a high rate of acceptability of referral to weight management services when offered as patients themselves were aware of the weight gain. A review of positive changes in the BMI after referral to the weight management program will be undertaken at 6 and 12 months to evaluate its acceptability and effectiveness. We advocate sensitive counselling of the risks of weight gain and regular monitoring of body weight throughout the span of the prescribing of these weight gaining agents.

Antidepressants and Vertebral and Hip Risk Fracture: An Updated Systematic Review and Meta-Analysis.

Although antidepressant drugs appear to play an active role in increasing fracture risk, their weight is still unclear. We conducted a PRISMA compliant systematic review and meta-analysis through PubMed/Scopus/Cochrane libraries and registered with PROSPERO (registration number CRD42021254006) to investigate the relationship between antidepressant drugs categories, including SSRIs, SNRIs, and TCAs, and the risk of hip and vertebral fractures. After screening 3122 items, we finally found 26 papers for qualitative analysis and 11 for quantitative synthesis. A total of 15,209,542 adult and elderly patients were identified, with a mean follow-up of 51 months and a major prevalence of women. We identified results largely for SSRIs, with only a small amount of data for SNRIs, TCAs, and NaSSA. No data were found among the most recent categories of antidepressants, such as vortioxetine and esketamine. All included studies reported hip fractures, while three of them also included vertebral fractures. Overall, we observed a significant effect of SSRIs on fracture risk with a mean effect of 0.98 (95% CI = 0.75–1.20). This meta-analysis reveals that the use of SSRIs increases the risk of fractures. Clinicians’ awareness in antidepressant prescription should optimize their potential while reducing this risk.

Abstract TP62: Predictive Factors For Depressive Symptoms In The Stroke Recovery Follow-up Period

Introduction: Although SSRIs are no longer widely prescribed for post-stroke motor recovery, fluoxetine demonstrated beneficial effects on post-stroke depression (PSD). Given potential side effects of SSRIs, targeted initiation among individuals at highest risk for PSD warrants consideration. While previous studies have identified stroke severity and psychiatric history as factors associated with PSD, the predictability of PSD remains unknown. The purpose of this study is to investigate inpatient predictive factors to better identify individuals who might derive the most benefit from targeted initiation of SSRIs. Methods: All adult patients presenting to our tertiary academic stroke center with acute ischemic stroke between 2016-2020 were enrolled in a prospectively-collected stroke registry. Patients were seen 4-6 weeks post-discharge and a subset were administered the PHQ-9 (Patient Health Questionnaire-9) to screen for PSD (PHQ-9 ≥5). Demographics, history of depression, stroke severity, and inpatient PHQ-9 scores were abstracted. Logistic regression was used to determine factors associated with PSD and an ROC analysis determined the predictability of PSD in the inpatient setting. Results: 307 individuals were administered the PHQ-9 at follow-up. This group was younger with less severe strokes, but had no difference in history of depression or inpatient PHQ-9 scores than those without follow-up screening. The mean age of the cohort was 65.5 years; 52% were female. Individuals with history of depression (OR=4.22, 95% CI: 2.40-7.42), inpatient depression (OR=2.82, 95% CI: 1.80-4.43), higher stroke severity (OR=1.05, 95% CI: 1.01-1.10), and those living alone (OR=1.86, 95% CI: 1.01-3.40) had increased odds of PSD at follow-up. Marital status, employment, and outpatient therapy were not associated PSD. The ROC curve using a positive inpatient PHQ-9 achieved an area under the curve (AUC) of 0.62 (95% CI:0.57-0.67), while the AUC was 0.69 (0.64-0.74) after adding history of depression. Conclusion: History of depression and a positive inpatient PHQ-9 appear to be most strongly associated with long-term PSD. Initiating SSRIs only in those individuals at higest risk for PSD may help reduce the burden of stroke recovery in this targeted population.

The Effects of Antidepressant Therapy on Health-Related Quality of Life in Patients with a Chronic Obstructive Pulmonary Disease and Depressive Symptoms

Abstract Background. Symptoms of depression are often present in patients with chronic obstructive pulmonary disease (COPD) and treatment of depression may substantially improve the quality of life of such patients. The aim of our study was to investigate factors that influence the efficacy of antidepressant therapy in terms of the quality of life in patients with COPD and a depressive disorder. Materials and Methods. The study was designed as a prospective cross-sectional study and conducted between October 2016 and December 2019 in the Primary Health Center, Kragujevac, Serbia. The study sample included 87 patients. Associations between putative risk factors and change in the quality-of-life score were tested by a multivariate linear regression model and interpreted by the regression coefficients. Results. Our study showed a clear positive effect of therapy with SSRIs on the severity of depression symptoms and the quality of life of patients with co-occurrence of COPD and depression. However, multiple linear regression shows that the effect of SSRIs was more prominent in patients with a higher degree of COPD severity since patients with lower FEV1 values had a more extensive increase in the Q-LES-Q-SF score (B=-0,034; p=0,020). Conclusion. Treatment of depression that accompanies COPD is an important segment of managing such patients, which significantly improves HRQoL. Patients with more severe COPD would especially benefit from such treatment since their response to SSRIs is more pronounced.

Escitalopram administration, relearning, and neuroplastic effects: A diffusion tensor imaging study in healthy individuals

BackgroundNeuroplastic processes are influenced by serotonergic agents, which reportedly alter white matter microstructure in humans in conjunction with learning. The goal of this double-blind, placebo-controlled imaging study was to investigate the neuroplastic properties of escitalopram and cognitive training on white matter plasticity during (re)learning as a model for antidepressant treatment and environmental factors. MethodsSeventy-one healthy individuals (age=25.6 ± 5.0, 43 females) underwent three diffusion magnetic resonance imaging scans: at baseline, after 3 weeks of associative learning (emotional/non-emotional content), and after relearning shuffled associations for an additional 3 weeks. During the relearning phase, participants received a daily dose of 10 mg escitalopram or placebo orally. Fractional anisotropy (FA), and mean (MD), axial (AD), and radial diffusivity (RD) were calculated within the FMRIB software library and analyzed using tract-based spatial statistics. ResultsIn a three-way repeated-measures marginal model with sandwich estimator standard errors, we found no significant effects of escitalopram and content on AD, FA, MD, and RD during both learning and relearning periods (pFDR>0.05). When testing for escitalopram or content effects separately, we also demonstrated no significant findings (pFDR>0.05) for any of the diffusion tensor imaging metrics. LimitationsThe intensity of the study interventions might have been too brief to induce detectable white matter changes. DiscussionPrevious studies examining the effects of SSRIs on white matter tracts in humans have yielded inconclusive outcomes. Our results indicate that relearning under escitalopram does not affect the white matter microstructures in healthy individuals when administered for 3 weeks.

Aduvant therapy of depression with hopantenic acid

Adequate SSRI monotherapy does not produce a sufficient clinical effect in some patients, and about 30% of patients do not respond to therapy at all. Favorable experience of combined prescription of SSRIs with various nootropic (neuroprotective) agents has been described in the literature.The aim of the study was to investigate the efficacy and tolerability of hopantenic acid as an adjuvant therapy for depression. We obtained significant data that inclusion of hopantenic acid at a dose of 2000 mg per day in a 12-week complex antidepressant therapy with paroxetine (20 mg per day) statistically significantly reduces the severity of depression symptoms. The drug's effect is achieved by improving patients' cognitive functions, reducing anxiety symptoms and side effects of SSRIs. Improved efficacy and tolerability of antidepressant therapy with hopantenic acid in the long term will allow to achieve more significant improvement in the quality of life of patients.