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Summary Objectives We aimed in the current cross-sectional study to evaluate rates and patterns of SD among drug naive women with mild to moderate depression against those receiving escitalopram. Study design Group (A) included 120 females diagnosed with mild to moderate depression. Group (B) served as controls included 60 age-matched volunteers. Main outcome measures Female participants were evaluated by the validated Arabic female sexual function index (ArFSFI), perceived stress situation scale (PSS), patient health questionnaire-9 scale (PHQ-9) and center for epidemiological studies-depression scale (CES-D). Results The study demonstrated that females with mild to moderate depression treated with escitalopram had better sexual function than those who were drug naive. Additionally, treated females got better scores of PSS, CES-D and PHQ-9 compared to those who were drug naive. The PSS and the CES-D and the PHQ-9 scales negatively correlated with the domains of desire, pain, arousal, lubrication, orgasm, satisfaction and total score of FSFI. Finally, a linear regression analysis after adjustment of FSFI as a dependent variable had revealed that the PSS scale, the PHQ-9 scale and the international index of erectile function-5 were significant independent predictors of the affected females’ sexual function. Conclusion Escitalopram is associated with lesser risk of SD in females with mild to moderate depression.

We report a 21-year-old man with bipolar disorder who was on a stable dose of escitalopram and risperidone. Tramadol and cough syrup (dextromethorphan) were added for his recent attack of upper respiratory tract infection. However, he developed various neurological symptoms. Haloperidol and ondansetron were added after hospitalisation. However, his condition deteriorated. A diagnosis of serotonin syndrome (SS) was made, and cyproheptadine was started. Cyproheptadine provided relief in most of the symptoms within 48 hours except for the presence of fever and rigidity. The addition of bromocriptine provided a complete resolution of the symptoms. We considered the presence of both SS and neuroleptic malignant syndrome (NMS) in this case. There are four similar cases in the literature. We discussed a diagnostic and therapeutic approach for patients who are on both serotonergic agents and neuroleptics and develop SS-like or NMS-like clinical features.

Large nest building behaviour (LNB), as expressed by a subpopulation of laboratory housed deer mice (Peromyscus maniculatus bairdii), is persistent and repetitive. However, the response of LNB to an anxiogenic environment has not yet been investigated. Here, we employed LNB and normal nesting (NNB) expressing mice, subdivided into three drug-exposed groups per cohort, i.e. water (28 days), escitalopram (50 mg/kg/day, 28 days) and lorazepam (2 mg/kg/day; 4 days) to investigate this theme. During the last 4 days of drug exposure, mice were placed inside anxiogenic open field arenas which contained a separate enclosed and dark area for 4 consecutive nights during which open field and/or nest building assessments were performed. We show that LNB behaviour in deer mice is stable, irrespective of the anxiety-related context in which it is assessed, and that LNB mice find an open field arena to be less aversive compared to NNB mice. Escitalopram and lorazepam differentially affected the nesting and open field behaviour of LNB expressing mice, confirming deer mouse LNB as a repetitive behavioural phenotype that is related to a compulsive-like process which is regulated by the serotonergic system.

Background: Studies have shown that pharmacological and psychological treatments are effective for children and adolescents with obsessive-compulsive disorder (OCD). However, few network meta-analyses have examined whether pharmacological or psychological treatments on their own, or combined, are most effective. Methods: We conducted a database search and selected randomized controlled trials of pharmacological or psychological treatments, alone or in combination, for children and adolescents with OCD. The primary outcome was change in symptom severity as a result of treatment, as assessed using the Yale-Brown Obsessive Compulsive Scale (BOCS) or Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS) . Findings: We included 18 studies with 1353 participants and 12 kinds of treatments. In terms of efficacy, all pharmacological and psychotherapy treatments were more effective than placebo. Among the 12 treatments, the efficacy of pharmacological treatment combined with cognitive behavioral therapy (CBT) was better than pharmacological treatment alone. When pharmacological treatment was used alone, escitalopram was significantly better than clomipramine(CY-BOCS average change 3.42; 95% CI 2.11, 4.65), fluvoxamine(CY-BOCS average change 3.59; 95% CI 1.09, 6.20), paroxetine(CY-BOCS average change 2 .80; 95% CI 0.01, 5.64) and sertraline(CY-BOCS average change 3.49; 95% CI 1.53, 5.64). Interpretation: The available evidence suggests that the combination of pharmacological and psychological treatment is likely to be most effective for children and adolescents with OCD. Funding: The National Nature Science Foundation of China (81801357, 81801350), the Science and Technology Education Program of the Sichuan Province (2020JDKP0013), the Key R&D Projects of the Science and Technology Department of Sichuan Province(2020YFS0259 ), and the Chengdu Key Technology R&D Program (2019-YF05– 00284-SN). Declaration of Interest: None to declare.

BackgroundPersonality traits may predict antidepressant discontinuation and response. However, previous studies were rather small, only explored a few personality traits and did not include adverse drug effects nor the interdependency between antidepressant discontinuation patterns and response.MethodsGENDEP included 589 patients with unipolar moderate-severe depression treated with escitalopram or nortriptyline for 12 weeks. Seven personality dimensions were measured using the self-reported 240-item Temperament and Character Inventory-Revised (TCI-R). We applied Cox proportional models to study discontinuation patterns, logistic and linear regression to investigate response and remission after 8 and 12 weeks, and mixed-effects linear models regarding time-varying treatment response and adverse drug reactions.ResultsLow harm avoidance, low cooperativeness, high self-transcendence and high novelty seeking were associated with higher risks for antidepressant discontinuation, independent of depressed mood, adverse drug reactions, drug, sex and age. Regression analyses showed that higher novelty seeking and cooperativeness scores were associated with a greater likelihood of response and remission after 8 and 12 weeks, respectively, but we found no correlations with response in the mixed-effects models. Only high harm avoidance was associated with more self-reported adverse effects.ConclusionsThis study, representing the largest investigation between several personality traits and response to two different antidepressants, suggests that correlations between personality traits and antidepressant treatment response may be confounded by differential rates of discontinuation. Future trials on personality in the treatment of depression need to consider this interdependency and study whether interventions aiming at improving compliance for some personality types may improve response to antidepressants.

Стаття присвячена проблемі головного болю у пацієнтів, які перенесли інсульт. Для постінсультного головного болю характерне зростання частоти нападів при збільшенні давності інсульту. Найбільш поширеним видом постінсультного головного болю є головний біль напруження. Високоефективним методом лікування є використання нестероїдних протизапальних засобів (лорноксикам) та антидепресантів (сертралін, есциталопрам та ін.).

The article deals with problem of the treatment of anxiety-depressive disorders in patients with gastroenterological disease and persistent symptoms of abdominal pain and dyspepsia. For objectification of psychoemotional disorders and choice of their correction, we have applied HADS scale. We have detected a high incidence of anxiety — in 93.75 % of such patients, depression — in 81.25 %, their combination — in 78.1 %. Gidazepam efficacy was evaluated in anxiety disorders and escitalopram one — in depressive disorders. It is shown that the use of psychocorrection enables to reverse gastroenterological symptoms: abdominal pain has completely gone in 71.9 % of patients, dyspeptic complaints — in 86.9 %, as well as to reduce anxiety-depressive symptoms.

Background World Health Organization has prescribed drug use indicators for evaluating rational prescribing. Very few studies have been conducted on rational prescriptions for psychotropic drugs; hence, this study was undertaken at a tertiary care center of North India. Methods After obtaining approval of the Institutional Ethics Committee, all prescriptions deposited with the dispensary of the psychiatry department of the hospital between 01 October 2017 and 31 December 2017 were included in the study. The prescriptions were analyzed for drug use indicators, namely the average number of drugs per encounter, percentage of prescriptions with generic name, percentage of prescriptions from the essential drug list, percentage of prescriptions with antibiotics, and percentage of prescriptions with an injection. In addition, the prescriptions were analyzed for patterns of psychotropics prescribed. Results A total of 3770 prescriptions were analyzed. On an average, 2.35 medicines were prescribed per prescription. Injectable comprised 2.39% of prescriptions and fixed drug combinations were 0.16% of the total. Of all prescriptions, 91.3% were by generic name, while 55.02% of prescriptions were from the essential drug list. Polypharmacy constituted 4.53% of prescriptions. Risperidone, escitalopram, sodium valproate, and clonazepam were the most commonly prescribed drugs. Conclusion While we fared well with respect to the percentage of prescriptions with injections and those with an antibiotic, we have not been able to achieve the prescribed standards in prescription with generic names, number of drugs per prescription, and prescriptions from the essential drug list. The study emphasizes that there is scope for improvement.

Selective serotonin reuptake inhibitors (SSRIs) are a group of drugs used to treat various psychiatric disorders such as major depression, generalised anxiety, and obsessive-compulsive syndrome. Although generally safe, SSRIs can lead to various adverse effects, including an increased risk of bleeding due to their effect on platelet activation and aggregation. Unexpected bleeding can occur at different sites, in people of different age groups, and in combination with other medications. The commonly reported risk factors associated with medication-induced bleeding in patients with mental disorders include co-administration of other drugs and liver cirrhosis or failure. We report a relatively less common adverse effect of SSRIs. This is the case of a Middle Eastern man, known to have seasonal allergic rhinitis, who developed self-limiting epistaxis following the use of escitalopram for a depressive disorder. Since a history of seasonal allergy can precipitate bleeding when using SSRIs, risk factors for bleeding associated with SSRIs, excluding the common causes, should be explored for better management and prevention.

У дискусійній статті розглянута проблема діагностики і терапії депресії в осіб похилого віку. Депресія — один із найпоширеніших розладів, що зустрічаються в загальномедичній практиці. Депресія є четвертою провідною причиною захворюваності та інвалідності, до 2020 року депресивні розлади посядуть друге місце в інтеграційній оцінці тягаря хвороб, який несе світова спільнота. В осіб похилого віку депресія є найбільш поширеним психічним розладом. У середньому поширеність депресії у літніх пацієнтів становить 12,3 %, прогресивно збільшуючись при погіршенні соматичного статусу та інвалідизації. Літні жінки страждають депресією у два рази частіше, літні чоловіки з депресією мають найвищий ризик завершеного суїциду. Наведено інформацію про те, що депресія ускладнює процес реабілітації, погіршує результати лікування, прогноз і перебіг соматичних захворювань, є фактором ризику розвитку деменції, підвищує ризик суїцидальної поведінки. Вік призводить до модифікації клінічної картини депресії у літніх людей. Для експрес-діагностики депресії у літніх людей використовується геріатрична шкала депресії. Терапія депресивних розладів базується на фармакотерапії, психоосвітніх програмах для пацієнтів та їх родичів, а також на психотерапії та психокорекції. При виборі антидепресантів для лікування депресивних розладів у літніх пацієнтів слід керуватися принципами ефективності та безпеки. Антидепресанти з групи селективних інгібіторів зворотного захоплення серотоніну мають доведений профіль безпеки та ефективності порівняно з іншими групами антидепресантів. Есциталопрам має високі показники результативності та частоти ремісії, оптимальний для профілактики рецидивів, що робить його препаратом вибору для терапії літніх пацієнтів із депресією.

Aim: This study aims to determine and compare the prevalence of Female Sexual Dysfunction (FSD) between patients on escitalopram and agomelatine, as well as to investigate possible factors associated with their usage. Study Design: Cross-sectional. Place and Duration of Study: Psychiatric Day Care Clinic, Department of Psychological Medicine, University Malaya Medical Centre (UMMC), Malaysia, between November 1, 2020 until February 1, 2021. Methodology: This study is a cross-sectional study involving 66 women with depression from the outpatient psychiatric clinic of a university hospital; 35 of whom were prescribed with escitalopram and 31 with agomelatine. The subjects were in remission and had no significant signs or symptoms of depression for at least 2 months. The prevalence of FSD between the two groups were compared after adjusting for underlying depression severity. Results: This study showed that the overall prevalence rate of FSD was 33.3%, with the prevalence being higher for those on escitalopram (42.9%) than those on agomelatine (22.6%), but did not achieve statistical significance (P=0.081). Out of the six domains of FSD, multivariate analyses revealed that there was a significant reduction of 69% in sexual desire disorder (95% CI:0.110, 0.855), P=0.022 for those on agomelatine compared to escitalopram. Controlling for drug dosage and depression severity (as measured using Montgomery-Asberg Depression Rating Scale), the odds for patients on agomelatine developing sexual desire disorder was 0.267 (95% CI:0.091, 0.783), P=0.016. Conclusion: There was no significant difference in FSD risk between patients on agomelatine and those on escitalopram. Patients on agomelatine were however less likely to develop sexual desire disorder, which demonstrates a slightly better sexual acceptability profile of agomelatine in women in this respect compared to escitalopram.

Introduction: Medicines acting on the central nervous system can increase the risk of postoperative delirium, but the specific medicines associated with greatest risk remain unclear. Objectives: We aimed to examine the risk of individual central nervous system-acting medicines used preoperatively on delirium after hip or knee surgery. Methods: A matched case-control study was conducted using data from the Australian Government Department of Veterans’ Affairs. We included people aged 65 years or older who had knee or hip surgery between 2000 and 2019. People with hip or knee surgery who developed postoperative delirium were cases and controls were people with hip or knee surgery but who did not develop postoperative delirium. Use of medicines including anxiolytics, sedatives, and hypnotics, opioid analgesics and antidepressants prior to surgery was compared between cases and controls. Results: A total of 2614 patient cases with postoperative delirium were matched by same sex, age (±2 years), and year of admission (±2 years) with 7842 controls without postoperative delirium. Cases were more likely to be exposed to nitrazepam (odds ratio [OR] = 1.81, 95% confidence interval [CI] 1.24–2.64), sertraline (OR = 1.50, 95% CI 1.20–1.87), mirtazapine (OR = 1.38, 95% CI 1.11–1.74), venlafaxine (OR = 1.42, 95% CI 1.02–1.98), citalopram (OR = 1.54, 95% CI 1.19–1.99), escitalopram (OR = 1.42, 95% CI 1.06–1.89) or fluvoxamine (OR = 5.01, 95% CI 2.15–11.68) prior to surgery than controls. At the class level, exposure to benzodiazepines (OR = 1.20, 95% CI 1.05–1.37) and antidepressants (OR = 1.64, 95% CI 1.47–1.83) prior to surgery was significantly higher in cases than in controls. The numbers needed to treat to harm for one additional delirium case were 43 for sertraline, 40 for citalopram, 57 for mirtazapine and 26 for nitrazepam. Whereas, the numbers needed to treat to harm were found to be 20 for sertraline, 17 for citalopram, 19 for mirtazapine and 10 for nitrazepam in the 85 years or older age group, indicating that the harmful effect of these medicines is pronounced as age advances. Conclusions: People who developed delirium following hip or knee surgery were more likely to be exposed to nitrazepam, sertraline, mirtazapine, venlafaxine, citalopram, escitalopram or fluvoxamine at the time of admission for surgery. Planning to reduce use of these medicines well prior to surgery may decrease the risk of postoperative delirium. Refereed/Peer-reviewed

It has been extensively debated whether selective serotonin reuptake inhibitors (SSRIs) are more efficacious than placebo in affective disorders, and it is not fully understood how SSRIs exert their beneficial effects. Along with serotonin transporter blockade, altered dopamine signaling and psychological factors may contribute. In this randomized clinical trial of participants with social anxiety disorder (SAD) we investigated how manipulation of verbally-induced expectancies, vital for placebo response, affect brain monoamine transporters and symptom improvement during SSRI treatment. Twenty-seven participants with SAD (17 men, 10 women), were randomized, to 9 weeks of overt or covert treatment with escitalopram 20 mg. The overt group received correct treatment information whereas the covert group was treated deceptively with escitalopram, described as an active placebo in a cover story. Before and after treatment, patients underwent positron emission tomography (PET) assessments with the [C-11]DASB and [C-11]PE2I radiotracers, probing brain serotonin (SERT) and dopamine (DAT) transporters. SAD symptoms were measured by the Liebowitz Social Anxiety Scale. Overt was superior to covert SSRI treatment, resulting in almost a fourfold higher rate of responders. PET results showed that SERT occupancy after treatment was unrelated to anxiety reduction and equally high in both groups. In contrast, DAT binding decreased in the right putamen, pallidum, and the left thalamus with overt SSRI treatment, and increased with covert treatment, resulting in significant group differences. DAT binding potential changes in these regions correlated negatively with symptom improvement. Findings support that the anxiolytic effects of SSRIs involve psychological factors contingent on dopaminergic neurotransmission while serotonin transporter blockade alone is insufficient for clinical response. Funding Agencies|Swedish Research CouncilSwedish Research CouncilEuropean Commission; Riksbankens Jubileumsfond-the Swedish Foundation for Humanities and Social Sciences; Kjell and Marta Beijer Foundation

OBJECTIVE: To compare associations between individual antidepressants and newborn outcomes. DESIGN: Retrospective cohort study SETTING: Deliveries in a large, US medical system. POPULATION: Women who received at least one antidepressant prescription 3 months prior to conception through delivery. METHODS: Eligible women had maternal characteristics and newborn outcomes extracted from medical record data. Exposure was defined by the timing of the prescription during pregnancy. MAIN OUTCOME MEASURES: Newborn outcomes (any adaptation syndrome, neonatal intensive care unit (NICU) admission) were analyzed for each antidepressant and compared using standard statistics and multivariable regression compared to exposure to bupropion. Odds of outcomes based on timing of exposure were also explored. RESULTS: A total of 3,694 women were analyzed. Rates of any adaptation syndrome (p

[EN] Many voltammetry methods have been developed to monitor brain extracellular dopamine levels. Fewer approaches have been successful in detecting serotonin in vivo. No voltammetric techniques are currently available to monitor both neurotransmitters simultaneously across timescales, even though they play integrated roles in modulating behavior. We provide proof-of-concept for rapid pulse voltammetry coupled with partial least squares regression (RPV-PLSR), an approach adapted from multi-electrode systems (i.e., electronic tongues) used to identify multiple components in complex environments. We exploited small differences in analyte redox profiles to select pulse steps for RPV waveforms. Using an intentionally designed pulse strategy combined with custom instrumentation and analysis software, we monitored basal and stimulated levels of dopamine and serotonin. In addition to faradaic currents, capacitive currents were important factors in analyte identification arguing against background subtraction. Compared to fast-scan cyclic voltammetry-principal components regression (FSCV-PCR), RPV-PLSR better differentiated and quantified basal and stimulated dopamine and serotonin associated with striatal recording electrode position, optical stimulation frequency, and serotonin reuptake inhibition. The RPV-PLSR approach can be generalized to other electrochemically active neurotransmitters and provides a feedback pipeline for future optimization of multi-analyte, fit-for-purpose waveforms and machine learning approaches to data analysis., Funding from the National Institute on Drug Abuse (DA045550) and National Institute of Mental Health (MH106806) was received. CSM was supported by the National Science Foundation Graduate Research Fellowship Program (DGE-1650604 and DGE-2034835). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation.

Available treatments for hot flashes in patients with breast cancer are not always tolerable or effective for all patients.Patients diagnosed to have primary breast cancer were randomly allocated to receive 10Eighty-two patients were randomly assigned to receive escitalopram (Both escitalopram ad PMRT can reveal nocturnal and diurnal HFs in terms of frequency and duration in patients with breast cancer.

Escitalopram is a selective serotonin reuptake inhibitor (SSRIs) antidepressant, drug that is currently used as first-line agents for the treatment of depression and it is also used in the treatment of other psychiatric disorders. The main goal of this study was to identify which brain areas are affected by escitalopram administration. This study was carried out on male Wistar rats that received escitalopram daily over 14 days and that were studied by 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG)-PET on the last day of treatment. Computed tomography (CT) images were acquired immediately before each PET scan and the main effects of drug administration were elucidated by Statistical Parametric Mapping. The results obtained indicated that repeated exposure to escitalopram increased metabolic activity in the retrosplenial and posterior cingulate cortices, while it decreased such activity in the ventral hippocampus, cerebellum, brainstem and midbrain regions, including the raphe nuclei and ventral tegmental area. Therefore, repeated exposure to escitalopram alters the activity of several brain areas closely related to the serotonergic system, and previously identified as key regions in the antidepressant effect induced by SSRIs. Furthermore, some of the changes found, such as the dampened metabolism in the ventral tegmental area, are similar to changes that have been described after treating with other fast-acting antidepressant approaches.

Background/aims The aim of this study was to identify the trends in antidepressant (AD) medication use in two Irish general practices over a 5-year period, 2016 to 2020. The rationale for this study is attributed to the growing prevalence of depression amongst the Irish general public as well as concerns surrounding long-term AD medication use. Methods The research was undertaken in 2021 examining AD prescription rates from 2016 to 2020. The medications of interest were selective serotonin and norepinephrine reuptake inhibitors (SSRI and SNRIs): sertraline, escitalopram, fluoxetine and venlafaxine. The number of medical card holders (MCH) and prescription dispensing rates were analysed for observable trends. Results AD medication use is rising amongst the Irish MCH population. The number of MCH prescribed AD grew from 9.42 to 12.3 per 100 MCH between the years 2016 and 2020, respectively. The year 2020 represented the largest proportion of MCH prescriptions, 6.32 AD prescriptions per 1000 MCH prescriptions. The years 2019 to 2020 represented the largest annual increase in prescription dispensing with a growth of 0.45 per 1000 MCH prescriptions. Annual figures show a continual increase in AD dispensing refill rates from 4.14 to 5.67 per 1000 MCH prescriptions in 2016 and 2020, respectively. Conclusion This study illustrates a steady rise in AD medication within the general practice setting, with an observed rise in prescription dispensing rates. The high proportion of refill prescriptions demonstrates the long-term use of AD medications. This may be indicative of chronic depression or may highlight a lack of appropriate medication cessation strategies.

Amygdala-ventrolateral prefrontal cortex (VLPFC) circuitry is disrupted in pediatric anxiety disorders, yet how selective serotonin reuptake inhibitors (SSRIs) affect this circuitry is unknown. We examined the impact of the SSRI escitalopram on functional connectivity (FC) within this circuit, and whether early FC changes predicted treatment response in adolescents with generalized anxiety disorder (GAD).Resting-state functional magnetic resonance (MR) images were acquired before and after 2 weeks of treatment in 41 adolescents with GAD (12-17 years of age) who received double-blind escitalopram or placebo for 8 weeks. Change in amygdala-based whole-brain FC and anxiety severity were analyzed.Controlling for age, sex, and pretreatment anxiety, escitalopram increased amygdala-VLPFC connectivity compared to placebo (F = 17.79, p = .002 FWE-corrected). This early FC change predicted 76.7% of the variability in improvement trajectory in patients who received escitalopram (p .001) but not placebo (p = .169); the predictive power of early amygdala-VLPFC FC change significantly differed between placebo and escitalopram (p = .013). Furthermore, this FC change predicted improvement better than baseline FC or clinical/demographic characteristics. Exploratory analyses of amygdala subfields' FC revealed connectivity of left basolateral amygdala (BLA) -VLPFC (F = 19.64, p .001 FWE-corrected) and superficial amygdala-posterior cingulate cortex (F = 22.92, p = .001 FWE-corrected) were also increased by escitalopram, but only BLA-VLPFC FC predicted improvement in anxiety over 8 weeks of treatment.In adolescents with GAD, escitalopram increased amygdala-prefrontal connectivity within the first 2 weeks of treatment, and the magnitude of this change predicted subsequent clinical improvement. Early normalization of amygdala-VLPFC circuitry might represent a useful tool for identifying future treatment responders as well as a promising biomarker for drug development.Neurofunctional Predictors of Escitalopram Treatment Response in Adolescents With Anxiety; https://www.clinicaltrials.gov/; NCT02818751.

Stroke is a leading cause of death and neurological disability worldwide. Survivors of ischemic stroke usually suffer from impairment in motor function, visual field defect, speech disorders and depression. Cerebral levels of several neurotransmitters such as dopamine, 5-hydroxytriptamine (5-HT) or serotonin, norepinephrine (NE) and glutamate alter during ischemia and contribute to the pathophysiology of cerebral ischemia. The overall effect of serotonin in cerebral ischemia is still unclear but there are evidences that enhancement of serotonin activity in the hippocampus exerts protection against neuronal damage after ischemia. Besides, several studies showed that selective serotonin reuptake inhibitors (SSRIs), serotonin/norepinephrine reuptake inhibitors (SNRIs) and serotonin agonists reduced cerebral infarct size and improved functional recovery after stroke. There are different mechanisms that may explain the neuroprotective effect of SSRIs such as fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram and escitalopram in cerebral ischemia. They exert antioxidant, antiapoptotic and anti-inflammatory activities which are responsible for their effectiveness in stroke. In this review we will discuss in details the role of serotonin in ischemia and the proposed mechanisms of the neuroprotective role of SSRIs in stroke.

Anxiety disorders are the most common mental disorders in adolescents. However, only 50% of pediatric patients with anxiety disorders respond to the first-line pharmacologic treatments-selective serotonin reuptake inhibitors (SSRIs). Thus, identifying the neurofunctional targets of SSRIs and finding pretreatment or early-treatment neurofunctional markers of SSRI treatment response in this population is clinically important. We acquired pretreatment and early-treatment (2 weeks into treatment) functional magnetic resonance imaging during a continuous processing task with emotional and neutral distractors in adolescents with generalized anxiety disorder (GAD, N = 36) randomized to 8 weeks of double-blind escitalopram or placebo. Generalized psychophysiological interaction analysis was conducted to examine the functional connectivity of the amygdala while patients viewed emotional pictures. Full-factorial analysis was used to investigate the treatment effect of escitalopram on amygdala connectivity. Correlation analyses were performed to explore whether pretreatment and early (week 2) treatment-related connectivity were associated with treatment response (improvement in anxiety) at week 8. Compared to placebo, escitalopram enhanced emotional processing speed and enhanced negative right amygdala-bilateral ventromedial prefrontal cortex (vmPFC) and positive left amygdala-right angular gyrus connectivity during emotion processing. Baseline amygdala-vmPFC connectivity and escitalopram-induced increased amygdala-angular gyrus connectivity at week 2 predicted the magnitude of subsequent improvement in anxiety symptoms. These findings suggest that amygdala connectivity to hubs of the default mode network represents a target of acute SSRI treatment. Furthermore, pretreatment and early-treatment amygdala connectivity could serve as biomarkers of SSRI treatment response in adolescents with GAD. The trial registration for the study is ClinicalTrials.gov Identifier: NCT02818751.

Rational With no available response biomarkers, matching an appropriate antidepressant to an individual can be a lengthy process. Improving understanding of processes underlying treatment responsivity in depression is crucial for facilitating work on response biomarkers. Objectives To identify differences in patterns of pre-treatment resting-state functional connectivity (rsFC) that may underlie response to antidepressant treatment. Methods After a baseline MRI scan, thirty-four drug-free patients with depression were treated with an SSRI escitalopram 10 mg daily for 6 weeks; response was defined as ≥ 50% decrease in Hamilton Depression Rating Scale (HAMD) score. Thirty-one healthy controls had a baseline clinical assessment and scan. Healthy participants did not receive treatment. Results Twenty-one (62%) of patients responded to escitalopram. Treatment responsivity was associated with enhanced rsFC of the right fronto-parietal network (FPN)—with the posterior DMN, somatomotor network (SMN) and somatosensory association cortex. The lack of treatment response was characterized by reduced rsFC: of the bilateral FPN with the contralateral SMN, of the right FPN with the posterior DMN, and of the extended sensorimotor auditory area with the inferior parietal lobule (IPL) and posterior DMN. Reduced rsFC of the posterior DMN with IPL was seen in treatment responders, although only when compared with HC. Conclusions The study supports the role of resting-state networks in response to antidepressant treatment, and in particular the central role of the frontoparietal and default mode networks.

Background Cytokine treatment with Interferon-alpha (IFN-α) represents a clinical model of immune associated depression, but it remains unclear if it is of the same entity as major depressive disorder (MDD). The study focuses on possible gender differences in IFN-α induced depression and effects of a pre-emptive antidepressant treatment. Methods Data from 181 patients with chronic hepatitis C infection (cHC) without history of mental illnesses undergoing treatment with IFN-α 2a and ribavirin were re-analyzed for gender effects. Patients with a pre-emptive antidepressant therapy with Escitalopram (n = 90, verum group) to prevent IFN-induced depression were compared to patients who received placebo (n = 91). Depressive symptoms before and during HCV-treatment were assessed using the Montgomery–Asberg Depression Rating Scale (MADRS), Beck's Depression Inventory (BDI) and the Hamilton Anxiety Rating Scale. Results We found significant differences regarding the incidence and severity of depressive symptoms between men and women for patients without antidepressant pre-treatment (placebo group). Significantly more women without pre-emptive antidepressant therapy suffered from clinically relevant depression (MADRS values ≥ 13, p = 0.041) and self-rated depressive symptoms (BDI ≥ 17, p = 0.024). Antidepressant pre-treatment showed comparable effects regarding the reduction of incidence and severity of depression in both women and men. Conclusions Compared to MDD, IFN-alpha-induced depression in patients with cHC is also characterized by gender differences with an increased risk for women but no gender difference regarding the effects of an antidepressant pre-treatment is found. Our data strengthens the hypothesis that Interferon-induced depression serves as a clinical model for immune related depressive disorders.

Background Cannabidiol (CBD), a major nonintoxicating constituent of cannabis, exhibits anxiolytic properties in preclinical and human studies and is of interest as a novel intervention for treating anxiety disorders. Existing first-line pharmacotherapies for these disorders include selective serotonin reuptake inhibitor and other antidepressants. Cannabidiol has well-described inhibitory action on cytochrome P450 (CYP450) drug-metabolizing enzymes and significant drug-drug interactions (DDIs) between CBD and various anticonvulsant medications (eg, clobazam) have been described in the treatment of epilepsy. Here, we examined the likelihood of DDIs when CBD is added to medications prescribed in the treatment of anxiety. Methods The effect of CBD on CYP450-mediated metabolism of the commonly used antidepressants fluoxetine, sertraline, citalopram, and mirtazapine were examined in vitro. Cannabidiol-citalopram interactions were also examined in vivo in patients (n = 6) with anxiety disorders on stable treatment with citalopram or escitalopram who received ascending daily doses of adjunctive CBD (200-800 mg) over 12 weeks in a recent clinical trial. Results Cannabidiol minimally affected the metabolism of sertraline, fluoxetine, and mirtazapine in vitro. However, CBD significantly inhibited CYP3A4 and CYP2C19-mediated metabolism of citalopram and its stereoisomer escitalopram at physiologically relevant concentrations, suggesting a possible in vivo DDI. In patients on citalopram or escitalopram, the addition of CBD significantly increased citalopram plasma concentrations, although it was uncertain whether this also increased selective serotonin reuptake inhibitor-mediated adverse events. Conclusions Further pharmacokinetic examination of the interaction between CBD and citalopram/escitalopram is clearly warranted, and clinicians should be vigilant around the possibility of treatment-emergent adverse effects when CBD is introduced to patients taking these antidepressants.

The consumption of new selective serotonin reuptake inhibitors (SSRIs) is raising dramatically especially in European countries. It contributes to occurrence of clinically important drug side effects. One of which can be hyponatremia. We present two case reports of 85-year-old and 84-year-old women who developed hyponatremia after escitalopram administration. We hypothesize that in both cases hyponatremia was connected with antidepressants administration. However, due to multiple comorbidities and polypharmacy it is often impossible to establish the exact mechanism of hyponatremia. Moreover, it is crucial to distinguish subtypes of drug-induced syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH), such as SSRI-induced SIADH, reset osmostat SIADH, thiazide-associated hyponatremia, thiazide-induced hyponatremia, mineralocorticoid responsive hyponatremia of older adults, in order to properly diagnose and treat geriatric patients. Administration of antidepressants or thiazides should be followed by a regular monitoring of serum sodium level.

Background Preclinical and clinical studies have indicated that impaired endogenous synthesis of glutathione during early postnatal development plays a significant role in the pathophysiology of schizophrenia. Moreover, some studies have suggested that antidepressants are able to increase the activity of atypical antipsychotics which may efficiently improve the treatment of negative and cognitive symptoms of schizophrenia. Methods In the present study, we investigated the influence of repeated co-treatment with escitalopram and aripiprazole on the schizophrenia-like behavior and BDNF mRNA expression in adult rats exposed to glutathione deficit during early postnatal development. Male pups between the postnatal days p5–p16 were treated with the inhibitor of glutathione synthesis, BSO (L-buthionine-(S,R)-sulfoximine) and the dopamine uptake inhibitor, GBR 12,909 alone or in combination. Escitalopram and aripiprazole were given repeatedly for 21 days before the tests. On p90–92 rats were evaluated in the behavioral and biochemical tests. Results BSO given alone and together with GBR 12,909 induced deficits in the studied behavioral tests and decreased the expression of BDNF mRNA. Repeated aripiprazole administration at a higher dose reversed these behavioral deficits. Co-treatment with aripiprazole and an ineffective dose of escitalopram also abolished the behavioral deficits in the studied tests. Conclusion The obtained data indicated that the inhibition of glutathione synthesis in early postnatal development induced long-term deficits corresponding to schizophrenia-like behavior and decreased the BDNF mRNA expression in adult rats, and these behavioral deficits were reversed by repeated treatment with a higher dose of aripiprazole and also by co-treatment with aripiprazole and ineffective dose of escitalopram.

Previous work has demonstrated that microRNAs (miRNAs) change as a function of antidepressant treatment (ADT) response. However, it is unclear how representative these peripherally detected miRNA changes are to those occurring in the brain. This study aimed to use peripherally extracted neuron-derived extracellular vesicles (NDEV) to circumvent these limitations and investigate neuronal miRNA changes associated with antidepressant response. Samples were collected at two time points (baseline and after 8 weeks of follow-up) from depressed patients who responded (N = 20) and did not respond (N = 20) to escitalopram treatment, as well as controls (N = 20). Total extracellular vesicles (EVs) were extracted from plasma, and then further enriched for NDEV by immunoprecipitation with L1CAM. EVs and NDEVs were characterized, and NDEV miRNA cargo was extracted and sequenced. Subsequently, studies in cell lines and postmortem tissue were conducted. Characterization of NDEVs revealed that they were smaller than other EVs isolated from plasma (p

Background: The pattern of prescribing Antidepressants to patients has been varying worldwide. Objective: We aim to observe the prescribing pattern of antidepressants as well as assess its various outcomes in patients, the rationality of the prescriptions, and the prevalence of antidepressant usage. Methodology: A prospective observational study of a total of 56 subjects receiving antidepressants was performed at the Psychiatry. They were screened for their various outcomes on using antidepressants. The written form of the medical record sheet was used to preserve the patient's Data. Prescription pattern, treatment chart, abnormal vitals were noted. Morisky's adherence scale was used to assess the adherence of patients to prescribed drugs. Hamilton depression rating scale was used to measure the patient's depressive stage. They were screened for possible ADRs. The causality and severity assessment of the observed ADRs was done by the WHO-UMC scale and Hartwig-Seigel scale respectively. Statistical analysis was done for all relevant data. Results: In our study, the age of patients varies from 18 years to 85 years. The maximum number of patients were from the age group of 31-40 years [28.57% (N=16)]. The 50% (N=28) of patients were diagnosed with Depressive mood disorder. A total of 169 drugs were prescribed out of which 52.07% (N=88) were Antidepressant drugs. Out of 88 Antidepressant drugs, 20% (N=18) patients received Venlafaxine, followed by 17% (N=15) Escitalopram. Out of 56, 26.78% (N=15) showed low adherence, 41.07% (N=23) showed medium adherence and 32.14% (N=18) showed High adherence.41.07% (N=23) patients were identified with drug use problems. Adverse drug reactions were suspected in 25% (N=14) patients. The most common type of Adverse reaction due to the drug was Weight gain (N=6 patients). Paroxetine drug was found with the highest number of ADRs 28.57% (N=4). Conclusion: Most common antidepressant prescribed was Venlafaxine. Most Patients in the community included suffered from Depressive mood disorder with a maximum number of patients appeared from the age group of the thirties to forties. Patients due to their unstable mental status were adhering to therapy at medium levels. Drug use problem was identified commonly with patients on sedatives resulting them to either forget taking the pills or missing the dose. Patients generally had a common Adverse drug reaction of weight gain. Proper lifestyle modifications and patient counselling is required to benefit patient from treatment.

Identifying biomarkers of antidepressant response may advance personalized treatment of major depressive disorder (MDD). We aimed to identify longitudinal changes in gene expression associated with response to antidepressants in a sample of MDD patients treated with escitalopram. Patients (N = 153) from the CAN-BIND-1 cohort were treated for 8 weeks, and depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale at 0, 2, 4, 6, and 8 weeks. We identified three groups of patients according to response status: early responders (22.9%), later responders (32.0%), and nonresponders (45.1%). RNA sequencing was performed in blood obtained at weeks 0, 2, and 8. RNA expression was modeled using growth models, and differences in the longitudinal changes in expression according to response were investigated using multiple regression models. The expression of RNAs related to response was investigated in the brains of depressed individuals, as well as in neuronal cells in vitro. We identified four RNAs (CERCAM, DARS-AS1, FAM228B, HBEGF) whose change over time was independently associated with a response status. For all except HBEGF, responders showed higher expression over time, compared to nonresponders. While the change in all RNAs differentiated early responders from nonresponders, changes in DARS-AS1 and HBEGF also differentiated later responders from nonresponders. Additionally, HBEGF was downregulated in the brains of depressed individuals, and increased in response to escitalopram treatment in vitro. In conclusion, using longitudinal assessments of gene expression, we provide insights into biological processes involved in the intermediate stages of escitalopram response, highlighting several genes with potential utility as biomarkers of antidepressant response.

Depression is the most prevalent psychiatric disorder in the world, affecting 4.4% of the global population. Despite an array of treatment modalities, depressive disorders remain difficult to manage due to many factors. Beginning with the introduction of fluoxetine to the United States in 1988, selective serotonin reuptake inhibitors (SSRIs) quickly became a mainstay of treatment for a variety of psychiatric disorders. The primary mechanism of action of SSRIs is to inhibit presynaptic reuptake of serotonin at the serotonin transporter, subsequently increasing serotonin at the postsynaptic membrane in the serotonergic synapse. The six major SSRIs that are marketed in the USA today, fluoxetine, citalopram, escitalopram, paroxetine, sertraline, and fluvoxamine, are a group of structurally unrelated molecules that share a similar mechanism of action. While their primary mechanism of action is similar, each SSRI has unique pharmacokinetics, pharmacodynamics, and side effect profile. One of the more controversial adverse effects of SSRIs is the black box warning for increased risk of suicidality in children and young adults aged 18–24. There is a lack of understanding of the complexities and interactions between SSRIs in the developing brain of a young person with depression. Adults, who do not have certain risk factors, which could be confounding factors, do not seem to carry this increased risk of suicidality. Ultimately, when prescribing SSRIs to any patient, a risk–benefit analysis must factor in the potential treatment effects, adverse effects, and dangers of the illness to be treated. The aim of this review is to educate clinicians on potential adverse effects of SSRIs.