Selective Serotonin Reuptake Inhibitors Sertraline Research Articles

The selective serotonin reuptake inhibitor sertraline alters learning from aversive reinforcements in patients with depression: evidence from a randomized controlled trial

The selective serotonin reuptake inhibitor sertraline alters learning from aversive reinforcements in patients with depression: evidence from a randomized controlled trial

Integrated physio-biochemical and transcriptomic analysis reveals the joint toxicity mechanisms of two typical antidepressants fluoxetine and sertraline on Microcystis aeruginosa

Selective serotonin reuptake inhibitor (SSRI) antidepressants are of increasing concern worldwide due to their ubiquitous occurrence and detrimental effects on aquatic organisms. However, little is known regarding their effects on the dominant bloom-forming cyanobacterium, Microcystis aeruginosa. Here, we investigated the individual and joint effects of two typical SSRIs fluoxetine (FLX) and sertraline (SER) on M. aeruginosa at physio-biochemical and molecular levels. Results showed that FLX and SER had strong growth inhibitory effects on M. aeruginosa with the 96-h median effect concentrations (EC50s) of 362 and 225 μg/L, respectively. Besides, the mixtures showed an additive effect on microalgal growth. Meanwhile, both individual SSRIs and their mixtures can inhibit photosynthetic pigment synthesis, cause oxidative damage, destroy cell membrane, and promote microcystin−leucine−arginine (MC-LR) synthesis and release. Moreover, the mixtures enhanced the damage to photosynthesis, antioxidant system, and cell membrane and facilitated MC-LR synthesis and release compared to individuals. Furthermore, transcriptomic analysis revealed that the dysregulation of the key genes related to transport, photosystem, protein synthesis, and non-ribosomal peptide structures was the fundamental molecular mechanism underlying the physio-biochemical responses of M. aeruginosa. These findings provide a better understanding of the toxicity mechanisms of SSRIs to microalgae and their risks to aquatic ecosystems.

The Effect of Anti-Depressants on Dental Implant Failure: A Systematic Review and Meta-Analysis.

The aim of this systematic review and meta-analysis is to analyze the risk of dental implant failure for patients who had a history of anti-depressant use. An electronic search was performed up to June 2023 in three databases, including PubMed/MEDLINE, Web of Science and Cochrane Central Register of Controlled Trials with data on comparison of implant failure rate for patients with and without the use of antidepressants were included. Meta-analyses for the risk ratio of implant failure rate at the patient level and implant level were performed. Eleven clinical studies were selected for inclusion in this review. The meta-analyses showed a risk ratio of 2.44 (95% confidence interval= 1.75 to 3.39, p< 0.0001) and 2.44 (95% CI= 1.73 to 3.46, p< 0.0001) for the implant failure at the patient level and implant level, respectively. The comparisons presented a low heterogeneity for the patient-level analysis and a moderate heterogeneity for the implant-level analysis among the pooled studies. Subgroup analyses also revealed that patients who received only selective serotonin reuptake inhibitors (SSRIs) or SSRIs with other type of anti-depressants had a higher risk of implant failure than those who were not on any anti-depressants. The current review demonstrates the use of anti-depressants, such as SSRIs, may increase the risk of dental implant failure at both patient level and implant level. Although limited evidence suggests that a certain type of SSRI (sertraline) may have more influence on implant failure than other SSRIs, future studies are needed to warrant this finding.

Research Report: A Link between Sertraline Treatment and Susceptibility to (Mis)information.

Recent research revealed that several psycho-cognitive processes, such as insensitivity to positive and negative feedback, cognitive rigidity, pessimistic judgment bias, and anxiety, are involved in susceptibility to fake news. All of these processes have been previously associated with depressive disorder and are sensitive to serotoninergic manipulations. In the current study, a link between chronic treatment with the selective serotonin reuptake inhibitor (SSRI) sertraline and susceptibility to true and fake news was examined. Herein, a sample of 1162 participants was recruited via Prolific Academic for an online study. Half of the sample reported taking sertraline (Zoloft) for at least 8 weeks (sertraline group), and the other half confirmed not taking any psychiatric medication (control group). The sertraline group was further divided according to their daily dosage (50, 100, 150, and 200 mg/day). All participants completed a susceptibility to misinformation scale, wherein they were asked to determine the veracity of the presented true and fake news and their willingness to behaviorally engage with the news. The results were compared between those of the sertraline groups and the control group. The results showed that sertraline groups did not differ significantly in the assessment of the truthfulness of information or their ability to discern the truth. However, those taking sertraline appeared to have a significantly increased likelihood of behavioral engagement with the information, and this effect was observed for both true and fake news. The research presented here represents the initial endeavor to comprehend the neurochemical foundation of the susceptibility to misinformation. The association between sertraline treatment and increased behavioral engagement with information observed in this study can be explained in light of previous studies showing positive correlations between serotonin (5-HT) system activity and the inclination to engage in social behaviors. It can also be attributed to the anxiolytic effects of sertraline treatment, which mitigate the fear of social judgment. The heightened behavioral engagement with information in people taking sertraline may, as part of a general phenomenon, also shape their interactions with fake news. Future longitudinal studies should reveal the specificity and exact causality of these interactions.

Post-Stroke Depression in Older Adults: An Overview.

Detailed data on post-stroke depression (PSD) in older adults are limited in spite of the high vulnerability of this population to stroke. In fact, PSD prevalence in older adults ranges from 16.0 to 43.9%; however, timing and instruments of evaluation often differ significantly across all available studies. The etiology, genetic and inflammatory factors, as well as structural brain alterations, are claimed as part of a multifaceted mechanism of action in PSD onset. Thus, the aim of this narrative review was to further elaborate on the prevalence, etiology, diagnosis, consequences and treatment of PSD in older adults. The consequences of PSD in older adults may be devastating, including a poor functional outcome after rehabilitation and lower medication adherence. In addition, lower quality of life and reduced social participation, higher risk of new stroke, rehospitalization, and mortality have been reported. In this scenario, treating PSD represents a crucial step to prevent these complications. Both pharmacological and non-pharmacological therapies are currently available. The pharmacological treatment utilizes antidepressant drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TAs) and new multimodal antidepressants (NMAs). Non-pharmacological therapies include psychological interventions and non-invasive brain stimulation techniques, while excluding drug administration. In the general population experiencing PSD, SSRIs (sertraline in particular) are the most prescribed, whereas the combination of antidepressants and psychotherapy is underused. Furthermore, about one-third of patients do not receive treatment for PSD. In regard to older adults with PSD, the possibility of more adverse effects or contraindications to antidepressant prescription due to comorbidities may limit the therapeutic window. Although drugs such as citalopram, escitalopram, sertraline, venlafaxine, and vortioxetine are usually well tolerated by older patients with PSD, the few randomized controlled trials (RCTs) specifically considering older adults with PSD have been conducted with fluoxetine, fluvoxamine, reboxetine, citalopram and nortriptyline, often with very small patient samples. Furthermore, data regarding the results of non-pharmacological therapies are scarce. High-quality RCTs recruiting large samples of older adults are needed in order to better manage PSD in this population. In addition, adequate screening and diagnosis instruments, with reliable timing of evaluation, should be applied.

GABAergic neuroactive steroid response to sertraline in premenstrual dysphoric disorder

RationalePremenstrual dysphoric disorder (PMDD) affects approximately 5% of menstruating individuals, with significant negative mood symptoms in the luteal phase of the menstrual cycle. PMDD’s pathophysiology and treatment mechanisms are poorly characterized, but may involve altered neuroactive steroid function in the brain. Selective serotonin reuptake inhibitors (SSRIs), a first-line PMDD treatment, reportedly alter gamma-aminobutyric acid (GABA)ergic neuroactive steroid levels in PMDD. AimsThe aims of this study were to determine whether the SSRI sertraline increased serum levels of neuroactive steroids that modulate the effect of GABA at GABA-A receptors (GABAAR) and if so, whether an increase was associated with improvement in PMDD symptoms. MethodsParticipants included controls and individuals with PMDD. Serum levels of 9 neuroactive steroids were measured (3α,5α-THP; 3α5β-THP; pregnenolone; 3α,5α-androsterone; 3α,5β-androsterone; 3α,5α-A-diol; 3α5β-A-diol; 3α,5α-THDOC; 3α5β-THDOC) in the follicular and luteal phases. In the subsequent luteal phase, neuroactive steroids were measured during sertraline treatment (50 mg sertraline from approximate ovulation to menses onset) in the PMDD group. Mixed models assessed associations among diagnostic group, menstrual cycle phase, and sertraline treatment. ResultsParticipants included 38 controls and 32 women with PMDD. There were no significant differences in neuroactive steroid levels between controls and participants with PMDD in the luteal phase (p > 0.05). Within the PMDD group, sertraline treatment significantly increased serum pregnanolone levels and the pregnanolone:progesterone ratio, and decreased 3α,5α-androsterone. ConclusionsThis was the first study to assess the impact of SSRI treatment on peripheral levels of GABAergic neuroactive steroids in PMDD. Within the PMDD group, sertraline treatment was associated with a significant increase in luteal phase serum pregnanolone levels and a significantly increased pregnanolone:progesterone ratio, a novel finding. Future research should examine alterations in the metabolic pathways among GABAergic neuroactive steroids in individuals with PMDD, in a placebo-controlled design.

Development and validation of RP-HPLC method for quantification of sertraline in nanofiber formulation

A selective serotonin reuptake inhibitor (SSRI) sertraline (SER) is one of the most often prescribed medications for the treatment of depression. The current study was aimed to develop a new, reliable, simple, and reproducible method for the estimation of SER in nanofiber formulation. The RP-HPLC method selected for estimation and validation was developed by choosing a mobile phase phosphoric acid (0.5%) and acetonitrile at the ratio 45: 55 %v/v, with a flow rate of 1 mL/min at a temperature of 30 ℃. The linearity of the solution was detected at 274 nm within the concentration range from 20 -120 µg/mL with a correlation value (R2) of 0.999 indicating a very strong relationship between dependent and independent variables suggesting the accuracy of the method selected. The concentration of SER in nanofibers was determined by the currently developed method. Validation parameters were used to evaluate, specificity, linearity, sensitivity, accuracy, precision, and ruggedness. About 98-102 (%v/v) of SER was found to be within standard limits and compliant with the standards set by the International Council of Harmonization (ICH) demonstrating the accuracy of the method used. An ICH Q2 (R1) guideline gives guidance on validation for analytical techniques. The RP-HPLC method developed can be used effectively for the analysis of various pharmaceutical dosage forms containing SER.

The serotonin transporter sustains human brown adipose tissue thermogenesis

Activation of brown adipose tissue (BAT) in humans is a strategy to treat obesity and metabolic disease. Here we show that the serotonin transporter (SERT), encoded by SLC6A4, prevents serotonin-mediated suppression of human BAT function. RNA sequencing of human primary brown and white adipocytes shows that SLC6A4 is highly expressed in human, but not murine, brown adipocytes and BAT. Serotonin decreases uncoupled respiration and reduces uncoupling protein 1 via the 5-HT2B receptor. SERT inhibition by the selective serotonin reuptake inhibitor (SSRI) sertraline prevents uptake of extracellular serotonin, thereby potentiating serotonin’s suppressive effect on brown adipocytes. Furthermore, we see that sertraline reduces BAT activation in healthy volunteers, and SSRI-treated patients demonstrate no 18F-fluorodeoxyglucose uptake by BAT at room temperature, unlike matched controls. Inhibition of BAT thermogenesis may contribute to SSRI-induced weight gain and metabolic dysfunction, and reducing peripheral serotonin action may be an approach to treat obesity and metabolic disease.

A systematic review and meta-analysis on the efficacy outcomes of selective serotonin reuptake inhibitors in depression in Alzheimer’s disease

BackgroundDepressive symptoms are the most common neuropsychiatric symptoms in patients with Alzheimer’s disease (AD). However, despite being common, no definite consensus recommendations exist for the management of depression in AD.ObjectiveTo assess the effects of selective serotonin reuptake inhibitors (SSRIs) on the alleviation of depressive symptoms in patients with AD.Material and methodsMedline, Scopus, Web of Science, Google Scholar, and PsychINFO were electronically searched from inception until October 2022. Response to therapy and mean depression scores between the treatment (or before) and placebo (or after) groups were the primary outcomes. For depression scores, the standard mean deviation and accompanying 95% confidence interval were determined. The risk of bias was determined using the funnel plot, trim and fill, Egger’s and Begg’s analyses.ResultsSSRIs attenuated depressive symptoms in patients with AD (0.905 SMD, 95%CI, 0.689 to 1.121, p < 0.000). At individual SSRI level, escitalopram, paroxetine, and sertraline significantly alleviated depressive symptoms in AD patients (0.813 SMD, 95%CI, 0.207 to 1.419, p = 0.009, 1.244 SMD, 95%CI, 0.939 to 1.548, p < 0.000, and 0.818 SMD, 95%CI, 0.274 to 1.362, p < 0.000). The funnel plot, trim and fill, Begg’s test (p = 0.052), and Egger’s test (p = 0.148), showed no significant risk of publication bias.ConclusionOur meta-analysis supports the use of SSRIs for the alleviation of depression in patients with AD. However, we recommend larger randomized clinical trials that would compare the efficacy of different SSRIs in AD patients with depression.

Lower sertraline plasma concentration in patients co-medicated with clozapine-Implications for pharmacological augmentation strategies in schizophrenia.

Augmentation of antipsychotic treatment with antidepressants represents a common and beneficial treatment strategy in patients suffering from schizophrenia. Combining clozapine and the selective serotonin reuptake inhibitor (SSRI) sertraline represents a clinically important strategy in patients with therapy-resistant schizophrenia, but there is limited knowledge about mutual pharmacokinetic interactions. In the present study, we assessed the impact of clozapine on sertraline plasma concentrations. Based on a therapeutic drug monitoring (TDM) database, sertraline plasma concentrations were compared between two groups: patients receiving a combined treatment with sertraline and clozapine (N= 15) and a matched control group receiving sertraline but no clozapine (N= 17). Group differences with respect to raw and dose-adjusted concentrations were assessed using nonparametric tests. Comedication with clozapine was associated with 67% lower median sertraline plasma concentrations (16 vs. 48 ng/mL; p= .022) and 28% lower median dose-adjusted plasma concentrations (C/D; 0.21 vs. 0.29 (ng/mL)/(mg/day); p= .049) as compared to the control group. Scatter plots revealed a complex relationship between the dosage of clozapine and dose-adjusted sertraline concentrations composed of an initial decrease at clozapine doses below 300 mg, an increase between 300 and 600 mg and a final decrease at 800 mg which was best modeled by a third order polynomial term. Cotreatment with clozapine may lead to reduced sertraline plasma concentrations which may be explained by clozapine-induced gastrointestinal hypo-mobility already present at low doses and cytochrome P450 3A4 inducing properties at high clozapine doses. For this drug combination, clinicians should consider TDM to confirm therapeutically effective plasma concentrations of sertraline.

Rhabdomyolysis in a male adolescent associated with monotherapy of fluvoxamine

Rhabdomyolysis is a syndrome resulting from striated muscular breakdown, which may occur due to drug therapy with agents such as selective serotonin reuptake inhibitors (SSRIs). Although studies have shown that...

Interpersonal psychotherapy versus sertraline for women with posttraumatic stress disorder following recent sexual assault: a randomized clinical trial

ABSTRACT Background: Sexual assault often triggers posttraumatic stress disorder (PTSD), a potentially chronic severe mental disorder. Most guidelines recommend selective serotonin reuptake inhibitors (SSRIs) and trauma-focused psychotherapies as treatment options. Interpersonal Psychotherapy (IPT), adapted for PTSD (IPT-PTSD), focuses on interpersonal consequences of trauma rather than confronting the trauma itself. Studies have found IPT-PTSD efficaciously reduced PTSD symptoms with limited attrition. No efficacy trials have compared IPT-PTSD and SSRI. We hypothesized IPT would reduce PTSD, anxiety, and depressive symptoms more than sertraline among women with PTSD following a recent sexual assault. Objectives: To compare the efficacy of IPT-PTSD to SSRI sertraline in a 14-week randomized clinical trial for women with PTSD following a recent sexual assault. Methods: Seventy-four women with PTSD who had suffered sexual assault in the last six months were randomly assigned to 14 weeks of IPT-PTSD (n = 39) or sertraline (n = 35). Instruments assessed PTSD, anxiety, and depressive symptoms. This randomized clinical trial was conducted in São Paulo, Brazil, using the Clinician-Administered PTSD Scale-5 (CAPS-5) as the primary outcome measure. Results: Both treatments significantly reduced PTSD, anxiety, and depressive symptoms, without between-group outcome differences. CAPS-5 mean decreased from 42.5 (SD = 9.4) to 27.1 (SD = 15.9) with sertraline and from 42.6 (SD = 9.1) to 29.1 (SD = 15.5) with IPT-PTSD. Attrition was high in both arms (p = .40). Conclusions: This trial showed within-group improvements without differences between IPT-PTSD and sertraline treatment of PTSD. Our findings suggest that non-exposure-based psychotherapies may benefit patients with PTSD, although we did not directly compare these treatments to an exposure therapy. Brazilian Clinical Trials Registry RBR-3z474z.

Risks of Digestive System Side-Effects of Selective Serotonin Reuptake Inhibitors in Patients with Depression: A Network Meta-Analysis.

PurposeSelective serotonin reuptake inhibitors (SSRIs) are the preferred treatments for depression. The most common adverse drug reactions are symptoms involving the digestive system, leading to low compliance in patients with depression. Therefore, it is important to assess the safety of SSRIs with respect to the digestive system. Several meta-analyses have compared the risks of digestive side effects of SSRIs and other antidepressants. We aimed to compare the risks of various SSRIs (fluoxetine, escitalopram, citalopram, paroxetine, and sertraline) for adverse reactions of the digestive system.MethodsSystematic searches returned 30 randomized controlled trials (n = 5004) of five antidepressants and placebos.ResultsFluoxetine had the lowest probability of digestive side effects, ranking fifth at 0.548. Sertraline had the highest probability of digestive side effects, with a probability of 0.611. For gastrointestinal tolerability, escitalopram was better than paroxetine (odds ratio [OR] =0.62, 95% confidence interval [CI] 0.43–0.87) and sertraline (OR=0.56, 95% CI 0.32–0.99).ConclusionFluoxetine exhibited distinct advantages compared to other SSRIs, while sertraline had the greatest likelihood of digestive system side effects. These findings will help doctors understand the relative advantages of various antidepressants.

Hypersensitivity of Zebrafish htr2b Mutant Embryos to Sertraline Indicates a Role for Serotonin Signaling in Cardiac Development.

Selective serotonin reuptake inhibitors (SSRIs) are antidepressants prescribed in 10% of pregnancies in the United States. Maternal use of SSRIs has been linked to an elevated rate of congenital heart defects, but the exact mechanism of pathogenesis is unknown. Previously, we have shown a decrease in cardiomyocyte proliferation, left ventricle size, and reduced cardiac expression of the serotonin receptor 5-HT 2B in offspring of mice exposed to the SSRI sertraline during pregnancy, relative to offspring of untreated mice. These results suggest that disruption of serotonin signaling leads to heart defects. Supporting this conclusion, we show here that zebrafish embryos exposed to sertraline develop with a smaller ventricle, reduced cardiomyocyte number, and lower cardiac expression of htr2b relative to untreated embryos. Moreover, zebrafish embryos homozygous for a nonsense mutation of htr2b ( htr2bsa16649 ) were sensitized to sertraline treatment relative to wild-type embryos. Specifically, the ventricle area was reduced in the homozygous htr2b mutants treated with sertraline compared with wild-type embryos treated with sertraline and homozygous htr2b mutants treated with vehicle control. Whereas long-term effects on left ventricle shortening fraction and stroke volume were observed by echocardiography in adult mice exposed to sertraline in utero, echocardiograms of adult zebrafish exposed to sertraline as embryos were normal. These results implicate the 5-HT 2B receptor functions in heart development and suggest zebrafish are a relevant animal model that can be used to investigate the connection between maternal SSRI use and elevated risk of congenital heart defects.

Impact of chosen cutoff on response rate differences between selective serotonin reuptake inhibitors and placebo

Response defined as a 50% reduction in the sum score of the Hamilton Depression Rating Scale (HDRS-17-sum) is often used to assess the efficacy of antidepressants. Critics have, however, argued that dichotomising ratings with a cutoff close to the median may lead to scores clustering on either side, the result being inflation of miniscule drug-placebo differences. Using pooled patient-level data sets from trials of three selective serotonin reuptake inhibitors (SSRIs) (citalopram, paroxetine and sertraline) (n = 7909), and from similar trials of duloxetine (n = 3478), we thus assessed the impact of different cutoffs on response rates. Response criteria were based on (i) HDRS-17-sum, (ii) the sum score of the HDRS-6 subscale (HDRS-6-sum) and (iii) the depressed mood item. The separation between SSRI and placebo with respect to response rates increased when HDRS-17-sum was replaced by HDRS-6-sum or depressed mood as effect parameter and was markedly dependent on SSRI dose. With the exception of extreme cutoff values, differences in response rates were largely similar regardless of where the cutoff was placed, and also not markedly changed by the exclusion of subjects close to the selected cutoff (e.g., ±10%). The observation of similar response rate differences between active drugs and placebo for different cutoffs was corroborated by the analysis of duloxetine data. In conclusion, the suggestion that using a cutoff close to the median when defining response has markedly overestimated the separation between antidepressants and placebo may be discarded.

Association of Selective Serotonin Reuptake Inhibitor Use With Abnormal Physical Movement Patterns as Detected Using a Piezoelectric Accelerometer and Deep Learning in a Nationally Representative Sample of Noninstitutionalized Persons in the US

Selective serotonin reuptake inhibitors (SSRIs) are a common first-line treatment for some psychiatric disorders, including depression and anxiety; although they are generally well tolerated, SSRIs have known adverse effects, including movement problems, sleep disruption, and gastrointestinal problems (eg, nausea and upset stomach). No large-scale studies using naturalistic, longitudinal, objective data have validated physical activity findings, and actigraphy data are well suited to address this task. To evaluate whether differences in physical movement exist among individuals treated with SSRIs compared with control participants and to identify the unique features of the movement of patients treated with SSRIs. This cross-sectional study examines longitudinally collected wearable movement data within a cross-sectional sample of 7162 participants from the 2005-2006 National Health and Nutrition Examination Survey (NHANES), a nationally representative population-based sample of noninstitutionalized persons in the US having both medication information and passive movement data. Statistical analysis was performed from April 1, 2021, to February 1, 2022. The use of SSRIs (sertraline hydrochloride, escitalopram oxalate, fluoxetine hydrochloride, paroxetine hydrochloride, and citalopram hydrobromide), as reported by participants interviewed by NNHANES personnel, was the primary exposure, measured as a binary variable (taking an SSRI vs not taking an SSRI). The primary outcome was the intensity of body movement as recorded by a piezoelectric accelerometer worn on the right hip for more than 1 week. Of the 7162 participants included in the study, the mean (SD) age was 33.7 (22.6) years, 266 (3.7%) were taking an SSRI, 3706 (51.7%) were female, 1934 (27.0%) were Black, 1823 (25.5%) were Mexican American, 210 (2.9%) were other Hispanic, 336 (4.7%) were other or multiracial, and 2859 (39.9%) were White (per the NHANES data collection protocol). A cross-validated, deep learning classifier was constructed that achieved fair performance predicting SSRI use (area under the curve, 0.67 [95% CI, 0.64-0.71] for the validation set and 0.66 [95% CI, 0.64-0.68] for the test set). To account for possible confounding by indication, we constructed a parallel model incorporating depression severity, finding only marginal performance improvement. When averaged across individuals and across 7 days, the results show less overall movement in the SSRI group (mean, 120.1 vertical acceleration counts/min [95% CI, 115.7-124.6 vertical acceleration counts/min]) compared with the non-SSRI control group (mean, 168.8 vertical acceleration counts/min [95% CI, 162.8-174.9 vertical acceleration counts/min]). This cross-sectional study found a moderate association between passive movement and SSRI use, as well as SSRI detection capacity of passive movement using time series deep learning models. The results support the use of passive sensors for exploration and characterization of psychotropic medication adverse effects.

The antidepressant Sertraline inhibits CatSper Ca2+ channels in human sperm.

STUDY QUESTIONDo selective serotonin reuptake inhibitor (SSRI) antidepressants affect the function of human sperm?SUMMARY ANSWERThe SSRI antidepressant Sertraline (e.g. Zoloft) inhibits the sperm-specific Ca2+ channel CatSper and affects human sperm function in vitro.WHAT IS KNOWN ALREADYIn human sperm, CatSper translates changes of the chemical microenvironment into changes of the intracellular Ca2+ concentration ([Ca2+]i) and swimming behavior. CatSper is promiscuously activated by oviductal ligands, but also by synthetic chemicals that might disturb the fertilization process. It is well known that SSRIs have off-target actions on Ca2+, Na+ and K+ channels in somatic cells. Whether SSRIs affect the activity of CatSper is, however, unknown.STUDY DESIGN, SIZE, DURATIONWe studied the action of the seven drugs belonging to the most commonly prescribed class of antidepressants, SSRIs, on resting [Ca2+]i and Ca2+ influx via CatSper in human sperm. The SSRI Sertraline was selected for in-depth analysis of its action on steroid-, prostaglandin-, pH- and voltage-activation of human CatSper. Moreover, the action of Sertraline on sperm acrosomal exocytosis and penetration into viscous media was evaluated.PARTICIPANTS/MATERIALS, SETTING, METHODSThe activity of CatSper was investigated in sperm of healthy volunteers, using kinetic Ca2+ fluorimetry and patch-clamp recordings. Acrosomal exocytosis was investigated using Pisum sativum agglutinin and image cytometry. Sperm penetration in viscous media was evaluated using the Kremer test.MAIN RESULTS AND THE ROLE OF CHANCESeveral SSRIs affected [Ca2+]i and attenuated ligand-induced Ca2+ influx via CatSper. In particular, the SSRI Sertraline almost completely suppressed Ca2+ influx via CatSper. Remarkably, the drug was about four-fold more potent to suppress prostaglandin- versus steroid-induced Ca2+ influx. Sertraline also suppressed alkaline- and voltage-activation of CatSper, indicating that the drug directly inhibits the channel. Finally, Sertraline impaired ligand-induced acrosome reaction and sperm penetration into viscous media.LIMITATIONS, REASONS FOR CAUTIONThis is an in vitro study. Future studies have to assess the physiological relevance in vivo.WIDER IMPLICATIONS OF THE FINDINGSThe off-target action of Sertraline on CatSper in human sperm might impair the fertilization process. In a research setting, Sertraline may be used to selectively inhibit prostaglandin-induced Ca2+ influx.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by the Swiss Centre for Applied Human Toxicology (SCAHT), the Département de l’Instruction Publique of the State of Geneva, the German Research Foundation (CRU326), the Interdisciplinary Center for Clinical Research, Münster (IZKF; Str/014/21), the Innovation Fund Denmark (grant numbers 14-2013-4) and the EDMaRC research grant from the Kirsten and Freddy Johansen’s Foundation. The authors declare that no conflict of interest could be perceived as prejudicing the impartiality of the research reported.TRIAL REGISTRATION NUMBERNA.

O-228 The SSRI antidepressant Sertraline inhibits CatSper calcium channels in human sperm

Abstract Study question Do Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants affect the function of human sperm? Summary answer The SSRI-antidepressant Sertraline (e.g. Zoloft) inhibits the sperm-specific Ca2+ channel CatSper and affects human sperm function in vitro. What is known already In human sperm, CatSper translates changes of the chemical microenvironment into changes of the intracellular Ca2+ concentration ([Ca2+]i) and swimming behavior. CatSper is promiscuously activated by oviductal ligands, but also by synthetic chemicals that might disturb the fertilization process. It is well known that SSRIs have off-target actions on Ca2+, Na+, and K+ channels in somatic cells. Whether SSRIs affect the activity of CatSper is, however, unknown. Study design, size, duration We studied the action of the seven drugs belonging to the most commonly prescribed class of antidepressants, SSRIs, on resting [Ca2+]i and Ca2+ influx via CatSper in human sperm. The SSRI Sertraline was selected for in-depth analysis of its action on steroid-, prostaglandin-, pH-, and voltage-activation of human CatSper. Moreover, the action of Sertraline on sperm acrosomal exocytosis and penetration into viscous media was evaluated. Participants/materials, setting, methods The activity of CatSper was investigated in sperm of healthy volunteers, using kinetic Ca2+ fluorimetry and patch-clamp recordings. Acrosomal exocytosis was investigated using Pisum sativum agglutinin (PSA) and image cytometry. Sperm penetration in viscous media was evaluated using the Kremer test. Main results and the role of chance Four SSRIs increased [Ca2+]i, two out of which also attenuated ligand-induced Ca2+ influx via CatSper. In contrast, Sertraline decreased [Ca2+]i and almost completely suppressed ligand-induced Ca2+ influx via CatSper. Remarkably, the drug was about four-fold more potent to suppress prostaglandin- versus steroid-induced Ca2+ influx. Sertraline also suppressed alkaline- and voltage-activation of CatSper, indicating that the drug directly inhibits human CatSper. Finally, Sertraline suppressed ligand-induced acrosome reaction and sperm penetration into viscous media. Limitations, reasons for caution This is an in vitro study. Future studies have to assess the physiological relevance in vivo. Wider implications of the findings The off-target action of Sertraline on CatSper in human sperm might impair the fertilization process. In a research setting, Sertraline may be used to selectively inhibit prostaglandin-induced Ca2+ influx. Trial registration number CRU326

A cross-sectional study of the relationship between CYP2D6 and CYP2C19 variations and depression symptoms, for women taking SSRIs during pregnancy.

Depression during pregnancy affects 10-15% of women, and 5% of women take antidepressants during pregnancy. Clinical guidelines provide recommendations for selective serotonin reuptake inhibitor (SSRI) drug choice and dose based on CYP2D6 and CYP2C19 genotype; however, they are based on evidence from non-pregnant cohorts. This study aimed to test the hypothesis that women with function-altering variants (increased, decreased, or no function) in these pharmacogenes, taking SSRIs prenatally, would have more depression symptoms than women whose pharmacogenetic variants are associated with normal SSRI metabolism. Comprehensive CYP2D6 and CYP2C19 genotyping using a range of methods, including gene copy number analysis, was performed as secondary analyses on two longitudinal cohorts of pregnant women (N= 83) taking the SSRIs paroxetine, citalopram, escitalopram, or sertraline. The Kruskal-Wallis test compared mean depression scores across four predicted metabolizer groups: poor (n= 5), intermediate (n= 10), normal (n= 53), and ultrarapid (n= 15). There were no significant differences between mean depression scores across the four metabolizer groups (H(3) = .73, p= .87, eta-squared = .029, epsilon-squared = .0089). This is the first study of the relationship in pregnancy between CYP2C19 pharmacogenetic variations and depression symptoms in the context of SSRI use. Findings from this initial study do not support the clinical use of pharmacogenetic testing for SSRI use during the second or third trimesters of pregnancy, but these findings should be confirmed in larger cohorts. There is an urgent need for further research to clarify the utility of pharmacogenetic testing for pregnant women, especially as companies offering direct-to-consumer genetic testing expand their marketing efforts.

Gender approach to psychotherapeutic correction in complex treatment of depressive disorders

The importance and necessity of studying the gender specificity of mental disorders has been repeatedly emphasized. Significant differences in the mechanisms of formation of depressive disorders in men and women determine the specificity of clinical-psychopathological and pathopsychological manifestations and determine the need for the use of differentiated therapeutic and diagnostic approaches. 147 patients with depressive disorders (76 female and 71 male) were examined. Clinical-psychopathological, psychodiagnostic and catamnetic research methods were used. Based on the data obtained during the work, a personalized system of therapy for depressive disorders with differentiated use of psychopharmacotherapy, psychotherapy and psychoeducation methods was developed and tested. As a result of the study, we concluded that for the treatment of patients with a depressive episode, a program should be used, which includes: pharmacotherapy (selective serotonin reuptake inhibitor Sertraline, melatoninergic antidepressant Agomelatine, anxiolytics), gender-specific individual and group psychotherapy and psychoeducation. For the treatment of patients with recurrent depressive disorder, a program should be used, which includes: pharmacotherapy (anxiolytics, combined serotonin and norepinephrine reuptake inhibitors (Mirtazapine, Venlafaxine)), gender-specific individual and group psychotherapy and psychoeducation. For the treatment of patients with a depressive episode of bipolar affective disorder, a program should be used, which includes: pharmacotherapy (using valproate, Lamotrigine, selective serotonin reuptake inhibitor Sertraline); gender-specific individual and group psychotherapy and psychoeducation. Keywords: depressive disorders, gender differences, psychotherapy, psychoeducation, treatment.