Selective Serotonin Reuptake Inhibitor Drugs Research Articles

Prevalence of Parasomnias and Restless Leg Syndrome in Patients taking Psychotropic Medications (Antidepressants and Antipsychotics): A Cross-Sectional Hospital-based Study

Prevalence of Parasomnias and Restless Leg Syndrome in Patients taking Psychotropic Medications (Antidepressants and Antipsychotics): A Cross-Sectional Hospital-based Study

(075) Practice Patterns of Sexual Medicine Experts Towards Postorgasmic Illness Syndrome

Abstract Introduction POIS is a rare, but debilitating cluster of symptoms, occurring after ejaculation with unknown mechanism. Unfortunately, limited information is available on POIS diagnosis, treatment, and disease management Objective To investigate the practice patterns of sexual medicine experts towards POIS Methods Worldwide sexual medicine experts were invited to participate anonymously in an online, open survey using SurveyMonkey. Results 211 sexual medicine experts filled the survey. The mean age of the participants was 45.4 years. The majority of the participants were urologists (83.9%). Most of the participants (53.5%) considered POIS to be an important sexual dysfunction that should be treated. Most participants stated that the available information about POIS was inadequate for both patients and physicians (65.9% and 66.3%, respectively). 47.9% of the participants stated psychological disorder, 46.4% stated bio-psycho-social reasons, 41.2% stated a transient deregulation of the autonomic nervous system, and 39.8% stated autoimmune or allergic type reaction for the responsibility for the pathophysiology of POIS. 56.4% of the participants stated that they would refer the patient for psychotherapy/sexual therapy to a sexologist, 41.7% would prefer antihistamine drugs to manage symptoms, and 38.4% would prefer Selective Serotonin Reuptake Inhibitor (SSRI) drugs for treatment of POIS. Conclusions This survey study among sexual medicine experts from different parts of the world has developed representative estimates of knowledge, attitudes and practice patterns regarding POIS worldwide. Furthermore, sexual medicine experts stated that there is not adequate information available about POIS for physicians and patients. Disclosure No.

Dose of selective serotonin reuptake inhibitors and risk of upper gastrointestinal bleeding in older adults.

Selective serotonin reuptake inhibitors (SSRIs) have been associated with an increased risk of upper gastrointestinal bleeding (UGIB) in older patients but little is known about the risk associated with individual SSRI drugs and doses. To quantify the risk of UGIB in relation to individual SSRI use in older adults. We conducted a nested case-control study within a cohort of 9565 patients aged ⩾65 years prescribed SSRIs from 2000 to 2013 using claims data of universal health insurance in Taiwan. Incident cases of UGIB during the follow-up period were identified and matched with three control subjects. Conditional logistic regression was used to estimate the odds ratio (OR) of UGIB associated with individual SSRI use and cumulative dose. UGIB risk increased with the increasing cumulative doses of SSRIs (adjusted OR: 1.28, 95% confidence interval (CI): 1.02-1.62 for the highest vs. the lowest tertile). Compared with users of other SSRIs, fluoxetine users were at an increased risk of UGIB (adjusted OR: 1.25, 95% CI: 1.03-1.50) with a dose-response manner, whereas paroxetine users had 29% decreased odds (95% CI: 0.56-0.91). The increased risk was only observed among current fluoxetine users. Fluoxetine therapy was associated with an increased risk of UGIB in a dose-response manner among older adults.

SSRIs in the course of COVID-19 pneumonia: Evidence of effectiveness of antidepressants on acute inflammation. Aretrospective study.

Relationships between inflammation and mood have been observed in terms of pro-inflammatory effects induced by depressive conditions and, in parallel, by an antidepressant-induced favorable effect on the recovery of inflammatory states. Selective serotonin reuptake inhibitor (SSRI) drugs were hypothesized to improve the prognosis of COVID-19 pneumonia, a typical acute inflammation, in terms of decreased mortality rate and pro-inflammatory cytokine serum levels. The medical records of COVID-19 pneumonia inpatients at Careggi University Hospital (Florence) were analyzed for prognosis and Interleukin 6 (IL-6) after admission for over a period of 22months. Medical records of patients treated at admission and not discontinued until discharge with an SSRI or with vortioxetine were identified. Two groups, one treated with antidepressants, the other not treated, were evaluated according to the mentioned parameters. Multiple linear regression and logistic regression were performed. The entire sample composed of 1236 records (recovered patients 77.1%, deceased patients 22.9%). The treated group (n=107) had a better prognosis than the untreated group in spite of age and comorbidity both being greater than in the untreated group. Correspondingly, IL-6 levels in the treated group were significantly lower (p<0.01) than the levels in the untreated group, in every comparison. Outcomes of this study support the hypothesis of the favorable influence of some antidepressants on the prognosis of COVID-19, possibly mediated by IL-6 modulation. Reduction in acute inflammation induced by the action of antidepressants was confirmed.

Cytotoxicity and reversal effect of sertraline, fluoxetine, and citalopram on MRP1- and MRP7-mediated MDR.

Cancer is one of the leading causes of death worldwide, and the development of resistance to chemotherapy drugs is a major challenge in treating malignancies. In recent years, researchers have focused on understanding the mechanisms of multidrug resistance (MDR) in cancer cells and have identified the overexpression of ATP-binding cassette (ABC) transporters, including ABCC1/MRP1 and ABCC10/MRP7, as a key factor in the development of MDR. In this study, we aimed to investigate whether three drugs (sertraline, fluoxetine, and citalopram) from the selective serotonin reuptake inhibitor (SSRI) family, commonly used as antidepressants, could be repurposed as inhibitors of MRP1 and MRP7 transporters and reverse MDR in cancer cells. Using a combination of in silico predictions and in vitro validations, we analyzed the interaction of MRP1 and MRP7 with the drugs and evaluated their ability to hinder cell resistance. We used computational tools to identify and analyze the binding site of these three molecules and determine their binding energy. Subsequently, we conducted experimental assays to assess cell viability when treated with various standard chemotherapies, both with and without the presence of SSRI inhibitors. Our results show that all three SSRI drugs exhibited inhibitory/reversal effects in the presence of chemotherapies on both MRP1-overexpressed cells and MRP7-overexpressed cells, suggesting that these medications have the potential to be repurposed to target MDR in cancer cells. These findings may open the door to using FDA-approved medications in combination therapy protocols to treat highly resistant malignancies and improve the efficacy of chemotherapy treatment. Our research highlights the importance of investigating and repurposing existing drugs to overcome MDR in cancer treatment.

Straightforward paper sensors for the detection of SSRI drugs using tyrosine functionalized GQDs: Fluorescence ‘turn-off’ turns on the crucial dosage monitoring

All socioeconomic classes are impacted by the COVID-19 epidemic, with stress being one of the biggest symptoms causing indigestion, breathlessness, heart disease, obesity, and many more. The most commonly used selective serotonin reuptake inhibitors (SSRIs) drugs include, escitalopram, sertraline, paroxetine, and fluoxetine are provided by doctors. If the medicines are not taken in the recommended dosage, at the correct intervals, which can occasionally be fatal because persons with depression are susceptible to mood fluctuations. There are no appropriate ways to monitor high dosages in clinical laboratories, the requirement for simple, novel material with cutting-edge technology to do so is essential. Herein, we report the application of a single fluorescent probe, Tyrosine-GQDs for the detection of SSRI drugs. Upon addition of SSRI drugs into the Tyrosine-GQDs, the fluorescence emission intensity of Tyrosine-GQDs decreased due to the complex formation through H-bonding which is evidenced by the rise of new peaks in fluorescence spectra and lifetime measurements. The calculated detection limit proves that the designed nanoprobe is highly sensitive and selective towards escitalopram, sertraline, paroxetine, and fluoxetine are 0.13 × 10−6 M, 0.15 × 10−6 M, 0.07 × 10−6 M, and 0.07 × 10−6 M, respectively. A paper-based fluorescent sensor is fabricated using the designed probe which is efficient in the detection of the dosage of SSRI drugs.

A comparative overview of SSRI-sertraline and SNRI-desvenlafaxine

Depression is a mood disorder that causes a persistent feeling of sadness and loss of interest. The common features of all the depressive disorders are sadness, emptiness, or irritable mood, accompanied by somatic and cognitive changes that significantly affect the individual’s capacity to function. Depression is commonly treated in primary care, and SSRI drugs are frequently used as the first line of treatment. Selective Serotonin Reuptake Inhibitors (SSRIs) have the advantage of the ease of dosing and low toxicity in overdose. They are also the first-line medications for late-onset depression. Selective Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs), which include venlafaxine, desvenlafaxine, duloxetine, and levomilnacipran can be used as first-line agents, particularly in patients with significant fatigue or pain syndromes associated with the episode of depression. SNRIs also have an important role as second-line agents in patients who have not responded to SSRIs. The pharmacokinetics, pharmacodynamics, uses, side effects, and contraindications of desvenlafaxine, an SNRI, and sertraline, an SSRI are compared in this article.

Review on Surface-Modified Electrodes for the Enhanced Electrochemical Detection of Selective Serotonin Reuptake Inhibitors (SSRIs).

Selective serotonin re-uptake inhibitors (SSRIs) are one of the most commonly prescribed classes of antidepressants used for the treatment of moderate to severe depressive disorder, personality disorders and various phobias. This class of antidepressants was created with improved margins of safety. However, genetic polymorphism may be responsible for the high variability in patients' responses to treatment, ranging from failure to delayed therapeutic responses to severe adverse effects of treatment. It is crucial that the appropriate amount of SSRI drugs is administered to ensure the optimum therapeutic efficacy and intervention to minimise severe and toxic effects in patients, which may be the result of accidental and deliberate cases of poisoning. Determining SSRI concentration in human fluids and the environment with high sensitivity, specificity and reproducibility, and at a low cost and real-time monitoring, is imperative. Electrochemical sensors with advanced functional materials have drawn the attention of researchers as a result of these advantages over conventional techniques. This review article aims to present functional materials such as polymers, carbon nanomaterials, metal nanomaterials as well as composites for surface modification of electrodes for sensitive detection and quantification of SSRIs, including fluoxetine, citalopram, paroxetine, fluvoxamine and sertraline. Sensor fabrication, sensor/analyte interactions, design rationale and properties of functional material and the electrocatalytic effect of the modified electrode on SSRI detection are discussed.

The anti-depression function of selective serotonin reuptake inhibitor

Depression is one of the world's most serious public health issues. What is worse, the number of people suffering from depression is expanding and shows a younger-age trend. The primary treatment for depression is drug therapy. Selective serotonin reuptake inhibitors (SSRIs), as the second generation of novel antidepressants, are highly recognized antidepressant medicines that are widely utilized in clinical practice and have become first-line drugs for the treatment of depression. This article provides a thorough and detailed introduction to SSRIs. It focuses mostly on the etiology of depression, the specific mechanism of SSRIs, the specific application of SSRIs, and properties of distinct SSRI drugs. This article looks at the superiority and significance of SSRI medicines in the treatment of depression. At the same time, the limitations and shortcomings of SSRI drugs were discussed, and the future development of SSRI drugs was envisaged.

The effect of antidepressants on the severity of COVID-19 in hospitalized patients: A systematic review and meta-analysis.

Clinical Depression and the subsequent low immunity is a comorbidity that can act as a risk factor for the severity of COVID-19 cases. Antidepressants such as Selective serotonin reuptake inhibitor and Serotonin-norepinephrine reuptake inhibitors are associated with immune-modulatory effects, which dismiss inflammatory responses and reduce lung tissue damage. The current systematic review and meta-analysis aims to evaluate the effect of antidepressant drugs on the prognosis and severity of COVID-19 in hospitalized patients. A systematic search was carried out in PubMed/Medline, EMBASE, and Scopus up to June 14, 2022. The following keywords were used: "COVID-19", "SARS-CoV-2", "2019-nCoV", "SSRI", "SNRI", "TCA", "MAOI", and "Antidepressant". A fixed or random-effect model assessed the pooled risk ratio (RR) with 95% CI. We considered P < 0.05 as statistically significant for publication bias. Data were analyzed by Comprehensive Meta-Analysis software, Version 2.0 (Biostat, Englewood, NJ). Fourteen studies were included in our systematic review. Five of them were experimental with 2350, and nine of them were observational with 290,950 participants. Eight out of fourteen articles revealed the effect of antidepressants on reducing the severity of COVID-19. Selective serotonin reuptake inhibitors drugs, including Fluvoxamine, Escitalopram, Fluoxetine, and Paroxetine, and among the Serotonin-norepinephrine inhibitors medications Venlafaxine, are reasonably associated with reduced risk of intubation or death. Five studies showed no significant effect, and only one high risk of bias article showed the negative effect of antidepressants on the prognosis of Covid-19. The meta-analysis of clinical trials showed that fluvoxamine could significantly decrease the severity outcomes of COVID-19 (RR: 0.763; 95% CI: 0.602-0.966, I2: 0.0). Most evidence supports that the use of antidepressant medications, mainly Fluvoxamine, may decrease the severity and improve the outcome in hospitalized patients with SARS-CoV-2. Some studies showed contradictory findings regarding the effects of antidepressants on the severity of COVID-19. Further clinical trials should be conducted to clarify the effects of antidepressants on the severity of COVID-19.

Influence of selective serotonin reuptake inhibitors (SSRIs) in the development of bruxism

ABSTRACT Objective To identify the relationship between the use of selective serotonin reuptake inhibitors (SSRIs) as pharmacological treatment and the development of bruxism. Methods A systematic literature search was performed in PubMed and Scopus databases, which included articles written within the last 30 years. The working hypothesis was that there is a significant association between using SSRIs as an antidepressant medication and developing bruxism. Results A total of four articles were included in the systematic review. All the articles are related to SSRI antidepressants and bruxism. Conclusion The results indicate that there is an apparent association between SSRI drug treatment and the development of bruxism. The methods of evaluation and analysis were different in each article and cannot be considered conclusive; however, there is sufficient information to elucidate the impact of SSRI drugs on the development of bruxism.

The Impact of SSRI Use on the Clinical Outcome and Prognosis of COVID-19 Patients: A Single-Center Prospective Study

Background: Recent studies have found a link between the usage of selective serotonin reuptake inhibitors (SSRIs) and a lower mortality rate in COVID-19 cases. Objective: The goal of current research was evaluating the effectiveness of SSRI drugs on improvement of COVID-19 patients. Methods: This prospective case-control study, compared SSRI-treated patients with matched control patients not treated with SSRIs at Masih Daneshvari Hospital on a population of 350 patients diagnosed with COVID-19 from March 15th 2021 to March 16th 2022. Results: ICU admission rates were significantly more in the control group than in the case group (44.8% vs. 25.9%; p-value=0.0002; Odds Ratio (OR)= 2.32). Intubation was reported for more cases in the control group than the case group (26.7% vs. 11.4%; p-value=0.0002; OR=2.84). Mortality rate was found to be significantly more in the control group than the case group (23.0% vs. 10.8%; p-value=0.0002; OR=2.46). Furthermore, the subgroup analyses on Fluvoxamine and Sertraline showed that Hospitalization period, ICU admission rates, and intubation were all reported to be significantly smaller in each case subgroups as against the control group. Conclusion: Our assessments underlined the potential efficacy of SSRIs in improving COVID-19 patients’ prognosis, since the use of SSRIs were shown to be associated with shorter hospital stay and ICU stay, lower ICU admission rates and intubation rates, and ultimately decreased mortality rates.

Therapeutic potential of selective serotonin reuptake inhibitor and anti-inflammatory COX-2 inhibitors drugs for epilepsy

Epilepsy is a neurological disease caused by disturbances in the electrical propagation between neurons, which causes great damage to patients' lives, and can even lead to death. There are several proposals to understand its biochemical functioning, so current pharmacological treatments are based on the interruption of electrical conduction or modulation of neurotransmitters, such as phenobarbital and phenytoin. Thus, the present work aims to analyze the therapeutic potential of drugs such as COX-2 inhibitors and selective serotonin reuptake inhibitors (SSRIs) in the control of epilepsy. Thus, a narrative review of the literature was carried out using the “PubMed” database in order to find the theoretical bases and experimental works that demonstrate the mechanism of such drugs. The work concludes that SSRIs and COX-2 inhibitors have several mechanisms that can theoretically treat epilepsy, this is due to the establishment of a higher concentration of the neurotransmitter serotonin, as well as a reduction in the formation of quinolinic acid, which is a potential neurotoxic agent. which contributes to epileptogenesis.

Severe Pulmonary Stenosis in a Newborn with Antenatal Exposure to Selective Serotonin Reuptake Inhibitor Drug: A Case Report

Depression in pregnancy is being recognized as a major contributor to adverse maternal and fetal outcomes. Recent years have seen significant research focused on the development of safe pharmacological methods to treat depression in pregnancy, resulting in the common use of selective serotonin reuptake inhibitors (SSRIs) as a first line of treatment. There have been a few reports of congenital birth defects associated with the consumption of SSRIs during pregnancy, particularly congenital heart defects. Several studies have attempted to evaluate the relationship between SSRI use and congenital heart defects in neonates, but they were inconclusive. In this report, a case where maternal SSRI intake during two consecutive pregnancies was associated with neonatal pulmonary valve stenosis, raising the possibility of a correlation between the usage of a certain SSRI, and a particular congenital heart defect has been described. Keywords: Congenital heart defects, Depression, Pregnancy, Pulmonary valve stenosis, Serotonin uptake inhibitors

A randomized clinical trial: Comparison of group acceptance and commitment therapy with drug on quality of life and depression in patients with obsessive-compulsive disorder.

Background:Acceptance and commitment therapy (ACT) is one of the newest treatment strategies that has been developed rapidly to improve the treatment of patients with obsessive–compulsive disorder (OCD). The aim of this study was to evaluate and compare the effect of ACT and selective serotonin reuptake inhibitors (SSRIs) drugs on the severity of depression symptoms and quality of life (QOL) in obsessive–compulsive patients.Materials and Methods:A randomized clinical trial with a control group was conducted including 27 patients with OCD. Based on the Diagnostic and Statistical Manual of Mental Disorders-5 criteria for OCD diagnosis, participants were recruited from Tamasha Counseling Center and obsessive–compulsive clinic in the Psychosomatic Research Center in Isfahan, Iran. Selected patients were allocated to two groups (14 in ACT the group and 13 in the drug group with SSRI with a simple random sampling method. ACT group was treated by an ACT therapist in eight 1-h sessions. Data were collected by the World Health Organization QOL Questionnaire (WHOQOL-BREF) and Depression subscale of DASS-42 at admission, after the intervention, and 3 months thereafter. Therapists and evaluators were blind to each other's work. Data were analyzed using analysis of variance with repeated measures method using IBM SPSS Statistics software (V 23, IBM Corporation, Armonk, NY, USA).Results:Results revealed that both treatments (ACT and SSRIs drug therapy) had significant impacts on reducing depression subscales scores and increasing WHOQOL-BREF scores at posttreatment (P < 0.05). There were no significant differences in QOL scores between the two groups after the intervention and follow-up (P > 0.05). Nevertheless, drug therapy presented a significantly greater improvement in depression scores of patients than those resulting from ACT (P = 0.005). The persistence of treatment effects continued after 3 months (follow-up) in both groups.Conclusion:ACT is equal to SSRIs drug therapy in terms of improving QOL in patients with OCD. However, SSRIs are more effective in treating depression in obsessive–compulsive patients. It may be presumed that ACT without any chemical side effect is equal to drug and is preferred for patients who either cannot use drugs or prefer not to have a drug treatment.

Fluoxetine can make marine organisms unhappy: a study on the sub-lethal effects on marine invertebrates

The environmental effects caused by selective serotonin reuptake inhibitor drugs have been investigated for marine organisms and coastal ecosystems but are scarce in neotropical organisms. This investigation aimed to evaluate the sublethal effects of fluoxetine on the embryonic development of the sea urchin Echinometra lucunter and the survival and swimming behavior of the brine shrimp Artemia sp. The organisms were exposed to four different concentrations of fluoxetine (30, 300, 3000 and 30000 ng L-1) and to a negative control (filtered seawater), following the respective standard testing protocols. We verified a significant reduction of the embryos development to pluteus larvae, starting from 3000 ng L-1 (54.0±10.9% normal larvae), in comparison with the controls (83.5±3.1%). The non-observed effect concentration (NOEC) was estimated at 300 ng L-1, and the lowest observed effect concentration (LOEC) was 3000 ng L-1. In the behavior tests with Artemia sp, no significant adverse effects were reported for mobility, swimming speed and inactivity time. These results show that Fluoxetine can interfere on the development of species like the sea urchin E. lucunter, but short term exposure did not affected the swimming behavior of the brine shrimp Artemia sp. Fluoxetine presents thus a potential to affect marine biota and disrupt the equilibrium of the coastal ecosystems.

Liquid chromatography-tandem mass spectrometric method for trace quantification of ethyl methanesulfonate: a genotoxic impurity in dapoxetine hydrochloride

BackgroundDapoxetine hydrochloride is a selective serotonin reuptake inhibitor drug for treating premature ejaculation. This study was designed to develop and validate a sensitive and selective LC–MS/MS method for trace analysis of genotoxic impurity ethyl methanesulfonate in Dapoxetine hydrochloride.ResultsChromatographic separation was achieved on the Shodex RSpak DS-413 column, 150 × 4.6 mm, 3.0 µm using eluent containing a equal volumes of acetonitrile and 0.1% v/v formic acid in water was used in the isocratic elution mode at a pump flow of 1.0 mL/min. No interference was observed at the retention time of ethyl methanesulfonate, indicating that the developed method is specific and selective for trace level quantification.The developed method was found to be linear in the concentration range of 1–50 ppm with coefficient of regression of 0.9997. Detection limit and quantification limit were determined to be 0.6 ppm and 1.0 ppm respectively. Acceptable RSD values (< 10.0%) and recovery results (> 90%) obtained from the accuracy and precison experiments indicate that the developed method is precise and accurate in the concentration range of 1–50 ppm. Ethyl methanesulfonate solutions were stable for two days when stored at room and refrigerated temperatures.ConclusionThe developed method has the ability to quantify ethyl methanesulfonate in dapoxetine hydrochloride. Thus, the anticipated method has high probability to adopt in the quality testing laboratories of pharmaceutical industry.

Influence of clinician gender, age, and geographic work location on the relative rankings of risk factors for biological complications with dental implant therapy

Statement of problemClinician perceptions of risk factors influencing biologic complications with dental implants are poorly understood but are relevant to how clinicians manage conversations with patients seeking dental implant therapy. PurposeThe purpose of this clinician survey was to assess the relative ranking of biologic risk factors with dental implants identified via the history, clinical examination, and clinical decisions and postimplant placement findings. Materials and methodsA 10-item survey instrument was tested, refined, and distributed to past participants of the Future Leaders in Prosthodontics (FLIP) workshop series asking for their opinion on the relative ranking of commonly identified risk factors in the areas of patient history, clinical examination, and clinical decisions and postimplant placement findings. Descriptive statistics and frequency tables were developed to identify age groupings, geographic work location, and gender. Group differences with respect to risk factor rankings were identified by using Kruskal-Wallis H tests, and, if significant, paired comparisons were conducted using the Mann-Whitney U test with adjustments for Type I error (α=.05). ResultsSignificant differences were found by gender, age, and geographic work location. Women viewed “implant placement in site of previous implant loss” (P=.013) and “treated moderate or severe chronic periodontitis” (P=.021) as having significantly greater relative importance than did men, yet men ranked “implant position closer than 1.5 mm from adjacent tooth” (P=.023), “currently using selective serotonin reuptake inhibitor drugs (SSRI)” (P=.001), and “heavy plaque index (PI>50%)” (P=.023) as having significantly greater relative importance than did women. Significant differences were found by geographic work location of practice with respondents from Australasia viewing “treatment plan includes prostheses that limit access for cleaning resulting in an increase in bacterial load” as having greater relative importance than did respondents from Africa (P<.001) and from South America (P<.001). Respondents from South America viewed “implant lacks 2.0 mm of attached tissue around implants” as having greater relative importance than did respondents from Australasia (P<.002) or Asia (P<.001). ConclusionsClinicians viewed the relative importance of risk factors for biologic complications with dental implants differently, and those differences varied by clinicians' age, gender, and geographic location of practice.

Fluoxetine increases brain MeCP2 immuno-positive cells in a female Mecp2 heterozygous mouse model of Rett syndrome through endogenous serotonin

Motor skill deficit is a common and invalidating symptom of Rett syndrome (RTT), a rare disease almost exclusively affecting girls during the first/second year of life. Loss-of-function mutations of the methyl-CpG-binding protein2 (MECP2; Mecp2 in rodents) gene is the cause in most patients. We recently found that fluoxetine, a selective serotonin (5-HT) reuptake inhibitor and antidepressant drug, fully rescued motor coordination deficits in Mecp2 heterozygous (Mecp2 HET) mice acting through brain 5-HT. Here, we asked whether fluoxetine could increase MeCP2 expression in the brain of Mecp2 HET mice, under the same schedule of treatment improving motor coordination. Fluoxetine increased the number of MeCP2 immuno-positive (MeCP2+) cells in the prefrontal cortex, M1 and M2 motor cortices, and in dorsal, ventral and lateral striatum. Fluoxetine had no effect in the CA3 region of the hippocampus or in any of the brain regions of WT mice. Inhibition of 5-HT synthesis abolished the fluoxetine-induced rise of MeCP2+ cells. These findings suggest that boosting 5-HT transmission is sufficient to enhance the expression of MeCP2 in several brain regions of Mecp2 HET mice. Fluoxetine-induced rise of MeCP2 could potentially rescue motor coordination and other deficits of RTT.

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.