Search

Depression represents one of the most common non-motor disorders in Parkinson's disease (PD) and it has been related to worse life quality, higher levels of disability, and cognitive impairment, thereby majorly affecting not only the patients but also their caregivers. Available pharmacological therapeutic options for depression in PD mainly include selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, and tricyclic antidepressants; meanwhile, agents acting on dopaminergic pathways used for motor symptoms, such as levodopa, dopaminergic agonists, and monoamine oxidase B (MAO-B) inhibitors, may also provide beneficial antidepressant effects. Recently, there is a growing interest in non-pharmacological interventions, including cognitive behavioral therapy; physical exercise, including dance and mind–body exercises, such as yoga, tai chi, and qigong; acupuncture; therapeutic massage; music therapy; active therapy; repetitive transcranial magnetic stimulation (rTMS); and electroconvulsive therapy (ECT) for refractory cases. However, the optimal treatment approach for PD depression is uncertain, its management may be challenging, and definite guidelines are also lacking. It is still unclear which of these interventions is the most appropriate and for which PD stage under which circumstances. Herein, we aim to provide an updated comprehensive review of both pharmacological and non-pharmacological treatments for depression in PD, focusing on recent clinical trials, systematic reviews, and meta-analyses. Finally, we discuss the pharmacological agents that are currently under investigation at a clinical level, as well as future approaches based on the pathophysiological mechanisms underlying the onset of depression in PD. [ABSTRACT FROM AUTHOR]

Abstract Background The effect of neuroinflammatory cytokines on cognitive deficits in patients with major depressive disorder (MDD) can be altered by selective serotonin reuptake inhibitors (SSRIs). This study aimed to examine serum interleukin-8 (IL-8) levels, cognitive function, and their associations in MDD patients with SSRIs. Methods Thirty SSRI-treated MDD patients and 101 healthy controls were recruited for this study. We examined cognitive performance using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum IL-8 levels using the Human Inflammatory Cytokine Cytometric Bead Array in both cases and controls. Results The RBANS test scores were significantly lower in MDD patients with SSRIs than in healthy controls after controlling for covariates (all p

Depression and anxiety are common, with one in six people experiencing symptoms in any given week. Of these people, 8.32 million are prescribed antidepressants. People living with HIV are likely to experience psychiatric disorder, with one in three experiencing depression and anxiety, and being at greater risk of developing post-traumatic stress disorder. Sexual side-effects of psychotropic medication are very common, cause distress, and can persist even after the medication has been withdrawn. Antidepressants are powerful drugs and can have severe interactions with many other substances. This article seeks to raise awareness of sexual side-effects of psychotropic medications and draw attention to ethical issues related to post selective serotonin reuptake inhibitor sexual dysfunction (PSSD). Additional risk factors and interactions between psychotropic medications and recreational drugs are identified. Recommendations are made to improve care and clinical outcomes through the development of therapeutic alliances. [ABSTRACT FROM AUTHOR]

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

In this study, a new green microwell spectrofluorimetric assay (MW-SFA) with high throughput was developed and validated, for the first time, for the determination of three selective serotonin reuptake inhibitors (SSRIs) in pharmaceutical dosage forms and plasma. These SSRIs were fluoxetine (FLX), fluvoxamine (FXM), and paroxetine (PXT), which are commonly prescribed drugs for depression treatment. The MW-SFA is based on the condensation reaction of SSRIs with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) in alkaline media to form highly fluorescent derivatives. The MW-SFA procedures were conducted in 96-microwell white opaque assay plates with a flat bottom and the fluorescence signals were measured using a microplate reader at their maximum excitation and emission wavelengths. The calibration curves were generated with good correlation coefficients (0.9992–0.9995) between the relative fluorescence intensity (RFI) and the SSRI concentrations in the range of 35–800 ng/mL. The limits of detection were in the range of 11–25 ng/mL, and the precision and accuracy were satisfactory. The proposed MW-SFA was successfully applied to the analysis of the SSRIs in their pharmaceutical dosage forms. The statistical analysis for the comparison between the MW-SFA assay results and those of pharmacopeial assays showed no significant differences between the assays in terms of their accuracy and precision. The application of the proposed MW-SFA was extended to successfully analyze SSRIs in plasma samples. The greenness of the assay was confirmed using three different metric tools. The assay was characterized with high throughput properties, enabling the sensitive simultaneous analysis of many samples in a short time. This assay is valuable for rapid routine applications in pharmaceutical quality control units and clinical laboratories for the determination of SSRIs. [ABSTRACT FROM AUTHOR]

Declining germline quality is a major cause of reproductive senescence. Potential remedies could be found by studying regulatory pathways that promote germline quality. Several lines of evidence, including a C. elegans male pheromone ascr#10 that counteracts the effects of germline aging in hermaphrodites, suggest that the nervous system plays an important role in regulating germline quality. Inspired by the fact that serotonin mediates ascr#10 signaling, here we show that serotonin reuptake inhibitors recapitulate the effects of ascr#10 on the germline and promote healthy oocyte aging in C. elegans. Surprisingly, we found that pharmacological increase of serotonin signaling stimulates several developmental processes in D. melanogaster , including improved oocyte quality, although underlying mechanisms appear to be different between worms and flies. Our results reveal a plausibly conserved role for serotonin in maintaining germline quality and identify a class of therapeutic interventions using available compounds that could efficiently forestall reproductive aging. [Display omitted] • Drugs that promote serotonergic signaling improve oocyte quality in worms and flies. • In C. elegans , these drugs increase proliferation of the oogenic germline. • In D. melanogaster , these drugs increase proliferation of somatic follicle cells. • Serotonin may improve oocyte provision via different mechanisms in different species. [ABSTRACT FROM AUTHOR]

Aims: Depression is known to have an overarching negative impact on the quality of life of afflicted individuals. Mitigation of depression associated adverse outcomes is mostly reliant upon timely diagnosis and decisive intervention. Antidepressants and adjunct drugs constitute the pharmacological modalities for the therapy of depression, in addition to supportive non-pharmacological methods of management. This prospective cross-sectional observational study aims at analyzing the utilization of antidepressants in American Psychiatric Association (APA) categories of depression in a remote North-East Indian teaching hospital. Methods: Patients clinically diagnosed with depression based on Diagnostic and Statistical Manual of Mental Disorders (DSM) and prescribed with antidepressant medication, were included in the study. The data were analyzed based on demographic characteristics, prescribed antidepressant medication and co-prescribed adjunct drugs. Results: A total of 316 patients were included in the study. The SSRI class of antidepressants were prescribed most frequently (89%) followed by TCAs (6%) & SNRIs (4.4%). Escitalopram was the single most frequently prescribed antidepressant (51%) followed by sertraline (23%) & fluoxetine (11.4%). The SSRIs were used most frequently in bipolar disorder (94.7%), followed by depressive episode (89.2%) & mixed anxiety depressive disorder (88.2%). The utilization of SSRIs was more frequent in the ( 50 age group (90.3%) and in males (92.5%). Sedatives including benzodiazepines, were used in 78.8% and atypical antipsychotics in 8.9% of the patients. Conclusion: SSRIs are the most frequently used antidepressant class across all categories of depression. Benzodiazepines have been extensively co-prescribed. The pharmacotherapy of depression in this hospital conforms to currently available clinical evidence and treatment guidelines. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This study describes the development and validation of a new green and high-throughput microwell spectrophotometric assay (MW-SPA) for the determination of three selective serotonin reuptake inhibitors (SSRIs) in their pharmaceutical dosage forms. These SSRIs are fluoxetine, fluvoxamine, and paroxetine, the most prescribed drugs for the treatment of depression. The proposed assay was based on the formation of orange-colored N-substituted naphthoquinone derivatives upon the reaction of SSRIs with 1,2-naphthoquinone-4-sulphonate (NQS) in alkaline media. The assay was conducted in 96-microwell assay plates, and the absorbances of the reaction products were measured by a microplate reader at their maximum absorbance wavelengths. The optimum conditions of the reaction were refined and established. Under these conditions, calibration curves were generated, and linear regression equations were computed. The linear relations between the absorbances and drug concentrations were linear with good correlation coefficients (0.9992–0.9997) in the range of 2–80 µg/mL. The assay limits of detection were in the range of 1.5–4.2 µg/mL. The precision was satisfactory as the values of relative standard deviation did not exceed 1.70%. The accuracy of the assay was ≥98.2%. The proposed MW-SPA was successfully applied to the analysis of the SSRIs in their pharmaceutical dosage forms with acceptable accuracy and precision; the label claims were 99.2–100.5% (±0.96–1.35%). The results of the proposed MW-SPA were compared with those of the official/pre-validated assays by statistical analysis with respect to the accuracy (by t-test) and precision (by F-test). No significant differences were found between the calculated and theoretical values of the t- and F-tests at the 95% confidence level, proving similar accuracy and precision in the determination of SSRIs by both assays. The greenness of the proposed assay was confirmed by two metric tools. In addition, the assay is characterized with a high-throughput property which enables the simultaneous analysis of many samples in a short time. Therefore, the assay is a valuable tool for rapid routine application in pharmaceutical quality control units for the determination of the investigated SSRIs. [ABSTRACT FROM AUTHOR]

Social anxiety disorder is common and impairing. The efficacy of pharmacotherapy is moderate, highlighting the need for alternative therapies. This study compared the efficacy of gaze-contingent music reward therapy (GC-MRT), an eye-tracking-based attention bias modification treatment, with a selective serotonin reuptake inhibitor (SSRI) treatment or a waiting list control condition in reducing social anxiety disorder symptoms. Superior clinical effects of similar magnitude were expected for the active treatments relative to the control condition. Participants were 105 treatment-seeking adults with social anxiety disorder, randomly allocated to 12 weeks of GC-MRT, SSRI, or waiting list control. Mean changes in clinician-rated and self-reported social anxiety symptoms from baseline to mid- and posttreatment assessments were compared between groups using generalized estimating equations. Changes in attentional dwell time on threat were also examined. Analysis indicated a significant differential reduction in symptoms between groups. Patients in the GC-MRT and SSRI groups had lower social anxiety scores at the mid- and posttreatment assessments compared with patients in the waiting list group. The efficacy of the active treatments did not differ. Only patients in the GC-MRT group showed reduction in dwell time on threat from baseline to posttreatment assessment. Eye-tracking-based attention bias modification is an acceptable and effective treatment option for social anxiety disorder. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To evaluate and categorize the survival benefit of tricyclic antidepressants (TCAs) in lung cancer patients based on systematic computational drug repositioning data. METHODS: Data were retrospectively extracted from the medical records of non-small cell lung cancer (NSCLC) patients from the University of Cincinnati Cancer Medical Center database. Patients receiving antidepressants during their course of anti-cancer treatment were compared with those without antidepressants. Data were analyzed using Kaplan–Meier survival curves with the log-rank test, and overall survival (OS) was calculated from the date of diagnosis until last follow-up or death. RESULTS: The median OS at 2 and 5 years for patients on antidepressants was 20.3 months (54.7% and 42%) vs 44.3 months (47.6% and 43.2%), which was not significant. The median OS for patients receiving TCAs, selective serotonin reuptake inhibitors, and other antidepressants was 3.17 months, 31.33 months, and 18.50 months, respectively. CONCLUSION: We found no significant survival benefit for TCA use in combination with anti-cancer agents in NSCLC patients.

Background: Antidepressant (AD) medications increase suicidality for some, or all, age groups. Some, or all, types of ADs, are frequently used in suicides involving overdoses. Methods: The article examines a previously unanalyzed data set summarizing 7,829 media reports of Coroners' inquests in England and Wales that mention ADs, between 2003 and 2020. Results: The most frequently cited ADs were SSRIs (48.9%) and tricyclics (24.6%). The specific drugs cited most often were the SSRI drug citalopram (19.8%) and the tricyclic drug amitriptyline (17.5%). Of 2,329 cases of death by overdose, 933 (40.1%) were overdoses of ADs, 512 of which (54.9%) did not involve other substances. The ADs most frequently named were amitriptyline (186), and citalopram (86). A further 929 were overdoses of unnamed medicines, a proportion of which may have been ADs. Limitations: The data set, which relies primarily on archives of local newspapers, is incomplete and therefore underestimates the total numbers involved. The accuracy of coroners' verdicts is not perfect. Conclusions: If preventing suicide is a primary reason for prescribing ADs, this data set includes several thousand people for whom the drugs clearly did not work. Furthermore, about 1,000 people used the drugs that were supposed to alleviate their depression to kill themselves. Systematic analyses of all inquests would be more informative. Meanwhile, reducing the overprescribing of these relatively ineffective and, for some, lethally dangerous substances is suggested, to reduce suicides. [ABSTRACT FROM AUTHOR]

New guidelines for identifying anxiety in pediatric patients constitute important changes in screening for primary care providers, including primary care NPs. This article seeks to guide NPs in both following the screening guidelines and providing strategic care for patients and their families. [ABSTRACT FROM AUTHOR]

There is growing evidence of the association of Microscopic Colitis (MC) with the use of specific medications such as proton pump inhibitors (PPIs), Selective serotonin reuptake inhibitors (SSRIs), Non-Steroidal anti-inflammatory drugs (NSAIDs), Statins and H2-receptor antagonists (H2RA). In our study, we calculated the pooled odds of MC in patients using these drugs. We performed a detailed search of major databases, including PubMed/Medline, Scopus, web of science, and Embase, to include the studies in which odds of MC were reported after using above mentioned drugs. A random-effects model was used to pool the estimates. Thirteen studies were included in our analysis consisting of 304,482 patients (34,194 cases and 270,018 controls). In eight studies, the control group consisted of a random population selected based on age, gender and same birth year, whereas 3 studies recruited patients who presented with diarrhea and underwent colonoscopy and biopsy to rule out MC. Two studies reported odds of MC for both diarrhea and random control groups. Patients taking PPIs were more likely to develop MC, AOR 2.65 (95% CI 1.81–3.50, I2 98.13%). Similarly, higher odds of association were found in patients taking SSRIs (OR 2.12, 95% CI 1.27–2.96, I2 96.46%), NSAIDs (OR 2.02, 95% CI 1.33–2.70, I2 92.70%) and Statins (OR 1.74, 95% CI 1.19–2.30, I2 96.36%). No difference in odds of developing MC was seen in patients using H2RA compared to the control group (OR 2.70, 95% CI 0.32–5.08, I2 98.67%). We performed a subgroup analysis based on the control group and found higher odds of MC in patients on PPIs compared to the random control group (OR 4.55, 95% CI 2.90–6.19, I2 98.13%). Similarly, higher odds of MC were noted for SSRI (OR 3.23, 95% CI 1.54–4.92, I2 98.31%), NSAIDs (OR 3.27, 95% CI 2.06–4.48, I2 95.38%), and Statins (OR 2.23, 95% CI 1.41–3.06, I2 98.11%) compared to the random control group. Contrary lower odds of MC were seen in the PPI and H2RA group compared to the diarrhea control group (OR 0.68, 95% CI 0.48–0.88, I2 7.26%), (OR 0.46, 95% CI 0.14–0.78, I2 0%) respectively. We found no difference in odds of MC in patients on SSRIs (OR 0.96, 95% CI 0.49–1.42, I2 37.89%), NSAIDs (OR 1.13, 95% CI 0.49–1.76, I2 59.37%) Statins (OR 0.91, 95% 0.66–1.17, I2 0%) and H2RA (OR 3.48, 95% CI −0.41–7.36, I2 98.89%) compared to the diarrhea control group. We also analyzed the association use of PPIs and NSAIDs with the development of collagenous colitis (CC) and lymphocytic colitis. Only the use of NSAIDs was associated with increased odds of developing collagenous colitis (OR 1.61, 95% CI 1.50–1.72, I2 0%). No increased odds of CC and LC were seen in PPI users. PPIs, NSAIDs, SSRIs, and Statins are associated with an increased risk of MC compared to the random control group. On the contrary, the use of PPIs, NSAIDs, SSRIs, and Statins is not associated with an increased risk of MC when compared to the diarrhea control group. [ABSTRACT FROM AUTHOR]

Background: The effect of neuroinflammatory cytokines on cognitive deficits in patients with major depressive disorder (MDD) can be altered by selective serotonin reuptake inhibitors (SSRIs). This study aimed to examine serum interleukin-8 (IL-8) levels, cognitive function, and their associations in MDD patients with SSRIs. Methods: Thirty SSRI-treated MDD patients and 101 healthy controls were recruited for this study. We examined cognitive performance using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum IL-8 levels using the Human Inflammatory Cytokine Cytometric Bead Array in both cases and controls. Results: The RBANS test scores were significantly lower in MDD patients with SSRIs than in healthy controls after controlling for covariates (all p < 0.001). Serum levels of IL-8 were higher in MDD patients with SSRIs than in healthy controls after adjusting for covariates (F = 3.82, p = 0.05). Serum IL-8 levels were positively correlated with sub-scores of delayed memory (r = 0.37, p = 0.04) and visuospatial/constructional (r = 0.43, p = 0.02) in MDD patients with SSRIs but not in in healthy controls (delayed memory score: r = -0.12, p = 0.24; visuospatial/constructional score: r = 0.02, p = 0.81). Conclusions: Our findings suggested that increased serum IL-8 level might not only be involved in the MDD psychopathology or the use of SSRIs but also correspond to improving MDD delayed memory and visuospatial/constructional function. [ABSTRACT FROM AUTHOR]

Depression and anxiety are highly prevalent in most neurological disorders and can have a major impact on the patient's disability and quality of life. However, mostly due to the heterogeneity of symptoms and the complexity of the underlying comorbidities, depression can be difficult to diagnose, resulting in limited recognition and in undertreatment. The early detection and treatment of depression simultaneously with the neurological disorder is key to avoiding deterioration and further disability. Although the neurologist should be able to identify and treat depression initially, a neuropsychiatry team should be available for severe cases and those who are unresponsive to treatment. Neurologists should be also aware that in neurodegenerative diseases, such as Alzheimer's or Parkinson's, different depression symptoms could develop at different stages of the disease. The treatment options for depression in neurological diseases include drugs, cognitive-behavioral therapy, and somatic interventions, among others, but often, the evidence-based efficacy is limited and the results are highly variable. Here, we review recent research on the diagnosis and treatment of depression in the context of Alzheimer's disease, Parkinson's disease, and strokes, with the aim of identifying common approaches and solutions for its initial management by the neurologist. [ABSTRACT FROM AUTHOR]

Background. Depression is the most common mental disorder, affecting about 3.8% of the population worldwide. Clinical symptoms of depression include sadness, anxiety and frequent mood swings, among others. Selective serotonin reuptake inhibitors (SSRIs), psychotherapy and behavioral therapy are commonly used for the treatment of this condition. Since SSRIs are associated with various side effects, extract of St. John's wort (SJW) has been suggested as an effective alternative. However, there are conflicting studies regarding its efficacy. Many studies have reported positive outcomes with low adverse effects, while others did not find it to be a suitable alternative. Objectives. To analyze the available studies using SJW for depression therapy and to thoroughly evaluate its effectiveness compared to SSRIs and placebo. Materials and methods. Relevant articles for our meta-analysis were found using Medline (via PubMed), Cinahl (via EBSCO), Scopus, and Web of Sciences databases. Studies were included as per the predefined Population, Intervention, Comparison, Outcomes and Study (PICOS) criteria. A demographic summary of the patients treated with either SJW, placebo or SSRIs was collected and Hamilton Depression Rating Scale (HAMD) scores were extracted. Risks of bias analysis, diagnostic odds ratio (OR), risk ratio (RR), and sensitivity calculation were evaluated using Revman software, and the publication bias was assessed using MedCalc software. Results. Fourteen clinical trials with a total of 2270 depression patients were included in accordance with the inclusion criteria. All analyzed papers were published between 2000 and 2022. For patients treated with either SSRIs or SJW, a pooled OR of 2.44 with a 95% confidence interval (95% CI) of 1.33-4.45 was obtained. The data were heterogeneous, with a tau2 value of 0.54, χ2 value of 31.05, degrees of freedom (df) value of 7, I2 value of 77%, and an overall Z-value of 2.90 with p = 0.004. Conclusions. Our research supports the use of SJW as it reduced the number of depressive patients and their HAMD scores while having fewer risks and side effects than conventional medications. [ABSTRACT FROM AUTHOR]

Selective serotonin reuptake inhibitors (SSRIs) are currently the most prescribed class of psychotropic medications. Their increased global manufacture and use have become growing concerns for aquatic toxicologists and environmental biologists, who assess both the direct and indirect effects of substances on the environment and on human health. In order to assess the potential impact of environmentally relevant levels of SSRIs on fish development, behaviour and reproduction, we exposed juvenile and adult zebrafish to a select group of SSRIs using two separate exposure paradigms. In the first paradigm, juvenile zebrafish were exposed to Fluoxetine (Prozac), Paroxetine (Paxil), Sertraline (Zoloft) or a mixture of the three beginning at environmentally relevant levels (10 µg/L) for 135 days (long-term exposure) beginning at 5 days post fertilization (dpf). In the second paradigm, adult zebrafish were exposed to matching concentrations of the same SSRIs for 35 days (short-term exposure). The long-term exposure paradigm proved to have little to no overt effect on growth or development at sub-lethal concentrations (10 and 100 µg/L). However, both the stress/anxiety response (novel tank tests) and reproduction (fecundity and fertility) were dramatically reduced. Importantly, the short-term exposure of reproductively mature fish led to similar adverse effects on both the stress response and reproduction. Following both the short and long duration exposure paradigms, a 2-week washout period led to a small reduction in the adverse effects. These findings highlight the potential for SSRIs to negatively impact population dynamics in zebrafish and may be of particular value should they be found in other fish species in the environment. [ABSTRACT FROM AUTHOR]

ObjectiveTo evaluate the efficacy and safety of agomelatin and selective serotonin reuptake inhibitors （SSRIs） in the treatment of depressive disorder via network Meta-analysis.MethodsThe literature databases such as China National Knowledge Network （CNKI）， Wanfang Data Knowledge Service Platform， VIP Database for Chinese Technical Periodical （VIP）， Chinese Biomedical Literature Database （CBM）， PubMed， Embase and Cochrane Library were searched from the inception to November 2021. Based on the preset inclusion and exclusion criteria， literature screening， quality assessment of methodology and data extraction were conducted by two researchers separately， then statistical analysis was carried out using ADDIS software.ResultsA total of 7 256 patients with depressive disorder in 22 randomized controlled trials were included. According to the consistency assessed in Bayesian network Meta-analysis and the estimation of the probability of being the best treatment， escitalopram （P=0.63） ranked first for response rate and paroxetine （P=0.31） was associated with the best ranking for cure rate in terms of the effectiveness， meantime， paroxetine （P=0.44） had the highest adverse events risk and sertraline （P=0.74） had the highest study drop-outs proportion in terms of safety.ConclusionEscitalopram and paroxetine may be superior to sertraline， agomelatine， citalopram and fluoxetine in the treatment of depressive disorder， furthermore， paroxetine and sertraline demonstrate poor safety profiles.

Objective: This study examined whether the COVID-19 pandemic was associated with changes in new selective serotonin reuptake inhibitor (SSRI) prescription fills.Methods: Using IQVIA Xponent data on new SSRI fills in Los Angeles (L.A.) County from March 2019 to June 2021, the authors implemented an interrupted time series analysis comparing the monthly volume and trend of overall fills and fills by age and gender from before to after the pandemic declaration.Results: The rate of new SSRI prescription fills briefly decreased after the pandemic declaration but then consistently increased through the rest of the study period. These increases were primarily driven by women, young adults (i.e., 18-39 year-olds), and those under 18 years old.Limitations: Sample is limited to one county and may not be generalizable to other municipalities.Conclusions: The COVID-19 pandemic was associated with significant increases in new SSRI fills among women, young adults, and those under 18. These increases were relatively small compared to increases in depressive symptoms during the same time period. [ABSTRACT FROM AUTHOR]

Background: Selective serotonin reuptake inhibitors (SSRIs) have been associated with type 2 diabetes mellitus (T2DM) in youths, possibly via 5-HT2C, H1 receptors and serotonin transporter (SERT). SSRIs have similar affinity for SERT but variable affinity for 5-HT2C and H1. This study assessed whether SSRIs with strong affinity for 5-HT2C and H1 (relative to SERT) were associated with T2DM risk compared with weak-affinity SSRIs.Methods: Using the UK Clinical Practice Research Datalink, we assembled a cohort of patients aged 5-24, newly prescribed a strong-affinity SSRI (citalopram, escitalopram, fluoxetine) or weak affinity (paroxetine, sertraline, fluvoxamine) between 1990 and 2019. We controlled for confounding using standardized mortality ratio weighting, estimated from calendar time-specific propensity scores. We used weighted Cox proportional hazards models to estimate hazard ratios (HRs) of incident T2DM with 95 % confidence intervals (CIs).Results: The cohort included 347,368 new users of strong-affinity SSRIs and 131,359 of weak-affinity SSRIs. Strong-affinity SSRIs were not associated with an increased T2DM risk compared with weak-affinity SSRIs (incidence rate 2.8 vs 2.7 per 1000 person-years; HR 1.03, 95 % CI 0.85-1.25). T2DM risk did not vary with duration of use, age or sex. However, the HR was numerically higher in youths with normal or low weight (HR 1.30, 95 % CI 0.85-1.98) and with prior antipsychotic use (HR 1.62, 95 % CI 0.83-3.18).Limitations: Median duration of SSRI use, in line with real-world SSRI prescribing, was relatively short.Conclusion: T2DM risk did not differ between strong- and weak-affinity SSRIs, providing reassurance for clinicians when choosing between SSRIs in youths. [ABSTRACT FROM AUTHOR]

Apathy is one of the most common manifestations of neurodegenerative pathology, including Alzheimer's disease (AD). Despite such a significant role of apathy in the course of the disease, there are no unambiguous recommendations for the treatment and prevention of this symptom complex. Some classes of psychotropic drugs commonly prescribed for AD, such as antidepressants of the SSRI class, may themselves cause apathy. The authors present a series of clinical observations describing four cases of deterioration in the condition of patients with AD during SSRI therapy. The features of the clinical course of the disease are discussed, new strategies for drug therapy are proposed.

Depression represents one of the most common non-motor disorders in Parkinson’s disease (PD) and it has been related to worse life quality, higher levels of disability, and cognitive impairment, thereby majorly affecting not only the patients but also their caregivers. Available pharmacological therapeutic options for depression in PD mainly include selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, and tricyclic antidepressants; meanwhile, agents acting on dopaminergic pathways used for motor symptoms, such as levodopa, dopaminergic agonists, and monoamine oxidase B (MAO-B) inhibitors, may also provide beneficial antidepressant effects. Recently, there is a growing interest in non-pharmacological interventions, including cognitive behavioral therapy; physical exercise, including dance and mind–body exercises, such as yoga, tai chi, and qigong; acupuncture; therapeutic massage; music therapy; active therapy; repetitive transcranial magnetic stimulation (rTMS); and electroconvulsive therapy (ECT) for refractory cases. However, the optimal treatment approach for PD depression is uncertain, its management may be challenging, and definite guidelines are also lacking. It is still unclear which of these interventions is the most appropriate and for which PD stage under which circumstances. Herein, we aim to provide an updated comprehensive review of both pharmacological and non-pharmacological treatments for depression in PD, focusing on recent clinical trials, systematic reviews, and meta-analyses. Finally, we discuss the pharmacological agents that are currently under investigation at a clinical level, as well as future approaches based on the pathophysiological mechanisms underlying the onset of depression in PD.

The author discusses a study by G. Arad and colleagues, published in the issue about the attention bias modification (ABM) approach to anxiety. Topics include limitations of many ABM studies, finding on the internal reliability of eye gaze assessment measure of attentional bias, and major strengths of Arad and colleagues' study.

Major Depressive Disorder (MDD) is a major cause of disability worldwide and is associated with serious lasting impairment. A leading hypothesis of the pathophysiology of MDD is the monoamine deficiency hypothesis which suggests that depression is caused by depletion of serotonin, norepinephrine, or dopamine in the central nervous system. Serotonin is the most widely studied neurotransmitter in the pathophysiology of depression, with studies showing that reduced central serotonin synthesis leads to depressive symptoms in individuals at risk for depression. Selective Serotonin Reuptake Inhibitors (SSRI) inhibit serotonin reuptake and subsequently increase the amount of serotonin available in synapses. Common side effects of SSRIs include increased suicidality of patients under the age of 25, sexual dysfunction, anxiety, dizziness, weight gain, gastrointestinal distress, and headache. Other side effects include prolonging the QT interval, coagulopathy, and the risk of serotonin syndrome, as well as SSRI discontinuation syndrome. Sites of increased bleeding related to SSRI use have been reported to occur in the upper gastrointestinal tract, as well as intracranially. Based on the current literature, three studies have found that SSRIs are not associated with increased bleeding and/or increased perioperative risk, while others have demonstrated that SSRIs are associated with an increased risk in perioperative use. The inhibition of serotonin reuptake can affect platelet aggregation since platelets also express the serotonin transporter. SSRIs can result in decreased storage of serotonin in platelet dense granules. Increased serotonin can also increase gastric acid secretion, which increases the risk for ulceration. SSRIs in combination with NSAIDs also show a significantly increased risk of upper GI bleeding. Some studies show an increased bleeding risk from 30% to 70% when taking a combination of vitamin K antagonists and SSRIs in hospitalized patients. Related to the high prevalence of conditions that are treated with SSRIs, the bleeding risk associated with this class of medication merits further study. [ABSTRACT FROM AUTHOR]

Objective: To systematically evaluate the effectiveness of exposure and response prevention (ERP) combined with medication on obsessivecompulsive disorder (OCD). Methods: PubMed, Web of Science, EBSCO, Cochrane, Embase, and Science Direct databases were searched to include randomized controlled trials of ERP combined with medication for OCD that met the criteria. The Yale Brown Obsessive Compulsive Scale was used as the primary outcome indicator, and Depression scales were used as secondary outcome indicators. An evaluation of bias risk was conducted to identify possible sources of bias based on methodological and clinical factors. Review Manager 5.3 and Stata 16.0 software was used to perform meta-analysis of the extracted data. Results: A total of 21 studies with 1113 patients were included. Metaanalysis showed that ERP combined with medication therapy was significantly better than medication therapy alone including selective serotonin reuptake inhibitors, clomipramine and risperidone (MD = -6.60, 95% CI: -8.35 to -4.84, P < 0.00001), but D-cycloserine (DCS) drugs do not enhance the effect of ERP intervention in patients with OCD (MD = 0.15, 95% CI: -0.87 to 1.17, P = 0.77). There is more significant maintenance by combined treatment method of medication plus ERP than medication treatment alone during the follow-up period (MD = -7.14, 95% CI: -9.17 to -5.10, P < 0.00001). DCS drugs did not enhance the effect of ERP intervention on depression in patients with OCD (SMD = -0.08, 95% CI: -0.31 to 0.15, P = 0.50). ERP combined with drug improved patients' depression levels significantly better than providing drug alone (SMD = -0.40, 95% CI: -0.68 to -0.11, P = 0.006). Conclusion: Patients with OCD have significant improvement in symptoms of obsessive-compulsive disorder and depression when ERP is combined with medication, however, not enough to prove that DCS can enhance ERP effectiveness. [ABSTRACT FROM AUTHOR]

Selective serotonin reuptake inhibitors (SSRIs) are widely used for a variety of diseases, and their impact on semen quality is unclear. We performed a systematic search in PubMed and Embase, and after a strict screening, we included 4 studies with a total of 222 male participants. In result, SSRIs reduced normal sperm morphology (95% CI [-16.29, -3.77], p = 0.002), sperm concentration (95%CI [-43.88, -4.18], p = 0.02), sperm motility (95%CI [-23.46, -0.47], p = 0.04) and sperm DNA fragmentation index (DFI) (95% CI [6.66,21.93], p = 0.0002), without a statistically significant effect on semen volume (95%CI [-0.75,0.65], p = 0.89). Moreover, the impact on both sperm morphology and sperm concentration were observed within the 3-month period of SSRIs use. In general, our meta-analysis showed that SSRIs have a negative effect on semen quality. More larger, randomized, well-controlled clinical studies should be conducted to support our conclusion. [ABSTRACT FROM AUTHOR]

Introduction: Solitary rectal ulcer syndrome (SURS) is a poorly understood and uncommon benign disorder of the lower gastrointestinal tract. It presents with various symptoms, often misinterpreted as inflammatory bowel disease. To date, there is no association between the use of selective serotonin reuptake inhibitors (SSRIs) and SURS., Case Description: A 29-year-old male on paroxetine for six months and with a non-contributory surgical history presented to the clinic due to three months of haematochezia, abdominal pain and mucoid discharge. Physical examination and a review of systems were unremarkable; a colonoscopy demonstrated a suspicious ulcerated lesion in the rectum, which was identified as SURS on biopsy. The patient was advised lifestyle and dietary modifications. In addition, paroxetine was discontinued, and patient was switched to venlafaxine, a serotonin-norepinephrine reuptake inhibitor. Subsequently, the patient's symptoms resolved gradually, and he did not report any signs of recurrence on follow-up., Conclusion: Literature confirms that SSRIs can increase the occurrence of GI ulceration yet focuses specifically on upper gastrointestinal bleeding rather than rectal bleeding. This finding raises the need for further research., Learning Points: SURS is often underdiagnosed or misdiagnosed as inflammatory bowel disease.The pathophysiology and aetiology behind SURS remain obscure.This case points to a potential correlation between SSRIs use and SURS development., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2024.)

Obsessive-compulsive disorder (OCD), characterized by persistent, intrusive thoughts (obsessions) and repetitive behaviors or mental acts (compulsions), can significantly impact a child's daily functioning, academic performance, and overall quality of life. As the prevalence of pediatric OCD continues to rise, there is a critical demand for evidence-based treatments that not only alleviate symptoms but also enhance the quality of life for affected children and adolescents. By identifying gaps in knowledge and suggesting directions for future research, this narrative review contributes to the ongoing discourse on pediatric OCD treatments. Ultimately, the synthesis of evidence aims to enhance our understanding and inform best practices in the compassionate and effective management of OCD in children and adolescents. The aim of this study is to provide a comprehensive overview of current trends and emerging strategies in the treatment of pediatric obsessive-compulsive disorder (OCD) and highlights the significance of tailoring treatment approaches to individual patient needs, considering factors such as symptom severity and treatment response. Concentrating on interventions supported by empirical evidence, the review delves into cognitive-behavioral therapy (CBT), pharmacotherapy, the synergistic effects of these modalities, and inventive therapeutic approaches, all while considering the distinctive developmental aspects pertinent to pediatric populations. We conducted this review by searching for titles in the PubMed database from 2013 to present. Our comprehensive literature review focused on advancements in treating pediatric OCD, using keywords like "Obsessive-compulsive disorder," "Pediatric," "treatment," "CBT," "SSRI," "Pharmacotherapy," and "combination therapy." While both pharmacotherapy and CBT show individual efficacy, the combination of these approaches appears to be more effective, especially for medication non-responders with no prior exposure to CBT, despite some mixed findings. These findings contribute significantly to the ongoing discussion on optimizing combined therapy strategies tailored to the complexities of pediatric OCD., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Khomami Zadeh et al.)

Citalopram is a selective serotonin reuptake inhibitor (SSRI) used to treat depression and is often detected in aquatic environments. Here, we measured the acute toxicity of citalopram at environmentally relevant concentrations to zebrafish embryos/larvae and utilized RNA-seq to reveal potential mechanisms of toxicity. We also assessed behavioral outcomes in larval zebrafish. Zebrafish embryos were exposed continuously to embryo rearing medium (ERM), or one concentration of 0.1, 1, 10, 100, and 1000 μg/L citalopram for 7 days post-fertilization (dpf). No acute toxicity was noted for citalopram over 7-days in developing zebrafish, nor were there any effects on hatch rates; however, exposure resulted in a dose-dependent decrease in heart rate at 2 dpf. Reactive oxygen species were also increased in 7-day old larvae zebrafish exposed to 100 μg/L citalopram. There were 29 genes differentially expressed in fish exposed to 10 μg/L citalopram [FDR <0.05] and 79 genes differentially expressed in fish exposed to 1000 μg/L citalopram [FDR <0.05]. In the 1000 μg/L citalopram treatment, there were several transcripts downregulated related to muscle function, including myhz2, myhz1, and myom1. Twenty-five gene set pathways were shared between exposure concentrations including 'IL6 Expression Targets', 'Thyroid Stimulating Hormone (TSH) Resistance in Congenital Hypothyroidism', and 'GFs/TNF - > Ion Channels.' Enrichment of KEGG pathways revealed that 1000 μg/L citalopram altered processes related to the proteosome and cardiac muscle contractions. Larval zebrafish at 7 dpf showed hypoactivity with exposure to ≥10 μg/L citalopram. This may be related to the downregulation of transcripts involved in muscle function. Overall, our results show that citalopram as a pharmaceutical pollutant may have an adverse influence on aquatic species' ability to survive by reducing their abilities to elude predators (e.g. cardiac output, locomotor activity). This study improves mechanistic understanding of the potential harm citalopram may cause fish and contributes to environmental risk assessments for SSRIs in aquatic species., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Christopher J. Martyniuk reports was provided by University of Florida. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

There is little evidence for psychopharmacotherapy in pica. A few studies reported some benefit from the use of SSRIs, atypical antipsychotics and methylphenidate. That said, evidence to deploy these agents remains, at large, flimsy. Here, despite scarcity, we review available literature and draw some generalities that can inform decision-making on clinical grounds., (Copyright © 1964–2024 by MedWorks Media Inc, Los Angeles, CA All rights reserved. Printed in the United States.)

To report a unique case of a patient who developed simultaneous bilateral maculopathy presumed from intake of fluoxetine. The optic coherence tomography (OCT) macular showed a subfoveal disruption in the outer retinal layer in both eyes (OU), higher in the left one (OS). Although reported cases of serotonin recapture inhibitors (SSRIs) Maculopathy so far have been caused by sertraline, fluoxetine shares the biological mechanism, and OCT findings and ocular symptoms are the same as published. We should be aware with ocular symptoms in patients that take fluoxetine., (Copyright © 2024 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

The monoamine hypothesis of depression attributes the symptoms of major depressive disorders to imbalances of serotonin, noradrenaline, and dopamine in the limbic areas of the brain. The preferential targeting of serotonin receptor (SERT) by selective serotonin reuptake inhibitors (SSRIs) has offered an opportunity to reduce the range of these side effects and improve patient adherence to pharmacotherapy. Clozapine remains an effective drug against treatment-resistant schizophrenia, defined as failing treatment with at least two different antipsychotic medications. Patients with schizophrenia who display a constellation of negative symptoms respond poorly to antipsychotic monotherapy. Negative symptoms include the diminution of motivation, interest, or expression. Conversely to the depressive symptomology of interest presently, supplementation of antipsychotics with SSRIs in schizophrenic patients with negative symptoms lead to synergistic improvements in the function of these patients. Fluvoxamine is one of the most potent inhibitors of CYP1A2 and can lead to an increase in clozapine levels. Similar increases in serum clozapine were detected in two patients taking sertraline. However, studies have been contradictory as well, showing no such increases, which are worrying. Clinicians should be aware that clozapine levels should be monitored with any coadministration with SSRIs.

ObjectiveTo explore the predictive role of the degree of prospective memory impairment on the treatment response to Selective Serotonin Reuptake Inhibitors （SSRIs） in patients with obsessive-compulsive disorder.MethodsA total of 30 patients with obsessive-compulsive disorder who met the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders， fourth edition， text revision （DSM-IV-TR） were selected， and all patients were treated with SSRIs for 4 weeks. The severity of obsessive-compulsive symptom was assessed using Yale-Brown Obsessive Compulsive Scale （Y-BOCS）， and the efficacy was evaluated by the reduction rate of Y-BOCS score. Moreover， the performance of event-based， time-based and activity-based prospective memory tasks were compared before and after treatment.ResultsAfter treatment， the total Y-BOCS score of patients was lower than before treatment ［（27.07±4.63） vs. （24.87±5.93）， F（1，29）=4.984， P=0.033］， meantime， the performance of event- and time- based prospective memory tasks was improved ［（0.78±0.21） vs. （0.88±0.11）， F（1，29）=9.022， P=0.005； （0.81±0.17） vs. （0.91±0.11）， F（1，29）=9.063， P=0.005］. Correlation analysis showed that the performance of event-based prospective memory at baseline was positively correlated with the reduction of Y-BOCS score （r=0.478， P=0.014）. The event-based prospective memory performance at baseline could positively predict the treatment response to SSRIs treatment in patients （β=0.441， P=0.014）.ConclusionThe event-based prospective memory function of patients with obsessive-compulsive disorder can positively predict SSRIs treatment outcome， and patients with better prospective memory performance yield better treatment responses.