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In this study, a dispersive liquid–liquid microextraction along with a back-extraction step (DLLME-BE) has been developed for the determination of thre antidepressant drugs (citalopram, sertraline, and venlafaxine) in biological samples prior to HPLC-UV. Briefly, the method involved two main steps: first, a deep eutectic solvent (DES) composed of tetrabutylammonium bromide (TBABr as a dispersive agent) and 1-dodecanol (as the extraction solvent) was decomposed in an aqueous phase and led to in situ dispersion of the organic phase and extraction of analytes.. Second, Air-assisted liquid–liquid microextraction (AALLME) was applied to back-extract analytes into 50 µL of an aqueous acceptor phase while many interferences were not able to extract into the acceptor solution. By performing this developed extraction method, a high sample clean-up was achieved. The maximum efficiency of analytes was obtained based on the optimisation of the main parameters. Validation of the method indicated that the limits of detection (LODs) and limits of quantifications (LOQs) were in the range of 0.7–3.9 µg L−1 and 2.1–9.8 µg L−1 respectively. The extraction recoveries and enrichment factors of analytes were obtained to be in the range of 87.1–99.1% and 89–102, respectively. Finally, the method was utilised for extraction of three antidepressant drugs in water, human urine and plasma samples. [ABSTRACT FROM AUTHOR]

Objective: This study investigated prescribing patterns of two cohorts of patients treated with selective serotonin reuptake inhibitors (SSRI) in primary care in Wales (UK), to better understand drivers for increased usage. Methods: This e‐cohort study included patients receiving a first READ‐coded SSRI prescription in SAIL in either 2005 or 2015. Patients were followed up for 3 years from date of SSRI prescription. Influence of age and other demographic data on prescribing patterns, and details of mental health or medication reviews that took place were identified. Results: In total 67,006 patients were included across the two cohorts; 29,534 in 2005, and 37,472 in 2015. Citalopram was the most commonly prescribed SSRI in both cohorts. A READ‐coded diagnosis relating to SSRI treatment could not be identified in 24,797 patients. The percentage of patients continuing treatment for 3 years was 6.9% and 11.3% in 2005 and 2015, respectively. In total, 21,150 (72%) patients in the 2005 cohort and 23,947 (64%) in the 2015 cohort received at least one medication review during follow‐up. Conclusions: The proportion of patients continuing longer term treatment was small, whilst the number of recorded mental health and medication reviews offers some reassurance that prescribing remained appropriate. [ABSTRACT FROM AUTHOR]

Compulsive sexual behavior disorder (CSBD) is a burgeoning diagnostic construct. No systematic reviews of CSBD pharmacotherapy interventions have been conducted. We addressed this gap using a three-aim approach. We reviewed researchers' theoretical arguments for various pharmacotherapies, outcomes from pharmacotherapy trials, and the generalizability of the extant findings. Our review included k = 13 studies, with n = 141 participants. An opioid model of reward seeking was the most popular framework, though inconsistently specified. A serotonin model was also documented, though with few details. Naltrexone was the most prominently examined pharmacotherapy and the only medication that reliably demonstrated a therapeutic effect for some (but not all) indicators compared to placebo. Paroxetine and citalopram were also documented in placebo-controlled trials, though their incremental benefit compared to placebo is suspect. Several additional pharmacotherapies have been documented in case series contexts. Across studies, only one female participant was identified. All trials were conducted in developed nations, and race was rarely assessed. We conclude that the case for pharmacotherapy for CSBD is limited and should preferably not occur outside of clinical trial contexts. Naltrexone offers the best evidence for a potential research program, though new theoretically informed approaches are welcome. Finally, we call for additional pharmacotherapy research in women and non-White populations. [ABSTRACT FROM AUTHOR]

Objective: Morbid hunger and hyperphagia (MHH) is a rare neurological disorder that can manifest following damage to the right frontal and temporal lobes. It can lead to detrimental short and long-term complications such as electrolyte imbalances, obesity, and cardiovascular diseases. This report details the case of a young male patient who developed MHH five months post-traumatic brain injury. Method: Single-case report. The patient exhibited colossal appetite, overeating, food-demanding behavior, and rapid weight gain. The prescription of quetiapine to manage his visual and auditory hallucinations was suspected of exacerbating the hyperphagia. A comprehensive, multidisciplinary rehabilitation approach was implemented, encompassing a meticulous dietary regime, environmental modifications, behavioral management, physical activities, therapeutic exercises, and pharmacological interventions, which included switching the anti-psychotics and introducing low-dose escitalopram. Results: Over the course of 6 months, the MHH gradually subsided, and the patient achieved the target bodyweight. The Glasgow Outcome Scale-Extended improved from 3 to 5. Conclusion: This is the first report on the use of escitalopram to manage secondary eating disorders. Our findings underscore the necessity to formally catalog and recognize disorders like MHH in diagnostic classifications to facilitate the systematic study of their pathophysiology, natural history, prognosis, and management strategies. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC), representing 85% of lung cancer cases, is characterized by its heterogeneity and progression through distinct stages. This study applied Weighted Gene Coexpression Network Analysis (WGCNA) to explore the molecular mechanisms of NSCLC and identify potential therapeutic targets. Gene expression data from the GEO database were analyzed across four NSCLC stages (NSCLC1, NSCLC2, NSCLC3, and NSCLC4), with the NSCLC2 dataset selected as the reference for module preservation analysis. WGCNA identified eight highly preserved modules— Cyan, Yellow, Red, Dark Turquoise, Turquoise, White, Purple, and Royal Blue—across datasets, which were enriched in key pathways such as “Cell cycle” and “Pathways in cancer”, involving processes like cell division and inflammatory responses. Hub genes, including PLK1, CDK1, and EGFR, emerged as critical regulators of tumor proliferation and immune responses. Estrogen receptor ESR1 was also highlighted, correlating with improved survival outcomes, suggesting its potential as a prognostic marker. Signature-based drug repurposing analysis identified promising therapeutic candidates, including GW-5074, which inhibits RAF and disrupts the EGFR–RAS–RAF–MEK–ERK signaling cascade, and olomoucine, a CDK1 inhibitor. Additional candidates like pinocembrin, which reduces NSCLC cell invasion by modulating epithelial-mesenchymal transition, and citalopram, an SSRI with anti-carcinogenic properties, were also identified. These findings provide valuable insights into the molecular underpinnings of NSCLC and suggest new directions for therapeutic strategies through drug repurposing. [ABSTRACT FROM AUTHOR]

Background/Objectives: Many pregnant women globally suffer from depression and are routinely prescribed selective serotonin reuptake inhibitors (SSRIs). These drugs function by blocking the re-uptake of serotonin by the serotonin transporter (SERT) into neurons, resulting in its accumulation in the presynaptic cleft. Despite a large amount of research suggesting a potential link to neurodevelopmental disorders in children whose mothers took these drugs during pregnancy, their possible adverse effects are still debated, and results are contradictory. On the other hand, there is an immediate need for improved cell-based models for developmental neurotoxicity studies (DNT) to minimize the use of animals in research. Methods: In this study, we aimed to assess the effects of clinically relevant concentrations of paroxetine (PAR), fluoxetine (FLX), and citalopram (CIT)—on maturing neurons derived from human neural stem cells using multiple endpoints. Results: Although none of the tested concentrations of FLX, CIT, or PAR significantly affected cell viability, FLX (10 µM) exhibited the highest reduction in viability compared to the other drugs. Regarding neurite outgrowth, CIT did not have a significant effect. However, FLX (10 µM) significantly reduced both mean neurite outgrowth and mean processes, PAR significantly reduced mean processes, and showed a trend of dysregulation of multiple genes associated with neuronal development at therapeutic-relevant serum concentrations. Conclusions: Transcriptomic data and uptake experiments found no SERT activity in the system, suggesting that the adverse effects of FLX and PAR are independent of SERT. [ABSTRACT FROM AUTHOR]

Background: In placebo‐controlled clinical trials, reboxetine, a selective noradrenaline reuptake inhibitor, increases urethral pressure and relieves stress urinary incontinence symptoms in women. Considering the close connection in neural regulation of the external urethral and anal sphincters, we hypothesized that reboxetine may also enhance anal sphincter pressure. Conversely, it is believed that selective serotonin reuptake inhibitors may contribute to fecal incontinence by reducing anal sphincter pressure. In this study, we investigated the effect of reboxetine and citalopram on anal opening pressure in healthy female volunteers. Methods: In a double‐blind, three‐way crossover trial, 24 female participants received single doses of 40 mg citalopram, 8 mg reboxetine, and matching placebos, with a minimum of 8‐day washout between sessions. Using anal acoustic reflectometry, we measured anal opening pressure during both resting and squeezing conditions at the estimated time of peak plasma concentration for both study drugs. Key Results: Compared with placebo, reboxetine increased anal opening pressure with 23.4 cmH2O (95% confidence interval [CI] 16.5–30.2, p < 0.001) during rest and with 22.5 cmH2O (95% CI 15.2–29.8, p < 0.001) during squeeze. Citalopram did not change anal opening pressure statistically significantly compared to placebo. Conclusions & Inferences: An 8‐mg dose of reboxetine increased anal opening pressure substantially in healthy women, suggesting potential benefits for fecal incontinence symptoms. In contrast, a 40‐mg dose of citalopram showed a marginal and statistically insignificant effect on anal opening pressure, indicating that selective serotonin reuptake inhibitors do not contribute to fecal incontinence by reducing anal sphincter tone. [ABSTRACT FROM AUTHOR]

Background: Depression is the most common mental illness in the world, found in nearly three in ten adolescents globally. This study aims to evaluate the prevalence of antidepressant prescriptions and the types of antidepressant therapy administered among adolescents diagnosed with depression in Germany. Methods: This retrospective cohort study, based on data provided by 30 child and adolescent psychiatrists, included adolescents aged 13–17 years with an initial diagnosis of depression between 2010 and 2022 (index date) documented in the IQVIATM Disease Analyzer database. Kaplan–Meier curves were used to investigate the one-year cumulative incidence of antidepressant prescriptions stratified by age, sex, and depression severity. Multivariable Cox regression analyses were used to assess the association between age, sex, depression severity, co-diagnoses, and antidepressant drug prescription. Results: A total of 6338 adolescents (mean age: 16 years, 67% female, 59% with moderate depression) were available. The cumulative incidence of antidepressant prescriptions was 61% and increased with age from 13 years old to 17 years old. Fluoxetine was the most prescribed drug, followed by Sertraline, Escitalopram, Serotonin and Norepinephrine reuptake inhibitors, herbal medications, and Mirtazapine. Obsessive–compulsive disorder and eating disorders were found to be significantly associated with antidepressant prescriptions within the spectrum of co-diagnosed conditions. Conclusions: Higher age, depression severity, and a co-diagnosis of an obsessive–compulsive disorder or eating disorder were significantly positively associated with antidepressant prescriptions in adolescents. Fluoxetine was the most frequently prescribed drug for depression. [ABSTRACT FROM AUTHOR]

Previous investigations have revealed the role of GABAergic and serotonergic systems in the modulation of pain behavior. This research aimed to examine the effects of intracerebroventricular (i.c.v.) infusion of GABAA receptor agonist and antagonist as well as citalopram on pain behavior in male mice. For i.c.v. microinjection, a guide cannula was surgically implanted in the left lateral ventricle of male mice. Pain behavior was evaluated using a tail-flick test. Tail flick latency was measured in each experimental group of mice every 15 min (for 60 min). I.c.v. microinjection of muscimol (0.5 and 1 µg/mouse; GABAA receptor agonist) into the left lateral ventricle dose-dependently induced an antinociceptive effect. On the other hand, i.c.v. infusion of bicuculline (1 µg/mouse; GABAA receptor antagonist) induced a hyperalgesia response. Moreover, intraperitoneally (i.p.) administration of citalopram (8 mg/kg) produced an antinociceptive effect. Co-treatment of citalopram (8 mg/kg) along with muscimol (0.25 µg/mouse) or bicuculline (0.25 µg/mouse) potentiated the antinociceptive effect produced by citalopram. We found an additive antinociceptive effect of citalopram and muscimol in male mice. In conclusion, our results suggested an interaction between citalopram and GABAergic agents on the modulation of pain behavior in male mice.

Introduction: Stroke is a rapidly progressive neurological disorder of cerebrovascular origin, after which most patients suffer from motor impairment. Yet, clinical studies have not fully confirmed or rejected the use or non-use of selective serotonin reuptake inhibitor drugs. The aim was to investigate the effect of citalopram and fluoxetine on motor function after stroke in acute cerebral stroke patients.Methods: This is a double-blind clinical trial study on 90 patients in 3 groups including fluoxetine 20, citalopram 20 and placebo daily for 90 days along with physiotherapy. Fogel-Meier score was assigned to all patients included in the study. The grading of the test is based on the direct observation of the performance, where each item is scored from 0-2. A 21-item questionnaire was also used to determine the severity of depression. Repeated measure Anova was used for data analysis.Results: The average age of the studied subjects was 61.9±8.02 years. 64.4% were male. There was no statistically significant difference in the demographic and clinical characteristics of patients in three groups in baseline. The average motor function score one, two and three months after the intervention was the highest in the fluoxetine group and the lowest in the placebo group, and this difference was statistically significant (P

Introduction: Depression therapy has been linked to negative effects on energy metabolism, which can be attributed to various factors, including an ongoing inflammatory process commonly seen in metabolic disorders. Unhealthy lifestyle choices of patients and the impact of antidepressants on body weight and lipid and glucose metabolism also contribute to these metabolic side effects. Although not as pronounced as other psychopharmaceuticals, the increasing use of antidepressants raises concerns about their potential impact on public health. The study aimed to evaluate the short- and long-term effects of the antidepressant citalopram and its long-term combination with a special diet on metabolic parameters in mice. Methods: Animals were randomly divided into 5 groups – control, control + special diet, citalopram (10 mg/kg for 35 days), citalopram + special diet (10 mg/kg for 35 days), and citalopram (10 mg/kg for 7 days). After a described time of administration, animals were anesthetized, blood and fat and liver tissues were collected. Biochemical parameters of lipid metabolism (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides) and glucose were analyzed using spectrophotometry and relevant adipokines and cytokines were evaluated by ELISA. Results: After a week of application of citalopram, we observed dyslipidemia that persisted even at the end of the 5-week experiment. Furthermore, after 5 weeks of citalopram administration, we observed a significant decrease in body weight gain and decreased leptin levels. Changes in lipid metabolism, higher levels of adipokines leptin and PAI-1 were observed due to the special diet after 5 weeks. Conclusions: Our research suggests that the effects of citalopram and a diet on the metabolism of mice can be significant, both in the short term (1 week) and in the long term (5 weeks). [ABSTRACT FROM AUTHOR]

Objective: There is growing evidence that adding non-steroidal anti-inflammatory drugs to some psychopharmacological treatments may help to improve symptoms in patients suffering from major depressive disorder. The present study examined the therapeutic efficacy of adding celecoxib to escitalopram and the safety of doing so. Method: In this double-blind randomized controlled trial, 60 patients with major depressive disorder were randomly assigned to either treatment with escitalopram plus celecoxib (intervention group) or escitalopram and placebo. All patients were evaluated blind to treatment group with the Hamilton Depression Rating Scale (HDRS) before the intervention as well at 4 and 8 weeks after initiating treatment. Chi-square and paired t-test were used to examine between-group differences at those assessment times. Results: There was no significant difference in depressive symptoms between intervention and placebo groups at baseline. However, at 4 and 8 weeks after the beginning of treatment, there were significant between-group differences in HDRS scores, favoring the intervention group. No between-group differences were found in treatment-related side effects. Conclusions: Adding celecoxib to escitalopram may improve symptoms of depression in patients with major depressive disorder without increasing the risk of drug-related side effects. [ABSTRACT FROM AUTHOR]

Selective serotonin reuptake inhibitors (SSRIs) are widely used drugs for the treatment of depression. Citalopram is one of the most prescribed SSRIs that is useful for the treatment of depression, obsessive–compulsive disorder, and anxiety disorders. On the other hand, crocin (active constitute of saffron) has pro-cognitive and mood enhancer effects. Also, both citalopram and crocin affect the function and expression of brain-derived neurotrophic factor (BDNF) and synaptophysin, two molecular factors that are involved in cognitive functions and mood. In the present study, we aim to investigate the interaction effect of citalopram and crocin on rats' performance in the open field test (locomotor activity and anxiety-like behavior) and the shuttle box (passive avoidance memory). Citalopram was injected at the doses of 10, 30, and 50 mg/kg, and crocin was injected at the dose of 50 mg/kg; all administrations were intraperitoneal. Real-time PCR was used to assess the expression level of BDNF and synaptophysin in the hippocampus. The results showed that citalopram (30 and 50 mg/kg) impaired passive avoidance memory and decreased BDNF and synaptophysin expression in the hippocampus, while crocin reversed memory impairment, and BDNF and synaptophysin expression in the hippocampus of rats received citalopram 30 mg/kg. Also, crocin partially showed these effects in rats that received citalopram 50 mg/kg. The results of the open field test were unchanged. In conclusion, we suggested that BDNF and synaptophysin may be involved in the effects of both citalopram and crocin. [ABSTRACT FROM AUTHOR]

Pharmaceuticals have been classified as an environmental concern due to their increasing consumption globally and potential environmental impact. We examined the toxicity of sediment‐associated diclofenac and citalopram administered as both single compounds and in a mixture to the sediment‐living amphipod Corophium volutator. This laboratory‐based study addressed the following research questions: (1) What is the toxicity of sediment‐associated diclofenac and citalopram to C. volutator? (2) Can the mixture effect be described with either of the two mixture models: concentration addition (CA) or independent action (IA)? (3) What is the importance of the choice of (i) exposure measure (start concentration, time‐weighted average [TWA], full exposure profile) and (ii) effect model (concentration–response vs. the toxicokinetic–toxicodynamic model general unified threshold model for survival in its reduced form [GUTS‐RED]) for the derived effect concentration values? Diclofenac was more toxic than citalopram to C. volutator as a single compound (10‐day exposure). Diclofenac exposure to C. volutator provided median lethal concentrations (LC50s) within the same range (11 µg g−1 dry wt sediment) using concentration–response based on TWA and both GUTS‐RED models. However, concentration–response based on measured start concentrations provided an approximately 90% higher LC50 (21.6 ± 2.0 µg g−1 dry wt sediment). For citalopram, concentration–response parameters were similar regardless of model or concentration used (LC50 85–97 µg g−1 dry wt sediment), however, GUTS‐RED with the assumption of individual tolerance resulted in a lower LC50 (64.9 [55.3–74.8] µg g−1 dry wt sediment). The mixture of diclofenac and citalopram followed the CA quite closely, whereas the result was synergistic when using the IA prediction. In summary, concentration–response based on TWA and GUTS‐RED provided similar and reasonably good fits compared to the data set. The implications are that GUTS‐RED will provide a more flexible model, which, in principle, can extend beyond the experimental period and make predictions based on variable exposure profiles (toxicity at different time frames and at different variable exposure scenarios) compared to concentration–response, which provides contaminant toxicity at one point in time. Environ Toxicol Chem 2024;43:1767–1777. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. [ABSTRACT FROM AUTHOR]

Selective serotonin reuptake inhibitors (SSRIs), including citalopram, are widely used antidepressants during pregnancy. However, the effects of prenatal exposure to citalopram on neurodevelopment remain poorly understood. We aimed to investigate the impact of citalopram exposure on early neuronal differentiation of human embryonic stem cells using a multi-omics approach. Citalopram induced time- and dose-dependent effects on gene expression and DNA methylation of genes involved in neurodevelopmental processes or linked to depression, such as BDNF, GDF11, CCL2, STC1, DDIT4 and GAD2. Single-cell RNA-sequencing analysis revealed distinct clusters of stem cells, neuronal progenitors and neuroblasts, where exposure to citalopram subtly influenced progenitor subtypes. Pseudotemporal analysis showed enhanced neuronal differentiation. Our findings suggest that citalopram exposure during early neuronal differentiation influences gene expression patterns associated with neurodevelopment and depression, providing insights into its potential neurodevelopmental impact and highlighting the importance of further research to understand the long-term consequences of prenatal SSRI exposure. [ABSTRACT FROM AUTHOR]

Background: The serotonin (5-HT) system can manipulate the processing of exogenous L-DOPA in the DA-denervated striatum, resulting in the modulation of L-DOPA-induced dyskinesia (LID). Objective: To characterize the effects of the serotonin precursor 5-hydroxy-tryptophan (5-HTP) or the serotonin transporter (SERT) inhibitor, Citalopram on L-DOPA-induced behavior, neurochemical signals, and underlying protein expressions in an animal model of Parkinson's disease. Methods: MitoPark (MP) mice at 20 weeks of age, subjected to a 14-day administration of L-DOPA/Carbidopa, displayed dyskinesia, referred to as LID. Subsequent investigations explored the effects of 5-HT-modifying agents, such as 5-HTP and Citalopram, on abnormal involuntary movements (AIMs), locomotor activity, neurochemical signals, serotonin transporter activity, and protein expression in the DA-denervated striatum of LID MP mice. Results: 5-HTP exhibited duration-dependent suppressive effects on developing and established LID, especially related to abnormal limb movements observed in L-DOPA-primed MP mice. However, Citalopram, predominantly suppressed abnormal axial movement induced by L-DOPA in LID MP mice. We demonstrated that 5-HTP could decrease L-DOPA-upregulation of DA turnover rates while concurrently upregulating 5-HT metabolism. Additionally, 5-HTP was shown to reduce the expressions of p-ERK and p-DARPP-32 in the striatum of LID MP mice. The effect of Citalopram in alleviating LID development may be attributed to downregulation of SERT activity in the dorsal striatum of LID MP mice. Conclusions: While both single injection of 5-HTP and Citalopram effectively mitigated the development of LID, the difference in mitigation of AIM subtypes may be linked to the unique effects of these two serotonergic agents on L-DOPA-derived DA and 5-HT metabolism. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) dysfunction is one of the most important mechanisms underlying depression. It seems that selective serotonin reuptake inhibitors (SSRIs) improve depression via affecting BDNF level. In this systematic review, for the first time, we aimed to review the effect of three SSRIs including fluoxetine, escitalopram, and sertraline, on both depression and BDNF level in preclinical and clinical studies. PubMed electronic database was searched, and 193 articles were included in this study. After reviewing all manuscripts, only one important difference was found: subjects. We found that SSRIs induce different effects in animals vs. humans. Preclinical studies showed many controversial effects, while human studies showed only two effects: improvement of depression, with or without the improvement of BDNF. However, most studies used chronic SSRIs treatment, while acute SSRIs were not effectively used and evaluated. In conclusion, it seems that SSRIs are reliable antidepressants, and the improvement effect of SSRIs on depression is not dependent to BDNF level (at least in human studies). [ABSTRACT FROM AUTHOR]

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