Mindfulness Meditation vs Escitalopram for Treatment of Anxiety Disorders: Secondary Analysis of a Randomized Clinical Trial.

This secondary analysis of a randomized clinical trial assesses patient-reported anxiety, depression, and quality of life among patients receiving mindfulness-based stress reduction vs escitalopram for the treatment of anxiety disorders.

SSRI antidepressant citalopram reverses the Warburg effect to inhibit hepatocellular carcinoma by directly targeting GLUT1.

Selective serotonin reuptake inhibitors (SSRIs) have shown promise in cancer therapy, particularly for hepatocellular carcinoma (HCC), but their molecular targets and mechanisms remain unclear. Here, we show that SSRIs exhibit significant anti-HCC effects independent of their classical target, the serotonin reuptake transporter (SERT). Using global inverse gene expression profiling, drug affinity responsive target stability assays, and in silico molecular docking, we demonstrate that citalopram targets glucose transporter 1 (GLUT1), resulting in reduced glycolytic flux. A mutant GLUT1 variant at the citalopram binding site (E380) diminishes the drug's inhibitory effects on the Warburg effect and tumor growth. In preclinical models, citalopram dampens the growth of GLUT1high liver tumors and displays a synergistic effect with anti-PD-1 therapy. Retrospective analysis reveals that SSRI use correlates with a lower risk of metastasis among patients with HCC. Our study describes a role for SSRIs in cancer metabolism, establishing a rationale for their repurposing as potential anti-cancer drugs for HCC.

Modulation of neural oscillations in escitalopram treatment: a Canadian biomarker integration network in depression study.

Current pharmacological agents for depression have limited efficacy in achieving remission. Developing and validating new medications is challenging due to limited biological targets. This study aimed to link electrophysiological data and symptom improvement to better understand mechanisms underlying treatment response. Longitudinal changes in neural oscillations were assessed using resting-state electroencephalography (EEG) data from two Canadian Biomarker Integration Network in Depression studies, involving pharmacological and cognitive behavioral therapy (CBT) trials. Patients in the pharmacological trial received eight weeks of escitalopram, with treatment response defined as ≥ 50% decrease in Montgomery-Åsberg Depression Rating Scale (MADRS). Early (baseline to week 2) and late (baseline to week 8) changes in neural oscillation were investigated using relative power spectral measures. An association was found between an initial increase in theta and symptom improvement after 2 weeks. Additionally, late increases in delta and theta, along with a decrease in alpha, were linked to a reduction in MADRS after 8 weeks. These late changes were specifically observed in responders. To assess specificity, we extended our analysis to the independent CBT cohort. Responders exhibited an increase in delta and a decrease in alpha after 2 weeks. Furthermore, a late (baseline to week 16) decrease in alpha was associated with symptom improvement following CBT. Results suggest a common late decrease in alpha across both treatments, while modulatory effects in theta may be specific to escitalopram treatment. This study offers insights into electrophysiological markers indicating a favorable response to antidepressants, enhancing our comprehension of treatment response mechanisms in depression.

Pharmacogenomic augmented machine learning in electronic health record alerts: A health system-wide usability survey of clinicians.

Pharmacogenomic (PGx) biomarkers integrated using machine learning can be embedded within the electronic health record (EHR) to provide clinicians with individualized predictions of drug treatment outcomes. Currently, however, drug alerts in the EHR are largely generic (not patient-specific) and contribute to increased clinician stress and burnout. Improving the usability of PGx alerts is an urgent need. Therefore, this work aimed to identify principles for optimal PGx alert design through a health-system-wide, mixed-methods study. Clinicians representing multiple practices and care settings (N = 1062) in urban, rural, and underserved regions were invited to complete an electronic survey comparing the usability of three drug alerts for citalopram, as a case study. Alert 1 contained a generic warning of pharmacogenomic effects on citalopram metabolism. Alerts 2 and 3 provided patient-specific predictions of citalopram efficacy with varying depth of information. Primary outcomes included the System's Usability Scale score (0-100 points) of each alert, the perceived impact of each alert on stress and decision-making, and clinicians' suggestions for alert improvement. Secondary outcomes included the assessment of alert preference by clinician age, practice type, and geographic setting. Qualitative information was captured to provide context to quantitative information. The final cohort comprised 305 geographically and clinically diverse clinicians. A simplified, individualized alert (Alert 2) was perceived as beneficial for decision-making and stress compared with a more detailed version (Alert 3) and the generic alert (Alert 1) regardless of age, practice type, or geographic setting. Findings emphasize the need for clinician-guided design of PGx alerts in the era of digital medicine.

Serotonin transporter 5-HTTLPR polymorphism and escitalopram treatment response in patients with major depressive disorder.

BACKGROUND: There is no doubt that genetic factors have the potential to predict the therapeutic outcomes of antidepressants in patients with major depressive disorder (MDD). This study investigated the association between genetic variants involved in serotonin signaling and brain-derived neurotrophic factor (BDNF) with the response to escitalopram treatment in patients with MDD. We focused on examining the influence of 5-HTTLPR (ins/del), HTR2A rs9316233, BDNF rs962369, CYP2C19 and CYP2D6 on the clinical response to escitalopram. METHODS: The patients were recruited from outpatient psychiatric clinics in Kosice between 2020 and 2022. Patients received escitalopram for 12 weeks at a fixed dose of 10 mg daily. Clinical assessment was done at baseline and after 4, 8, and 12 weeks using the 21-item Hamilton Depression Rating Scale (HAMD-21). RESULTS: At the end of week 12, 57 (65%) patients were defined as responders to escitalopram treatment, while 31 (35%) patients were non-responders. Genotyping revealed that carriers of the short allele (S) of 5-HTTLPR exhibit a significantly lower therapeutic response to escitalopram measured by HAMD-21 than the long allele (L) carriers (p = 0.01). Adjusting for CYP2C19 and CYP2D6 metabolizer genotypes did not modify the observed relationship between 5-HTTLPR and treatment response. No significant associations were found for HTR2A rs9316233 or BDNF rs962369 variants and the treatment response. CONCLUSIONS: These findings underscore the utility of 5-HTTLPR genotyping in guiding escitalopram therapy for MDD patients. Further research with larger cohorts is warranted to validate these results and elucidate additional genetic determinants of antidepressant efficacy.

Acupuncture and Escitalopram for Treating Major Depression Clinical Study (AE-TMDCS): protocol for a factorial randomised controlled trial.

INTRODUCTION: Major depressive disorder (MDD), the second leading cause of disability globally, is considered to be associated with a consequent deterioration in the quality of life and can lead to a major economic burden on medical service and suicide-related costs. Previous research has shown that acupuncture may be beneficial for treating MDD. However, there is a lack of rigorous evidence from previous studies comparing acupuncture with antidepressant medications. This study aims to assess the therapeutic potential of acupuncture in the management of depressive disorders. METHODS AND ANALYSIS: A multicentre, randomised, participant-blind, sham-controlled, 2×2 factorial clinical trial, Acupuncture and Escitalopram for Treating Major Depression Clinical Study, aims to compare the efficacy of acupuncture versus escitalopram in treating depression. This study will be conducted at three hospitals in China, enrolling 260 patients with moderate-to-severe major depression, as defined by DSM-5 criteria and Hamilton Depression Rating Scale (HDRS-17) Scores above 17. Participants will be randomly assigned in equal proportions to one of four groups (acupuncture/escitalopram, sham acupuncture/escitalopram, acupuncture/placebo and sham acupuncture/placebo) and undergo 30 sessions across 10 weeks. The primary outcome is change in HDRS-17 Score and secondary outcomes include BDI, Clinical Global Impression, Generalised Anxiety Disorder-7 and Mini-Mental State Examination Scores, alongside potential biological markers. ETHICS AND DISSEMINATION: Ethical approval for the study was granted by the Ethics Committees of the Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine (2023-7th-HIRB-020), Shanghai Mental Health Centre (2022-86) and Shanghai Pudong New Area Hospital of Traditional Chinese Medicine (2023-003). Informed consent will be obtained from all participants. The study's findings are intended for publication in a scholarly journal. TRIAL REGISTRATION: NCT05901571.

Serotonin syndrome caused by escitalopram in Parkinson's disease psychosis: a case report.

BACKGROUND: Serotonin syndrome and Parkinson's disease (PD) are two diseases whose symptoms partially overlap; this poses challenges in distinguishing them in clinical practice. Early manifestations such as tremor, akathisia, diaphoresis, hypertonia and hyperreflexia are common in mild-to-moderate serotonin syndrome and can also occur in PD. Without prompt recognition and treatment, serotonin syndrome can rapidly progress, potentially leading to severe complications such as multiple organ failure within hours. Given their disparate treatment strategies, accurate clinical distinction is crucial for effective treatment. This case study explores a patient with serotonin syndrome triggered by escitalopram in the context of PD psychosis (PDP), providing insights into diagnosis and treatment planning. CASE PRESENTATION: A 75-year-old Asian woman with a one-year history of PD, a two-month history of PDP, and a six-year history of depression presented with symptoms including hyperreflexia, tremor, hypertonia, impaired level of consciousness, and inappropriate behavior following a recent one-month adjustment in medication. Initially suspected of being drug-induced parkinsonism or worsening PD, therapeutic drug monitoring revealed warning levels of escitalopram. Subsequent diagnoses confirmed serotonin syndrome. This syndrome may result from increased cortical serotonin activity at the serotonin2A receptor due to dopamine and serotonin imbalances in PDP, compounded by increased dopamine-mediated serotonin release. Additionally, being an intermediate metabolizer of cytochrome P450 enzyme 2C19, the patient experienced excessive escitalopram accumulation, exacerbating her condition. CONCLUSIONS: This case underscores the critical need to differentiate between symptoms of serotonin syndrome and PD, particularly in manifestations like tremor and hypertonia. Careful consideration of receptor profiles in patients with PDP is essential when selecting antidepressants to mitigate the risk of serotonin syndrome.

Effect of meditation or escitalopram on work performance in patients with anxiety disorders.

OBJECTIVE: This study aimed to 1) examine how psychopharmacotherapy and mindfulness-based stress reduction (MBSR) influence absenteeism and job performance among individuals with anxiety disorders and 2) compare the effectiveness of these treatments in improving work performance. METHODS: Adults (N = 67) with a primary anxiety disorder were recruited to participate in the study. Participants were randomized to escitalopram, a common treatment for anxiety disorders, or MBSR. Absenteeism and job performance were measured with the Health and Work Performance (HPQ) questionnaire prior to treatment and at the week 24 follow up. RESULTS: At week 24, individuals in the escitalopram arm and the MBSR arm showed significant improvements in partial days of missed work due to mental/physical health problems from baseline (1.00 [0.00-2.50] to 0.00 [0.00 = 1.00], p = .034 and 0.00 [0.00-2.00] to 0.00 [0.00 = 1.00], p = .001, respectively). In the MBSR arm only, job performance increased from baseline to week 24 (65.00 [50.00-80.00] to 75.00 [67.50-82.50], p = .017). None of the outcome variables significantly varied by group at baseline or week 24. CONCLUSIONS: Our study finds evidence that MBSR improves work performance equivalently to SSRI medication among individuals with anxiety disorders. Given the limitations of SSRIs, MBSR should be considered as an alternative to individuals who desire improved anxiety symptoms and work outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03522844.

Bacillus subtilis JATP3 improved the immunity of weaned piglets by improving intestinal flora and producing citalopram.

The purpose of this study was to evaluate the ability of Bacillus subtilis JATP3 to stimulate immune response and improve intestinal health in piglets during the critical weaning period. Twelve 28-day-old weaned piglets were randomly divided into two groups. One group was fed a basal diet, while the other group was fed a basal diet supplemented with B. subtilis JATP3 (1 × 109 CFU/mL; 10 mL) for 28 days. The results revealed a significant increase in the intestinal villus gland ratio of weaned piglets following the inclusion of B. subtilis JATP3 (P < 0.05). Inclusion of a probiotic supplement improve the intestinal flora of jejunum and ileum of weaned piglets. Metabolomics analysis demonstrated a notable rise in citalopram levels in the jejunum and ileum, along with elevated levels of isobutyric acid and isocitric acid in the ileum. The results of correlation analysis show that indicated a positive correlation between citalopram and microbial changes. Furthermore, the probiotic-treated group exhibited a significant upregulation in the relative expression of Claudin, Zonula Occludens 1 (ZO-1), and Interleukin 10 (IL-10) in the jejunum and ileum, while displaying a noteworthy reduction in the relative expression of Interleukin 1ß (IL-1ß). Overall, these findings suggest that B. subtilis JATP3 can safeguard intestinal health by modulating the structure of the intestinal microbiota and their metabolites, wherein citalopram might be a key component contributing to the therapeutic effects of B. subtilis JATP3.

A large-scale observational comparison of antidepressants and their effects.

BACKGROUND: Selective Serotonin Reuptake Inhibitors (SSRIs) represent a diverse class of medications widely prescribed for depression and anxiety. Despite their common use, there is an absence of large-scale, real-world evidence capturing the heterogeneity in their effects on individuals. This study addresses this gap by utilizing naturalistic search data to explore the varied impact of six different SSRIs on user behavior. METHODS: The study sample included ∼508 thousand Bing users with searches for one of six SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) from April-December 2022, comprising 510 million queries. Cox proportional hazard models were employed to examine 30 topics (e.g., shopping, tourism, health) and 195 health symptoms (e.g., anxiety, weight gain, impotence), using each SSRI as a reference. We assessed the relative hazard ratios between drugs and, where feasible, ranked the SSRIs based on their observed effects. We used Cox proportional hazard models in order to account for both the likelihood of users searching for a particular topic or symptom and the associated time to that search. The temporal aspect aided in distinguishing between potential symptoms of the disorder, short-term medication side effects, and later appearing side effects. RESULTS: Differences were found in search behaviors associated with each SSRI. E.g., fluvoxamine was associated with a significantly higher likelihood of searching weight gain compared to all other SSRIs (HRs 1.85-2.93). Searches following citalopram were associated with significantly higher rates of later impotence queries compared to all other SSRIs (HRs 5.11-7.76), except fluvoxamine. Fluvoxamine was associated with a significantly higher rate of health related searches than all other SSRIs (HRs 2.11-2.36). CONCLUSIONS: Our study reveals new insights into the varying SSRI impacts, suggesting distinct symptom profiles. This novel use of large-scale, naturalistic search data contributes to pharmacovigilance efforts, enhancing our understanding of intra-class variation among SSRIs, potentially uncovering previously unidentified drug effects.

Efficacy of selective serotonin reuptake inhibitors-related antidepressants in Alzheimer's disease: a meta-analysis.

OBJECTIVE: To study the effects of selective serotonin reuptake inhibitors (SSRIs) on cognitive functions, mental improvements, and adverse effects in patients with Alzheimer's disease (AD). METHODS: Registered in INPLASY (INPLASY202450004), five drugs (citalopram, s-citalopram, quetiapine, olanzapine, and sertraline) were selected as representatives. A comprehensive search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library up to May 15, 2024. Search terms were combined using Boolean operators, specifically 'AND' between different categories (e.g., 'Alzheimer's Disease' AND 'SSRIs') and 'OR' within the same category (e.g., 'citalopram OR s-citalopram OR quetiapine OR olanzapine OR sertraline'), to ensure a thorough retrieval of relevant studies. The selection followed rigorous inclusion and exclusion criteria for meta-analysis. RESULTS: Fourteen articles from 1118 were selected for meta-analysis. The indicators, including Neuropsychiatric Inventory (NPI), Mini-Mental State Examination (MMSE), Brief Psychiatric Rating Scale (BPRS), and Cornell Scale for Depression in Dementia (CSDD), were used to assess the effects of the drugs on AD treatment. According to the results of NPI, CSDD, BPRS, MMSE, and security assessments, the five antidepressants have significant advantages in AD treatment compared with placebo, while the MMSE of the patient treated with the antidepressants did not show notable changes compared with patients treated only with placebo. Statistical analyses were conducted using Review Manager 5.3, employing random-effects models to account for study heterogeneity and sensitivity analyses to test the robustness of our findings. CONCLUSION: This study suggests that SSRI-related antidepressants have great potential values in AD treatment, and further research on the application of SSRI-related antidepressants in AD treatment is necessary.

Lack of Acute Agomelatine Effect in a Model of Social Anxiety in Healthy Volunteers: A Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Agomelatine is an antidepressant drug that acts as an agonist of melatoninergic MT1/2 receptors and an antagonist of serotonergic 5-HT2C receptors. Studies suggest that agomelatine has anxiolytic properties in social anxiety, but there are no studies that assessed the effects of this compound in human experimental anxiety induced by a public speaking test. The objective of our investigation was to assess the effects of agomelatine on human experimental anxiety using the Simulation Public Speaking Test (SPST). METHODS: Agomelatine (25 mg, n = 14), citalopram (20 mg, n = 14), venlafaxine (75 mg, n = 14), or placebo (n = 14) were administered in single doses to healthy volunteers in a double-blind study. Subjective anxiety was assessed with the Visual Analogue Mood Scale. Arterial blood pressure, heart rate, and blood levels of prolactin and cortisol were also recorded, as well as plasma levels of the 3 drugs. RESULTS: The SPST induced significant subjective, physiological, and hormonal effects in all groups. The SPST also increased the anxiety and decreased mental sedation Visual Analogue Mood Scale factors during the anticipatory and performance phases of the test. Citalopram increased anxiety during the test in females, whereas agomelatine and venlafaxine were not different from placebo. CONCLUSIONS: Confirming previous results, a serotonin selective reuptake inhibitor, citalopram, caused an anxiogenic effect in the SPST only in females. Acute administration of a low dose of agomelatine failed to modify the behavioral and physiological changes caused by this test. Future studies using higher doses and repeated administration should investigate if agomelatine behavioral and physiological effects could be detected in human experimental anxiety models.

Molecular basis of human noradrenaline transporter reuptake and inhibition.

Noradrenaline, also known as norepinephrine, has a wide range of activities and effects on most brain cell types1. Its reuptake from the synaptic cleft heavily relies on the noradrenaline transporter (NET) located in the presynaptic membrane2. Here we report the cryo-electron microscopy (cryo-EM) structures of the human NET in both its apo state and when bound to substrates or antidepressant drugs, with resolutions ranging from 2.5 Å to 3.5 Å. The two substrates, noradrenaline and dopamine, display a similar binding mode within the central substrate binding site (S1) and within a newly identified extracellular allosteric site (S2). Four distinct antidepressants, namely, atomoxetine, desipramine, bupropion and escitalopram, occupy the S1 site to obstruct substrate transport in distinct conformations. Moreover, a potassium ion was observed within sodium-binding site 1 in the structure of the NET bound to desipramine under the KCl condition. Complemented by structural-guided biochemical analyses, our studies reveal the mechanism of substrate recognition, the alternating access of NET, and elucidate the mode of action of the four antidepressants.

Morbid hunger and hyperphagia post-traumatic brain injury in a young male: good prognosis with escitalopram and multidisciplinary rehabilitation.

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.

Effect of reboxetine and citalopram on anal opening pressure in healthy women: A randomized, double-blind, placebo-controlled crossover study.

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.

Medication-Induced Weight Change Across Common Antidepressant Treatments : A Target Trial Emulation Study.

BACKGROUND: Antidepressants are among the most commonly prescribed medications, but evidence on comparative weight change for specific first-line treatments is limited. OBJECTIVE: To compare weight change across common first-line antidepressant treatments by emulating a target trial. DESIGN: Observational cohort study over 24 months. SETTING: Electronic health record (EHR) data from 2010 to 2019 across 8 U.S. health systems. PARTICIPANTS: 183 118 patients. MEASUREMENTS: Prescription data determined initiation of treatment with sertraline, citalopram, escitalopram, fluoxetine, paroxetine, bupropion, duloxetine, or venlafaxine. The investigators estimated the population-level effects of initiating each treatment, relative to sertraline, on mean weight change (primary) and the probability of gaining at least 5% of baseline weight (secondary) 6 months after initiation. Inverse probability weighting of repeated outcome marginal structural models was used to account for baseline confounding and informative outcome measurement. In secondary analyses, the effects of initiating and adhering to each treatment protocol were estimated. RESULTS: Compared with that for sertraline, estimated 6-month weight gain was higher for escitalopram (difference, 0.41 kg [95% CI, 0.31 to 0.52 kg]), paroxetine (difference, 0.37 kg [CI, 0.20 to 0.54 kg]), duloxetine (difference, 0.34 kg [CI, 0.22 to 0.44 kg]), venlafaxine (difference, 0.17 kg [CI, 0.03 to 0.31 kg]), and citalopram (difference, 0.12 kg [CI, 0.02 to 0.23 kg]); similar for fluoxetine (difference, -0.07 kg [CI, -0.19 to 0.04 kg]); and lower for bupropion (difference, -0.22 kg [CI, -0.33 to -0.12 kg]). Escitalopram, paroxetine, and duloxetine were associated with 10% to 15% higher risk for gaining at least 5% of baseline weight, whereas bupropion was associated with 15% reduced risk. When the effects of initiation and adherence were estimated, associations were stronger but had wider CIs. Six-month adherence ranged from 28% (duloxetine) to 41% (bupropion). LIMITATION: No data on medication dispensing, low medication adherence, incomplete data on adherence, and incomplete data on weight measures across time points. CONCLUSION: Small differences in mean weight change were found between 8 first-line antidepressants, with bupropion consistently showing the least weight gain, although adherence to medications over follow-up was low. Clinicians could consider potential weight gain when initiating antidepressant treatment. PRIMARY FUNDING SOURCE: National Institutes of Health.

A target trial emulation comparing the antidepressant effectiveness of selective serotonin reuptake inhibitors (SSRIs) highlighting the importance of patent-related confounding by indication.

BACKGROUND: The comparative effectiveness of selective serotonin reuptake inhibitors (SSRIs) has been subjected to relatively little research. However, a recent study based on target trial emulation suggested that sertraline may be more effective than escitalopram. AIMS: To investigate whether sertraline, citalopram, and escitalopram differ in their effectiveness-assessed via the risk of psychiatric hospital admission and suicide following treatment initiation. The choice to focus on sertraline, citalopram, and escitalopram was made to limit confounding by indication, as the Danish depression treatment guideline from 2007 specifically listed these three SSRIs as first choice. METHOD: We conducted a target trial emulation based on data from Danish registers. We identified all individuals that initiated treatment for depression with sertraline, citalopram, or escitalopram in the period from January 1, 2007, to March 1, 2019. These individuals were followed until psychiatric hospital admission or suicide (separate analyses), death, 1 year after treatment initiation or end of data. Cox proportional hazards regression adjusted for relevant baseline covariates was performed to emulate randomized treatment allocation, comparing the rate of psychiatric hospital admission and suicide for individuals treated with sertraline (used as reference), citalopram or escitalopram, respectively. For escitalopram, we conducted a sensitivity analysis excluding data from the period during which the drug was sold under patent, as the price of the drug during that time likely entailed a different prescription pattern, increasing the risk of ("patent-related") confounding by indication. RESULTS: We identified 56,865, 118,145, and 31,083 individuals initiating treatment with sertraline, citalopram, and escitalopram, respectively. Using sertraline as reference, the adjusted hazard rate ratio (aHRR) for psychiatric admission was 0.98 (95% CI = 0.91-1.05) for citalopram and 1.21 (95% CI = 1.10-1.32) for escitalopram. Notably, in the sensitivity analysis only including patients initiating treatment after the escitalopram patent had expired, the increased risk of psychiatric hospital admission associated with escitalopram treatment was no longer present (aHRR = 0.98, 95% CI = 0.82-1.18). The results of the analyses of suicide were inconclusive, due to few outcome events. CONCLUSIONS: Sertraline, citalopram, and escitalopram do not seem to have differential effectiveness in the treatment of depression. Taking potential patent-related, time varying, confounding by indication (via severity) into account is critical for pharmacoepidemiological studies, including those employing target trial emulation.

Escitalopram moderately outperforms citalopram towards anti-neuroinflammation and neuroprotection in 6-hydroxydopamine-induced mouse model of Parkinson's disease.

Citalopram and escitalopram are structurally close-related antidepressants and both forms are widely used in the world. We aimed to comparatively evaluate the anti-neuroinflammatory and neuroprotective effects of escitalopram and citalopram in Parkinson's disease (PD) mouse model. Mice were randomly divided into six groups and received 6-hydroxydopamine (6-OHDA) or vehicle administration. The mice were then treated with escitalopram, citalopram or saline for consecutive 7 days. Behaviors, neuroinflammation, neurotransmitters, and neurotoxicity were assessed. Results showed that citalopram but not escitalopram worsened body weight loss and increased freezing time in the PD mice. Both drugs had no impact on the anxiety-like behaviors but ameliorated the depressive-like behaviors as in elevated plus maze and sucrose splash tests. Escitalopram but not citalopram ameliorated motor discoordination in the PD mice as in rotarod test. In accordance, escitalopram but not citalopram attenuated the 6-OHDA-induced nigrostriatal dopaminergic loss. Further mechanistic investigations showed that both drugs mitigated activations of microglia and astrocytes and/or levels of pro-inflammatory cytokines in the PD mice, but escitalopram showed appreciably better effects in the substantia nigra. Neurotransmitter examination in the prefrontal cortex suggested that the two drugs had comparable effects on the disturbed neurotransmitters in the PD mice, but citalopram was prone to disrupt certain normal homeostasis. In conclusion, escitalopram is moderately superior than citalopram to suppress neuroinflammation and to protect against dopaminergic neuronal death and motor discoordination in the 6-OHDA-induced PD mice. Our findings imply that escitalopram shall be prescribed with priority over citalopram to treat PD patients with depression as escitalopram may meanwhile provide greater additional benefits to the patients.

Selective serotonin re-uptake inhibitors affect craniofacial structures in a mouse model.

Selective serotonin re-uptake inhibitors (SSRI) widely used in the treatment of depression, anxiety, obsessive compulsive disorder, fibromyalgia, and migraine are among the most heavily prescribed drug class in the United States (US). Along with an overall rise in SSRI use, these medications are increasingly used by pregnant individuals and recent preclinical and clinical studies have indicated that SSRIs may increase the prevalence of congenital abnormalities and birth defects of the craniofacial region. Our group has developed pre-clinical models of study, including those that mimic the clinical use of SSRI in mice. Here we designed a study to interrogate a commonly prescribed SSRI drug, Citalopram, for its effects on craniofacial and dental development when introduced in utero. Pre-natal exposure to a clinically relevant dose of citalopram resulted in changes in craniofacial form identified by an increase in endocast volume in SSRI exposed postnatal day 15 mouse pups. More specifically, cranial length and synchondrosis length increased in SSRI exposed pups as compared to control pups of the same age. Additionally, growth center (synchondrosis) height and width and palate length and width decreased in SSRI exposed pups as compared to control un-exposed pups. Effects of SSRI on the molars was minimal. Craniofacial growth and development continue to be an area of interest in the investigation of in utero pharmaceutical drug exposure. Altogether these data indicate that prenatal SSRI exposure affects craniofacial form in multiple tissues and specifically at growth sites and centers of the skull.