Dysregulation of adipogenesis and disrupted lipid metabolism by the antidepressants citalopram and sertraline.

Selective Serotonin Reuptake Inhibitors (SSRIs) are widely used medications for the treatment of major depressive disorder. However, long-term SSRI use has been associated with weight gain and altered lipid profiles. These findings suggest that SSRIs may have negative effects on metabolism. Exposure to certain chemicals called 'obesogens' is known to promote lipid accumulation and obesity by modulating adipogenesis. Here, we investigated whether citalopram (CIT) and sertraline (SER) interfere with the process of adipogenesis, using human mesenchymal stem cells (MSCs) in a 2D and a 3D model. Assessment of intracellular lipid accumulation by fluorescence staining was used as a measure for enhanced adipogenesis. To explore possible mechanisms behind SSRIs' effects, receptor mediated activity was studied using responsive cell lines for various nuclear receptors. Furthermore, RNA sequencing was performed in the 3D model, followed by differential gene expression and pathway analysis. A dose dependent increase in lipid accumulation was observed in both models with CIT and SER. For the 3D model, the effect was seen in a range close to reported steady-state plasma concentrations (0.065-0.65 µM for SER and 0.12-0.92 µM for CIT). Pathway analysis revealed unexpected results of downregulation in adipogenesis-related pathways and upregulation in phospholipids and lysosomal pathways. This was confirmed by an observed increase in lysosomes in the 2D model. Our findings suggest lysosomal dysfunction and disrupted lipid metabolism in mature adipocytes, leading to excessive phospholipid synthesis. Moreover, important adipogenic processes are inhibited, potentially leading to dysfunctional adipocytes, which might have implications in the maintenance of a healthy metabolic balance.

Utility of vitamin C in ameliorating citalopram-induced testicular toxicity via modulating nitro-oxidative stress and apoptosis in mice.

There is a growing concern that antidepressant drugs impair sexual function and adversely impact spermatogenesis and male fertility. Vitamin C is a natural antioxidant that plays a vital role in the male reproductive system. The present study investigated the ameliorating potential of vitamin C against citalopram (CTL)-evoked testicular toxicity and spermatogenesis impairment in mice. Mice were randomly divided into six groups: control, CTL, vitamin C 100, vitamin C 200, CTL plus vitamin C 100, and CTL plus vitamin C 200. Adult male mice were intraperitoneally (ip) injected with 10 mg/kg of CTL for 35 days with or without vitamin C. At the end of the study, body and testes weight, sperm parameters, histopathology of testes, testosterone level, testicular levels of malondialdehyde (MDA), nitric oxide (NO), total antioxidant capacity (TAC), and apoptosis (TUNEL assay) were evaluated. Our findings revealed that vitamin C restored spermatogenesis by improving sperm count, motility, viability, morphology, and chromatin integrity. Testosterone levels and testes histopathology were significantly improved in the vitamin C-administrated groups. Furthermore, vitamin C administration markedly alleviated CTL-induced nitro-oxidative damage, enhancing TAC levels, and reducing NO and MDA levels. Whilst CTL therapy induced a significant increase in the number of TUNEL-positive cells compared to the control, the administration of vitamin C significantly prevented the apoptotic effects of CTL. Together, vitamin C therapy protects against CTL-induced testicular damage via mitigating nitro-oxidative stress and apoptosis, which provides evidence for vitamin C as a beneficial therapy against antidepressant drug-associated reproductive toxicity and male sub/infertility.

Efficacy of empagliflozin as adjunctive therapy to citalopram in major depressive disorder: a randomized double-blind, placebo-controlled clinical trial.

BACKGROUND: Major depressive disorder is one of the most common psychiatric disorders, which is associated with a high disease burden. Current treatments using antidepressants have limitations, so using medication with neuromodulating and anti-inflammatory properties alongside them could be helpful. In a clinical trial, we studied the effectiveness of empagliflozin, a blood sugar-lowering drug, as an adjunctive therapy to reduce the severity of depression symptoms. METHODS: A number of outpatients with moderate to severe depression (Hamilton Depression Rating Scale (HDRS) > = 17) who were not under related medication or had not taken medication for at least the last two months, had an age range of 18-60 years and had written informed consent to enter the study (N = 90) were randomly divided into two groups receiving placebo or empagliflozin (10 mg daily) combined with citalopram (40 mg daily) based on permuted block randomization method in an 8-week randomized, double-blind, placebo-controlled clinical trial. They were evaluated using the HDRS in weeks 0, 4, and 8. RESULTS: HDRS scores were equal to 28.42(± 3.83), 20.20(± 3.82), and 13.42(± 3.42) in the placebo group during weeks 0,4, and 8, respectively. These scores were 27.36(± 3.77), 13.76(± 1.40), and 7.00(± 1.13), respectively, for the group treated with empagliflozin. Compared to the control group, patients treated with empagliflozin using repeated-measures ANOVA showed greater improvement in reducing the severity of depression symptoms over time (p value = 0.0001). CONCLUSIONS: Considering the promising findings in this clinical trial, further study of empagliflozin as adjunctive therapy in MDD with larger sample sizes and longer follow-ups is recommended.

Disruption of Lipid Profile, Glucose Metabolism, and Leptin Levels following Citalopram Administration and High-Carbohydrate and High-Cholesterol Diet in Mice.

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).

The efficacy and safety of adding celecoxib to escitalopram for improving symptoms of major depressive disorder.

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.

Exploring the Roles of Vitamins C and D and Etifoxine in Combination with Citalopram in Depression/Anxiety Model: A Focus on ICAM-1, SIRT1 and Nitric Oxide.

The study of intercellular adhesion molecule-1 (ICAM-1) and SIRT1, a member of the sirtuin family with nitric oxide (NO), is emerging in depression and anxiety. As with all antidepressants, the efficacy is delayed and inconsistent. Ascorbic acid (AA) and vitamin D (D) showed antidepressant properties, while etifoxine (Etx), a GABAA agonist, alleviates anxiety symptoms. The present study aimed to investigate the potential augmentation of citalopram using AA, D and Etx and related the antidepressant effect to brain and serum ICAM-1, SIRT1 and NO in an animal model. BALB/c mice were divided into naive, control, citalopram, citalopram + etx, citalopram + AA, citalopram + D and citalopram + etx + AA + D for 7 days. On the 8th day, the mice were restrained for 8 h, followed by a forced swim test and marble burying test before scarification. Whole-brain and serum expression of ICAM-1, Sirt1 and NO were determined. Citalopram's antidepressant and sedative effects were potentiated by ascorbic acid, vitamin D and etifoxine alone and in combination (p < 0.05), as shown by the decreased floating time and rearing frequency. Brain NO increased significantly (p < 0.05) in depression and anxiety and was associated with an ICAM-1 increase versus naive (p < 0.05) and a Sirt1 decrease (p < 0.05) versus naive. Both ICAM-1 and Sirt1 were modulated by antidepressants through a non-NO-dependent pathway. Serum NO expression was unrelated to serum ICAM-1 and Sirt1. Brain ICAM-1, Sirt1 and NO are implicated in depression and are modulated by antidepressants.

Establishment and Validation of a Transdermal Drug Delivery System for the Anti-Depressant Drug Citalopram Hydrobromide.

To enhance the bioavailability and antihypertensive effect of the anti-depressant drug citalopram hydrobromide (CTH) we developed a sustained-release transdermal delivery system containing CTH. A transdermal diffusion meter was first used to determine the optimal formulation of the CTH transdermal drug delivery system (TDDS). Then, based on the determined formulation, a sustained-release patch was prepared; its physical characteristics, including quality, stickiness, and appearance, were evaluated, and its pharmacokinetics and irritation to the skin were evaluated by applying it to rabbits and rats. The optimal formulation of the CTH TDDS was 49.2% hydroxypropyl methyl cellulose K100M, 32.8% polyvinylpyrrolidone K30, 16% oleic acid-azone, and 2% polyacrylic acid resin II. The system continuously released an effective dose of CTH for 24 h and significantly enhanced its bioavailability, with a higher area under the curve, good stability, and no skin irritation. The developed CTH TDDS possessed a sustained-release effect and good characteristics and pharmacokinetics; therefore, it has the potential for clinical application as an antidepressant.

Demographic, co-intoxicants and other characteristics of citalopram-involved overdose deaths.

Selective serotonin reuptake inhibitors (SSRIs) including citalopram are commonly used antidepressants that can be involved in drug-related deaths along with opioids and other substances. This study characterized citalopram involvement in West Virginia (WV) drug-related deaths compared to other SSRI and non-SSRI-related deaths. All 2005-2021 WV drug-related deaths were analyzed in this retrospective study. Demographics, other substances involved, and comorbidities in cases in which citalopram was listed on the death certificate were compared to other SSRI-related and total non-SSRI deaths. Citalopram concentrations and the association between citalopram presence with predicted fentanyl concentrations were determined. Citalopram was the most common antidepressant present in the deaths (4.5% of 14,363 total), with most (81%) unintentional. Male: female ratios in citalopram cases (0.9:1) were significantly lower than in non-SSRI deaths (2.3:1). Almost two-thirds of citalopram deaths had ≥ 4 substances involved compared to 26% of non-SSRI deaths. Overall, oxycodone was most frequently identified in citalopram deaths (fentanyl more commonly in recent years), followed by alprazolam and diazepam. Cardiovascular comorbidity was significantly more common in citalopram than non-SSRI deaths. No association was found between citalopram presence and predicted fentanyl concentrations. Most citalopram-related deaths were unintentional and involved proportionately more females, with larger numbers of concurrent substances present and more cardiovascular comorbidity compared to non-SSRI deaths. Citalopram is widely used and less toxic than many antidepressants. The extent to which it contributed to overdose deaths can be difficult to ascertain given the multiple substances usually present.

Selective and Rapid Optical Detection of Citalopram Using a Fluorescent Probe Based on Carbon Quantum Dots Embedded in Silica Molecularly Imprinted Polymer.

In this study, a citalopram optical nano-sensor was developed. Citalopram is a well-known antidepressant drug that reduces the reuptake of serotonin in neurons as a result, serotonin neurotransmission, the primary response to antidepressant treatments, increases in many parts of the brain. This study introduces a carbon quantum dots (CQDs)-based optical nanosensor for rapid detection of citalopram. This fluorescent nanosensor was made through the polymerization of tetraethyl orthosilicate in the presence of CQDs as the fluorescent materials and citalopram as the template molecule. Following the polymerization, the templated molecules were washed and removed from the structure, and the matrix of the polymer was left with some cavities that resembled citalopram in terms of size and shape. The final structure which is used as a chemical nanosensor, is named carbon quantum dots embedded silica molecularly imprinted polymer (CQDs-SMIP). The materials used in designing nano-sensors were characterized using FTIR, UV/Vis, and fluorescence spectroscopy, as well as high-resolution transmission electron microscopy (HR-TEM), and field emission scanning electron microscopy (FESEM). CQDs-SMIP showed a strong fluorescence emission at 420 nm in the absence of the template molecule. The fluorescence intensity of the nanosensor decreased in the presence of citalopram. The correlation between the extent of the fluorescence quenching and the concentration of citalopram provided the nano-sensor signal. The nano-sensor was used to measure citalopram in complex matrices such as human plasma and urine samples with remarkable selectivity and sensitivity. The detection limit of 10.3 µg.L-1 over a linear range of 100 to 700 µg.L-1, and RSD of 3.15% was obtained. This nano-sensor was applied to analyze of citalopram in plasma and human urine samples with remarkable results.

Dear Doctor Letters regarding citalopram and escitalopram: guidelines vs real-world data.

Dear Doctor Letters (DDLs, Direct Healthcare Professional Communications) from 2011 provided guidance regarding QTc-prolonging effects with risk of torsade de pointes during treatment with citalopram and escitalopram. This study examines the DDLs' effects on prescription behavior. Data from 8842 inpatients treated with citalopram or escitalopram with a primary diagnosis of major depressive disorder (MDD) were derived from a European pharmacovigilance study (Arzneimittelsicherheit in der Psychiatrie, AMSP) from 2001 to 2017. It was examined to what extent new maximum doses were adhered to and newly contraindicated combinations with QTc-prolonging drugs were avoided. In addition, the prescriptions of psychotropic drugs before and after DDLs were compared in all 43,480 inpatients with MDD in the data set. The proportion of patients dosed above the new limit decreased from 8 to 1% in patients ≤ 65 years and from 46 to 23% in patients > 65 years old for citalopram versus 14-5% and 47-31% for escitalopram. Combinations of es-/citalopram with other QTc-prolonging psychotropic drugs reduced only insignificantly (from 35.9 to 30.9%). However, the proportion of patients with doses of quetiapine > 150 mg/day substantially decreased within the combinations of quetiapine and es-/citalopram (from 53 to 35%). After the DDLs, prescription of citalopram decreased and of sertraline increased. The DDLs' recommendations were not entirely adhered to, particularly in the elderly and concerning combination treatments. This might partly be due to therapeutic requirements of the included population. Official warnings should consider clinical needs.

Deep venous thrombosis and hyponatremia associated with citalopram use for behavioral symptoms in Parkinson's disease: a case report.

BACKGROUND: Evidence is limited regarding the optimal therapeutic approach for neuropsychiatric symptoms associated with Parkinson's disease dementia (PDD). Selective serotonin reuptake inhibitors (SSRIs) are widely used for mood disorders and behavioral symptoms in older adults with cognitive impairment, but they have limited efficacy in patients with PDD. The effect of SSRIs on hemostasis is also unclear. This report describes a patient with PDD who developed deep venous thrombosis (DVT) and hyponatremia after initiating citalopram treatment. CASE PRESENTATION: An 86-year-old woman with PDD presented to our emergency department with altered mental status, generalized weakness, and left lower leg swelling. Citalopram was begun 4 weeks previously for behavioral changes and was discontinued 2 days before presentation because of excessive fatigue. At presentation, her plasma sodium level was 123 mg/dL. Brain computed tomography showed age-related changes. Doppler ultrasound revealed a DVT in the left lower leg. The patient was treated with hypertonic saline and intravenous heparin. After normalization of her sodium, she was discharged on donepezil and apixaban. At follow-up, her sodium remained normal, and her cognition and behavior were noticeably improved. CONCLUSION: Older adults with Parkinson's disease are sensitive to adverse effects of psychotropic agents, including SSRIs, which are not recommended first-line agents for behavioral symptoms in PDD. Upon initiating SSRIs in older patients with functional decline and multiple comorbidities, physicians need to evaluate the patient's risk factors for bleeding or thrombosis. Physical activities should also be maintained as much as possible.

Evidence of the Dysbiotic Effect of Psychotropics on Gut Microbiota and Capacity of Probiotics to Alleviate Related Dysbiosis in a Model of the Human Colon.

Growing evidence indicates that non-antibiotic therapeutics significantly impact human health by modulating gut microbiome composition and metabolism. In this study, we investigated the impact of two psychotropic drugs, aripiprazole and (S)-citalopram, on gut microbiome composition and its metabolic activity, as well as the potential of probiotics to attenuate related dysbiosis using an ex vivo model of the human colon. After 48 h of fermentation, the two psychotropics demonstrated distinct modulatory effects on the gut microbiome. Aripiprazole, at the phylum level, significantly decreased the relative abundances of Firmicutes and Actinobacteria, while increasing the proportion of Proteobacteria. Moreover, the families Lachnospiraceae, Lactobacillaceae, and Erysipelotrichaceae were also reduced by aripiprazole treatment compared to the control group. In addition, aripiprazole lowered the levels of butyrate, propionate, and acetate, as measured by gas chromatography (GC). On the other hand, (S)-citalopram increased the alpha diversity of microbial taxa, with no differences observed between groups at the family and genus level. Furthermore, a probiotic combination of Lacticaseibacillus rhamnosus HA-114 and Bifidobacterium longum R0175 alleviated gut microbiome alterations and increased the production of short-chain fatty acids to a similar level as the control. These findings provide compelling evidence that psychotropics modulate the composition and function of the gut microbiome, while the probiotic can mitigate related dysbiosis.

Computational Study of Photodegradation Process and Conversion Products of the Antidepressant Citalopram in Water.

Citalopram (CIT) is a commonly prescribed medication for depression. However, the photodegradation mechanism of CIT has not yet been fully analyzed. Therefore, the photodegradation process of CIT in water is studied by density functional theory and time-dependent density functional theory. The calculated results show that during the indirect photodegradation process, the indirect photodegradation of CIT with ·OH occurs via OH-addition and F-substitution. The minimum activation energy of C10 site was 0.4 kcal/mol. All OH-addition and F-substitution reactions are exothermic. The reaction of 1O2 with CIT includes the substitution of 1O2 for F and an addition reaction at the C14 site. The Ea value of this process is 1.7 kcal/mol, which is the lowest activation energy required for the reaction of 1O2 with CIT. C-C/C-N/C-F cleavage is involved in the direct photodegradation process. In the direct photodegradation of CIT, the activation energy of the C7-C16 cleavage reaction was the lowest, which was 12.5 kcal/mol. Analysis of the Ea values found that OH-addition and F-substitution, the substitution of 1O2 for F and addition at the C14 site, as well as the cleavage reactions of C6-F/C7-C16/C17-C18/C18-N/C19-N/C20-N are the main pathways of photodegradation of CIT.

Delayed citalopram administration reduces brain inflammation and enhances skilled motor function after ischaemic stroke in 'MacGreen' mice.

Recent evidence suggests that treatment with antidepressants may promote functional recovery. However, the timeframe in which these pharmacological agents can influence stroke recovery is not well understood. This research investigated whether delayed administration of citalopram, used clinically in the management of post-stroke depression, could improve long-term functional recovery following experimental stroke. MacGreen mice carrying an enhanced green fluorescent protein reporter gene in monocyte and macrophage populations were subjected to 45 min occlusion of the middle cerebral artery. Animals were administered citalopram (10 mg/kg/day, n = 20) or saline (n = 20) starting 3 days after stroke for 28 days. Neurological deficits and skilled motor performance in the staircase task were recorded for 9 weeks post stroke. Grey and white matter structural lesions were quantified at Week 9, and enhanced green fluorescent protein immunohistochemistry was used to evaluate the effect of citalopram on inflammation. Twenty-five animals were included in the final analysis. Citalopram-treated animals (n = 13) showed a significant increase in impaired forepaw use in the staircase task compared with saline-treated animals (n = 12) 2, 3 and 7 weeks post stroke but no difference in neurological score at any time point examined. Citalopram treatment was associated with decreased monocyte/macrophage cell density and increased white matter tract integrity within the ipsilateral cortex. In conclusion, delayed administration of citalopram decreased brain inflammation and produced functional gains in our mouse model of stroke. Beneficial effects on skilled motor functions were long-lasting.

Tantali fibromyalgic supplicium: Is there any relief with the antidepressant employment? A systematic review.

Widespread musculoskeletal pain characterizes fibromyalgia (FM), accompanied by sleep, fatigue, and mood problems. Chronic stress and depression play a crucial role in the etiology and pathophysiology of FM. They may contribute to a dysregulation of the central pain mechanisms together with the neuroendocrine and immune systems. Pharmacological treatments are the first-line therapy to reduce the symptoms of FM. The US Food and Drug Administration (FDA) indicated gabapentinoid, pregabalin, duloxetine, and milnacipran for adult patients. An alternative approach is widely used, based on therapies including interventions in patient education, behavioral therapy, exercise, pain management, and a healthy diet. A systematic search was performed on PubMed, MEDLINE, EMBASE, and Web of Science databases. The authors established the selection, inclusion, and exclusion criteria. We found a total of 908 articles. This systematic review will include ten articles selected after excluding duplicates and reading the abstracts and full texts. All studies related the effect of drugs to various symptoms caused by fibromyalgia patients with depression, such as insomnia/sleepiness, depression, suicide, difficulty walking/working, pain, fatigue, and nervousness. Although, we concluded that antidepressant drugs are effective in treating depression and pain in fibromyalgia, further studies are needed to understand the etiology of this disease and to find a combination of therapies to increase tolerability and adherence of the patient to the drug, decreasing the adverse effects.

Effect of single doses of citalopram and reboxetine on urethral pressure: A randomized, double-blind, placebo- and active-controlled three-period crossover study in healthy women.

AIMS: Urethral closure function is essential for urinary continence in women and decreased urethral pressure is associated with stress urinary incontinence (SUI). For decades, the effects of serotonergic drugs on central neural control of urethral closure have been investigated and discussed. Epidemiological studies suggest that the use of selective serotonin reuptake inhibitors (SSRIs), such as citalopram, is associated with SUI. However, the literature findings are conflicting. This study aimed to evaluate citalopram's effect on opening urethral pressure (OUP) in healthy women. METHODS: We conducted a randomized, double-blind, placebo- and active-controlled crossover study in 24 healthy women. On three study days, which were separated by 8 days of washout, the subjects received single doses of either 40 mg citalopram (and placeboreboxetine ), 8 mg reboxetine (and placebocitalopram ), or two placebos. Study drugs were administered at a 1-h interval due to a difference in estimated time to peak plasma concentration (tmax ). We measured OUP with urethral pressure reflectometry under both resting and squeezing conditions of the pelvic floor at estimated tmax for both study drugs (one timepoint). RESULTS: Compared to placebo, citalopram increased OUP by 6.6 cmH2 0 (95% confidence interval [CI] 0.04-13.1, p = 0.048) in resting condition. In squeezing condition, OUP increased by 7.1 cmH2 0 (95% CI: 1.3-12.9, p = 0.01). Reboxetine increased OUP by 30.0 cmH2 0 in resting condition compared to placebo (95% CI: 23.5-36.5, p < 0.001), and 27.0 cmH2 0 (95% CI: 21.2-32.8, p < 0.001) in squeezing condition. CONCLUSION: Citalopram increased OUP slightly compared to placebo suggesting that SSRI treatment does not induce or aggravate SUI.

Proton pump inhibitors may enhance the risk of citalopram- and escitalopram-associated sudden cardiac death among patients receiving hemodialysis.

PURPOSE: Polypharmacy is common in the hemodialysis population and increases the likelihood that patients will be exposed to clinically significant drug-drug interactions. Concurrent use of proton pump inhibitors (PPIs) with citalopram or escitalopram may potentiate the QT-prolonging effects of these selective serotonin reuptake inhibitors through pharmacodynamic and/or pharmacokinetic interactions. METHODS: We conducted a retrospective cohort study using data from the U.S. Renal Data System (2007-2017) and a new-user design to examine the differential risk of sudden cardiac death (SCD) associated with citalopram/escitalopram initiation vs. sertraline initiation in the presence and absence of PPI use among adults receiving hemodialysis. We studied 72 559 patients:14 983 (21%) citalopram/escitalopram initiators using a PPI; 26 503 (36%) citalopram/escitalopram initiators not using a PPI;10 779 (15%) sertraline initiators using a PPI; and 20 294 (28%) sertraline initiators not using a PPI (referent). The outcome of interest was 1-year SCD. We used inverse probability of treatment weighted survival models to estimate weighted hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Compared with sertraline initiators not using a PPI, citalopram/escitalopram initiators using a PPI had the numerically highest risk of SCD (HR [95% CI] = 1.31 [1.11-1.54]), followed by citalopram/escitalopram initiators not using a PPI (HR [95% CI] = 1.22 [1.06-1.41]). Sertraline initiators using a PPI had a similar risk of SCD compared with those not using a PPI (HR [95% CI] = 1.03 [0.85-1.26]). CONCLUSIONS: Existing PPI use may elevate the risk of SCD associated with citalopram or escitalopram initiation among hemodialysis patients.

Differential effects of citalopram on the intake of high fat or high carbohydrates diets in female and male rats.

Chronic administration of selective serotonin reuptake inhibitors (SSRI), usually prescribed as antidepressants, decreases total energy intake; however, at present the differential effect on the intake of distinct macronutrients and on female vs. male organisms is not clear. On this basis, female and male adult Wistar rats were exposed to two types of diets: (1) a standard balanced diet (BD); or (2) two types of diets simultaneously, (a) one high in carbohydrates (HC); the other (b) high in fat (HF). Both study groups were given a dose of 10 mg/kg/day i.p. of citalopram or a vehicle for 21 days. Food and water consumption and body weight were recorded daily at baseline (BL), during treatment (TX), and post-treatment (PTx1-PTx2). The male rats exposed to BD reduced total energy consumption during treatment with citalopram, but body weight gain decreased both females and males compared to BL. During exposure to the two types of diets, citalopram treatment reduced fat consumption with respect to BL and PTx1 only in the male group. This group also decreased its total energy consumption during TX compared to PTx1. Finally, the females gained less body weight in TX than PTx1, while weight gain in the males during TX decreased with respect to BL and PTx1. Results show a differential effect of citalopram on females vs. males that was dependent on the type of macronutrient administered.

Enantioselective HPLC analysis of escitalopram oxalate and its impurities using a cellulose-based chiral stationary phase under normal- and green reversed-phase conditions.

Normal-phase and reversed-phase high-performance liquid chromatography methods for the separation of the active pharmaceutical ingredient escitalopram from its (R)-enantiomer impurity have been developed on the cellulose-based Chiralcel OJ-H chiral stationary phase. Both methods share two features: they use ethanol as a cosolvent and are able to give a complete enantioseparation without interference from other associated chiral impurities. With the green eluent mixture ethanol-water-diethylammine 70:30:0.1 (v/v/v), the resolution between escitalopram and (R)-enantiomer was 2.09 at 30°C. The limits of quantification for the (S) and (R) enantiomers were 4.5 and 3.8 µg mL-1 , respectively.

Torsade de pointes caused by citalopram during the pacemaker battery-depletion phase: A case report.

Drug-induced QT prolongation, primarily antiarrhythmic drugs, is a common cause of torsade de pointes (TdP). Although there have been previous reports of drug-induced TdP in patients, it has not been well documented when caused by citalopram during the pacemaker battery-depletion phase. To improve delirium recognition, we report a case of citalopram-induced TdP during the pacemaker battery-depletion phase. An 84-year-old Chinese female was brought to the hospital presenting recurrent syncope. She lost consciousness and was admitted after her syncope TdP was documented. Her pacemaker was inspected and found to be operating in an extremely ineffective manner. Although she had prolonged QT interval after the pacemaker was replaced, she did not suffer another syncope attack, and ECG monitoring revealed no cardiac arrhythmia or TdP. During her admission, she was treated with citalopram for depression. Citalopram was discontinued when the QT interval shortened progressively. In this study, we described a case of citalopram-induced TdP during the depletion phase of a pacemaker battery. This case should serve as a cautionary lesson to clinicians to avoid using citalopram during the pacemaker battery-depletion phase.