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.

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.

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 68-Year-Old Man with Depression and Acute Renal Failure Due to Rhabdomyolysis Associated with Alcohol Intoxication While Taking Low-Dose Escitalopram: A Case Report.

BACKGROUND Rhabdomyolysis, an uncommon but recognized adverse effect of selective serotonin reuptake inhibitor (SSRI) antidepressants, can precipitate acute renal injury (AKI), especially when combined with risk factors such as alcohol consumption. This report describes a 68-year-old man with acute renal failure due to rhabdomyolysis associated with alcohol intoxication while taking low-dose escitalopram, an SSRI antidepressant. CASE REPORT The patient, with a history of bipolar affective disorder managed with escitalopram, presented with symptoms of general malaise, diarrhea, myalgias, and transient loss of consciousness following substantial ethanol consumption. Laboratory tests indicated severe rhabdomyolysis with a creatine kinase level of 37 672 U/L and myoglobin level >5710 ng/ml, leading to an AKI diagnosis. The discontinuation of escitalopram, along with hydration and renal replacement therapy, facilitated renal recovery. However, the reintroduction of escitalopram resulted in the recurrence of rhabdomyolysis, suggesting a probable causal link, confirmed using the Naranjo Adverse Drug Reaction Probability Scale. CONCLUSIONS This report highlights the importance of identifying the medication history in patients presenting with acute renal failure and rhabdomyolysis and the association with SSRIs, which can be exacerbated by alcohol. This case underscores the importance of vigilant medication history assessment in patients presenting with AKI and rhabdomyolysis, particularly concerning the use of SSRIs like escitalopram, which can pose heightened risks in the context of alcohol use. It highlights the need for clinical caution in managing patients on long-term SSRI therapy, especially when reintroducing such medications after an episode of rhabdomyolysis.

The safety and efficacy of escitalopram and sertraline in post-stroke depression: a randomized controlled trial.

OBJECTIVES: This study aims to evaluate the safety and efficacy of escitalopram and sertraline in post-stroke depression (PSD) patients, to provide more reliable therapeutics for cardiovascular and psychiatric clinical practice. METHODS: We recruited 60 patients (aged 40-89 years old) with an ICD-10 diagnosis of PSD, who were then randomly assigned to two groups and treated with flexible doses of escitalopram (10 to 20 mg/day, n = 30) or sertraline (50 to 200 mg/day, n = 30) for consecutive 8 weeks, respectively. The 24-item Hamilton Depression Rating Scale (HAMD-24), the 14-item Hamilton Anxiety Rating Scale (HAMA-14), the Treatment Emergent Symptom Scale (TESS), the Montreal Cognitive Assessment Scale (MOCA), and the Activity of Daily Living scale (ADL) were used to assess patients before, during, and after treatment for depression, anxiety, adverse effects, cognitive function, and daily living activities. Repeated measures ANOVA, the Mann-Whitney U test, the chi-square test (χ2), or Fisher's exact test was employed to assess baseline demographics, response rate, adverse effects rate, and changes in other clinical variables. RESULTS: Significant reduction in HAMD-24 and HAMA-14 scores was evaluated at baseline, as well as 1, 3, 4, 6, and 8 weeks of drug intervention (p < 0.01). There was a significant group difference in post-treatment HAMD-24 scores (p < 0.05), but no difference was observed in HAMA-14 scores (p > 0.05). Further analysis showed a significant variance in the HAMD-24 scores between the two groups at the end of the first week (p < 0.01). The incidence of adverse effects in both patient groups was mild, but there was a statistically significant difference between the two groups (p < 0.05). The improvement in cognitive function and the recovery of daily living abilities were comparable between both groups (p > 0.05). CONCLUSION: Escitalopram and sertraline showed comparable efficacy for anxiety symptoms, cognitive function, and daily living abilities in PSD patients. In addition, escitalopram was more appropriate for alleviating depressive symptoms. To validate the conclusion, trials with a larger sample size are in demand in the future. The registration number is ChiCTR1800017373.

Unveiling potential adverse events associated with escitalopram oxalate: A real-world analysis based FDA adverse event reporting system database.

OBJECTIVE: The study aimed to conduct a multidimensional evaluation of potential adverse events (AEs) of escitalopram oxalate based on the FDA adverse event reporting system (FAERS) database. METHODS: This study utilized the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma-poisson shrinker (MGPS) to mine and analyze data from the FAERS database from the first quarter of 2004 to the second quarter of 2023. RESULTS: There was a total of 19,854 AE reports related to escitalopram oxalate, extracting 625 preferred terms (PTs), and covering 27 system organ classes (SOCs). The results showed that the number of reports by females was significantly higher than males, accounting for 57.68%. The reporting number was higher in 2018 and 2019, accounting for 9.50% and 10.18% of the total reports, respectively. The main reporters were consumers and other health professionals, accounting for 26.99% and 26.75% respectively. The majority of the reports were primarily from the United States. Newly emerging AE signals such as intentional overdose (n = 691, ROR 8.51, PRR 8.45, IC 3.05, Empirical Bayesian Geometric Mean (EBGM) 8.35), suicide attempt (n = 665, ROR 8.58, PRR 8.52, IC 3.06, EBGM 8.42), serum serotonin (n = 5, ROR 1044.78, PRR 1044.71, IC 2.56, EBGM 392.39), anti-actin antibody positive (n = 5, ROR 626.87, PRR 626.83, IC 2.56, EBGM 313.91), among others, were not mentioned in the drug's label. CONCLUSION: While escitalopram oxalate has clear benefits in the treatment of depression and other mental health disorders, the presence of AEs also suggests risks associated with its use. Particularly concerning are risks of suicide and changes in serum serotonin levels.

Pharmacogenetic Factors Influence Escitalopram Pharmacokinetics and Adverse Events in Youth with a Family History of Bipolar Disorder: A Preliminary Study.

Introduction: Escitalopram is an effective and generally well-tolerated antidepressant, but children of parents with bipolar disorder (BD) may be at increased risk for adverse events associated with antidepressants, including increased irritability, restlessness, impulsivity, and manic symptoms. This risk may be influenced by polymorphisms in genes encoding cytochrome P450 enzymes (CYP2C19 or CYP2D6), the serotonin transporter (SLC6A4), and the serotonin receptor 2A subtype (HTR2A). We explored whether gene-drug interactions influence the emergence of adverse events in depressed and/or anxious youth with a family history of BD. Materials and Methods: Children and adolescents aged 12-17 years with a first-degree relative with bipolar I disorder were treated with escitalopram and monitored for adverse effects, underwent pharmacogenetic testing, and provided serum escitalopram levels. Emergence of adverse events was determined by study clinicians, and symptoms were tracked using the Treatment-Emergent Activation and Suicidality Assessment Profile (TEASAP) and Pediatric Adverse Events Rating Scale. Clinical Pharmacogenetics Implementation Consortium guidelines were used to determine CYP2C19 and CYP2D6 phenotypes. Results: Slower CYP2C19 metabolizers had greater dose-normalized 24-hour area under the curve (AUC0-24; p = 0.025), trough concentrations (Ctrough; p = 0.013), and elimination half-lives (t1/2; p < 0.001). CYP2D6 phenotype was not significantly associated with any pharmacokinetic parameter. Slower CYP2D6 metabolizers had increased TEASAP akathisia (p = 0.015) scores. HTR2A A/A and A/G genotypes were associated with increased TEASAP "self-injury, suicidality, and harm to others" subscale scores (p = 0.017). Escitalopram maximum concentration, AUC0-24, CYP2C19 phenotype, and SLC6A4 genotype were not associated with adverse events. Conclusions: CYP2C19 phenotype influences escitalopram pharmacokinetics whereas CYP2D6 phenotype does not. Slower CYP2D6 metabolism was associated with increased akathisia, and HTR2A A/A or A/G genotypes were associated with increased risk of self-harm or harm to others. Larger cohorts are needed to identify associations between genetic test results and antidepressant-associated adverse events. Trial Registration: ClinicalTrials.gov identifier: NCT02553161.

Pharmacokinetic correlates of clinical response in a naturalistic sample of escitalopram-treated patients.

OBJECTIVE: We assessed pharmacokinetic correlates of treatment response to escitalopram using a large therapeutic drug monitoring database. METHODS: A large naturalistic sample of patients receiving escitalopram was analyzed. Responders were defined as 'very much improved' or 'much improved' based on the Clinical Global Impression - Improvement score, CGI-I. We compared responders (n = 83) vs. non-responders (n = 388) with the primary outcome being the escitalopram plasma concentration and concentration corrected by the daily dose (C/D ratio). Effects of age, sex, body-mass-index (BMI), and C/D ratio were assessed in a multivariate logistic regression model predicting response. RESULTS: There were no statistically significant differences in clinical and demographic characteristics between responders vs. non-responders. There were also no differences between escitalopram daily doses or plasma concentrations, while C/D ratios were significantly higher in non-responders than in responders (1.6 ± 1.7 vs. 1.2 ± 0.9 (ng/mL)/(mg/day), p = 0.007); C/D ratios (odds ratio 0.52, 95% confidence interval 0.34-0.80, p < 0.003) were associated with response to escitalopram, after controlling for age, sex, and BMI. CONCLUSIONS: Patients with low clearance of escitalopram as reflected upon high C/D ratios may be less likely respond to escitalopram. Identifying these patients during dose titration may support clinical decision-making, including switching to a different antidepressant instead of increasing daily dose.

Machine Learning-Based Prediction of Escitalopram and Sertraline Side Effects With Pharmacokinetic Data in Children and Adolescents.

Selective serotonin reuptake inhibitors (SSRI) are the first-line pharmacologic treatment for anxiety and depressive disorders in children and adolescents. Many patients experience side effects that are difficult to predict, are associated with significant morbidity, and can lead to treatment discontinuation. Variation in SSRI pharmacokinetics could explain differences in treatment outcomes, but this is often overlooked as a contributing factor to SSRI tolerability. This study evaluated data from 288 escitalopram-treated and 255 sertraline-treated patients ≤ 18 years old to develop machine learning models to predict side effects using electronic health record data and Bayesian estimated pharmacokinetic parameters. Trained on a combined cohort of escitalopram- and sertraline-treated patients, a penalized logistic regression model achieved an area under the receiver operating characteristic curve (AUROC) of 0.77 (95% confidence interval (CI): 0.66-0.88), with 0.69 sensitivity (95% CI: 0.54-0.86), and 0.82 specificity (95% CI: 0.72-0.87). Medication exposure, clearance, and time since the last dose increase were among the top features. Individual escitalopram and sertraline models yielded an AUROC of 0.73 (95% CI: 0.65-0.81) and 0.64 (95% CI: 0.55-0.73), respectively. Post hoc analysis showed sertraline-treated patients with activation side effects had slower clearance (P = 0.01), which attenuated after accounting for age (P = 0.055). These findings raise the possibility that a machine learning approach leveraging pharmacokinetic data can predict escitalopram- and sertraline-related side effects. Clinicians may consider differences in medication pharmacokinetics, especially during dose titration and as opposed to relying on dose, when managing side effects. With further validation, application of this model to predict side effects may enhance SSRI precision dosing strategies in youth.

Influence of CYP2C19, CYP2D6, and ABCB1 Gene Variants and Serum Levels of Escitalopram and Aripiprazole on Treatment-Emergent Sexual Dysfunction: A Canadian Biomarker Integration Network in Depression 1 (CAN-BIND 1) Study.

OBJECTIVES: Treatment-emergent sexual dysfunction is frequently reported by individuals with major depressive disorder (MDD) on antidepressants, which negatively impacts treatment adherence and efficacy. We investigated the association of polymorphisms in pharmacokinetic genes encoding cytochrome-P450 drug-metabolizing enzymes, CYP2C19 and CYP2D6, and the transmembrane efflux pump, P-glycoprotein (i.e., ABCB1), on treatment-emergent changes in sexual function (SF) and sexual satisfaction (SS) in the Canadian Biomarker Integration Network in Depression 1 (CAN-BIND-1) sample. METHODS: A total of 178 adults with MDD received treatment with escitalopram (ESC) from weeks 0-8 (Phase I). At week 8, nonresponders were augmented with aripiprazole (ARI) (i.e., ESC + ARI, n = 91), while responders continued ESC (i.e., ESC-Only, n = 80) from weeks 8-16 (Phase II). SF and SS were evaluated using the sex effects (SexFX) scale at weeks 0, 8, and 16. We assessed the primary outcomes, SF and SS change for weeks 0-8 and 8-16, using repeated measures mixed-effects models. RESULTS: In ESC-Only, CYP2C19 intermediate metabolizer (IM) + poor metabolizers (PMs) showed treatment-related improvements in sexual arousal, a subdomain of SF, from weeks 8-16, relative to CYP2C19 normal metabolizers (NMs) who showed a decline, F(2,54) = 8.00, p < 0.001, q = 0.048. Specifically, CYP2C19 IM + PMs reported less difficulty with having and sustaining vaginal lubrication in females and erection in males, compared to NMs. Furthermore, ESC-Only females with higher concentrations of ESC metabolite, S-desmethylcitalopram (S-DCT), and S-DCT/ESC ratio in serum demonstrated more decline in SF (r = -0.42, p = 0.004, q = 0.034) and SS (r = -0.43, p = 0.003, q = 0.034), respectively, which was not observed in males. ESC-Only females also demonstrated a trend for a correlation between S-DCT and sexual arousal change in the same direction (r = -0.39, p = 0.009, q = 0.052). CONCLUSIONS: CYP2C19 metabolizer phenotypes may be influencing changes in sexual arousal related to ESC monotherapy. Thus, preemptive genotyping of CYP2C19 may help to guide selection of treatment that circumvents selective serotonin reuptake inhibitor-related sexual dysfunction thereby improving outcomes for patients. Additionally, further research is warranted to clarify the role of S-DCT in the mechanisms underlying ESC-related changes in SF and SS. This CAN-BIND-1 study was registered on clinicaltrials.gov (Identifier: NCT01655706) on 27 July 2012.

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.

Effect of solution focused group therapy on depressive symptoms and cognitive flexibility of depressive disorder patient. / ç„¦ç‚¹è§£å†³å›¢ä½“æ²»ç–—å¯¹æŠ‘éƒç—‡æ‚£è€ æŠ‘éƒç—‡çŠ¶å’Œè®¤çŸ¥çµæ´»æ€§çš„å½±å“.

OBJECTIVES: Depression is often accompanied by various degrees of cognitive decline, with a high incidence. Guidelines recommend medication combined with psychological therapy. Solution focused group therapy (SFGT) is a newer group psychotherapy technique. This study aims to explore the difference between SFGT combined with escitalopram and only use escitalopram in treating depression. METHODS: A total of 84 patients who met the diagnostic criteria of international classification of diseases-10 (ICD-10) were enrolled into the combined group (SFGT combined with escitalopram, n=42) and the control group (only escitalopram, n=42) for an 8-week treatment. Patients were measured with the 24-item Hamilton Depression Scale (HAMD-24) and the Cognitive Flexibility Inventory (CFI) at baseline (T0), week 4 (T1), and week 8 (T2), respectively. Differences in depressive symptoms and cognitive flexibility between the 2 groups were compared and analyzed. RESULTS: At T2, 8 patients were dislodged in the combined group and 10 in the control group. There was no difference in the subscales and total scores of HAMD-24 and CFI between the 2 groups at T0 (all P>0.05). At T1 and T2, compared with the control group, the total scores and anxiety somatization, cognitive impairment, delay, and a sense of despair subscales scores of HAMD-24 were lower, and the total scores and subscales scores of CFI in the combined group were higher (all P<0.05). CONCLUSIONS: SFGT combined with escitalopram is more effective than monotherapy for improving the anxiety somatization symptoms, cognitive impairment, retardation symptoms and despair symptoms, and increasing the cognitive flexibility.

[Effectiveness, safety and adherence to therapy with Elicea Q-Tab in real clinical practice]. / Effektivnost', bezopasnost' i priverzhennost' terapii preparatom Elitseya Ku-Tab v real'noi klinicheskoi praktike.

OBJECTIVE: To evaluate the effectiveness and safety of escitalopram in the form of oral dispersible tablets (Elicea Q-Tab) in real-life clinical practice in patients with depressive and anxiety disorders. MATERIAL AND METHODS: The study included 1.892 outpatient patients, 1.860 of whom completed participation in accordance with the protocol and entered the statistical analysis. Most patients were diagnosed with depressive and anxiety disorders of varying severity, as a rule, these diagnoses were established for the first time. The drug was most often prescribed at a dosage of 10 mg/day. The patients were monitored for 90 days and at each of the 3 visits, scales were used to assess the clinical condition (CGI-S and CGI-I), scales «Interaction with people, maintaining relationships (social functioning)¼ and «Availability of work, task completion, school attendance (professional functioning)¼, scales satisfaction with the convenience of admission/appointment and the effectiveness of treatment, various indicators of quality of life (autonomy, social and professional functioning, hobbies and hobbies), as well as the severity of cognitive disorders were measured. RESULTS: Patients treated with escitalopram in the form of oral tablets dispersible in the oral cavity (Elicea Q-Tab) showed an improvement in their clinical condition (a decrease in CGI-S scores from 3.65 at visit 1 to 2.63 by visit 3, by 28%; a decrease in CGI-I scores from 2.39 at visit 1 to 1.57 to visit 3, by 34%), as well as improving the quality of life, social (from 2.74 points on 1 visit to 4.32 on 2 visits, by 58%) and professional functioning (from 2.81 on 1 visit to 4.35 on 2 visits, by 55%), the level of concentration (from 3.28 points on 1 visit up to 4.5 on 3 visits, by 37%). Doctors and patients noted high satisfaction with the effectiveness and convenience of using the drug, the frequency of adverse events was low. CONCLUSION: The study showed that escitalopram in the form of oral tablets dispersible in the oral cavity (Elicea Q-Tab) is an efficient and safe treatment for depressive and anxiety disorders in real-world clinical settings. Patients and physicians have evaluated the drug positively and it can be considered as an effective agent in psychiatric practice.

Pro-arrhythmic effect of escitalopram and citalopram at serum concentrations commonly observed in older patients - a study based on a cohort of 19,742 patients.

BACKGROUND: For a decade, patients have been advised against using high citalopram- and escitalopram-doses due to risk for ventricular arrhythmia and cardiac arrest. Still, these drugs are widely used to treat depression and anxiety especially in older patients. It is unclear why they are cardiotoxic and at what serum concentrations patients are at risk for arrhythmias. Thus, how many patients that are at risk for iatrogenic cardiac arrest is unknown. METHODS: We studied the arrhythmogenic effects of citalopram, escitalopram and their metabolites on human cardiomyocytes. Concentrations showing pro-arrhythmic activity were compared with observed drug and metabolite serum concentrations in a cohort of 19,742 patients (age 12-105 years) using escitalopram or citalopram in Norway (2010-2019). As arrhythmia-risk is related to maximum serum concentration, this was simulated for different age-groups from the escitalopram patient material. FINDINGS: Therapeutic concentrations of both citalopram and escitalopram but not their metabolites showed pro-arrhythmic changes in the human cardiac action potential. Due to age-dependent reduction of drug clearance, the proportion of patients above threshold for arrhythmia-risk increased with age. 20% of patients >65 years were predicted to reach potentially pro-arrhythmic concentrations, following intake of 10 mg escitalopram. INTERPRETATION: All patients that are using escitalopram or citalopram and have genetic disposition for acquired long-QT syndrome, are >65 years, are using additional pro-arrhythmic drugs or have predisposition for arrhythmias, should be monitored with therapeutic drug monitoring (TDM) to avoid exposure to potentially cardiotoxic concentrations. Serum concentrations should be kept below 100 nM, to reduce arrhythmia-risk. FUNDING: This study was funded by The Research Council of Norway (project number: 324062).

Evaluation and Comparison of Citalopram and Venlafaxine for Management of Hot Flashes in Women with Breast Cancer.

BACKGROUND: Breast cancer is the most common cancer in women worldwide. Premature menopause and hot flashes are the main complications of breast cancer treatments. About 40 to 50 percent of breast cancer women who undergo chemotherapy are experiencing premature menopause symptoms, including hot flashes. Some endocrine therapies such as tamoxifen and aromatase inhibitors are associated with induction or aggravating hot flashes. Hot flashes are often debilitating and significantly impair daily functions. Therefore many therapeutic options have been studied so far for the management of this adverse effect. However, there are still some clinical challenges in managing hot flashes in patients with breast cancer. OBJECTIVE: We aimed to evaluate and compare the efficacy of venlafaxine and citalopram on hot flashes in breast cancer women receiving tamoxifen. DESIGN: We conducted a double-blind, placebo-controlled trial in forty-one, 35 to 65 years old female patients. The study lasted for four weeks, and the follow-up was for two months. Venlafaxine and citalopram treatments started with doses of 37.5 mg or 10 mg, respectively. Venlafaxine and citalopram dosages were increased in the second week to 75 and 20 mg, respectively. The study was conducted during the year 2017. KEY RESULTS: The results indicated that the total efficacy was significantly different in groups receiving citalopram, venlafaxine, and placebo. Total efficacy in the placebo group, venlafaxine, and citalopram was 14.3, 53.8, and 64.3%, respectively (p=0.02). During the second week, the efficacy in groups receiving citalopram, venlafaxine, and placebo was 57.1, 53.8, and 14.3%, respectively (p=0.04). Generally, both citalopram and venlafaxine were well tolerated. The associated adverse effects were mild to moderate in both groups. CONCLUSIONS: Although citalopram was associated with more adverse effects, including constipation, it was more effective in reducing the frequency of hot flashes when compared to venlafaxine or placebo.

Effects of nicorandil on QT prolongation and myocardial damage caused by citalopram in rats.

Citalopram is a selective serotonin re-uptake inhibitor (SSRI) antidepressant; it exhibits the greatest cardiotoxic effect among SSRIs. Citalopram can cause drug-induced long QT syndrome (LQTS) and ventricular arrhythmias. We investigated the protective effect of nicorandil, a selective mitochondrial KATP (mito-KATP) channel opener, on LQTS and myocardial damage caused by citalopram in male rats. In a preliminary study, we determined that the minimum citalopram dose that prolonged the QT interval was 102 mg/kg injected intraperitoneally. For the main study, rats were divided randomly into five experimental groups: untreated control, normal saline + citalopram, nicorandil + citalopram, 5-hydroxydecanoate (5-HD) + citalopram, 5-HD + nicorandil + citalopram. Biochemical and histologic data from blood and heart tissue samples from six untreated control rats were evaluated. Electrocardiographic parameters including QRS duration, QT interval, corrected QT interval (QTc) and heart rate (HR) were assessed, and biochemical parameters including malondialdehyde, reduced glutathione, glutathione peroxidase, superoxide dismutase were measured. We also performed histomorphologic and immunohistochemical examination of heart tissue. Citalopram prolonged QT-QTc intervals significantly and increased significantly the histomorphologic score and proportion of apoptotic cells, but produced no differences in the oxidant and antioxidant parameters. Nicorandil did not prevent citalopram induced QT-QTc interval prolongation and produced no significant changes in oxidant and antioxidant parameters; however, it did reduce histologic damage and apoptosis caused by citalopram.

Fetal SSRI antidepressant exposure and infant sleep: Findings from the MPEWS pregnancy cohort study.

This longitudinal study examines the association between fetal Selective Serotonergic Reuptake Inhibitor antidepressant exposure and infant sleep behaviours at six and 12 months of age and focus on three of the most commonly prescribed antidepressants in pregnancy. This study utilises data on 698 women recruited at less than 20 weeks of pregnancy and are followed up at six and 12 months postpartum. Women were recruited into one of three groups: those taking either sertraline, citalopram or escitalopram antidepressants in pregnancy (n = 85); women with a depressive disorder who were not taking antidepressants (non-medicated depressed, NMD; n = 82); and, and a control group of women (n = 531). At six and 12 months, data were collected on breastfeeding and sleep location and infant sleep was measured using the Brief Infant Sleep Questionnaire. Antidepressants sertraline, escitalopram and citalopram were not associated with increased infant waking or time awake. However, sertraline was associated with longer time for an infant to go to sleep. This study provides reassurance that SSRI antidepressants and, in particular, sertraline, escitalopram and citalopram are not associated with infant sleep behaviours that are commonly regarded as problematic including night waking. Further replication of these findings, including with direct measures of infant sleep, are recommended.