Escitalopram in the Treatment of Major Depressive Disorder in Adolescent Patients†

Yang, Lily; Scott, Lesley J.

doi:10.2165/11204690-000000000-00000

Cited by 5 publications

(4 citation statements)

References 12 publications

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“…The interquartile range from patients with depression was 16.0–41.5 ng/mL, and with 13.5–25.3 ng/mL it was somewhat lower in responders. The overall response rate of 59.5% was in line with previous studies [ 22 ]. The majority of samples included in this study were follow-up measurements.…”

Section: Discussionsupporting

confidence: 91%

Concentrations of escitalopram in blood of patients treated in a naturalistic setting: focus on patients with alcohol and benzodiazepine use disorder

Hart

Heesen

Schmitz

et al. 2022

Eur Arch Psychiatry Clin Neurosci

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The selective serotonin reuptake inhibitor escitalopram (ESC) is indicated for the treatment of major depressive disorder (MDD) and of generalized anxiety disorder (GAD). Monitoring of blood levels (BLs) is strongly indicated due to ESC’s high interindividual pharmacokinetic variability. The aim of this study was to analyse clinical efficacy and pharmacokinetic influences on ESC BLs, in patients with depressive disorder alone and with comorbid alcohol or benzodiazepine use disorder. Data were collected from patients treated under naturalistic conditions for whom Therapeutic Drug Monitoring (TDM) was requested to guide antidepressant drug therapy and analysed retrospectively. Particular emphasis was given to patients with alcohol or benzodiazepine use disorder. Responders according to the clinical global impression (CGI) scale were compared with nonresponders for their ESC blood level (BL). The patient sample included 344 patients from 16 psychiatric hospitals in Germany. Influencing factors that could explain 22% of ESC BLs were dose, sex and age. Variability was high between individuals, and doses up to 40 mg were common in real-world settings. Patients treated with ESC monotherapy who responded showed a trend towards higher BLs compared to nonresponders with a concentration of 15 ng/mL separating both groups. Pathological changes in liver function (indicated by elevated GGT in combination with an AST/ALT ratio ≥ 1) resulted in higher dose-corrected ESC concentrations. Influencing factors that could explain 22% of ESC blood levels were dose, sex, and age. Our findings confirm the currently recommended lower threshold level and support the need for standard TDM analyses in everyday clinical practice. The ICD 10 diagnosis alcohol dependence alone does not lead to pharmacokinetic changes in the metabolism of ESC, but altered liver function does.

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Section: Discussionsupporting

confidence: 91%

Concentrations of escitalopram in blood of patients treated in a naturalistic setting: focus on patients with alcohol and benzodiazepine use disorder

Hart

Heesen

Schmitz

et al. 2022

Eur Arch Psychiatry Clin Neurosci

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“…The routine TDM setting did not allow us to control patient adherence to the treatment nor to control for other influences, e. g., psychosocial factors or medication side effects, on therapeutic decisions. The treatment success rate of 71% in our sample was higher than previously reported response rates in patients with depression 22 . The low occurrence of side effects in only six patients suggests an incomplete registration of side effects in the medical files.…”

Section: Discussioncontrasting

confidence: 82%

Low Escitalopram Concentrations in Patients with Depression predict Treatment Failure: A Naturalistic Retrospective Study

Hart

Amann

Brand³

et al. 2023

Pharmacopsychiatry

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Introduction Cross sectional therapeutic drug monitoring (TDM) data mining introduces new opportunities for the investigation of medication treatment effects to find optimal therapeutic windows. Medication discontinuation has been proven useful as an objective surrogate marker to assess treatment failure. This study aimed to investigate the treatment effects of escitalopram and pharmacokinetic influences on blood levels using retrospectively assessed data from a TDM database. Methods Data was collected from 134 patients longitudinally treated with escitalopram for whom TDM was requested to guide drug therapy. Escitalopram metabolism was estimated by the log-transformed dose-corrected concentrations and compared within subpopulations differing in age, gender, renal function, smoking status, body mass index, and comedication. Results Patients with a depressive episode who were treated with escitalopram and discontinued the treatment within the hospital stay showed lower serum concentrations compared to patients who continued escitalopram treatment with a concentration of 15 ng/mL separating both groups. Variability was high between individuals and factors influencing blood levels, including dose, sex, and age. Comedication that inhibits cytochrome P450 (CYP) 2C19 isoenzymes were further found to influence escitalopram pharmacokinetics independent of dose, age or sex. Discussion Medication switch is a valuable objective surrogate marker to assess treatment effects under real-world conditions. Of note, treatment discontinuation is not always a cause of insufficient response but may also be related to other factors such as medication side effects. TDM might not only be useful in addressing these issues but titrating drug concentrations into the currently recommended reference range for escitalopram will also increase response in non-responders and avoid treatment failure in underdosed patients.

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“…Escitalopram is primarily metabolized in the liver by cytochrome P (CYP)450, particularly CYP2C19, which is a highly polymorphic enzyme that causes interindividual pharmacokinetic differences ( Rao, 2007 ; Pastoor and Gobburu, 2014 ), and is excreted mainly through the kidneys. The effect of age ( Dolder et al, 2010 ; Yang and Scott, 2010 ), gender ( Montejo et al, 2015 ), smoking ( Oliveira et al, 2017 ; Scherf-Clavel et al, 2019 ), CYP2C19 phenotype ( Huang et al, 2021 ), hepatic impairment ( Areberg et al, 2006 ), and renal impairment ( Dolder et al, 2010 ) on the pharmacokinetics of escitalopram have been investigated. The findings of these studies were instrumental in developing specific dosing recommendations for escitalopram for specific populations ( Hicks et al, 2015 ; Brouwer et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Population pharmacokinetics model for escitalopram in Chinese psychiatric patients: effect of CYP2C19 and age

et al. 2022

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Objective: To establish a population pharmacokinetic model in Chinese psychiatric patients to characterize escitalopram pharmacokinetic profile to identify factors influencing drug exposure, and through simulation to compare the results with the established therapeutic reference range.Methods: Demographic information, dosing regimen, CYP2C19 genotype, concomitant medications, and liver and kidney function indicators were retrospectively collected for inpatients taking escitalopram with therapeutic drug monitoring from 2018 to 2021. Nonlinear mixed-effects modeling was used to model the pharmacokinetic characteristics of escitalopram. Goodness-of-fit plots, bootstrapping, and normalized prediction distribution errors were used to evaluate the model. Simulation for different dosing regimens was based on the final estimations.Results: The study comprised 106 patients and 337 measurements of serum sample. A structural model with one compartment with first-order absorption and elimination described the data adequately. The population-estimated apparent volume of distribution and apparent clearance were 815 and 16.3 L/h, respectively. Age and CYP2C19 phenotype had a significant effect on the apparent clearance (CL/F). CL/F of escitalopram decreased with increased age, and CL/F of poor metabolizer patients was significantly lower than in extensive and immediate metabolizer patients. The final model-based simulation showed that the daily dose of adolescents with poor metabolizer might be as high as 15 mg or 20 mg and referring to the therapeutic range for adults may result in overdose and a high risk of adverse effects in older patients.Conclusion: A population pharmacokinetics model of escitalopram was successfully created for the Chinese population. Depending on the age of the patients, CYP2C19 genotype and serum drug concentrations throughout treatment are required for adequate individualization of dosing regimens. When developing a regimen for older patients, especially those who are poor metabolizers, vigilance is required.

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Escitalopram in the Treatment of Major Depressive Disorder in Adolescent Patients†

Cited by 5 publications

References 12 publications

Concentrations of escitalopram in blood of patients treated in a naturalistic setting: focus on patients with alcohol and benzodiazepine use disorder

Concentrations of escitalopram in blood of patients treated in a naturalistic setting: focus on patients with alcohol and benzodiazepine use disorder

Low Escitalopram Concentrations in Patients with Depression predict Treatment Failure: A Naturalistic Retrospective Study

Population pharmacokinetics model for escitalopram in Chinese psychiatric patients: effect of CYP2C19 and age

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