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

Abstract

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.

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

“…The mean serum concentration and C/D ratio in our study were in line with previously reported findings [13,[19][20][21], although, higher than those indicated in the TDM guidelines [9]. In line with reporting of previous studies, we found increasing C/D ratios with age [2,21]. In our study, patients at the age 60 years and older have more than twice as high escitalopram concentrations compared to patients aged 30 years and younger (C/D ratios: 2.56 ± 1.47 vs. 1.06 ± 0.55).…”

“…We furthermore present an overview of escitalopram pharmacokinetics, in a sample of older-aged patients and patients being treated with several concomitant medications. The mean serum concentration and C/D ratio in our study were in line with previously reported findings 13 19 20 21 , although, higher than those indicated in the TDM guidelines 9 . In line with reporting of previous studies, we found increasing C/D ratios with age 2 21 .…”

“…A woman will, in general, achieve a 47 % higher escitalopram concentration compared to a man under the same escitalopram dose. These findings suggest that TDM is of particular importance in patients with hepatic or renal functional impairments with higher age contributing to these variables [21]. Further caution is required in patients on CYP-interfering polypharmacy with CYP 2D6, CYP 2C19 or CYP 3A4 inhibiting substances.…”

Update Lessons from PET Imaging Part II: A Systematic Critical Review on Therapeutic Plasma Concentrations of Antidepressants

“…65 In addition, 80% of SERT thresholds derived from PET studies are in line with lower efficacy concentrations reported for the drug that predict response to the treatment. [66][67][68] One study demonstrated that treatment response was related to pretreatment SERT binding ratios in the key regions of depression. 20 SNRIs are believed to exert their action by a combination of SERT and NET engagement with varying activities at both transporters, making it more complicated to determine a specific threshold.…”

“…65 In addition, 80% of SERT thresholds derived from PET studies are in line with lower efficacy concentrations reported for the drug that predict response to the treatment. 66–68 One study demonstrated that treatment response was related to pretreatment SERT binding ratios in the key regions of depression. 20…”