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

ABSTRACT

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.

KEYWORDS:

• Antidepressants
• escitalopram
• pharmacokinetics
• Therapeutic drug monitoring
• treatment response

Declaration of interest

E Haen received speaker’s or consultancy fees from the following pharmaceutical companies: Servier, Novartis, and Janssen-Cilag. He is managing director of AGATE. He is editor of an internet-based drug – drug interaction program (www.psiac.de). G Schoretsanitis has served as a consultant for HLS Therapeutics and Thermo Fisher and has received speaker’s fees from HLS Therapeutics. M Paulzen has received speaker’s fees from Janssen, ROVI, Neuraxpharm, Lundbeck, and Otsuka. He has served as a consultant for Novartis, Otsuka, Idorsia, and ROVI. He is editor of an internet-based drug – drug interaction program (www.psiac.de). N Kuzo has received educational grants from Lundbeck. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A peer reviewer on this manuscript has received an honorarium from Expert Review of Clinical Pharmacology for their review work. The reviewers have no other relevant financial relationships to disclose.

Ethics statement

The retrospective analysis of clinical data was in accordance with the 1964 Declaration of Helsinki and its later amendments and was waived by the local regulatory authority of RWTH Aachen University hospital, as for this type of study, no formal patient consent was required.

Author contributions

Conception and design of the study: E Haen, C Hiemke, T Frodl, G Schoretsanitis, M Paulzen, and N Kuzo. Analysis of the data: N Kasperk and N Kuzo. Interpretation of the data: E Haen, C Hiemke, T Frodl, G Schoretsanitis, M Paulzen, and N Kuzo. Drafting of the manuscript: G Schoretsanitis and N Kuzo. Critically revising manuscript for intellectual content: All authors. Final approval of the version to be published: All authors. All authors agree to be accountable for all aspects of the work.

Supplemental data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/17512433.2024.2314211.

Additional information

Funding

This paper was not funded.