Antidepressant drug switching in the Swiss population with a focus on Escitalopram and drugs with pharmacogenetic dosing guidelines: a drug utilization study using claims data

The Pharmacogenomics Journal ARTICLE www.nature.com/tpj OPEN Antidepressant drug switching in the Swiss population with a focus on Escitalopram and drugs with pharmacogenetic dosing guidelines: a drug utilization study using claims data M. M. Roth1,2, C. R. Meier1,2, C. A. Huber3, H. E. Meyer zu Schwabedissen4, S. Allemann 5,6 ✉ and C. Schneider1,2,6 © The Author(s) 2025 1234567890();,: Depression affects around 10% of the Swiss population. While SSRIs are commonly prescribed, only 30–40% of patients achieve remission. Pharmacogenetic (PGx) factors may explain part of this high rate of SSRI treatment failure. This study examined antidepressant (AD) switching among Swiss patients using escitalopram, focusing on whether they switched to ADs with PGx dosing guidelines (PGx AD) or ADs without PGx dosing guidelines (non-PGx ADs). Data from Swiss health insurance records identified 41 275 patients who used escitalopram between July 2020 and June 2022. While 6.4% (n = 2 638) switched to another antidepressant, only 35.4% of these opted for a PGx AD. Men, younger adults showed higher switching rates, whereas patients on antipsychotic medications switched less. Individuals younger than 20 years old and women were more likely to switch to PGx AD whereas the elderly were less likely to switch to PGx AD. The Pharmacogenomics Journal (2025)25:24 ; https://doi.org/10.1038/s41397-025-00382-1 INTRODUCTION Depression is a mental health condition affecting approximately 10% of the Swiss population. The chronic and recurrent nature of depression necessitates effective long-term management [1]. Selective serotonin reuptake inhibitors (SSRIs) represent a fundamental element of the pharmacological management of major depressive disorder (MDD). In many guidelines, SSRIs are considered the first-line AD drug class, although some associations are moving towards patient individualization, such as the Association of Scientific Medical Societies (AWMF) [2–5]. However, treatment outcomes are often suboptimal, with 30–50% of patients not responding adequately to AD treatment. As a result, many patients experience adverse effects or an insufficient therapeutic response, leading clinicians to consider switching patients to alternative ADs [6–8]. A study conducted in the United Kingdom revealed that approximately 9.3% of patients initiating treatment with escitalopram required a switch to another AD [9]. One of the reasons for an inadequate response to escitalopram could be the genetic make-up of the patient. The metabolism of escitalopram and other SSRIs is catalysed by cytochrome P450 enzymes; particularly CYP2C19 and CYP2D6 are of relevance in the metabolism of SSRIs [10]. These enzymes exhibit significant inter-individual variability due to genetic polymorphisms, which can influence drug metabolism and, consequently, the efficacy and tolerability of substrate drugs [10, 11]. In accordance with this assumption, Jukić et al. found that patients categorized as poor metabolizers of CYP2C19 switched from escitalopram 3.3 times more frequently than those with normal metabolic capacity [12]. To the best of our knowledge, AD switching patterns on a population level have not yet been assessed in Switzerland. Not all ADs are affected by PGx and therefore do not have PGx dosing guidelines [10, 13–16]. The primary objective of this study was to examine the switching pattern of escitalopram to alternative ADs and to compare the rates of switching to PGx AD versus non-PGx ADs in the Swiss population. Rather than aiming to evaluate treatment effects or clinical decision-making at the individual level, the study sought to generate population-level insights into current prescribing practices in the Swiss healthcare context. METHODS Study design and data source We conducted a descriptive, retrospective study using claims data from Helsana Group, a Swiss health insurance company that covers approximately 15% of the Swiss population across all age groups. Helsana Group claims data include information on outpatient drug claims, categorized according to the World Health Organization’s Anatomical Therapeutic Chemical (ATC) classification system, as well as demographic information such as canton of residence, year of birth, and sex. However, clinical information, lifestyle factors such as smoking status and weight, use of over-the-counter medications, and treatment indications were not available in our anonymized dataset. The Helsana Group database has already been used in various drug safety and utilization studies [17–20]. 1 Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, 4003 Basel, Switzerland. Hospital Pharmacy, University Hospital Basel, 4056 Basel, Switzerland. 3Department of Health Sciences, Helsana Insurance Group, 8001 Zürich, Switzerland. 4Biopharmacy, Department of Pharmaceutical Sciences, University of Basel, 4003 Basel, Switzerland. 5Pharmaceutical Care, Department of Pharmaceutical Sciences, University of Basel, 4003 Basel, Switzerland. 6These authors contributed equally: S. Allemann, C. Schneider. ✉email: 2 Received: 20 December 2024 Revised: 7 July 2025 Accepted: 16 July 2025 M.M. Roth et al. 2 Study population The study period ranged from July 1, 2020, to June 30, 2022. This study focused on escitalopram, the most frequently claimed AD in 2021. Our study population included all individuals with claims for escitalopram and at least one other medication for AD during the specified period. Table 1. Characteristics of the study population. Characteristics of the study population Without switches [N, %] [N, %] 13 943, 84.1 2 638, 15.9 Male 4 567, 32.8 953, 36.1 Female 9 376, 67.2 1 685, 63.9 Age mean (SD) 56.2 (20.8) 54.8 (20.8) Antidepressants We identified AD claims using the ATC codes N06AA (non-selective monoamine reuptake inhibitors or tricyclic ADs), N06AB (selective serotonin reuptake inhibitors), code), N06AF + N06AG (monoamine oxidase inhibitors (MAOIs)), and N06AX (other ADs) that subsume nonuniform underlying mechanisms of action (atypical ADs), such as serotoninnorepinephrine reuptake inhibitors (SNRIs) and tetracyclic ADs. We classified the respective AD as “pharmacogenetic” if any dosing guidelines were available in the Pharmacogenetic Knowledge Base (PharmGKB) in August 2024 [21]. The presence of a dosing guideline in PharmGKB corresponds to the highest evidence level (Level 1 A), which indicates variant-specific prescribing guidance in a current clinical guideline or FDAapproved drug label, supported by at least one additional peer-reviewed publication [22]. Based on this criterion, we identified dosing recommendations for the following 12 ADs: imipramine, clomipramine, trimipramine, amitriptyline, nortriptyline, doxepin, citalopram, paroxetine, sertraline, fluvoxamine, escitalopram, and venlafaxine. We excluded the lowest strengths for trazodone (50 mg) and mirtazapine (15 mg) b (...truncated)