Nicholas Kasperk, Ekkehard Haen, Christoph Hiemke, Thomas Frodl, Georgios Schoretsanitis, Michael Paulzen, Nazar Kuzo
{"title":"艾司西酞普兰治疗患者自然样本临床反应的药代动力学相关性。","authors":"Nicholas Kasperk, Ekkehard Haen, Christoph Hiemke, Thomas Frodl, Georgios Schoretsanitis, Michael Paulzen, Nazar Kuzo","doi":"10.1080/17512433.2024.2314211","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>We assessed pharmacokinetic correlates of treatment response to escitalopram using a large therapeutic drug monitoring database.</p><p><strong>Methods: </strong>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 (<i>n</i> = 83) vs. non-responders (<i>n</i> = 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.</p><p><strong>Results: </strong>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), <i>p</i> = 0.007); C/D ratios (odds ratio 0.52, 95% confidence interval 0.34-0.80, <i>p</i> < 0.003) were associated with response to escitalopram, after controlling for age, sex, and BMI.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"247-253"},"PeriodicalIF":3.6000,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pharmacokinetic correlates of clinical response in a naturalistic sample of escitalopram-treated patients.\",\"authors\":\"Nicholas Kasperk, Ekkehard Haen, Christoph Hiemke, Thomas Frodl, Georgios Schoretsanitis, Michael Paulzen, Nazar Kuzo\",\"doi\":\"10.1080/17512433.2024.2314211\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>We assessed pharmacokinetic correlates of treatment response to escitalopram using a large therapeutic drug monitoring database.</p><p><strong>Methods: </strong>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 (<i>n</i> = 83) vs. non-responders (<i>n</i> = 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.</p><p><strong>Results: </strong>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), <i>p</i> = 0.007); C/D ratios (odds ratio 0.52, 95% confidence interval 0.34-0.80, <i>p</i> < 0.003) were associated with response to escitalopram, after controlling for age, sex, and BMI.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":12207,\"journal\":{\"name\":\"Expert Review of Clinical Pharmacology\",\"volume\":\" \",\"pages\":\"247-253\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2024-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Expert Review of Clinical Pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/17512433.2024.2314211\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/2/5 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert Review of Clinical Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17512433.2024.2314211","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/5 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
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.
期刊介绍:
Advances in drug development technologies are yielding innovative new therapies, from potentially lifesaving medicines to lifestyle products. In recent years, however, the cost of developing new drugs has soared, and concerns over drug resistance and pharmacoeconomics have come to the fore. Adverse reactions experienced at the clinical trial level serve as a constant reminder of the importance of rigorous safety and toxicity testing. Furthermore the advent of pharmacogenomics and ‘individualized’ approaches to therapy will demand a fresh approach to drug evaluation and healthcare delivery.
Clinical Pharmacology provides an essential role in integrating the expertise of all of the specialists and players who are active in meeting such challenges in modern biomedical practice.