{"title":"Total valproate versus free valproate in therapeutic drug monitoring for bipolar disorder: A cross-sectional study","authors":"Mullezhath Babu Nimesh Krishna MD, Jyothsna Chinnapura Seetharam MD, Archana Mishra DM, Rituparna Maiti MD, Biswa Ranjan Mishra MD, Anand Srinivasan DM","doi":"10.1111/appy.12555","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Introduction</h3>\n \n <p>The debate about observing total versus free serum valproate levels for therapeutic drug monitoring (TDM) has been unresolved for decades. This study was planned to assess the agreement between the total versus free valproate levels and the advantage of one method over the other in TDM.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>The present cross-sectional study was done on 93 patients with bipolar disorder. The intraclass correlation coefficient, Bland Altman analysis, and Lin's concordance analysis were done to assess the agreement between the total and free valproate concentrations. Linear and polynomial models were constructed to evaluate the relation between the two measurements. Receiver operating characteristics analysis was done to compare the accuracy for differentiating remission from non-remission on Young's mania rating scale (YMRS).</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>The intraclass correlation coefficient and Lin's concordance correlation coefficient were 0.491 (<i>p</i> = .002) and 0.055 (95% CI:0.037, 0.073), respectively. Bland Altman's analysis showed proportional bias. A polynomial model of second order was found to be the best fit for the prediction of free valproate from the data for total valproate, and 81.4% of the variability in free valproate could be explained when adjusted for albumin levels. The area under the curve for total valproate was 0.60 when compared to free valproate 0.56 for differentiating between remission and non-remission, but the comparison between the two ROC analyses was not statistically significant.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Free valproate does not provide any added advantage over the total valproate levels; hence, total valproate levels may continue to be used as the marker for drug monitoring.</p>\n </section>\n </div>","PeriodicalId":8618,"journal":{"name":"Asia‐Pacific Psychiatry","volume":"16 2","pages":""},"PeriodicalIF":2.8000,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Asia‐Pacific Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/appy.12555","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PSYCHIATRY","Score":null,"Total":0}
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Abstract
Introduction
The debate about observing total versus free serum valproate levels for therapeutic drug monitoring (TDM) has been unresolved for decades. This study was planned to assess the agreement between the total versus free valproate levels and the advantage of one method over the other in TDM.
Methods
The present cross-sectional study was done on 93 patients with bipolar disorder. The intraclass correlation coefficient, Bland Altman analysis, and Lin's concordance analysis were done to assess the agreement between the total and free valproate concentrations. Linear and polynomial models were constructed to evaluate the relation between the two measurements. Receiver operating characteristics analysis was done to compare the accuracy for differentiating remission from non-remission on Young's mania rating scale (YMRS).
Results
The intraclass correlation coefficient and Lin's concordance correlation coefficient were 0.491 (p = .002) and 0.055 (95% CI:0.037, 0.073), respectively. Bland Altman's analysis showed proportional bias. A polynomial model of second order was found to be the best fit for the prediction of free valproate from the data for total valproate, and 81.4% of the variability in free valproate could be explained when adjusted for albumin levels. The area under the curve for total valproate was 0.60 when compared to free valproate 0.56 for differentiating between remission and non-remission, but the comparison between the two ROC analyses was not statistically significant.
Conclusion
Free valproate does not provide any added advantage over the total valproate levels; hence, total valproate levels may continue to be used as the marker for drug monitoring.
期刊介绍：
Asia-Pacific Psychiatry is an international psychiatric journal focused on the Asia and Pacific Rim region, and is the official journal of the Pacific Rim College of Psychiatrics. Asia-Pacific Psychiatry enables psychiatric and other mental health professionals in the region to share their research, education programs and clinical experience with a larger international readership. The journal offers a venue for high quality research for and from the region in the face of minimal international publication availability for authors concerned with the region. This includes findings highlighting the diversity in psychiatric behaviour, treatment and outcome related to social, ethnic, cultural and economic differences of the region. The journal publishes peer-reviewed articles and reviews, as well as clinically and educationally focused papers on regional best practices. Images, videos, a young psychiatrist''s corner, meeting reports, a journal club and contextual commentaries differentiate this journal from existing main stream psychiatry journals that are focused on other regions, or nationally focused within countries of Asia and the Pacific Rim.
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