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16-05-2024 | Venlafaxine | Research Article

Developing a machine learning model for predicting venlafaxine active moiety concentration: a retrospective study using real-world evidence

Authors: Luyao Chang, Xin Hao, Jing Yu, Jinyuan Zhang, Yimeng Liu, Xuxiao Ye, Ze Yu, Fei Gao, Xiaolu Pang, Chunhua Zhou

Published in: International Journal of Clinical Pharmacy | Issue 4/2024

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Abstract

Background

Venlafaxine is frequently prescribed for patients with depression. To control the concentration of venlafaxine within the therapeutic window for the best treatment effect, a model to predict venlafaxine concentration is necessary.

Aim

Our objective was to develop a prediction model for venlafaxine concentration using real-world evidence based on machine learning and deep learning techniques.

Method

Patients who underwent venlafaxine treatment between November 2019 and August 2022 were included in the study. Important variables affecting venlafaxine concentration were identified using a combination of univariate analysis, sequential forward selection, and machine learning techniques. Predictive performance of nine machine learning and deep learning algorithms were assessed, and the one with the optimal performance was selected for modeling. The final model was interpreted using SHapley Additive exPlanations.

Results

A total of 330 eligible patients were included. Five influential variables that affect venlafaxine concentration were venlafaxine daily dose, sex, age, hyperlipidemia, and adenosine deaminase. The venlafaxine concentration prediction model was developed using the eXtreme Gradient Boosting algorithm (R2 = 0.65, mean absolute error = 77.92, root mean square error = 93.58). In the testing cohort, the accuracy of the predicted concentration within ± 30% of the actual concentration was 73.49%. In the subgroup analysis, the prediction accuracy was 69.39% within the recommended therapeutic range of venlafaxine concentration within ± 30% of the actual value.

Conclusion

The XGBoost model for predicting blood concentration of venlafaxine using real-world evidence was developed, guiding the adjustment of regimen in clinical practice.
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Literature
1.
go back to reference Morton WA, Sonne SC, Verga MA. Venlafaxine: a structurally unique and novel antidepressant. Ann Pharmacother. 1995;29(4):387–95.CrossRefPubMed Morton WA, Sonne SC, Verga MA. Venlafaxine: a structurally unique and novel antidepressant. Ann Pharmacother. 1995;29(4):387–95.CrossRefPubMed
2.
go back to reference Harvey AT, Rudolph RL, Preskorn SH. Evidence of the dual mechanisms of action of venlafaxine. Arch Gen Psychiatry. 2000;57(5):503–9.CrossRefPubMed Harvey AT, Rudolph RL, Preskorn SH. Evidence of the dual mechanisms of action of venlafaxine. Arch Gen Psychiatry. 2000;57(5):503–9.CrossRefPubMed
3.
go back to reference Fogelman SM, Schmider J, Venkatakrishnan K, et al. O- and N-demethylation of venlafaxine in vitro by human liver microsomes and by microsomes from cDNA-transfected cells: effect of metabolic inhibitors and SSRI antidepressants. Neuropsychopharmacol. 1999;20(5):480–90.CrossRef Fogelman SM, Schmider J, Venkatakrishnan K, et al. O- and N-demethylation of venlafaxine in vitro by human liver microsomes and by microsomes from cDNA-transfected cells: effect of metabolic inhibitors and SSRI antidepressants. Neuropsychopharmacol. 1999;20(5):480–90.CrossRef
4.
go back to reference Ostad Haji E, Hiemke C, Pfuhlmann B. Therapeutic drug monitoring for antidepressant drug treatment. Curr Pharm Design. 2012;18(36):5818.CrossRef Ostad Haji E, Hiemke C, Pfuhlmann B. Therapeutic drug monitoring for antidepressant drug treatment. Curr Pharm Design. 2012;18(36):5818.CrossRef
5.
go back to reference Paulzen M, Groppe S, Tauber SC, et al. Venlafaxine and O-desmethylvenlafaxine concentrations in plasma and cerebrospinal fluid. J Clin Psychiatry. 2015;76(1):25–31.CrossRefPubMed Paulzen M, Groppe S, Tauber SC, et al. Venlafaxine and O-desmethylvenlafaxine concentrations in plasma and cerebrospinal fluid. J Clin Psychiatry. 2015;76(1):25–31.CrossRefPubMed
6.
go back to reference Shelton R. Serotonin and norepinephrine reuptake inhibitors. Cham: Springer; 2019. p. 145–80. Shelton R. Serotonin and norepinephrine reuptake inhibitors. Cham: Springer; 2019. p. 145–80.
7.
go back to reference Montgomery SA, Mahe V, Haudiquet V, et al. Effectiveness of venlafaxine, extended release formulation, in the short-term and long-term treatment of generalized anxiety disorder: results of a survival analysis. J Clin Psychopharmacol. 2002;22(6):561–7.CrossRefPubMed Montgomery SA, Mahe V, Haudiquet V, et al. Effectiveness of venlafaxine, extended release formulation, in the short-term and long-term treatment of generalized anxiety disorder: results of a survival analysis. J Clin Psychopharmacol. 2002;22(6):561–7.CrossRefPubMed
8.
go back to reference Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology; 2017 Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology; 2017
9.
go back to reference Hiemke C. Consensus guideline based therapeutic drug monitoring (TDM) in psychiatry and neurology. Curr Drug Deliv. 2016;13(3):353.CrossRefPubMed Hiemke C. Consensus guideline based therapeutic drug monitoring (TDM) in psychiatry and neurology. Curr Drug Deliv. 2016;13(3):353.CrossRefPubMed
10.
go back to reference Schoretsanitis G, Paulzen M, Unterecker S, et al. TDM in psychiatry and neurology: A comprehensive summary of the consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology, update 2017; a tool for clinicians. World J Biol Psychiatry. 2018;19(3):162–74.CrossRefPubMed Schoretsanitis G, Paulzen M, Unterecker S, et al. TDM in psychiatry and neurology: A comprehensive summary of the consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology, update 2017; a tool for clinicians. World J Biol Psychiatry. 2018;19(3):162–74.CrossRefPubMed
16.
go back to reference Palacios M. The quality of research with real-world evidence. Colomb Med (Cali). 2019;50(3):140–1.PubMed Palacios M. The quality of research with real-world evidence. Colomb Med (Cali). 2019;50(3):140–1.PubMed
17.
go back to reference Robson C. Real world research. 3rd ed. London: Wiley; 2011. Robson C. Real world research. 3rd ed. London: Wiley; 2011.
21.
go back to reference Hao Y, Zhang J, Yang L, et al. A machine learning model for predicting blood concentration of quetiapine in patients with schizophrenia and depression based on real-world data. Br J Clin Pharmacol. 2023;89(9):2714–25.CrossRefPubMed Hao Y, Zhang J, Yang L, et al. A machine learning model for predicting blood concentration of quetiapine in patients with schizophrenia and depression based on real-world data. Br J Clin Pharmacol. 2023;89(9):2714–25.CrossRefPubMed
22.
go back to reference Spratt DE, Tang S, Sun Y, et al. Artificial intelligence predictive model for hormone therapy use in prostate cancer. NEJM Evid. 2023;2(8):EVIDoa2300023.CrossRefPubMedPubMedCentral Spratt DE, Tang S, Sun Y, et al. Artificial intelligence predictive model for hormone therapy use in prostate cancer. NEJM Evid. 2023;2(8):EVIDoa2300023.CrossRefPubMedPubMedCentral
23.
go back to reference Lundberg S, Lee SI. A unified approach to interpreting model Predictions//Nips.2017. Lundberg S, Lee SI. A unified approach to interpreting model Predictions//Nips.2017.
24.
go back to reference Chen T, Guestrin C. In: Proceedings of the 22nd ACM SIGKDD international conference on knowledge discovery and data mining. XGBoost: A scalable tree boosting system. San Francisco, CA: ACM; 2016. pp. 785–94. Chen T, Guestrin C. In: Proceedings of the 22nd ACM SIGKDD international conference on knowledge discovery and data mining. XGBoost: A scalable tree boosting system. San Francisco, CA: ACM; 2016. pp. 785–94.
27.
go back to reference Zhang R, Liu Y, Cao J, et al. The incidence and risk factors analysis of acute kidney injury in hospitalized patients received diuretics: a single-center retrospective study. Front Pharmacol. 2022;13:924173.CrossRefPubMedPubMedCentral Zhang R, Liu Y, Cao J, et al. The incidence and risk factors analysis of acute kidney injury in hospitalized patients received diuretics: a single-center retrospective study. Front Pharmacol. 2022;13:924173.CrossRefPubMedPubMedCentral
28.
go back to reference Rodríguez-Pérez R, Bajorath J. Evolution of support vector machine and regression modeling in chemoinformatics and drug discovery. J Comput Aided Mol Des. 2022;36(5):355–62.CrossRefPubMedPubMedCentral Rodríguez-Pérez R, Bajorath J. Evolution of support vector machine and regression modeling in chemoinformatics and drug discovery. J Comput Aided Mol Des. 2022;36(5):355–62.CrossRefPubMedPubMedCentral
31.
go back to reference General Chair-Krishnapuram B, General Chair-Shah M, Program Chair-Smola A, et al. Proceedings of the 22nd ACM SIGKDD international conference on knowledge discovery and data mining//Acm Sigkdd international conference on knowledge discovery & data mining. ACM; 2016. General Chair-Krishnapuram B, General Chair-Shah M, Program Chair-Smola A, et al. Proceedings of the 22nd ACM SIGKDD international conference on knowledge discovery and data mining//Acm Sigkdd international conference on knowledge discovery & data mining. ACM; 2016.
32.
go back to reference Hansen MR, Kuhlmann IB, Pottegård A, et al. Therapeutic drug monitoring of venlafaxine in an everyday clinical setting: analysis of age, sex and dose concentration relationships. Basic Clin Pharmacol. 2017;121(4):298–302.CrossRef Hansen MR, Kuhlmann IB, Pottegård A, et al. Therapeutic drug monitoring of venlafaxine in an everyday clinical setting: analysis of age, sex and dose concentration relationships. Basic Clin Pharmacol. 2017;121(4):298–302.CrossRef
33.
go back to reference Richards-Belle A, Austin-Zimmerman I, Wang B, et al. Associations of antidepressants and antipsychotics with lipid parameters: Do CYP2C19/CYP2D6 genes play a role? A UK population-based study J Psychopharmacol. 2023;37(4):396–407.PubMed Richards-Belle A, Austin-Zimmerman I, Wang B, et al. Associations of antidepressants and antipsychotics with lipid parameters: Do CYP2C19/CYP2D6 genes play a role? A UK population-based study J Psychopharmacol. 2023;37(4):396–407.PubMed
34.
go back to reference Whyte EM, Romkes M, Mulsant BH, et al. CYP2D6 genotype and venlafaxine-XR concentrations in depressed elderly. Int J Geriatr Psychiatry. 2006;21(6):542–9.CrossRefPubMed Whyte EM, Romkes M, Mulsant BH, et al. CYP2D6 genotype and venlafaxine-XR concentrations in depressed elderly. Int J Geriatr Psychiatry. 2006;21(6):542–9.CrossRefPubMed
35.
go back to reference Dean L. Venlafaxine therapy and CYP2D6 genotype. In: Pratt VM, Scott SA, Pirmohamed M, Esquivel B, Kattman BL, Malheiro AJ, editors. Medical genetics summaries. Bethesda: National Center for Biotechnology Information (US); 2015. Dean L. Venlafaxine therapy and CYP2D6 genotype. In: Pratt VM, Scott SA, Pirmohamed M, Esquivel B, Kattman BL, Malheiro AJ, editors. Medical genetics summaries. Bethesda: National Center for Biotechnology Information (US); 2015.
36.
go back to reference Lessard E, Yessine M, Hamelin BA, et al. Diphenhydramine alters the disposition of venlafaxine through inhibition of CYP2D6 activity in humans. J Clin Psychopharm. 2001;21(2):175–84.CrossRef Lessard E, Yessine M, Hamelin BA, et al. Diphenhydramine alters the disposition of venlafaxine through inhibition of CYP2D6 activity in humans. J Clin Psychopharm. 2001;21(2):175–84.CrossRef
37.
go back to reference Paulzen M, Schoretsanitis G, Hiemke C, et al. Reduced clearance of venlafaxine in a combined treatment with quetiapine. Prog Neuropsychopharmacol Biol Psychiatry. 2018;13(85):116–21.CrossRef Paulzen M, Schoretsanitis G, Hiemke C, et al. Reduced clearance of venlafaxine in a combined treatment with quetiapine. Prog Neuropsychopharmacol Biol Psychiatry. 2018;13(85):116–21.CrossRef
38.
go back to reference Wang Z, Li L, Huang S, et al. Joint population pharmacokinetic modeling of venlafaxine and O-desmethyl venlafaxine in healthy volunteers and patients to evaluate the impact of morbidity and concomitant medication. Front Pharmacol. 2022;13:978202.CrossRefPubMedPubMedCentral Wang Z, Li L, Huang S, et al. Joint population pharmacokinetic modeling of venlafaxine and O-desmethyl venlafaxine in healthy volunteers and patients to evaluate the impact of morbidity and concomitant medication. Front Pharmacol. 2022;13:978202.CrossRefPubMedPubMedCentral
Metadata
Title
Developing a machine learning model for predicting venlafaxine active moiety concentration: a retrospective study using real-world evidence
Authors
Luyao Chang
Xin Hao
Jing Yu
Jinyuan Zhang
Yimeng Liu
Xuxiao Ye
Ze Yu
Fei Gao
Xiaolu Pang
Chunhua Zhou
Publication date
16-05-2024
Publisher
Springer International Publishing
Keyword
Venlafaxine
Published in
International Journal of Clinical Pharmacy / Issue 4/2024
Print ISSN: 2210-7703
Electronic ISSN: 2210-7711
DOI
https://doi.org/10.1007/s11096-024-01724-y

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