Monitoring of the Antipsychotic Therapy Effectiveness
https://doi.org/10.30629/2618-6667-2022-20-4-128-138
Abstract
Background: there is seminal medicine direction in the diagnosis and therapy of mental disorders, namely personalized medicine. Its concept embodies an individual approach to treatment based on the genotype and phenotype of the patient. Objective: the presented paper deal with the main modern approaches to the individualization of psychopharmacotherapy: genotyping, determination of the level of biomarkers and therapeutic drug monitoring (TDM). Methods: databases of medical and biological publications (MEDLINE, PubMed); clinical observations. Results: examples of genetic tests that allow optimizing the therapy of mental illness are presented. The concept of biomarkers as diagnostic and therapeutic indicators in personalized medicine is considered. Other promising areas of scientific research are briefly described: metabolism, transporters, neurotransmitters (mediators), epigenetics. Population modeling of antibiotic pharmacokinetics also deserves attention. Specific examples of TDM content of antipsychotics are given. Conclusion: the reviewed research directions focused on the introduction of the principles of personalized and translational medicine into routine psychiatric practice.
About the Author
I. I. Miroshnichenko
Mental Health Research Centre
Russian Federation
Russian Federation
Igor I. Miroshnichenko - Dr. of Sci. (Med.), Head of Pharmacokinetics Laboratory, Mental Health Research Centre.
Moscow
References
1. Bothos E, Ntoumou E, Kelaidoni K, Roukas D, Drakoulis N, Papasavva M, Karakostis FA, Moulos P, Karakostis K. Clinical pharmacogenomics in action: design, assessment and implementation of a novel pharmacogenetic panel supporting drug selection for diseases of the central nervous system (CNS). J Transl Med. 2021;19(1):1-17. doi: 10.1186/s12967-021-02816-3
2. Clarke NJ. Mass spectrometry in precision medicine: phenotypic measurements alongside pharmacog-enomics. Clin Chem. 2016;62(1):70-76. doi: 10.1373/clinchem.2015.239475
3. Sinha J, Duffull SB, Green B, Al-Sallami HS. Evaluating Lean Liver Volume as a Potential Scaler for In Vitro-In Vivo Extrapolation of Drug Clearance in Obesity Using the Model Drug Antipyrine. Curr Drug Metab. 2020;21(10):746-750. doi: 10.2174/1389200221666200515105800
4. Mahesh M, Madsen M. Addressing Technetium-99m Shortage. J Am Coll Radiol. 2017;14(5):681-683. doi: 10.1016/j.jacr.2017.02.007
5. Lally J, MacCabe JH. Antipsychotic medication in schizophrenia: a review. Br Med Bull. 2015;114(1):169-179. doi: 10.1093/bmb/ldv017
6. Seeman P. Targeting the dopamine D2 receptor in schizophrenia. Expert Opin. Ther. Targets. 2006;10(4):515-531. doi: 10.1517/14728222.10.4.515
7. De Deurwaerdere P, Chagraoui A, Di Giovanni G. Serotonin/dopamine interaction: Electrophysiological and neurochemical evidence. Prog Brain Res. 2021;261:161-264. doi: 10.1016/bs.pbr.2021.02.001
8. Cumming P, Abi-Dargham A, Grunder G. Molecular imaging of schizophrenia: Neurochemical findings in a heterogeneous and evolving disorder. Behav Brain Res. 2021;1;398:113004. doi: 10.1016/j.bbr.2020.113004
9. Leucht S, Crippa A, Siafis S, Patel MX, Orsini N, Davis JM. Dose-response meta-analysis of antipsychotic drugs for acute schizophrenia. Am J Psychiatry. 2020;177(4):342-353. doi: 10.1176/appi.ajp.2019.19010034
10. Butnariu M.Bioequivalence and bioavailability of receptors dopamine (D2) and serotonin in the action of antipsychotic drugs. J. Bioequiv Availab. 2017;9:e76. doi: 10.4172/jbb.10000e76
11. Wong DF., Raoufinia A, Bricmont P, Brasic JR, McQuade RM, Forbes FA, Kikuchi T, Kuwabara T. An open-label, positron emission tomography study of the striatal D2/D3 receptor occupancy and pharmacokinetics of single-dose oral brexpipra-zole in healthy participants. Eur J Clin Pharmacol. 2021;77(5):717-725. doi: 10.1007/s00228-020-03021-9
12. Mamaligas AA, Cai Y, Ford CP. Nicotinic and opioid receptor regulation of striatal dopamine D2-receptor mediated transmission. Sci Rep. 2016;6:37834. doi: 10.1038/srep37834
13. Golimbet VE. Genomics in psychology and psychiatry. Mol Biol (Mosk). 2004;38(1):165-170. (In Russ.). PMID: 15042846
14. Lin JH, Lu AYH. Role of pharmacokinetics and metabolism in drug discovery and development. Pharmacol Rev. 1997;49:403-449. PMID: 9443165
15. Landis MS. Physicochemical property trends of marketed prodrugs. Ther Deliv 2013;4(2):225-237. doi: 10.4155/tde.12.150
16. Kibitov AO, Ivashchenko DV, Sychev DA. Pharmacogenetic approach to increase efficacy and safety of schizophrenia treatment with antipsychotics. Sovremennaya terapiya psikhiatricheskikh rasstroistv. 2017;1:2-13. (In Russ.). doi: 10.21265/PSYPH.2017.40.4982
17. Shchulkin AV, Chernykh IV, Popova NM, Slepnev AA, Yakusheva EN. Evaluation of female sex hormones influence on the protein-transporter p-glycoprotein functioning in vitro. Biomeditsinskaya Khimiya. 2020;66(6):444-449. doi: 10.18097/PBMC20206606444
18. Piatkov I, Caetano D, Assur Y, Lau SL, Jones T, Boyages SC, McLean M. ABCB1 and ABCC1 single-nucleotide polymorphisms in patients treated with clozapine. Pharmgenomics Pers Med. 2017;10:235-242. doi: 10.2147/PGPM.S142314
19. Güzey C, Scordo MG, Spina E, Landsem VM, Spigset O. Antipsychotic-induced extrapyramidal symptoms in patients with schizophrenia: associations with dopamine and serotonin receptor and transporter polymorphisms. Eur. J Clin Pharmacol. 2007;63(3):233-241. doi: 10.1007/s00228-006-0234-8
20. Carli M, Kolachalam S, Longoni B, Pintaudi A, Baldini M, Aringhieri S, Fasciani I, Annibale P, Maggio R, Scarselli M. Atypical antipsychotics and metabolic syndrome: from molecular mechanisms to clinical differences. Pharmaceuticals. 2021;14(3):238. doi: 10.3390/ph14030238
21. Grubor M, Zivkovic M, Sagud M, Perkovic MN, Mihaljevic-Peles A, Pivac N, Muck-Seler D, Strac DS. HTR1A, HTR1B, HTR2A, HTR2C and HTR6 gene polymorphisms and extrapyramidal side effects in haloperidol-treated patients with schizophrenia. Int J Mol Sci. 2020;21(7):2345. doi: 10.3390/ijms21072345
22. Zubiaur P, Soria-Chacartegui P, Villapalos-Garcfa G, Gordillo-Perdomo JJ, Abad-Santos F. The pharmacogenetics of treatment with olanzapine. Pharmacogenomics. 2021;22(14):939-958. doi: 10.2217/pgs-2021-0051
23. Lisoway AJ, Chen CC, Zai CC, Tiwari AK, Kennedy JL. Toward personalized medicine in schizophrenia: Genetics and epigenetics of antipsychotic treatment. Schizophr Res. 2021; 232:112-124. doi: 10.1016/j.schres.2021.05.010
24. McClarty BM, Fisher DW, Dong H. Epigenetic alterations impact on antipsychotic treatment in elderly patients. Curr Treat Options Psychiatry. 2018;5(1):17-29. PMID: 29755923
25. Fisel P, Schaeffeler E, Schwab M. DNA methylation of ADME genes. Clin Pharmacol Ther. 2016;99:512-527. doi: 10.1002/cpt.343
26. Stroup TS, Gerhard T, Crystal S, Huang C, Olfson M. Comparative effectiveness of clozapine and standard antipsychotic treatment in adults with schizophrenia. Am. J. Psychiatry. 2 016;173:166-173 . doi: 10.1176/appi.ajp.2015.15030332
27. Kar N, Barreto S, Chandavarkar R. Clozapine monitoring in clinical practice: beyond the mandatory requirement. Clin Psychopharmacol Neurosci. 2016;14(4): 323-329. doi: 10.9758/cpn.2016.14.4.323
28. Miroshnichenko II, Baymeeva NV, Platova AI. Determination of serum/plasma concentrations of psychotropic drugs in therapeutic drug monitoring. Pharmacokinetics and Pharmacodynamics. 2021;(1):3-13. (In Russ.). doi: 10.37489/2587-7836-2021-1-3-13
29. Bauer RJ. NONMEM Tutorial Part I: Description of Commands and Options, with Simple Examples of Population Analysis. CPT Pharmacometrics Syst Pharmacol. 2019;8(8):525-537. doi: 10.1002/psp4.12404 Epub ahead of print. PMID: 31056834; PMCID: PMC6709426
30. Miroshnichenko II, Platova AI. Personalized psychopharmacotherapy: State of problem. Psychiatry (Moscow) (Psikhiatriya). 2015;67(3):85-94. (In Russ.).
31. Aronson JK, Ferner RF. Biomarkers — a general review. Curr Protoc Pharmacol. 2017;17(76):9.23.1-9.23.17. doi: 10.1002/cpph.19
32. Siu LL, Conley BA, Boerner S, LoRusso PM. Next-generation sequencing to guide clinical trials. Clin. Cancer Res. 2015;21(20):4536-4544. doi: 10.1158/1078-0432.CCR-14-3215
33. Bondy B. Genetics in psychiatry: Are the promises met? World J Biol Psychiatry. 2011;12(2):81-88. doi: 10.3109/15622975.2010.546428
34. McClay JL, Adkins DE, Aberg K, Stroup S, Perkins DO, Vladimirov VI, Lieberman JA, Sullivan PF, van den Oord EJ. Genome-wide pharmacogenomic analysis of response to treatment with antipsychotics. Mol Psychiatry. 2011;16(1):76-85. doi: 10.1038/mp.2009.89
35. Mossner R, Schuhmacher A, Wagner M, Lennertz L, Steinbrecher A, Quednow BB, Rujescu D, Rietschel M, Maier W. The schizophrenia risk gene ZNF804A influences the antipsychotic response of positive schizophrenia symptoms. Eur. Arch. Psychiatry Clin. Neurosci. 2012;262(3):193-197. doi: 10.1007/s00406-011-0235-1
36. Klyushnik TP, Smulevich AB, Zozulya SA, Voronova EI. Neurobiology of schizophrenia (to the construction of clinical and biological model). Psychiatry (Moscow) (Psikhiatriya) . 2 0 21;19(1):6-15 . (In Russ.). doi: 10.30629/2618-6667-2021-19-1-6-15
37. Laskaris L, Mancuso S, Shannon Weickert C, Zalesky A, Chana G, Wannan C, Bousman C, Baune BT, McGorry P, Pantelis C, Cropley VL. Brain morphology is differentially impacted by peripheral cytokines in schizophrenia-spectrum disorder. Brain Behav Immun. 2021;95:299-309. doi: 10.1016/j.bbi.2021.04.002
38. Moschny N, Hefner G, Grohmann R, Eckermann G, Maier HB, Seifert J, Heck J, Francis F, Bleich S, Toto S, Meissner C. Therapeutic drug monitoring of second- and third-generation antipsychotic drugs-influence of smoking behavior and inflammation on pharmacokinetics. Pharmaceuticals. 2021;14:514. doi: 10.3390/ph14060514
39. Bora E. Developmental trajectory of cognitive impairment in bipolar disorder: comparison with schizophrenia. Eur Neuropsychopharmacol. 2015;25:158-168. doi: 10.1016/j.euroneuro.2014.09.007
40. Albert PR. What is a functional genetic polymorphism? Defining classes of functionality. J Psychiatry Neuros-ci. 2011;36(6):363-365. doi: 10.1503/jpn.110137
41. Wu XJ, Zhang J, Yu JC, Cao GY, Shi YG, Zhang YY, Wang MG. Establishment of norvancomycin fluorescence polarization immunoassay for therapeutic drug monitoring. J Antibiot. 2012;65(1):35-39. doi: 10.1038/ja.2011.89
42. Grebe SK, Singh RJ. LC-MS/MS in the clinical laboratory — where to from here? Clin Biochem Rev. 2011;32(1):5-31. PMID: 21451775
43. Miroshnichenko II, Baymeeva NV. Simultaneous determination of antipsychotic drugs and their active metabolites by LC-MS-MS and its application to therapeutic drug monitoring. J Chromatogr Sci. 2018;56(6):510-517. doi: 10.1093/chromsci/bmy024
44. Brandhorst G, Oellerich M, Maine G, Taylor P, Veen G, Wallemacq P. Liquid chromatography-tandem mass spectrometry or automated immunoassays: what are the future trends in therapeutic drug monitoring? Clin Chem. 2012;58:821-825. doi: 10.1373/clinchem.2011.167189
45. Eliasson E, Lindh JD, Malmstrom RE, Beck O, Dahl ML. Therapeutic drug monitoring for tomorrow. Eur J Clin Pharmacol. 2013;69(1):25-32. doi: 10.1007/s00228-013-1504-x
46. Capiau S, Veenhof H, Koster RA, Bergqvist Y, Boettcher M, Halmingh O, Keevil BG, Koch CP, Linden R, Pistos C, Stolk LM, Touw DJ, Stove CP, Alffenaar JC. Official international association for therapeutic drug monitoring and clinical toxicology guideline: development and validation of dried blood spotbased methods for therapeutic drug monitoring. Ther Drug Monit. 2019;41(4):409-430. doi: 10.1097/FTD.0000000000000643
47. Sun X, Song L, Yang W, Zhang L, Liu M, Li X, Tian G, Wang W. Nanopore Sequencing and Its Clinical Applications. Methods Mol Biol. 2020;2204:13-32. doi: 10.1007/978-1-0716-0904-0_2
48. Lastochkina OV, Gorelov PV. Biological microchips — a new level of laboratory research. Analyti-ka 2017;36(5):76-86 (In Russ.). doi: 10.22184/2227-572X.2017.36.5.76.86
49. Zeier Z, Carpenter L, Kalin NH, Rodriguez CI, McDonald WM, Widge AS, Nemeroff CB. Clinical implementation of pharmacogenetic decision support tools for antidepressant drug prescribing. Am J Psychiatry. 2018,175(9):873-886. doi: 10.1176/appi.ajp.2018.17111282
50. Ramsey T, Griffin E, Liu Q, Brennan MD, Vaishnavi S. Use of pharmacogenetic testing in routine clinical practice improves outcomes for psychiatry patients. J Psychiatry. 2016;19:377. doi: 10.4172/23785756.1000377
51. Gervasini G, Benitez J, Carrillo JA. Pharmacogenetic testing and therapeutic drug monitoring are complementary tools for optimal individualization of drug therapy. Eur J Clin Pharmacol. 2010;66:755-774. doi: 10.1007/s00228-010-0857-7
52. Carvalho Henriques B, Yang EH, Lapetina D, Carr MS, Yavorskyy V, Hague J, Aitchison KJ. How Can Drug Metabolism and Transporter Genetics Inform Psychotropic Prescribing? Front. Genet. 2020;11:491895. doi: 10.3389/fgene.2020.491895
53. de Leon J. Personalizing dosing of risperidone, paliperidone and clozapine using therapeutic drug monitoring and pharmacogenetics. Neuropharmacology. 2020;168:107656. doi: 10.1016/j.neuro-pharm.2019.05.033
54. Baldelli S, Cheli S, Montrasio C, Cattaneo D, Clementi E. Therapeutic drug monitoring and pharmacogenetics of antipsychotics and antidepressants in real life settings: A 5-year single centre experience. World J Biol Psychiatry. 2021;22(1):34-45. doi: 10.1080/15622975.2020.1747112
55. Miroshnichenko II, Pozhidaev IV, Ivanova SA, Baymeeva NV. Therapeutic drug monitoring of olanzapine and cytochrome P450 genotyping in non-smoking subjects. Ther Drug Monit. 2020;42(2):325-329. doi: 10.1097/FTD.0000000000000695
56. Ľupták M, Michaličková D, Fišar Z, Kitzlerová E, Hroudová J. Novel approaches in schizophrenia-from risk factors and hypotheses to novel drug targets. World J Psychiatry. 2021;11(7):277-296. doi: 10.5498/wjp.v11.i7.277
Review
For citations:
Miroshnichenko I.I. Monitoring of the Antipsychotic Therapy Effectiveness. Psychiatry (Moscow) (Psikhiatriya). 2022;20(4):128-138. (In Russ.) https://doi.org/10.30629/2618-6667-2022-20-4-128-138
Views:
345
Email this article 
