Impact of Pharmacogenetic Testing on Clozapine Treatment Efficacy in Patients with Treatment-Resistant Schizophrenia

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2024 Mar 28

PMID 38540209

Authors

Estela Sanguesa

Emilio Fernandez-Egea

Julia Concha

Cristina B Garcia

Maria Pilar Ribate

Affiliations

Soon will be listed here.

Abstract

Managing schizophrenia with clozapine poses a significant challenge due to prevalent therapeutic failures. The increasing interest in personalized medicine underscores the importance of integrating pharmacogenetic information for effective pharmacotherapeutic monitoring in patients. The objective of this study was to explore the correlation between , , , , and polymorphisms and clozapine response in 100 patients with Treatment-Resistant Schizophrenia. Different scales such as the Positive and Negative Syndrome Scale (PANSS), the Warwick-Edinburgh Mental Wellbeing Scale (SWEMWBS), the Global Assessment of Functioning Scale (GAF), the Brief Negative Symptom Scale (BNSS), and pharmacokinetic parameters were used to analyse the efficacy of the treatment. Patients who exclusively responded to clozapine compared to the patients with augmentation strategies exhibited distinctive features, such as lower doses, plasma levels, and presented less-pronounced symptomatology. Genetic associations were explored, highlighting , and the *1F/*1F polymorphism for the gene.

Citing Articles

Receptor Pharmacogenomics: Deciphering Genetic Influence on Drug Response.

Anghel S, Dinu-Pirvu C, Costache M, Voiculescu A, Ghica M, Anuta V Int J Mol Sci. 2024; 25(17).

PMID: 39273318 PMC: 11395000. DOI: 10.3390/ijms25179371.

Effect of Common Cold on Serum Clozapine Concentrations in Hospitalized Patients with Schizophrenia.

Cao Y, Xia Q, Liang J, Wang J, Shan F, Dai B Neuropsychiatr Dis Treat. 2024; 20:1563-1570.

PMID: 39156033 PMC: 11330252. DOI: 10.2147/NDT.S473973.

References

Arranz M, Munro J, Birkett J, Bolonna A, Mancama D, Sodhi M . Pharmacogenetic prediction of clozapine response. Lancet. 2000; 355(9215):1615-6. DOI: 10.1016/s0140-6736(00)02221-2. View

Amin M . P-glycoprotein Inhibition for Optimal Drug Delivery. Drug Target Insights. 2013; 7:27-34. PMC: 3762612. DOI: 10.4137/DTI.S12519. View

Olmos I, Ibarra M, Vazquez M, Maldonado C, Fagiolino P, Giachetto G . Population Pharmacokinetics of Clozapine and Norclozapine and Switchability Assessment between Brands in Uruguayan Patients with Schizophrenia. Biomed Res Int. 2019; 2019:3163502. PMC: 6431368. DOI: 10.1155/2019/3163502. View

Carbon M, Correll C . Clinical predictors of therapeutic response to antipsychotics in schizophrenia. Dialogues Clin Neurosci. 2015; 16(4):505-24. PMC: 4336920. View

Lee S, Ryu S, Kim S, Kim M, Kim S, Kim J . Association study of 27 annotated genes for clozapine pharmacogenetics: validation of preexisting studies and identification of a new candidate gene, ABCB1, for treatment response. J Clin Psychopharmacol. 2012; 32(4):441-8. DOI: 10.1097/JCP.0b013e31825ac35c. View

Kay S, Fiszbein A, Opler L . The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987; 13(2):261-76. DOI: 10.1093/schbul/13.2.261. View

Consoli G, Lastella M, Ciapparelli A, Catena DellOsso M, Ciofi L, Guidotti E . ABCB1 polymorphisms are associated with clozapine plasma levels in psychotic patients. Pharmacogenomics. 2009; 10(8):1267-76. DOI: 10.2217/pgs.09.51. View

Bortolato M, Pivac N, Muck Seler D, Nikolac Perkovic M, Pessia M, Di Giovanni G . The role of the serotonergic system at the interface of aggression and suicide. Neuroscience. 2013; 236:160-85. PMC: 3657560. DOI: 10.1016/j.neuroscience.2013.01.015. View

Fribourg M, Moreno J, Holloway T, Provasi D, Baki L, Mahajan R . Decoding the signaling of a GPCR heteromeric complex reveals a unifying mechanism of action of antipsychotic drugs. Cell. 2011; 147(5):1011-23. PMC: 3255795. DOI: 10.1016/j.cell.2011.09.055. View

10.

Eum S, Lee A, Bishop J . Pharmacogenetic tests for antipsychotic medications: clinical implications and considerations. Dialogues Clin Neurosci. 2016; 18(3):323-337. PMC: 5067149. View

11.

Arranz M, De Leon J . Pharmacogenetics and pharmacogenomics of schizophrenia: a review of last decade of research. Mol Psychiatry. 2007; 12(8):707-47. DOI: 10.1038/sj.mp.4002009. View

12.

Seeman P . Clozapine, a fast-off-D2 antipsychotic. ACS Chem Neurosci. 2013; 5(1):24-9. PMC: 3894721. DOI: 10.1021/cn400189s. View

13.

Wenthur C, Lindsley C . Classics in chemical neuroscience: clozapine. ACS Chem Neurosci. 2013; 4(7):1018-25. PMC: 3715841. DOI: 10.1021/cn400121z. View

14.

Arranz M, Collier D, Munro J, Sham P, Kirov G, Sodhi M . Analysis of a structural polymorphism in the 5-HT2A receptor and clinical response to clozapine. Neurosci Lett. 1996; 217(2-3):177-8. View

15.

Arranz M, Collier D, Sodhi M, Ball D, Roberts G, Price J . Association between clozapine response and allelic variation in 5-HT2A receptor gene. Lancet. 1995; 346(8970):281-2. DOI: 10.1016/s0140-6736(95)92168-0. View

16.

Martin-Guerrero S, Alonso P, Iglesias A, Cimadevila M, Brea J, Loza M . His452Tyr polymorphism in the human 5-HT receptor affects clozapine-induced signaling networks revealed by quantitative phosphoproteomics. Biochem Pharmacol. 2021; 185:114440. DOI: 10.1016/j.bcp.2021.114440. View

17.

Ritchie T, Noble E . Association of seven polymorphisms of the D2 dopamine receptor gene with brain receptor-binding characteristics. Neurochem Res. 2003; 28(1):73-82. DOI: 10.1023/a:1021648128758. View

18.

Samanaite R, Gillespie A, Sendt K, McQueen G, MacCabe J, Egerton A . Biological Predictors of Clozapine Response: A Systematic Review. Front Psychiatry. 2018; 9:327. PMC: 6070624. DOI: 10.3389/fpsyt.2018.00327. View

19.

Wendland J, Martin B, Kruse M, Lesch K, Murphy D . Simultaneous genotyping of four functional loci of human SLC6A4, with a reappraisal of 5-HTTLPR and rs25531. Mol Psychiatry. 2006; 11(3):224-6. DOI: 10.1038/sj.mp.4001789. View

20.

Kohlrausch F, Severino-Gama C, Lobato M, Belmonte-de-Abreu P, Carracedo A, Hutz M . The CYP1A2 -163C>A polymorphism is associated with clozapine-induced generalized tonic-clonic seizures in Brazilian schizophrenia patients. Psychiatry Res. 2013; 209(2):242-5. DOI: 10.1016/j.psychres.2013.02.030. View