The effectiveness of personalized medication based on drug-related genes, for schizophre- nia patients with resistance to traditional drugs.
La eficacia de la medicación personalizada basada en genes relacionados con fármacos, para pacientes con esquizofrenia resistente a los fármacos tradicionales.
Palabras clave:
citoquinas inflamatorias, factores neurotróficos, PANSS, habilidades sociales, ADL, CYP2D6
Resumen
Nuestro objetivo fue estudiar el impacto de la medicación personalizada basada en genes relacionados con medicamentos para pacientes con esquizofrenia resistentes a los medicamentos tradicionales. Se seleccionaron 110 pacientes con esquizofrenia que buscaron tratamiento en nuestra instalación médica entre junio de 2021 y febrero de 2023, y se dividieron al azar en dos grupos: un grupo (n=55) recibió medicación convencional, mientras que el otro grupo (n=55) recibió medicación personalizada basada en su perfil genético. El estudio comparó los niveles de citocinas inflamatorias y factores neurotróficos, así como las puntuaciones en la Escala de Síntomas Positivos y Negativos (PANSS), la Escala Breve de Evaluación Psiquiátrica (BPRS), los Instrumentos Psicométricos de Habilidades Sociales (SSPI) y la Escala de Habilidades de Vida Diaria (ADL) entre los dos grupos. Después del tratamiento, ambos grupos mostraron niveles reducidos de TNF-α y IL-1β en comparación con los niveles previos al tratamiento, con el grupo guiado por genes mostrando aún niveles más bajos (p<0,05). Por el contrario, los niveles de NGF y BDNF aumentaron en ambos grupos después del tratamiento, con el grupo guiado por genes demostrando incluso niveles más altos (p<0,05). Además, las puntuaciones de PANSS y BPRS disminuyeron en ambos grupos después del tratamiento, con el grupo guiado por genes mostrando incluso puntuaciones más bajas (p<0,05). Mientras que las puntuaciones de SSPI y ADL aumentaron en ambos grupos después del tratamiento, con el grupo guiado por genes mostrando puntuaciones más altas (p<0,05). La eficacia general del tratamiento en el grupo guiado por genes fue superior a la del grupo tratado convencionalmente (p<0,05). La medicación personalizada guiada por farmacogenética tiene el potencial de mejorar la función cognitiva, facilitar la recuperación neurológica, mejorar el funcionamiento social y mejorar las habilidades de vida diaria de las personas con esquizofrenia, facilitando así su reintegración exitosa en la sociedad.
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Yan Y, Qifeng D, Daiwei Z, Haiping Z. A random control trial of group psychological crisis intervention on defensive style and anxiety for the first-degree relatives of patients with schizophrenia. Chinese Ment Heal J. 2021;35(6):466-471.
Xiong H, Zhang H, Chen X, Cheng Y, Huang C. Clinical characteristics and related factors of pneumonia in patients with aplastic anemia. Chinese J Infect Chemother. 2019;19(1):27-31. https://doi.org/10.16718/j.1009-7708.2019.01.006
Green MF, Horan WP, Lee J, McCleery, Reddy L F, Wynn JK. Social disconnection in schizophrenia and the general community. Schizophrenia bulletin. 2018;44(2):242-249. https://doi. org/10.1093/schbul/sbx082
Barut JK, Dietrich MS, Zanoni PA, Ridner SH. Sense of belonging and hope in the lives of persons with schizophrenia. Arch Psych Nursing. 2016;30(2):178-184. https:// doi.org/10.1016/j.apnu.2015.08.009
Ying J, Jue L, Minghuan Z, Zuo H, Dianhong S, Jia L. Comparison of efficacy and safety between sodium valproate and modified electroconvulsive therapy in cloza pine-resistant refractory schizophrenia. J Tongji Univ Medical Sci. 2022;43(2):388- 393.
Xu QW, Liu X, Yao QK, Zheng ZJ. CYP correlation study of refractory schizophrenia drug gene detection. J Hainan Med Coll. 2019;25(5).
Kane M. CYP2D6 overview: allele and phenotype frequencies. Medical Genetics Summaries [Internet]: National Center for Biotechnology Information (US); 2021.
Pouget JG, Shams TA, Tiwari AK, Müller DJ. Pharmacogenetics and outcome with antipsychotic drugs. Dialogues Clin Neurosci. 2014;16(4):555-566. https://doi. org/10.31887/DCNS.2014.16.4/jpouget
Zanello A, Berthoud L, Ventura J, Merlo MC. The Brief Psychiatric Rating Scale (version 4.0) factorial structure and its sensitivity in the treatment of outpatients with unipolar depression. Psychiatry Res. 2013;210(2):626-633. https://doi. org/10.1016/j.psychres.2013.07.001
Depp CA, Loughran C, Vahia I, Molinari V. Chapter 5-Assessing Psychosis in Acute and Chronic Mentally Ill Older Adults. In: Lichtenberg PA, editor. Handbook of Assessment in Clinical Gerontology (Second Edition). San Diego: Academic Press; 2010. p. 123-54. https://doi.org/10.1016/ B978-0-12-374961-1.10005-3
Edemekong PF, Bomgaars DL, Sukumaran S, Schoo C. Activities of Daily Living. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan. 2023 Jun 26. [PubMed ID: 29261878].
Yu W, Tong J, Sun X, Chen F, Zhang J, Pei Y, Zhang T, Zhang J, Zhu B. Analysis of medication adherence and its influencing factors in patients with schizophrenia in the Chinese Institutional Environment. Int J Environ Res and public health. 2021;18(9). https://doi. org/10.3390/ijerph18094746
Yun F, Yanfang Z, Xuehao W, Jinghui T, Mengzhuang G, Fude Y, Baopeng T, Yun-long T. Allostatic load and its relationship with cognitive deficits in patients with first-episode schizophrenia. Chinese Ment Heal J. 2021;35(10):814-819.
Patel KR, Cherian J, Gohil K, Atkinson D. Schizophrenia: overview and treatment options. P & T: a peer-reviewed journal for formulary management. 2014;39(9):638-645.
Zhi L, Qinfang B, Ning L, Fangbin C, Ying C, Xiaoyan W, Falin Q, Pharmaceutical care in 3 Patients with cchizophrenia created with clozapine. Her Med. 2021;40(5):674- 677. https://doi.org/10.3870/j.issn.1004-0781.2021.05.019
Guo-qin H, Qin-yu L, Jing Z, Ming-huan Z, Shun-ying Y, Zheng-hui Y, Jian C. Association study of non-coding variant of NOS1AP gene with schizophrenia. Journal of Shanghai Jiaotong University (Medical Science) 2021;41(1):29-34. https://doi.org/10.3969/j.issn.1674- 8115.2021.01.005
Omelchenko MA, Atadzhykova YA, Migalina VV, Nikiforova IY, Kaleda VG. Clinical and pathopsychological characteristics of juvenile depression with attenuated schizophrenic spectrum symptoms. Neurosci Behav Physiol 2022;52(3):330-335. https:// doi.org/10.1007/s11055-022-01244-0
Wannasuphoprasit Y, Andersen SE, Arranz MJ, Catalan R, Jurgens G, Kloosterboer SM.. CYP2D6 genetic variation and antipsychotic-induced weight gain: a systematic review and meta-analysis. Front Psychol 2021;12:768748. https://doi. org/10.3389/fpsyg.2021.768748
Dean L. Risperidone therapy and CYP2D6 genotype. In: Pratt VM, Scott SA, Pirmohamed M, Esquivel B, Kattman BL, Malheiro AJ, editors. Medical Genetics Summaries. Bethesda (MD): National Center for Bio-technology Information (US); 2012. [Pub- Med ID: 28520384].
Rüdesheim S, Wojtyniak JG, Selzer D, Hanke N, Mahfoud F, Schwab M. Physiologically based pharmacokinetic modeling of metoprolol enantiomers and α-hydroxymetoprolol to describe CYP2D6 drug-gene interactions. Pharmaceutics 2020;12(12). https://doi.org/10.3390/ pharmaceutics12121200
Novalbos J, López-Rodríguez R, Román M, Gallego-Sandín S, Ochoa D, Abad-Santos F. Effects of CYP2D6 genotype on the pharmacokinetics, pharmacodynamics, and safety of risperidone in healthy volunteers. J Clin Psychopharmacol 2010;30(5):504-511. https://doi.org/ 10.1097/JCP.0b013e3181ee84c7
Elmokadem A, Bruno CD, Housand C, Jordie EB, Chow CR, Lesko LJ. Brexpiprazole pharmacokinetics in CYP2D6 poor metabolizers: using physiologically based pharmacokinetic modeling to optimize time to effective concentrations. J Clin Pharmacol 2022;62(1):66-75. https://doi. org/10.1002/jcph.1946
Zhu F JM, Ma Q. Correlation of serum inflammatory factors with clinical symptoms and cognitive functions in schizophrenia. J Xi’an Jiaotong Univ Medical Sci 2021;42(2):301-305. https://doi.org/ 10.7652/jdyxb202102023
Ding X-W, Li R, Geetha T, Tao Y-X, Babu JR. Nerve growth factor in metabolic complications and Alzheimer’s disease: Physiology and therapeutic potential. Biochim Biophys Acta-(BBA) Molecular Basis of Disease. 2020;1866(10):165858. https:// doi.org/10.1016/j.bbadis.2020.165858
Aloe L, Rocco ML, Bianchi P, Manni L. Nerve growth factor: from the early discoveries to the potential clinical use. J Translat Med. 2012;10(1):239. https://doi. org/10.1186/1479-5876-10-239
Gao L, Zhang Y, Sterling K, Song W. Brain-derived neurotrophic factor in Alzheimer’s disease and its pharmaceutical potential. Translational Neurodegeneration. 2022;11(1):4. https://doi.org/10.1186/ s40035-022-00279-0
Li Y, Li F, Qin D, Chen H, Wang J, Wang J. The role of brain derived neurotrophic factor in central nervous system. Front Aging Neurosc. 2022;14:986443. https:// doi.org/10.3389/fnagi.2022.986443
Fuentes-Claramonte P, Ramiro N, Torres L, Argila-Plaza I, Salgado-Pineda P, Soler-Vidal J. Negative schizophrenic symptoms as prefrontal cortex dysfunction: Examination using a task measuring goal neglect. NeuroImage: Clinical. 2022;35:103119. https://doi.org/ 10.1016/j.nicl.2022.103119
Yali W, Xiaoping Z To study the efficacy and safety of phenobarbital and phenytoin combined with valproate sodium in the treatment of epileptic mental disorders. Cardiovasc Dis J Integr Tradit Chinese West Med. 2020;8(34):5-9.
Fleischhacker W, Galderisi S, Laszlovszky I, Szatmári B, Barabássy Á, Acsai K, Szalai E, Harsányi J, Earley W, Patel M, Németh G. The efficacy of cariprazine in negative symptoms of schizophrenia: Post hoc analyses of PANSS individual items and PANSS-derived factors. European Psychiatry.2019;58:1-9. https://doi. org/10.1016/j.eurpsy.2019.01.015
Šimić I, Potočnjak I, Kraljičković I, Stanić Benić M, Čegec I, Juričić Nahal D. CYP2D6 *6/*6 genotype and drug interactions as cause of haloperidol-induced extrapyramidal symptoms. Pharmacogenomics. 2016;17(13):1385-0389. https:// doi.org/10.2217/pgs-2016-0069
Cui Y, Yan H, Su Y, Wang L, Lu T, Zhang D. CYP2D6 genotype-based dose recommendations for risperidone in Asian people. Front Pharmacol 2020;11:936. https://doi. org/10.3389/fphar.2020.00936
Xiong H, Zhang H, Chen X, Cheng Y, Huang C. Clinical characteristics and related factors of pneumonia in patients with aplastic anemia. Chinese J Infect Chemother. 2019;19(1):27-31. https://doi.org/10.16718/j.1009-7708.2019.01.006
Green MF, Horan WP, Lee J, McCleery, Reddy L F, Wynn JK. Social disconnection in schizophrenia and the general community. Schizophrenia bulletin. 2018;44(2):242-249. https://doi. org/10.1093/schbul/sbx082
Barut JK, Dietrich MS, Zanoni PA, Ridner SH. Sense of belonging and hope in the lives of persons with schizophrenia. Arch Psych Nursing. 2016;30(2):178-184. https:// doi.org/10.1016/j.apnu.2015.08.009
Ying J, Jue L, Minghuan Z, Zuo H, Dianhong S, Jia L. Comparison of efficacy and safety between sodium valproate and modified electroconvulsive therapy in cloza pine-resistant refractory schizophrenia. J Tongji Univ Medical Sci. 2022;43(2):388- 393.
Xu QW, Liu X, Yao QK, Zheng ZJ. CYP correlation study of refractory schizophrenia drug gene detection. J Hainan Med Coll. 2019;25(5).
Kane M. CYP2D6 overview: allele and phenotype frequencies. Medical Genetics Summaries [Internet]: National Center for Biotechnology Information (US); 2021.
Pouget JG, Shams TA, Tiwari AK, Müller DJ. Pharmacogenetics and outcome with antipsychotic drugs. Dialogues Clin Neurosci. 2014;16(4):555-566. https://doi. org/10.31887/DCNS.2014.16.4/jpouget
Zanello A, Berthoud L, Ventura J, Merlo MC. The Brief Psychiatric Rating Scale (version 4.0) factorial structure and its sensitivity in the treatment of outpatients with unipolar depression. Psychiatry Res. 2013;210(2):626-633. https://doi. org/10.1016/j.psychres.2013.07.001
Depp CA, Loughran C, Vahia I, Molinari V. Chapter 5-Assessing Psychosis in Acute and Chronic Mentally Ill Older Adults. In: Lichtenberg PA, editor. Handbook of Assessment in Clinical Gerontology (Second Edition). San Diego: Academic Press; 2010. p. 123-54. https://doi.org/10.1016/ B978-0-12-374961-1.10005-3
Edemekong PF, Bomgaars DL, Sukumaran S, Schoo C. Activities of Daily Living. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan. 2023 Jun 26. [PubMed ID: 29261878].
Yu W, Tong J, Sun X, Chen F, Zhang J, Pei Y, Zhang T, Zhang J, Zhu B. Analysis of medication adherence and its influencing factors in patients with schizophrenia in the Chinese Institutional Environment. Int J Environ Res and public health. 2021;18(9). https://doi. org/10.3390/ijerph18094746
Yun F, Yanfang Z, Xuehao W, Jinghui T, Mengzhuang G, Fude Y, Baopeng T, Yun-long T. Allostatic load and its relationship with cognitive deficits in patients with first-episode schizophrenia. Chinese Ment Heal J. 2021;35(10):814-819.
Patel KR, Cherian J, Gohil K, Atkinson D. Schizophrenia: overview and treatment options. P & T: a peer-reviewed journal for formulary management. 2014;39(9):638-645.
Zhi L, Qinfang B, Ning L, Fangbin C, Ying C, Xiaoyan W, Falin Q, Pharmaceutical care in 3 Patients with cchizophrenia created with clozapine. Her Med. 2021;40(5):674- 677. https://doi.org/10.3870/j.issn.1004-0781.2021.05.019
Guo-qin H, Qin-yu L, Jing Z, Ming-huan Z, Shun-ying Y, Zheng-hui Y, Jian C. Association study of non-coding variant of NOS1AP gene with schizophrenia. Journal of Shanghai Jiaotong University (Medical Science) 2021;41(1):29-34. https://doi.org/10.3969/j.issn.1674- 8115.2021.01.005
Omelchenko MA, Atadzhykova YA, Migalina VV, Nikiforova IY, Kaleda VG. Clinical and pathopsychological characteristics of juvenile depression with attenuated schizophrenic spectrum symptoms. Neurosci Behav Physiol 2022;52(3):330-335. https:// doi.org/10.1007/s11055-022-01244-0
Wannasuphoprasit Y, Andersen SE, Arranz MJ, Catalan R, Jurgens G, Kloosterboer SM.. CYP2D6 genetic variation and antipsychotic-induced weight gain: a systematic review and meta-analysis. Front Psychol 2021;12:768748. https://doi. org/10.3389/fpsyg.2021.768748
Dean L. Risperidone therapy and CYP2D6 genotype. In: Pratt VM, Scott SA, Pirmohamed M, Esquivel B, Kattman BL, Malheiro AJ, editors. Medical Genetics Summaries. Bethesda (MD): National Center for Bio-technology Information (US); 2012. [Pub- Med ID: 28520384].
Rüdesheim S, Wojtyniak JG, Selzer D, Hanke N, Mahfoud F, Schwab M. Physiologically based pharmacokinetic modeling of metoprolol enantiomers and α-hydroxymetoprolol to describe CYP2D6 drug-gene interactions. Pharmaceutics 2020;12(12). https://doi.org/10.3390/ pharmaceutics12121200
Novalbos J, López-Rodríguez R, Román M, Gallego-Sandín S, Ochoa D, Abad-Santos F. Effects of CYP2D6 genotype on the pharmacokinetics, pharmacodynamics, and safety of risperidone in healthy volunteers. J Clin Psychopharmacol 2010;30(5):504-511. https://doi.org/ 10.1097/JCP.0b013e3181ee84c7
Elmokadem A, Bruno CD, Housand C, Jordie EB, Chow CR, Lesko LJ. Brexpiprazole pharmacokinetics in CYP2D6 poor metabolizers: using physiologically based pharmacokinetic modeling to optimize time to effective concentrations. J Clin Pharmacol 2022;62(1):66-75. https://doi. org/10.1002/jcph.1946
Zhu F JM, Ma Q. Correlation of serum inflammatory factors with clinical symptoms and cognitive functions in schizophrenia. J Xi’an Jiaotong Univ Medical Sci 2021;42(2):301-305. https://doi.org/ 10.7652/jdyxb202102023
Ding X-W, Li R, Geetha T, Tao Y-X, Babu JR. Nerve growth factor in metabolic complications and Alzheimer’s disease: Physiology and therapeutic potential. Biochim Biophys Acta-(BBA) Molecular Basis of Disease. 2020;1866(10):165858. https:// doi.org/10.1016/j.bbadis.2020.165858
Aloe L, Rocco ML, Bianchi P, Manni L. Nerve growth factor: from the early discoveries to the potential clinical use. J Translat Med. 2012;10(1):239. https://doi. org/10.1186/1479-5876-10-239
Gao L, Zhang Y, Sterling K, Song W. Brain-derived neurotrophic factor in Alzheimer’s disease and its pharmaceutical potential. Translational Neurodegeneration. 2022;11(1):4. https://doi.org/10.1186/ s40035-022-00279-0
Li Y, Li F, Qin D, Chen H, Wang J, Wang J. The role of brain derived neurotrophic factor in central nervous system. Front Aging Neurosc. 2022;14:986443. https:// doi.org/10.3389/fnagi.2022.986443
Fuentes-Claramonte P, Ramiro N, Torres L, Argila-Plaza I, Salgado-Pineda P, Soler-Vidal J. Negative schizophrenic symptoms as prefrontal cortex dysfunction: Examination using a task measuring goal neglect. NeuroImage: Clinical. 2022;35:103119. https://doi.org/ 10.1016/j.nicl.2022.103119
Yali W, Xiaoping Z To study the efficacy and safety of phenobarbital and phenytoin combined with valproate sodium in the treatment of epileptic mental disorders. Cardiovasc Dis J Integr Tradit Chinese West Med. 2020;8(34):5-9.
Fleischhacker W, Galderisi S, Laszlovszky I, Szatmári B, Barabássy Á, Acsai K, Szalai E, Harsányi J, Earley W, Patel M, Németh G. The efficacy of cariprazine in negative symptoms of schizophrenia: Post hoc analyses of PANSS individual items and PANSS-derived factors. European Psychiatry.2019;58:1-9. https://doi. org/10.1016/j.eurpsy.2019.01.015
Šimić I, Potočnjak I, Kraljičković I, Stanić Benić M, Čegec I, Juričić Nahal D. CYP2D6 *6/*6 genotype and drug interactions as cause of haloperidol-induced extrapyramidal symptoms. Pharmacogenomics. 2016;17(13):1385-0389. https:// doi.org/10.2217/pgs-2016-0069
Cui Y, Yan H, Su Y, Wang L, Lu T, Zhang D. CYP2D6 genotype-based dose recommendations for risperidone in Asian people. Front Pharmacol 2020;11:936. https://doi. org/10.3389/fphar.2020.00936
Publicado
2024-05-21
Cómo citar
Zhou, S., Zhang, G., Wang, Z., Wei, L., Zhu, M., & He, J. (2024). The effectiveness of personalized medication based on drug-related genes, for schizophre- nia patients with resistance to traditional drugs.: La eficacia de la medicación personalizada basada en genes relacionados con fármacos, para pacientes con esquizofrenia resistente a los fármacos tradicionales. Investigación Clínica, 65(2), 206-219. https://doi.org/10.54817/IC.v65n2a07
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