Psicotrópicos y Farmacogenética
DOI:
https://doi.org/10.47924/neurotarget202115Palabras clave:
psicofarmacología, farmacogenética, farmacogenómica, trastornos psiquiátricos, trastorno bipolarResumen
La enfermedad mental representa un importante asunto de salud tanto en el plano individual como socioeconómico. Esto se debe en parte a las subóptimas opciones de tratamiento en la actualidad: los fármacos psicotrópicos existentes, incluyendo antidepresivos, antipsicóticos y estabilizadores del estado de ánimo son efectivos sólo en un grupo de pacientes o producen respuestas parciales y se encuentran usualmente asociados con efectos adversos discapacitantes que desalientan la adherencia. La farmacogenética estudia cómo la información genética impacta en la respuesta a drogas y sus efectos adversos, con el objetivo de proveer tratamientos personalizados, maximizando así la eficacia y tolerancia. Los primeros estudios farmacogenéticos se focalizaron en genes candidatos, conocidos previamente como relevantes para la farmacocinética y farmacodinamia de medicamentos psicotrópicos. Los resultados no fueron conclusivos. Pero algunos candidatos replicados fueron identificados e incluidos como biomarcadores farmacogenéticos en el etiquetado de medicamentos y en algunos kits comerciales. Con el advenimiento de la revolución genómica, se hizo posible estudiar la variación genética en una escala sin precedentes, a lo largo de todo el genoma sin necesidad de hipótesis a priori. Esto podría conducir a la prescripción personalizada de las medicaciones existentes, gracias a nuevos conocimientos sobre la genética de la enfermedad mental. Se lograron hallazgos prometedores, pero los métodos para la generación y análisis de datos genómicos y de secuenciación aún están en evolución. Las futuras pruebas farmacogenéticas pueden consistir en cientos / miles de polimorfismos a lo largo del genoma o vías moleculares seleccionadas para tener en cuenta las complejas interacciones entre variantes de diversos genes.
Métricas
Citas
Patel V, Chisholm D, Parikh R, Charlson F J, Degenhardt L, Dua T, et al. Addressing the burden of mental, neurological, and substance use disorders: Key messages from disease controlpriorities, 3rd edition. The Lancet, 1672–1685; 2016.
Bloom, DE, Cafiero ET, Jan e-Llopis E, Abrahams-Gessel S, Bloom LR, Fathima S, et al. (2011). The global economic burden of non-communicable diseases. Geneva: World Economic Forum. Retrieved from Brandl EJ, Kennedy JL, & M€uller DJ Pharmacogenetics of antipsychotics. The Canadian Journal of Psychiatry. 2014; 59(2): 76–88.
Lieberman JA, Stroup TS, McEvoy J P, Swartz M S, Rosenheck RA, Perkins DO, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. The New England Journal of Medicine. 2005; 353(12): 1209–1223.
Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: A STAR*D report. The American Journal of Psychiatry. 2006; 163(11): 1905–1917.
Thase ME. STEP-BD and bipolar depression: What have we learned? Current Psychiatry Reports. 2007; 9(6): 497–503.
Cacabelos R, Martinez-Bouza R, Carril JC, Fernandez-Novoa L, Lombardi V, Carrera I, et al. Genomics and pharmacogenomics of brain disorders. Current Pharmaceutical Biotechnology. 2012; 13(5): 674–725.
Zhang F, & Lupski JR. Non-coding genetic variants in human disease. Human Molecular Genetics. 2015; 24(R1): R102–R110.
Reich DE, & Lander ES. On the allelic spectrum of human disease. Trends in Genetics: TIG. 2001; 17(9): 502–510.
McCarthy S, Das S, Kretzschmar W, Delaneau O, Wood AR, Teumer A, et al. A reference panel of 64,976 haplotypes for genotype imputation. Nature Genetics. 2016; 48(10): 1279–1283.
Porcelli S, Fabbri C, Spina E, Serretti A, & De Ronchi, D. Genetic polymorphisms of cytochrome P450 enzymes and antidepressant metabolism. Expert Opinion on Drug Metabolism & Toxicology. 2011; 7(9): 1101–1115.
Porcelli S, Drago A, Fabbri C, & Serretti A. Mechanisms of antidepressant action: An integrated dopaminergic perspective. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2011; 35(7): 1532–1543.
Fabbri C, Crisafulli C, Calabró M, Spina E, & Serretti A. Progress and prospects in pharmacogenetics of antidepressant drugs. Expert Opinion on Drug Metabolism & Toxicology. 2016; 12(10): 1157–1168.
Breitenstein B, Scheuer S, Pfister H, Uhr M, Lucae S, Holsboer F, et al. The clinical application of ABCB1 genotyping in antidepressant treatment: A pilot study. CNS Spectrums. 2014; 19(2): 165–175.
Nutt D, Demyttenaere K, Janka Z, Aarre T, Bourin M, Canonico P L, et al. The other face of epression, reduced positive affect: The role of catecholamines in causation and cure. Journal of Psychopharmacology (Oxford, England). 2007; 21(5): 461–471.
Kato M, & Serretti A. Review and meta-analysis of antidepressant pharmacogenetic findings in major depressive disorder. Molecular Psychiatry. 2010; 15(5): 473–500.
Porcelli S, Fabbri C,& Serretti A. Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with antidepressant efficacy. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology. 2012; 22(4): 239–258.
Fabbri C, Di Girolamo G, & Serretti A. Pharmacogenetics of antidepressant drugs: An update after almost 20 years of research. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 2013; 162(6): 487–520.
Niitsu T, Fabbri C, Bentini F, & Serretti A. Pharmacogenetics in major depression: A comprehensive meta-analysis. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2013; 45: 183–194.
McMahon F J, Buervenich S, Charney D, Lipsky R, Rush A J, Wilson A F, et al. Variation in the gene encoding the serotonin 2A receptor is associated with outcome of antidepressant treatment. American Journal of Human Genetics. 2006; 78(5): 804–814.
Baune BT, Hohoff C, Roehrs T, Deckert J, Arolt V, & Domschke K. Serotonin receptor 1A_1019C/ G variant: Impact on antidepressant pharmacoresponse in melancholic depression? Neuroscience Letters. 2008; 436(2): 111–115.
Fabbri C, Porcelli S, & Serretti A. From pharmacogenetics to pharmacogenomics: The way toward the personalization of antidepressant treatment. Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie. 2014; 59(2): 62–75.
Perlis R H, Adams D H, Fijal B, Sutton VK, Farmen M, Breier A, et al. Genetic association study depression. The Journal of Clinical Psychiatry. 2010; 71(5): 599–605.
Glatt C E, & Lee FS. Common polymorphisms in the age of research domain criteria (RDoC): Integration and translation. Biological Psychiatry. 2016; 79(1): 25–31.
Govindarajan A, Rao BSS, Nair D, Trinh M, Mawjee N, Tonegawa S, et al. Transgenic brain-derived neurotrophic factor expression causes both anxiogenic and antidepressant effects. Proceedings of the National Academy of Sciences of the United States of America. 2006; 103(35): 13208–13213.
Stamm TJ, Rampp C, Wiethoff K, Stingl J, Mössner R, O Malley G, et al. The FKBP5 polymorphism rs1360780 influences the effect of an algorithm-based antidepressant treatment and is associated with remission in patients with major depression. Journal of Psychopharmacology (Oxford, England). 2016; 30(1): 40–47.
Li CI, Samuels DC, Zhao YY, Shyr Y, & Guo Y. Power and sample size calculations for high throughput sequencing-based experiments. Briefings in Bioinformatics. https://doi.org/10.1093/ bib/bbx061. Epub ahead of print. 2017.
GENDEP Investigators, MARS Investigators, STAR*D Investigators, Wolfgang M, Mors O, Hauser J, et al. Common genetic variation and antidepressant efficacy in major depressive disorder: A meta-analysis of three genome-wide pharmacogenetic studies. The American Journal of Psychiatry. 2013; 170(2): 207–217.
Tansey KE, Guipponi M, Perroud N, Bondolfi G, Domenici E, Evans D, et al. Genetic predictors of response to serotonergic and noradrenergic antidepressants in major depressive disorder: A genome-wide analysis of individual-level data and a meta-analysis. PLoS Medicine. 2012; 9(10): e1001326.
Biernacka J M, Sangkuhl K, Jenkins G, Whaley RM, Barman P, Batzler A, et al. The International SSRI Pharmacogenomics Consortium (ISPC): A genomewide association study of antidepressant treatment response. Translational Psychiatry. 2016; 6(11): e937.
Myung W, Kim J, Lim SW, Shim S, Won HH, Kim S, et al. A genome-wide association study of antidepressant response in Koreans. Translational Psychiatry. 2015; 5(11): e672.
Adkins DE, Clark SL, Aberg K, Hettema J M, Buksza´r J, McClay J L, et al. Genome-wide pharmacogenomic study of citalopram-induced side effects in STAR*D. Translational Psychiatry. 2012; 2(7): e129.
Clark S L, Adkins DE, Aberg K, Hettema JM, McClay JL, Souza RP, et al. Pharmacogenomic study of side-effects for antidepressant treatment options in STAR*D. Psychological Medicine. 2012; 42(6): 1151–1162.
Fabbri C, Crisafulli C, Gurwitz D, Stingl J, Calati R, Albani D, et al. Neuronal cell adhesion genes and antidepressant response in three independent samples. The Pharmacogenomics Journal. 2015; 15(6): 538–548.
Cocchi E, Fabbri C, Han C, Lee SJ, Patkar AA, Masand PS, et al. Genome-wide association study of antidepressant response: Involvement of the inorganic cation transmembrane transporter activity pathway. BMC Psychiatry. 2016; 16(1): 106.
Hunter AM, Leuchter A F, Power RA, Muthen B, McGrath PJ, Lewis CM, et al. A genome-wide association study of a sustained pattern of antidepressant response. Journal of Psychiatric Research. 2013; 47(9): 1157–1165.
Fabbri C, Marsano A, Albani D, Chierchia A, Calati R, Drago A, et al. PPP3CC gene: A putative modulator of antidepressant response through the B-cell receptor signaling pathway. The Pharmacogenomics Journal. 2014; 14(5): 463–472.
Center for Drug Evaluation and Research. Genomics—Table of pharmacogenomic biomarkers in drug labeling. 2017.
Whirl-Carrillo M, McDonagh EM, Hebert JM, Gong L, Sangkuhl K., Thorn CF, et al. Pharmacogenomics knowledge for personalized medicine. Clinical Pharmacology and Therapeutics. 2012; 92(4): 414–417.
Goes FS. Genetics of bipolar disorder. Psychiatric Clinics of North America. 2016; 39(1): 139–155.
Budde M, Degner D, Brockm€oller J, Schulze TG. Pharmacogenomic aspects of bipolar disorder: An update. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology. 2017; 27(6): 599–609.
Pisanu C, Melis C, Squassina A. Lithium pharmacogenetics: Where do we stand? Drug Development Research. 2016; 77(7): 368–373.
Rybakowski JK, Suwalska A, Skibinska M, Dmitrzak-Weglarz M, Leszczynska-Rodziewicz A, Hauser J. Response to lithium prophylaxis: Interaction between serotonin transporter and BDNF genes. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics: The Official Publication of the International Society of Psychiatric Genetics. 2007; 144B(6): 820–823.
Rybakowski JK. Genetic influences on response to mood stabilizers in bipolar disorder: Current status of knowledge. CNS Drugs. 2013; 27(3): 165–173.
Rybakowski JK, Abramowicz M, Szczepankiewicz A, Michalak M, HauserJ, Czekalski S. The association of glycogen synthase kinase-3beta (GSK-3β) gene polymorphism with kidney function in long-term lithium-treated bipolar patients. International Journal of Bipolar Disorders. 2013; 1(1): 8.
Chen CH, Lee CS, Lee MTM, Ouyang WC, Chen CC, Chong MY, et al. Variant GADL1 and response to lithium therapy in bipolar I disorder. The New England Journal of Medicine. 2014; 370(2): 119–128.
Perlis RH, Smoller JW, Ferreira MAR, McQuillin A, Bass N, Lawrence J, et al. A genomewide association study of response to lithium for prevention of recurrence in bipolar disorder. The American Journal of Psychiatry. 2009; 166(6): 718–725.
Descargas
Publicado
Cómo citar
Número
Sección
Licencia
Derechos de autor 2021 Leandro Piedimonte , Daniela Flores Helguero
Esta obra está bajo una licencia internacional Creative Commons Atribución 4.0.
Este artículo se distribuye bajo la licencia Creative Commons Attribution 4.0 License. A menos que se indique lo contrario, el material publicado asociado se distribuye bajo la misma licencia.
