Influence of CYP2D6*4 polymorphism on the outcome of treatment with serotonergic drugs. Role of community pharmacy in its optimization
DOI:
https://doi.org/10.60103/phc.v26.e841Keywords:
Serotonin Agents; Cytochrome P-450 CYP2D6; Drug Metabolism, Poor, CYP2D6-Related; pharmacogenetic; community pharmacyAbstract
Introduction: Genetic polymorphisms in hepatic metabolizing enzymes are one of the main reasons for interindividual differences in response to drugs. Most serotonergic medications are metabolized by the CYP2D6 isoform of CYP450, therefore, variations in the sequence of the gene that codes for this enzyme and, specifically, the genetic identification of the CYP2D6*4 variant can help us predict the response. The objective of the study is to relate the treatment effectiveness, safety and adherence of patients treated with serotonergics drugs with the different genotypes responsible for the normal metabolizer (NM), intermediate metabolizer (IM) and poor metabolizer (PM) phenotypes.
Method: A quasi-experimental study was carried out from the community pharmacy. The principal investigator made the service offer and carried out an initial interview where he obtained information about the patient's clinical parameters and health problems. Afterwards, a saliva sample was taken and subsequently genotyped at the hospital using an allele-specific competitive Polymerase Chain Reaction (PCR). Subsequently, the patient's health problems were related to the medication on a specific date and the patient's clinical situation was contrasted with the existing scientific evidence. Finally, Medication-Related Problems (PRM) and Negative Outcomes associated with Medication (RNM) are identified.
Results and conclusions: Twenty-three patients were interviewed, only 4 obtained the IM phenotype, while the rest were NM. Patients phenotyped as IM had greater effectiveness of serotonergic treatment – probably due to a high drug concentration – and greater adherence to treatment than NM patients. However, they showed more Medication-Associated Negative Outcomes (RNM), especially dose-dependent ones. Even so, the evidenced influence of the genetic polymorphism on the response to serotonergic treatment makes us recommend its inclusion in the FORO AF-FC classification as a new Medication-Related Problem (PRM). In any case, given the small sample size, the results were not statistically significant. More research is required to reach firm conclusions.
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David DJ, Gardier AM. Les bases de pharmacologie fondamentale du système sérotoninergique: application à la réponse antidépressive. Encephale [Internet]. 2016;42(3):255-63. doi: 10.1016/j.encep.2016.03.012 Disponible en: https://pubmed.ncbi.nlm.nih.gov/27112704/
Milosavljevic F, Bukvic N, Pavlovic Z, Miljevic C, Pešic V, Molden E, et al. Association of CYP2C19 and CYP2D6 poor and intermediate metabolizer status with antidepressant and antipsychotic exposure: A systematic review and meta-analysis: A systematic review and meta-analysis. JAMA Psychiatry [Internet]. 2021;78(3):270-80. doi: 10.1001/jamapsychiatry.2020.3643. Disponible en: https://pubmed.ncbi.nlm.nih.gov/33237321/
Ingelman-Sundberg M. Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity. Pharmacogenomics J [Internet]. 2005;5(1):6-13. doi: 10.1038/sj.tpj.6500285. Disponible en: https://pubmed.ncbi.nlm.nih.gov/15492763/
Lynch T, Price A. The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am Fam Physician [Internet]. 2007;76(3):391-6. Disponible en: https://pubmed.ncbi.nlm.nih.gov/17708140/
Solomon HV, Cates KW, Li KJ. Does obtaining CYP2D6 and CYP2C19 pharmacogenetic testing predict antidepressant response or adverse drug reactions? Psychiatry Res [Internet]. 2019; 271:604-13. doi: 10.1016/j.psychres.2018.12.053. Disponible en: https://pubmed.ncbi.nlm.nih.gov/30554109/
CYP2D6 cytochrome P450 family 2 subfamily D member 6 [Homo sapiens (human)] - Gene - NCBI [Internet]. Nih.gov. Disponible en: https://www.ncbi.nlm.nih.gov/gene?cmd=Retrieve&dopt=full_report&list_uids=1565
rs3892097 (SNP) - Population genetics - Homo_sapiens - Ensembl genome browser 109 [Internet]. Ensembl.org. Disponible en: https://www.ensembl.org/Homo_sapiens/Variation/Population?db=core;v=rs3892097;vdb=variation
Rodríguez-Arcas MJ, García-Jiménez E, Montesinos-Hernández A, Martínez-Martínez F, Conesa-Zamora P. Pharmacotherapeutic Follow-up and Pharmacogenetics of CYP2C9 and CYP3A4 in Antihypertensive Therapy: A Pilot Study in a Community Pharmacy. Ther Innov Regul Sci. 2013Jul;47(4):489-494. doi: 10.1177/2168479013492736. PMID: 30235515.
Marro Borau G, Marro Ramón D. Observación y análisis. Farm Prof [Internet]. 2004;18(6):70–4. Disponible en: https://www.elsevier.es/es-revista-farmacia-profesional-3-articulo-observacion-analisis-13063308
Foro de Atención Farmacéutica-Farmacia Comunitaria (Foro AF-FC). Guía práctica para los Servicios Profesionales Farmacéuticos Asistenciales en la Farmacia Comunitaria. Madrid: Consejo General de Colegios Oficiales de Farmacéuticos; 2019.
Kroenke K, Spitzer RL, Williams JB, Löwe B. The Patient Health Questionnaire Somatic, Anxiety, and Depressive Symptom Scales: a systematic review. Gen Hosp Psychiatry. 2010 Jul-Aug;32(4):345-59
Morisky DE, Green LW, Levine DM. Concurrent and predictive validity of a self-reported measure of medication adherence. Med Care [Internet]. 1986;24(1):67-74. Disponible en: http://dx.doi.org/10.1097/00005650-198601000-00007
Keers R, Aitchison KJ. Gender differences in antidepressant drug response. Int Rev Psychiatry [Internet]. 2010;22(5):485–500. doi: 10.3109/09540261.2010.496448. Disponible en: https://pubmed.ncbi.nlm.nih.gov/21047161/
Subdirección General de Información Sanitaria. Salud mental en datos: prevalencia de los problemas de salud y consumo de psicofármacos y fármacos relacionados a partir de registros clínicos de atención primaria. BDCAP Series 2. [Publicación en Internet]. Madrid: Ministerio de Sanidad. 2021.
Instituto Nacional de Estadística [Internet]. Ine.es. Disponible en: https://www.ine.es/ss/Satellite?L=es_ES&c=INESeccion_C&cid=1259926457058&p=%5C&pagename=ProductosYServicios%2FPYSLayout¶m1=PYSDetalle¶m3=125992482288
Molina López T, Caraballo Camacho M de la O, Palma Morgado D, López Rubio S, Domínguez Camacho JC, Morales Serna JC. Prevalencia de polimedicación y riesgo vascular en la población mayor de 65 años. Aten Primaria [Internet]. 2012;44(4):216-22. doi: 10.1016/j.aprim.2011.03.010. Disponible en: https://pubmed.ncbi.nlm.nih.gov/21924797/
Chialda L, Griffith LS, Heinig A, Pahl A. Prospective use of CYP pharmacogenetics and medication analysis to facilitate improved therapy – a pilot study. Per Med [Internet]. 2008;5(1):37–45. Disponible en: https://pubmed.ncbi.nlm.nih.gov/29783392/
Rodríguez Arcas, M.J. Estudio piloto desde la farmacia comunitaria sobre el efecto farmacogenético del CYP 2C9, 2D6 y 3A4 y el seguimiento farmacoterapéutico en la terapia antihipertensiva. Granada: Universidad de Granada, 2014. 222 p. Disponible en: http://hdl.handle.net/10481/31334
García Zaragoza E, Gil Girbau M, Murillo Fernández MD, Vázquez Valcuende J, Vergoñós Tomàs A. Dispensación, adherencia y uso adecuado del tratamiento: guía práctica para el farmacéutico comunitario. Ed. SEFAC. Madrid, 2017.
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