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Pharmacogenetic Guided Opioid Therapy Improves Chronic Pain Outcomes and Comorbid Mental Health: A Randomized, Double-Blind, Controlled Study

Interindividual variability in analgesic response is at least partly due to well-characterized polymorphisms that are associated with opioid dosing and adverse outcomes. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has put forward recommendations for the CYP2D6 phenotype, but the l...

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Autores principales: Agulló, Laura, Aguado, Isidro, Muriel, Javier, Margarit, César, Gómez, Alba, Escorial, Mónica, Sánchez, Astrid, Fernández, Alicia, Peiró, Ana M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10341655/
https://www.ncbi.nlm.nih.gov/pubmed/37445931
http://dx.doi.org/10.3390/ijms241310754
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author Agulló, Laura
Aguado, Isidro
Muriel, Javier
Margarit, César
Gómez, Alba
Escorial, Mónica
Sánchez, Astrid
Fernández, Alicia
Peiró, Ana M.
author_facet Agulló, Laura
Aguado, Isidro
Muriel, Javier
Margarit, César
Gómez, Alba
Escorial, Mónica
Sánchez, Astrid
Fernández, Alicia
Peiró, Ana M.
author_sort Agulló, Laura
collection PubMed
description Interindividual variability in analgesic response is at least partly due to well-characterized polymorphisms that are associated with opioid dosing and adverse outcomes. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has put forward recommendations for the CYP2D6 phenotype, but the list of studied drug-gene pairs continues to grow. This clinical trial randomized chronic pain patients (n = 60), referred from primary care to pain unit care into two opioid prescribing arms, one guided by CYP2D6, μ-opioid receptor (OPRM1), and catechol-O-methyl transferase (COMT) genotypes vs. one with clinical routine. The genotype-guided treatment reduced pain intensity (76 vs. 59 mm, p < 0.01) by improving pain relief (28 vs. 48 mm, p < 0.05), increased quality of life (43 vs. 56 mm p < 0.001), and lowered the incidence of clinically relevant adverse events (3 [1–5] vs. 1 [0–2], p < 0.01) and 42% opioid dose (35 [22–61] vs. 60 [40–80] mg/day, p < 0.05) as opposed to usual prescribing arm. The final health utility score was significantly higher (0.71 [0.58–0.82] vs. 0.51 [0.13–0.67] controls, p < 0.05) by improving sleepiness and depression comorbidity, with a significant reduction of 30–34% for headache, dry mouth, nervousness, and constipation. A large-scale implementation analysis could help clinical translation, together with a pharmaco-economic evaluation.
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spelling pubmed-103416552023-07-14 Pharmacogenetic Guided Opioid Therapy Improves Chronic Pain Outcomes and Comorbid Mental Health: A Randomized, Double-Blind, Controlled Study Agulló, Laura Aguado, Isidro Muriel, Javier Margarit, César Gómez, Alba Escorial, Mónica Sánchez, Astrid Fernández, Alicia Peiró, Ana M. Int J Mol Sci Article Interindividual variability in analgesic response is at least partly due to well-characterized polymorphisms that are associated with opioid dosing and adverse outcomes. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has put forward recommendations for the CYP2D6 phenotype, but the list of studied drug-gene pairs continues to grow. This clinical trial randomized chronic pain patients (n = 60), referred from primary care to pain unit care into two opioid prescribing arms, one guided by CYP2D6, μ-opioid receptor (OPRM1), and catechol-O-methyl transferase (COMT) genotypes vs. one with clinical routine. The genotype-guided treatment reduced pain intensity (76 vs. 59 mm, p < 0.01) by improving pain relief (28 vs. 48 mm, p < 0.05), increased quality of life (43 vs. 56 mm p < 0.001), and lowered the incidence of clinically relevant adverse events (3 [1–5] vs. 1 [0–2], p < 0.01) and 42% opioid dose (35 [22–61] vs. 60 [40–80] mg/day, p < 0.05) as opposed to usual prescribing arm. The final health utility score was significantly higher (0.71 [0.58–0.82] vs. 0.51 [0.13–0.67] controls, p < 0.05) by improving sleepiness and depression comorbidity, with a significant reduction of 30–34% for headache, dry mouth, nervousness, and constipation. A large-scale implementation analysis could help clinical translation, together with a pharmaco-economic evaluation. MDPI 2023-06-28 /pmc/articles/PMC10341655/ /pubmed/37445931 http://dx.doi.org/10.3390/ijms241310754 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Agulló, Laura
Aguado, Isidro
Muriel, Javier
Margarit, César
Gómez, Alba
Escorial, Mónica
Sánchez, Astrid
Fernández, Alicia
Peiró, Ana M.
Pharmacogenetic Guided Opioid Therapy Improves Chronic Pain Outcomes and Comorbid Mental Health: A Randomized, Double-Blind, Controlled Study
title Pharmacogenetic Guided Opioid Therapy Improves Chronic Pain Outcomes and Comorbid Mental Health: A Randomized, Double-Blind, Controlled Study
title_full Pharmacogenetic Guided Opioid Therapy Improves Chronic Pain Outcomes and Comorbid Mental Health: A Randomized, Double-Blind, Controlled Study
title_fullStr Pharmacogenetic Guided Opioid Therapy Improves Chronic Pain Outcomes and Comorbid Mental Health: A Randomized, Double-Blind, Controlled Study
title_full_unstemmed Pharmacogenetic Guided Opioid Therapy Improves Chronic Pain Outcomes and Comorbid Mental Health: A Randomized, Double-Blind, Controlled Study
title_short Pharmacogenetic Guided Opioid Therapy Improves Chronic Pain Outcomes and Comorbid Mental Health: A Randomized, Double-Blind, Controlled Study
title_sort pharmacogenetic guided opioid therapy improves chronic pain outcomes and comorbid mental health: a randomized, double-blind, controlled study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10341655/
https://www.ncbi.nlm.nih.gov/pubmed/37445931
http://dx.doi.org/10.3390/ijms241310754
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