Impact of CYP2D6 genotype on opioid use disorder deprescription: an observational prospective study in chronic pain with sex-differences
Introduction: Opioid deprescription is the process of supervised tapering and safe withdrawal when a potentially inappropriate use is detected. This represents a challenge in chronic non-cancer pain (CNCP) patients who may respond differently to the procedure. Our aim was to analyze the potential im...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-05-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1200430/full |
| _version_ | 1797815424796065792 |
|---|---|
| author | Javier Muriel Jordi Barrachina Jordi Barrachina Guillermo Del Barco Cristian Carvajal Mónica Escorial Mónica Escorial César Margarit César Margarit Pura Ballester Ana María Peiró Ana María Peiró Ana María Peiró |
| author_facet | Javier Muriel Jordi Barrachina Jordi Barrachina Guillermo Del Barco Cristian Carvajal Mónica Escorial Mónica Escorial César Margarit César Margarit Pura Ballester Ana María Peiró Ana María Peiró Ana María Peiró |
| author_sort | Javier Muriel |
| collection | DOAJ |
| description | Introduction: Opioid deprescription is the process of supervised tapering and safe withdrawal when a potentially inappropriate use is detected. This represents a challenge in chronic non-cancer pain (CNCP) patients who may respond differently to the procedure. Our aim was to analyze the potential impact of CYP2D6 phenotypes and sex on the clinical and safety outcomes during an opioid use disorder (OUD) tapering process.Methods: A prospective observational study was conducted on CNCP ambulatory OUD patients (cases, n = 138) who underwent a 6-month opioid dose reduction and discontinuation. Pain intensity, relief and quality of life (Visual analogue scale, VAS 0–100 mm), global activity (GAF, 0–100 scores), morphine equivalent daily dose (MEDD), analgesic drugs adverse events (AEs) and opioid withdrawal syndrome (OWS, 0–96 scores) were recorded at basal and final visits. Sex differences and CYP2D6 phenotypes (poor (PM), extensive (EM) and ultrarapid (UM) metabolizers based on CYP2D6*1, *2, *3, *4, *5, *6, *10, *17, *41, 2D6*5, 2D6 × N, 2D6*4 × 2 gene variants) were analyzed.Results: Although CYP2D6-UM consumed three-times less basal MEDD [40 (20–123) mg/day, p = 0.04], they showed the highest number of AEs [7 (6–11), p = 0.02] and opioid withdrawal symptoms (46 ± 10 scores, p = 0.01) after deprescription. This was inversely correlated with their quality of life (r = −0.604, p < 0.001). Sex-differences were evidenced with a tendency to a lower analgesic tolerability in females and lower quality of life in men.Discussion: These data support the potential benefits of CYP2D6-guided opioid deprescription, in patients with CNCP when OUD is detected. Further studies are required to understand a sex/gender interaction. |
| first_indexed | 2024-03-13T08:23:38Z |
| format | Article |
| id | doaj.art-40e09b62fefa478bb5ccf8ccb3272307 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-13T08:23:38Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-40e09b62fefa478bb5ccf8ccb32723072023-05-31T05:04:20ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-05-011410.3389/fphar.2023.12004301200430Impact of CYP2D6 genotype on opioid use disorder deprescription: an observational prospective study in chronic pain with sex-differencesJavier Muriel0Jordi Barrachina1Jordi Barrachina2Guillermo Del Barco3Cristian Carvajal4Mónica Escorial5Mónica Escorial6César Margarit7César Margarit8Pura Ballester9Ana María Peiró10Ana María Peiró11Ana María Peiró12Pharmacogenetic Unit, Clinical Pharmacology Unit, Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, SpainPharmacogenetic Unit, Clinical Pharmacology Unit, Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, SpainOccupational Observatory, University Miguel Hernández, Elche, SpainOccupational Observatory, University Miguel Hernández, Elche, SpainOccupational Observatory, University Miguel Hernández, Elche, SpainPharmacogenetic Unit, Clinical Pharmacology Unit, Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, SpainOccupational Observatory, University Miguel Hernández, Elche, SpainPharmacogenetic Unit, Clinical Pharmacology Unit, Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, SpainPain Unit, Department of Health of Alicante-General Hospital, Alicante, SpainPharmacogenetic Unit, Clinical Pharmacology Unit, Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, SpainPharmacogenetic Unit, Clinical Pharmacology Unit, Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, SpainPain Unit, Department of Health of Alicante-General Hospital, Alicante, SpainBioengineering Institute, Toxicology and Environmental Health, University Miguel Hernández, Elche, SpainIntroduction: Opioid deprescription is the process of supervised tapering and safe withdrawal when a potentially inappropriate use is detected. This represents a challenge in chronic non-cancer pain (CNCP) patients who may respond differently to the procedure. Our aim was to analyze the potential impact of CYP2D6 phenotypes and sex on the clinical and safety outcomes during an opioid use disorder (OUD) tapering process.Methods: A prospective observational study was conducted on CNCP ambulatory OUD patients (cases, n = 138) who underwent a 6-month opioid dose reduction and discontinuation. Pain intensity, relief and quality of life (Visual analogue scale, VAS 0–100 mm), global activity (GAF, 0–100 scores), morphine equivalent daily dose (MEDD), analgesic drugs adverse events (AEs) and opioid withdrawal syndrome (OWS, 0–96 scores) were recorded at basal and final visits. Sex differences and CYP2D6 phenotypes (poor (PM), extensive (EM) and ultrarapid (UM) metabolizers based on CYP2D6*1, *2, *3, *4, *5, *6, *10, *17, *41, 2D6*5, 2D6 × N, 2D6*4 × 2 gene variants) were analyzed.Results: Although CYP2D6-UM consumed three-times less basal MEDD [40 (20–123) mg/day, p = 0.04], they showed the highest number of AEs [7 (6–11), p = 0.02] and opioid withdrawal symptoms (46 ± 10 scores, p = 0.01) after deprescription. This was inversely correlated with their quality of life (r = −0.604, p < 0.001). Sex-differences were evidenced with a tendency to a lower analgesic tolerability in females and lower quality of life in men.Discussion: These data support the potential benefits of CYP2D6-guided opioid deprescription, in patients with CNCP when OUD is detected. Further studies are required to understand a sex/gender interaction.https://www.frontiersin.org/articles/10.3389/fphar.2023.1200430/fullCYP2D6sex-differencesopioid use disorderdeprescriptionchronic painpharmacogenetics |
| spellingShingle | Javier Muriel Jordi Barrachina Jordi Barrachina Guillermo Del Barco Cristian Carvajal Mónica Escorial Mónica Escorial César Margarit César Margarit Pura Ballester Ana María Peiró Ana María Peiró Ana María Peiró Impact of CYP2D6 genotype on opioid use disorder deprescription: an observational prospective study in chronic pain with sex-differences Frontiers in Pharmacology CYP2D6 sex-differences opioid use disorder deprescription chronic pain pharmacogenetics |
| title | Impact of CYP2D6 genotype on opioid use disorder deprescription: an observational prospective study in chronic pain with sex-differences |
| title_full | Impact of CYP2D6 genotype on opioid use disorder deprescription: an observational prospective study in chronic pain with sex-differences |
| title_fullStr | Impact of CYP2D6 genotype on opioid use disorder deprescription: an observational prospective study in chronic pain with sex-differences |
| title_full_unstemmed | Impact of CYP2D6 genotype on opioid use disorder deprescription: an observational prospective study in chronic pain with sex-differences |
| title_short | Impact of CYP2D6 genotype on opioid use disorder deprescription: an observational prospective study in chronic pain with sex-differences |
| title_sort | impact of cyp2d6 genotype on opioid use disorder deprescription an observational prospective study in chronic pain with sex differences |
| topic | CYP2D6 sex-differences opioid use disorder deprescription chronic pain pharmacogenetics |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1200430/full |
| work_keys_str_mv | AT javiermuriel impactofcyp2d6genotypeonopioidusedisorderdeprescriptionanobservationalprospectivestudyinchronicpainwithsexdifferences AT jordibarrachina impactofcyp2d6genotypeonopioidusedisorderdeprescriptionanobservationalprospectivestudyinchronicpainwithsexdifferences AT jordibarrachina impactofcyp2d6genotypeonopioidusedisorderdeprescriptionanobservationalprospectivestudyinchronicpainwithsexdifferences AT guillermodelbarco impactofcyp2d6genotypeonopioidusedisorderdeprescriptionanobservationalprospectivestudyinchronicpainwithsexdifferences AT cristiancarvajal impactofcyp2d6genotypeonopioidusedisorderdeprescriptionanobservationalprospectivestudyinchronicpainwithsexdifferences AT monicaescorial impactofcyp2d6genotypeonopioidusedisorderdeprescriptionanobservationalprospectivestudyinchronicpainwithsexdifferences AT monicaescorial impactofcyp2d6genotypeonopioidusedisorderdeprescriptionanobservationalprospectivestudyinchronicpainwithsexdifferences AT cesarmargarit impactofcyp2d6genotypeonopioidusedisorderdeprescriptionanobservationalprospectivestudyinchronicpainwithsexdifferences AT cesarmargarit impactofcyp2d6genotypeonopioidusedisorderdeprescriptionanobservationalprospectivestudyinchronicpainwithsexdifferences AT puraballester impactofcyp2d6genotypeonopioidusedisorderdeprescriptionanobservationalprospectivestudyinchronicpainwithsexdifferences AT anamariapeiro impactofcyp2d6genotypeonopioidusedisorderdeprescriptionanobservationalprospectivestudyinchronicpainwithsexdifferences AT anamariapeiro impactofcyp2d6genotypeonopioidusedisorderdeprescriptionanobservationalprospectivestudyinchronicpainwithsexdifferences AT anamariapeiro impactofcyp2d6genotypeonopioidusedisorderdeprescriptionanobservationalprospectivestudyinchronicpainwithsexdifferences |