PMID- 37324467
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230619
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 14
DP  - 2023
TI  - Impact of CYP2D6 genotype on opioid use disorder deprescription: an observational 
      prospective study in chronic pain with sex-differences.
PG  - 1200430
LID - 10.3389/fphar.2023.1200430 [doi]
LID - 1200430
AB  - 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 x N, 2D6*4 x 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.
CI  - Copyright (c) 2023 Muriel, Barrachina, Del Barco, Carvajal, Escorial, Margarit, 
      Ballester and Peiro.
FAU - Muriel, Javier
AU  - Muriel J
AD  - Pharmacogenetic Unit, Clinical Pharmacology Unit, Alicante Institute for Health 
      and Biomedical Research (ISABIAL), Alicante, Spain.
FAU - Barrachina, Jordi
AU  - Barrachina J
AD  - Pharmacogenetic Unit, Clinical Pharmacology Unit, Alicante Institute for Health 
      and Biomedical Research (ISABIAL), Alicante, Spain.
AD  - Occupational Observatory, University Miguel Hernandez, Elche, Spain.
FAU - Del Barco, Guillermo
AU  - Del Barco G
AD  - Occupational Observatory, University Miguel Hernandez, Elche, Spain.
FAU - Carvajal, Cristian
AU  - Carvajal C
AD  - Occupational Observatory, University Miguel Hernandez, Elche, Spain.
FAU - Escorial, Monica
AU  - Escorial M
AD  - Pharmacogenetic Unit, Clinical Pharmacology Unit, Alicante Institute for Health 
      and Biomedical Research (ISABIAL), Alicante, Spain.
AD  - Occupational Observatory, University Miguel Hernandez, Elche, Spain.
FAU - Margarit, Cesar
AU  - Margarit C
AD  - Pharmacogenetic Unit, Clinical Pharmacology Unit, Alicante Institute for Health 
      and Biomedical Research (ISABIAL), Alicante, Spain.
AD  - Pain Unit, Department of Health of Alicante-General Hospital, Alicante, Spain.
FAU - Ballester, Pura
AU  - Ballester P
AD  - Pharmacogenetic Unit, Clinical Pharmacology Unit, Alicante Institute for Health 
      and Biomedical Research (ISABIAL), Alicante, Spain.
FAU - Peiro, Ana Maria
AU  - Peiro AM
AD  - Pharmacogenetic Unit, Clinical Pharmacology Unit, Alicante Institute for Health 
      and Biomedical Research (ISABIAL), Alicante, Spain.
AD  - Pain Unit, Department of Health of Alicante-General Hospital, Alicante, Spain.
AD  - Bioengineering Institute, Toxicology and Environmental Health, University Miguel 
      Hernandez, Elche, Spain.
LA  - eng
PT  - Journal Article
DEP - 20230531
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC10264765
OTO - NOTNLM
OT  - CYP2D6
OT  - chronic pain
OT  - deprescription
OT  - opioid use disorder
OT  - pharmacogenetics
OT  - sex-differences
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/06/16 06:42
MHDA- 2023/06/16 06:43
PMCR- 2023/05/31
CRDT- 2023/06/16 04:11
PHST- 2023/04/04 00:00 [received]
PHST- 2023/05/15 00:00 [accepted]
PHST- 2023/06/16 06:43 [medline]
PHST- 2023/06/16 06:42 [pubmed]
PHST- 2023/06/16 04:11 [entrez]
PHST- 2023/05/31 00:00 [pmc-release]
AID - 1200430 [pii]
AID - 10.3389/fphar.2023.1200430 [doi]
PST - epublish
SO  - Front Pharmacol. 2023 May 31;14:1200430. doi: 10.3389/fphar.2023.1200430. 
      eCollection 2023.