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P-952 - Candidate Genes for Pharmacogenetic Management of Methadone Optimal Dose

Published online by Cambridge University Press:  15 April 2020

F. Vorspan ,
K. Ksouda ,
L. Labat Delveaux ,
A. Hajj ,
X. Decleves ,
V. Bloch ,
S. Mouly ,
J. Callebert ,
J.-M. Scherrmann  and
J.P. Lepine
...Show all authors
F. Vorspan
Affiliation:
U705, UMR8206, INSERM, CNRS, Paris, France Service de Psychiatrie, APHP, Hopital Fernand Widal, Paris, France
K. Ksouda
Affiliation:
Service de Psychiatrie, APHP, Hopital Fernand Widal, Paris, France
L. Labat Delveaux
Affiliation:
Pharmacie-Pharmacologie-Toxicologie, APHP, Hopital Cochin, Paris, France
A. Hajj
Affiliation:
Service de Biochimie et Biologie Moléculaire, APHP, Paris, France
X. Decleves
Affiliation:
Service de Biochimie et Biologie Moléculaire, APHP, Paris, France
V. Bloch
Affiliation:
U705, UMR8206, INSERM, CNRS, Paris, France Service de Psychiatrie, APHP, Hopital Fernand Widal, Paris, France
S. Mouly
Affiliation:
Service de Biochimie et Biologie Moléculaire, APHP, Paris, France
J. Callebert
Affiliation:
Service de Psychiatrie, APHP, Hopital Fernand Widal, Paris, France Laboratoire de Pharmacocinétique, Université Paris Descartes, UFR Pharmacie, Paris, France
J.-M. Scherrmann
Affiliation:
Service de Biochimie et Biologie Moléculaire, APHP, Paris, France
J.P. Lepine
Affiliation:
U705, UMR8206, INSERM, CNRS, Paris, France Service de Psychiatrie, APHP, Hopital Fernand Widal, Paris, France Laboratoire de Biologie Cellulaire, Paris Descartes University, Paris, France
J.-L. Laplanche
Affiliation:
Service de Biochimie et Biologie Moléculaire, APHP, Paris, France
K. Peoc’h
Affiliation:
Service de Biochimie et Biologie Moléculaire, APHP, Paris, France

Abstract

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Introduction

Methadone, a Mu-opioid receptor agonist, is currently used as a maintenance treatment in opioid dependant patients. However, its therapeutic index is narrow, and side effects are life threatening. Non-optimal dosing results in withdrawal symptoms and further heroin craving and use. The optimal dose is defined as the dose necessary to obtain a stable substitution. This optimal maximal dose can then be decreased, the final goal being to stop substitution.

Objectives

To identify factors to optimize the methadone optimal daily dose.

Aims

We aimed to identify genetic variants (SNP) associated with the methadone optimal dose. In a candidate gene approach, we focused on OPRM1, which encodes the opioid receptor Mu, and on DRD2/ANKK1 SNP's, implied in the reward dopaminergic signalling.

Methods

Caucasians patients (n = 98) followed for methadone maintenance treatment were included in this prospective study. Candidate SNPs were genotyped (ANKK1: TaqI A; DRD2: c.957C>T; OPRM1: c.A118G). The plasmatic methadone level was determined using mass spectrometry in 59 patients.

Results

Two polymorphisms were significantly associated to the optimal methadone doses: OPRM1 c.A118G (p = 0.03) and DRD2 TaqI A (p = 0.035).

The TaqIA polymorphism is located within ANKK1, which encodes a serine threonine kinase which role remains elusive. Its molecular link to methadone pharmacodynamy remains to be established. None of these polymorphisms was associated neither to the current methadone doses, nor to the methadone plasmatic concentration.

Conclusion

This description is the first step to optimize the prescription of methadone in caucasian populations.

Type
Abstract
Information
European Psychiatry , Volume 27 , Issue S1: Abstracts of the 20th European Congress of Psychiatry , 2012 , pp. 1
Copyright
Copyright © European Psychiatric Association 2012
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