CYP2D6 phenotypes and opioid metabolism: the path to personalized analgesia

ABSTRACT

Introduction

Opioids play a fundamental role in chronic pain, especially considering when 1 of 5 Europeans adults, even more in older females, suffer from it. However, half of them do not reach an adequate pain relief. Could pharmacogenomics help to choose the most appropriate analgesic drug?

Areas covered

The objective of the present narrative review was to assess the influence of cytochrome P450 2D6 (CYP2D6) phenotypes on pain relief, analgesic tolerability, and potential opioid misuse. Until December 2021, a literature search was conducted through the MEDLINE, PubMed database, including papers from the last 10 years. CYP2D6 plays a major role in metabolism that directly impacts on opioid (tramadol, codeine, or oxycodone) concentration with differences between sexes, with a female trend toward poorer pain control. In fact, CYP2D6 gene variants are the most actionable to be translated into clinical practice according to regulatory drug agencies and international guidelines.

Expert Opinion

CYP2D6 genotype can influence opioids’ pharmacokinetics, effectiveness, side effects, and average opioid dose. This knowledge needs to be incorporated in pain management. Environmental factors, psychological together with genetic factors, under a sex perspective, must be considered when you are selecting the most personalized pain therapy for your patients.

KEYWORDS:

• Chronic pain
• personalized analgesia
• CYP2D6 phenotypes
• opioid metabolism
• pharmacogenetics
• sex

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Article highlights

• Chronic pain is a silent epidemic situation that occurs in 1 of 5 European adults, and this is even more in older females.

• The goal of a personalized analgesia is to enhance functioning and reduce suffering, while minimizing the risk of analgesics adverse effects. This can depend on medical but also, psychological and genetic conditions.

• Close to 27% of the European population struggles with proper metabolism of CYP2D6 drugs. Here, pharmacogenomics could play a role in opioid use to assess analgesic effectiveness, tolerability, and mean dose opioid prescription, even more so in females due to hormonal factors.

• Implementing CYP2D6 to guide pain management, with a sex perspective, is feasible to develop a safer and more effective treatment for chronic pain in adults.

Supplementary material

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Additional information

Funding

This paper was not funded.