Role of cytochrome phenotyping in patients with chronic noncancer pain with inadequate response to tramadol.

Authors

Deborah Montmeat, Xavier Declèves, Alicja Puszkiel, Serge Perrot, Anne-Priscille Trouvin

Published in

Pain reports. Volume 11. Issue 4. Pages e1474. Epub Jul 17, 2026.

Abstract

The opioid crisis is one of the most serious public health emergencies in the United States today. Opioid prescribing requires vigilance and reducing inappropriate opioid prescriptions is a key to decreasing opioid misuse. For that reason, we often focus solely on therapeutic indications or dosage while overlooking the polymorphisms of metabolism. Cytochromes P450 (CYP) are highly susceptible to interindividual and intraindividual variations and the analgesic activity of tramadol is dependent on the activity of CYP2D6.
To evaluate whether CYP phenotyping could identify metabolic abnormalities in patients with chronic non-cancer pain (CNCP) who experienced an inadequate response to tramadol and to assess the impact of phenotype-guided therapeutic adaptation on patient care.
This exploratory study assessed CYP's activity using a phenotyping drug cocktail protocol adapted from the Geneva cocktail in patients suffering from CNCP who experienced an inadequate response to tramadol, either ineffectiveness or side effects leading to discontinuation of tramadol. Patients' drug therapy was subsequently tailored according to their cytochromes' activity, and its impact was evaluated one year later using patient-reported outcomes.
72.7% of patients who had side effects resulting in treatment discontinuation had slow metabolism for CYP2D6; 87.5% of patients who had experienced ineffectiveness with tramadol had slow metabolism for CYP2D6. The patients believed that this test led to a great improvement in their therapeutic management on average.
An inadequate response to tramadol in a patient with CNCP could trigger consideration of metabolic phenotype exploration to facilitate personalised pain management and reduce unwarranted opioid prescription.

PMID:
42519360
Bibliographic data and abstract were imported from PubMed on 29 Jul 2026.

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