Analgesic therapy failure in a COMT HPS/HPS diplotype carrier heterozygous for the CYP2D6 *4 allele with fibromyalgia-a case report.

INTRODUCTION

The cytochrome P450 enzyme 2D6 (CYP2D6) and the catechol-O-methyltransferase (COMT) enzyme are involved in catecholamine metabolism, potentially influencing pain modulation. Catechol-O-methyltransferase has 3 major haplotypes related to pain sensitivity: low (LPS), average (APS), and high (HPS). However, the reliability of these haplotypes in predicting clinical outcomes is not well investigated. We present a 40-year-old female patient with fibromyalgia. Despite extensive pharmacotherapy with 120 mg/d duloxetine, 150 mg/d pregabalin, 80 mg/d oxycodone, 2 g/d paracetamol, and 1.6 g/d ibuprofen, she suffered from severe pain.

OBJECTIVES

We aim to investigate the patient's susceptibility to analgesic therapy failure (TF) and pain sensitivity with pharmacogenotyping.

METHODS

PGx panel testing, including CYP2D6 and COMT rs4680, was conducted by a commercial provider. Additional genotyping of COMT rs6269, rs4633 and rs4818 was performed applying PCR, restriction fragment length polymorphism assay and sanger sequencing.

RESULTS

The patient was identified as COMT HPS/HPS diplotype carrier and CYP2D6 intermediate metabolizer. CYP2D6 is mainly responsible for the bioactivation of oxycodone into oxymorphone. Reduced CYP2D6 activity may result in a lower oxycodone activation. Considering the coadministration of duloxetine (a moderate CYP2D6 inhibitor), the TF of oxycodone could also be the result of a drug-drug-gene interaction. No other medications were affected by her genetic profile.

CONCLUSION

We hypothesize that the broad TF of pain medications and associated high pain sensitivity could be related to the patient's genetic predisposition in CYP2D6 and COMT, warranting further investigation in a larger patient sample.