Pharmacogenetic Guided Opioid Therapy Improves Chronic Pain Outcomes and Comorbid Mental Health: A Randomized, Double-Blind, Controlled Study

• Published in: International journal of molecular sciences 2023-06, Vol.24 (13), p.10754
• Main Authors: Agulló, Laura, Aguado, Isidro, Muriel, Javier, Margarit, César, Gómez, Alba, Escorial, Mónica, Sánchez, Astrid, Fernández, Alicia, Peiró, Ana M
• Format: Article
• Language: English
• Subjects: Analgesics; Analgesics, Opioid - adverse effects; Analysis; Care and treatment; Catechol; Catechol O-Methyltransferase - genetics; Chronic pain; Chronic Pain - chemically induced; Chronic Pain - drug therapy; Chronic Pain - genetics; Clinical trials; Comorbidity; COMT; Constipation; CYP2D6; CYP2D6 protein; Cytochrome P-450 CYP2D6 - genetics; Cytochrome P450; Dopamine; Dosage; Double-blind studies; Enzymes; Fentanyl; Genetic aspects; Headache; Humans; Insomnia; Mental Health; Metabolism; Metabolites; Morphine; Narcotics; Opioid receptors; opioids; OPRM1; Pain; Pain management; Patients; Pharmacogenetics; Phenotypes; Polymorphism; Practice Patterns, Physicians; Primary care; Quality of Life; Receptors, Opioid, mu - genetics; Sleep and wakefulness
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms241310754

Interindividual variability in analgesic response is at least partly due to well-characterized polymorphisms that are associated with opioid dosing and adverse outcomes. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has put forward recommendations for the phenotype, but the list of studied drug-gene pairs continues to grow. This clinical trial randomized chronic pain patients ( = 60), referred from primary care to pain unit care into two opioid prescribing arms, one guided by , μ-opioid receptor ( ), and catechol-O-methyl transferase ( ) genotypes vs. one with clinical routine. The genotype-guided treatment reduced pain intensity (76 vs. 59 mm, < 0.01) by improving pain relief (28 vs. 48 mm, < 0.05), increased quality of life (43 vs. 56 mm < 0.001), and lowered the incidence of clinically relevant adverse events (3 [1-5] vs. 1 [0-2], < 0.01) and 42% opioid dose (35 [22-61] vs. 60 [40-80] mg/day, < 0.05) as opposed to usual prescribing arm. The final health utility score was significantly higher (0.71 [0.58-0.82] vs. 0.51 [0.13-0.67] controls, < 0.05) by improving sleepiness and depression comorbidity, with a significant reduction of 30-34% for headache, dry mouth, nervousness, and constipation. A large-scale implementation analysis could help clinical translation, together with a pharmaco-economic evaluation.