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The Clinical Pharmacogenetics Implementation Consortium (CPIC) has put forward recommendations for the CYP2D6 phenotype, but the list of studied drug-gene pairs continues to grow. This clinical trial randomized chronic pain patients (n = 60), referred from primary care to pain unit care into two opioid prescribing arms, one guided by CYP2D6, \u03bc-opioid receptor (OPRM1), and catechol-O-methyl transferase (COMT) genotypes vs. one with clinical routine. The genotype-guided treatment reduced pain intensity (76 vs. 59 mm, p &lt; 0.01) by improving pain relief (28 vs. 48 mm, p &lt; 0.05), increased quality of life (43 vs. 56 mm p &lt; 0.001), and lowered the incidence of clinically relevant adverse events (3 [1\u20135] vs. 1 [0\u20132], p &lt; 0.01) and 42% opioid dose (35 [22\u201361] vs. 60 [40\u201380] mg\/day, p &lt; 0.05) as opposed to usual prescribing arm. The final health utility score was significantly higher (0.71 [0.58\u20130.82] vs. 0.51 [0.13\u20130.67] controls, p &lt; 0.05) by improving sleepiness and depression comorbidity, with a significant reduction of 30\u201334% for headache, dry mouth, nervousness, and constipation. A large-scale implementation analysis could help clinical translation, together with a pharmaco-economic evaluation.<\/jats:p>","DOI":"10.3390\/ijms241310754","type":"journal-article","created":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T00:41:45Z","timestamp":1687999305000},"page":"10754","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Pharmacogenetic Guided Opioid Therapy Improves Chronic Pain Outcomes and Comorbid Mental Health: A Randomized, Double-Blind, Controlled Study"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8739-0456","authenticated-orcid":false,"given":"Laura","family":"Agull\u00f3","sequence":"first","affiliation":[{"name":"Pharmacogenetic Unit, Clinical Pharmacology Department, Alicante Institute for Health and Biomedical Research (ISABIAL), General University Hospital of Alicante, c\/Pintor Baeza, 12, 03010 Alicante, Spain"},{"name":"Clinical Pharmacology, Toxicology and Chemical Safety Unit, Institute of Bioengineering, Miguel Hern\u00e1ndez University, Avda. de la Universidad s\/n, 03202 Elche, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isidro","family":"Aguado","sequence":"additional","affiliation":[{"name":"Pharmacogenetic Unit, Clinical Pharmacology Department, Alicante Institute for Health and Biomedical Research (ISABIAL), General University Hospital of Alicante, c\/Pintor Baeza, 12, 03010 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0048-9451","authenticated-orcid":false,"given":"Javier","family":"Muriel","sequence":"additional","affiliation":[{"name":"Pharmacogenetic Unit, Clinical Pharmacology Department, Alicante Institute for Health and Biomedical Research (ISABIAL), General University Hospital of Alicante, c\/Pintor Baeza, 12, 03010 Alicante, Spain"},{"name":"Clinical Pharmacology, Toxicology and Chemical Safety Unit, Institute of Bioengineering, Miguel Hern\u00e1ndez University, Avda. de la Universidad s\/n, 03202 Elche, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9sar","family":"Margarit","sequence":"additional","affiliation":[{"name":"Pain Unit, Department of Health of Alicante, General University Hospital of Alicante, c\/Pintor Baeza, 12, 03010 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"G\u00f3mez","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, Toxicology and Chemical Safety Unit, Institute of Bioengineering, Miguel Hern\u00e1ndez University, Avda. de la Universidad s\/n, 03202 Elche, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Escorial","sequence":"additional","affiliation":[{"name":"Pharmacogenetic Unit, Clinical Pharmacology Department, Alicante Institute for Health and Biomedical Research (ISABIAL), General University Hospital of Alicante, c\/Pintor Baeza, 12, 03010 Alicante, Spain"},{"name":"Clinical Pharmacology, Toxicology and Chemical Safety Unit, Institute of Bioengineering, Miguel Hern\u00e1ndez University, Avda. de la Universidad s\/n, 03202 Elche, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"San Vicente del Raspeig II Health Center, c\/Alicante, 78, Sant Vicent del Raspeig, 03690 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"San Vicente del Raspeig II Health Center, c\/Alicante, 78, Sant Vicent del Raspeig, 03690 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2385-3749","authenticated-orcid":false,"given":"Ana M.","family":"Peir\u00f3","sequence":"additional","affiliation":[{"name":"Pharmacogenetic Unit, Clinical Pharmacology Department, Alicante Institute for Health and Biomedical Research (ISABIAL), General University Hospital of Alicante, c\/Pintor Baeza, 12, 03010 Alicante, Spain"},{"name":"Clinical Pharmacology, Toxicology and Chemical Safety Unit, Institute of Bioengineering, Miguel Hern\u00e1ndez University, Avda. de la Universidad s\/n, 03202 Elche, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s11920-018-0872-4","article-title":"Psychiatry and Pain Management: At the Intersection of Chronic Pain and Mental Health","volume":"20","author":"Goesling","year":"2018","journal-title":"Curr. 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