Squassina Alessio, Paribello Pasquale, Pinna Marco, Contu Martina, Pisanu Claudia, Congiu Donatella, Severino Giovanni, Meloni Anna, Carta Andrea, Conversano Claudio, Mola Francesco, Del Zompo Maria, d'Aversa Federico Bernoni, Minelli Alessandra, Gennarelli Massimo, Pinna Federica, Carpiniello Bernardo, Manchia Mirko
Section of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
Section of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
Prog Neuropsychopharmacol Biol Psychiatry. 2025 Mar 20;137:111292. doi: 10.1016/j.pnpbp.2025.111292. Epub 2025 Feb 17.
Response to antidepressants (ADs) is highly variable and partly genetically driven, but the utility of pharmacogenetic testing in guiding ADs treatment is still controversial. We conducted a retrospective, naturalistic study to explore the utility of CYP2C6 and CYP2C19 genotyping in ADs treatment in a sample of 156 patients diagnosed with major depressive disorder from south Sardinia (Italy). Clinical data, including history of medication regimens, adverse reactions, and response to ADs were collected over the last five years preceding recruitment. Patients received pharmacogenetic testing at recruitment and were classified depending on whether their history of treatment regimen followed the recommendations of the Clinical Pharmacogenetics Implementation Consortium (CPIC)). Non-responders to ADs had a larger number of therapeutic regimens and of medication changes due to lack of response compared to responders. Patients with at least one incongruent regimen had a larger number of total therapeutic changes and fewer congruent regimens. Metabolizing phenotypes of CYP2D6 were not associated with response to ADs or changes in regimen of any kind. However, the group of ultra-rapid metabolizers for CYP2C19 showed significantly smaller improvement in symptoms while the poor-metabolizers showed a larger number of medication changes for side effects compared to normal, intermediate and rapid metabolizers. Our findings suggest that the implementation of pharmacogenetic testing based on CYP2C19 could be clinically useful in guiding AD treatment, but further studies are warranted to investigate the clinical implications of implementing PGx testing in depression.
对抗抑郁药（ADs）的反应差异很大，部分由基因驱动，但药物遗传学检测在指导ADs治疗中的效用仍存在争议。我们进行了一项回顾性、自然主义研究，以探讨CYP2C6和CYP2C19基因分型在意大利撒丁岛南部156例被诊断为重度抑郁症患者的ADs治疗中的效用。在招募前的过去五年中收集了临床数据，包括用药方案史、不良反应和对ADs的反应。患者在招募时接受了药物遗传学检测，并根据其治疗方案史是否遵循临床药物遗传学实施联盟（CPIC）的建议进行分类。与有反应者相比，ADs无反应者由于缺乏反应而有更多的治疗方案和用药变化。至少有一个不一致方案的患者有更多的总治疗变化和更少的一致方案。CYP2D6的代谢表型与对ADs的反应或任何类型的方案变化均无关联。然而，与正常、中间和快速代谢者相比，CYP2C19超快速代谢者组的症状改善明显较小，而慢代谢者因副作用而有更多的用药变化。我们的研究结果表明，基于CYP2C19的药物遗传学检测的实施在指导AD治疗方面可能具有临床实用性，但有必要进一步研究以调查在抑郁症中实施药物基因组学检测的临床意义。
