Pharmacokinetic Markers of Clinical Outcomes in Severe Mental Illness: A Systematic Review

Abstract

The term severe mental illness (SMI) encompasses those psychiatric disorders exerting the highest clinical burden and socio-economic impact on the affected individuals and their communities. Pharmacogenomic (PGx) approaches hold great promise in personalizing treatment selection and clinical outcomes, possibly reducing the burden of SMI. Here, we sought to review the literature in the field, focusing on PGx testing and particularly on pharmacokinetic markers. We performed a systematic review on PUBMED/Medline, Web of Science, and Scopus. The last search was performed on the 17 September 2022, and further augmented with a comprehensive pearl-growing strategy. In total, 1979 records were screened, and after duplicate removal, 587 unique records were screened by at least 2 independent reviewers. Ultimately, forty-two articles were included in the qualitative analysis, eleven randomized controlled trials and thirty-one nonrandomized studies. The observed lack of standardization in PGx tests, population selection, and tested outcomes limit the overall interpretation of the available evidence. A growing body of evidence suggests that PGx testing might be cost-effective in specific settings and may modestly improve clinical outcomes. More efforts need to be directed toward improving PGx standardization, knowledge for all stakeholders, and clinical practice guidelines for screening recommendations.

Pharmacogenetics of Long-Term Outcomes of Schizophrenia Spectrum Disorders: The Functional Role of CYP2D6 and CYP2C19

“…Studies investigating the role of CYP in patients on clozapine have found opposite results indicating no association between CYP functional activity and change in PANSS overall symptom severity scores [ 30 , 41 ]. Furthermore, a recent systematic review demonstrated mixed findings regarding CYP2D6’s role, with most studies reporting no significant association with PANSS overall scores and few reporting slight associations with subscales of positive domains [ 42 ]. This suggests that CYP2D6, among others, may play a role in medications that target positive and cognitive symptom domains, however, more research is needed to uncover its true association.…”