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Abstract
Adverse events, response failures and medication non-compliance are common in patients receiving medications for the treatment of mental illnesses. A systematic literature review assessed whether pharmacokinetic (PK) or pharmacodynamic (PD) responses to 26 commonly prescribed antipsychotic and antidepressant medications, including efficacy or side effects, are associated with nucleotide polymorphisms in eight commonly studied genes in psychiatric pharmacotherapy: CYP2D6, CYP2C19, CYP2C9, CYP1A2, CYP3A4, HTR2C, HTR2A, and SLC6A4. Of the 294 publications included in this review, 168 (57%) showed significant associations between gene variants and PK or PD outcomes. Other studies that showed no association often had insufficient control for confounding variables, such as co-medication use, or analysis of medications not substrates of the target gene. The strongest gene–outcome associations were for the PK profiles of CYP2C19 and CYP2D6 (93% and 90%, respectively), for the PD associations between HTR2C and weight gain (57%), and for SLC6A4 and clinical response (54%), with stronger SLC6A4 response associations for specific drug classes (60–83%). The preponderance of evidence supports the validity of analyzing nucleotide polymorphisms in CYP and pharmacodynamic genes to predict the metabolism, safety, or therapeutic efficacy of psychotropic medications commonly used for the treatment of depression, schizophrenia, and bipolar illness.
Acknowledgements
This review is dedicated to the memory of David A. Mrazek, a pioneer in the theory and clinical application of psychiatric pharmacogenomics. The advice and editorial comments provided by James Burns and Bryan Dechairo during the preparation of this report are greatly appreciated.
Declaration of interest: AssureRx Health, Inc. (Mason, OH, USA) sponsored the study. One co-author (A.A.) is employed by the sponsor. David Mrazek is a posthumous co-author and developed intellectual property that has been licensed by the sponsor. He also received research funding from the sponsor to create and maintain a bibliographic system designed to regularly monitor the scientific literature. Four co-authors (J.H., A.S., V.C., and J.G.) are employees of Cedar Associates LLC, which received funding for participating in this research. The authors alone are responsible for the content and writing of the paper.