Authors: Heather Hare, Kevin B Sneed, Yashwant Pathak.
Background: Scientific understanding of precision medicine is rapidly evolving as new associations are made between genetic variants and tolerance to pharmaceuticals [1]. Although pharmacogenetic testing and guidelines exist for many medications, there is limited clinical application of these technologies in part due to limitations of the evidence supporting its use in psychiatric treatment as well as lack of awareness by providers and patients [2]. This narrative literature review aims to assess and summarize the past decade of research in the field of psychiatric pharmacogenetics. Specifically, it will focus on the relationship between antidepressant/antipsychotic drug responses and polymorphisms in nine commonly studied genes: CYP1A2, CYP2B6, CYP2C19, CYP2D6, CYP3A4, CYP3A5, SLC6A4, HTR2A, and DRD2.
Methods: Literature from PubMed and Embase that was published between the years 2010 and 2020 was found using strategic keywords and search phrases. Each study represented was a randomized controlled trial or clinical trial tested in adults over the age of eighteen.
Results: Of the six CYP450 enzymes that were evaluated, all displayed impacts on the metabolism of psychiatric drugs except CYP3A4, although only one polymorphism (*1B) was included in analysis of that particular gene. Inconclusive results were discovered regarding SLC6A4 5-HTTLPR polymorphisms and further review should be done to determine its relationship with SSRI response. Additionally, review of literature pertaining to DRD2 showed unsubstantial evidence, as four out of seven articles found no connection between treatment or adverse drug reactions (ADR) associated with DRD2. In contrast, influential findings were documented by literature concerning HTR2A polymorphisms and therapeutic consequences and the evidence collected on benefits of pharmacogenomic testing supports the implementation of testing to guide psychiatric treatment with confidence that use may result in fewer failed trials prior to response or remission.
Conclusion: Many polymorphic mutations have a significant impact on individual responses to psychiatric treatment and implementation of pharmacogenomic testing in a clinic setting may be beneficial to psychiatric patients. Further review of polymorphic relationships should be done, especially in the case of SLC6A4 and DRD2 variations.
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