Pharmacogenomics in Psychiatry: Starting With the Molecular Basics

John Miller, MD, discussed foundational and clinical aspects of pharmacogenomics relevant to psychiatric practice. Miller began by reviewing basic molecular biology, emphasizing the central role of DNA transcription and translation in producing gene products that ultimately influence pharmacokinetics and pharmacodynamics.

He described how genetic variation contributes to interindividual differences in drug metabolism, noting that “when it's time to make a gene product from that DNA, the DNA will open up and the various enzymes that will transcribe the information on that gene attached.”¹ He used this framework to contextualize variability in psychiatric medication response. Miller focused on cytochrome P450 (CYP) enzyme systems, highlighting their importance in metabolizing common psychotropics.² He explained phenotypic variability (eg, poor, intermediate, extensive, and ultrarapid metabolizers) and its implications for drug efficacy and adverse effects.

The discussion underscored how pharmacogenomic testing may help guide medication selection and dosing, particularly in cases of treatment resistance or unusual side effect profiles. Clinical implementation was addressed with caution. Miller noted that while pharmacogenomic testing can provide useful insights, it should not replace clinical judgment. Instead, results should be integrated with patient history, comorbidities, and concurrent medications. He also discussed limitations, including variability in test panels, incomplete evidence for some gene-drug pairs, and challenges in interpretation. As he stated, “we're looking at a very simplistic diagram of a eukaryotic cell,” underscoring that real-world biology and treatment response are far more complex than simplified models suggest.

Miller concluded by encouraging psychiatrists to develop a working knowledge of pharmacogenomics while maintaining a balanced perspective on its current utility. He emphasized that, although promising, pharmacogenomics remains an adjunctive tool rather than a definitive solution for optimizing psychiatric treatment.

Dr Miller is Medical Director, Brain Health, Exeter, New Hampshire; Editor in Chief, Psychiatric Times; Volunteer Consulting Psychiatrist, Seacoast Mental Health Center, Exeter; Consulting Psychiatrist, Insight Meditation Society, Barre, Massachusetts.

References

1. Pinto N, Dolan ME. Clinically relevant genetic variations in drug metabolizing enzymes. Curr Drug Metab. 2011;12(5):487-97.

2. Zhao M, Ma J, Li M, et al. Cytochrome P450 enzymes and drug metabolism in humans. Int J Mol Sci. 2021;22(23):12808.