The emergence, implementation, and future growth of pharmacogenomics in psychiatry: a narrative review

Abstract

Psychotropic medication efficacy and tolerability are critical treatment issues faced by individuals with psychiatric disorders and their healthcare providers. For some people, it can take months to years of a trial-and-error process to identify a medication with the ideal efficacy and tolerability profile. Current strategies (e.g. clinical practice guidelines, treatment algorithms) for addressing this issue can be useful at the population level, but often fall short at the individual level. This is, in part, attributed to interindividual variation in genes that are involved in pharmacokinetic (i.e. absorption, distribution, metabolism, elimination) and pharmacodynamic (e.g. receptors, signaling pathways) processes that in large part, determine whether a medication will be efficacious or tolerable. A precision prescribing strategy know as pharmacogenomics (PGx) assesses these genomic variations, and uses it to inform selection and dosing of certain psychotropic medications. In this review, we describe the path that led to the emergence of PGx in psychiatry, the current evidence base and implementation status of PGx in the psychiatric clinic, and finally, the future growth potential of precision psychiatry via the convergence of the PGx-guided strategy with emerging technologies and approaches (i.e. pharmacoepigenomics, pharmacomicrobiomics, pharmacotranscriptomics, pharmacoproteomics, pharmacometabolomics) to personalize treatment of psychiatric disorders.

Keywords: antidepressants; antipsychotics; implementation; mental health; pharmacogenomics; precision medicine; psychiatry; psychopharmacology; psychotropics.

Figure 1.

Major events in the emergence of pharmacogenomics in psychiatry. AMP, Association of Molecular Pathology; CPIC, Clinical Pharmacogenetics Implementation Consortium; CPNDS, Canadian Pharmacogenomics Network for Drug Safety; DPWG, Dutch Pharmacogenetics Working Group; FDA, Food and Drug Administration; ISPG, International Society of Psychiatric Genetics; PGRN, Pharmacogenomics Global Research Network; PGx, pharmacogenomic; PharmGKB, Pharmacogenomics Knowledge Base; PharmVar, Pharmacogene Variation Consortium.

Figure 2.

Conceptual model of precision psychotropic prescribing decision support in the future. PK, pharmacokinetic; PD, pharmacodynamic. Adapted from Maruf and Bousman (2021).