Personalized prescribing: a new medical model for clinical implementation of psychotropic drugs

Abstract

The use of pharmacogenetic tests was already being proposed in psychiatry in the early 2000s because genetic factors were known to influence drug pharmacokinetics and pharmacodynamics. However, sufficient levels of evidence to justify routine use have been achieved for only a few tests (eg, major histocompatibility complex, class I, B, allele 1502 [HLA-B*1502] for carbamazepine in epilepsy and bipolar disorders); many findings are too preliminary or, when replicated, of low clinical relevance because of a small effect size. Although drug selection and dose adaptation according to cytochrome P450 genotypes are sound, a large number of patients need to be genotyped in order to prevent one case of severe side effect and/or nonresponse. The decrease in cost for genetic analysis shifts the cost: benefit ratio toward increasing use of pharmacogenetic tests. However, they have to be combined with careful clinical evaluations and other tools (eg, therapeutic drug monitoring and phenotyping) to contribute to the general aim of providing the best care for psychiatric patients.

Enhancing the role played by clinical pharmacists in psychiatric settings to better integrate clinical psychopharmacology into the decision-making process

“…Our network of expertise also promotes the use of TDM among prescribers as an objective means of contributing to the decision-making process in psychopharmacotherapy ( [20,21,32,36] and Table 1). This integration of TDM is in line with the recommendations proposed by the TDM task force of the "Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie" (AGNP) [46,47]) and the extensive experience developed in this area within the pharmacogenetics and clinical psychopharmacology unit of the Vaud university hospital [48].…”

Effects of Pharmacokinetic Gene Variation on Therapeutic Drug Levels and Antidepressant Treatment Response

“…However, it is not clear if results emerging from RCTs with commercial kits are relevant for clinical settings; for example, due to restrictions in inclusion criteria and therapy protocols 3 13 and even more so, which genes are relevant. Applying PGx in clinical routine has begun only recently as there are several limitations that complicate the understanding of how and when using PGx in a clinical setting 6 7 14 . Limitations include the lack of a clear relationship between serum concentration and efficacy for some drugs, polypharmacy, high prevalence of comorbidities, overlapping phenotypes, the lack of guidelines on how to use pharmacogenetic information and the polygenic architecture of the response on antidepressants 1 3 6 7 14 15 .…”

“…Applying PGx in clinical routine has begun only recently as there are several limitations that complicate the understanding of how and when using PGx in a clinical setting 6 7 14 . Limitations include the lack of a clear relationship between serum concentration and efficacy for some drugs, polypharmacy, high prevalence of comorbidities, overlapping phenotypes, the lack of guidelines on how to use pharmacogenetic information and the polygenic architecture of the response on antidepressants 1 3 6 7 14 15 . The Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group have published peer-reviewed, evidence-based pharmacogenetic guidelines for CYP2D6 and CYP2C19 genotypes and dosing, in particular for tricyclic antidepressants and selective serotonin reuptake inhibitors 16 17 18 19 .…”

Exploratory focused pharmacogenetic testing reveals novel markers associated with risperidone pharmacokinetics in Saudi children with autism

“…Additionally, the few previous studies ( Nuntamool et al, 2017 ; Rafaniello et al, 2017 ) that attempted to examine a limited number of other typical candidate pharmacogenetic (PGx) markers in RIS ADME ( ABCB1 , ABCG2 , CYP3A4 , DRD2 , DRD3 , and HTR2A ) did not have a large enough sample size to make robust conclusions about a panel of genes or their variants or SNPs that should be included for individualized RIS therapy in ASD patients. Given the currently available conflicting data originating from candidate gene association study methods, “actionable” PGx markers related to antipsychotic dosing and selection, in general and with respect to different psychiatric conditions, have a limited application in routine clinical practice, even in developing countries, due to imperfect guidelines for interpretation and implementation ( Eap, 2016 ; Eum et al, 2022 ).…”