Using pharmacokinetics and pharmacogenetics to optimize psychiatric treatments: A systematic review

Neuropsychiatrists often resort to drugs with broad interindividual pharmacokinetic variability metabolized by highly polymorphic enzymes such as CYP2D6 and CYP2C19. Pharmacokinetics and  pharmacogenetics offer considerable promise as techniques capable to allow individualized adjustments in treatments with psychoactive drugs. The  purpose of this study was to review the existing evidence for the application of  pharmacokinetics and pharmacodynamics to the dosing of drugs used in  neuropsychiatry.

A literature search was conducted in PubMed and Embase to find  prospective studies published between January 2000 and April 2021 that used  determination of psychotropic drug plasma levels or genotyping to improve  response to treatment or minimize adverse events in adult patients with  psychiatric conditions. MeSH terms and free search terms were used. Each  article was reviewed by two independent reviewers to ensure that they met the  inclusion criteria. A quantitative method was established to assess the  quality of the articles selected. Results: A total of 27 articles met the inclusion  criteria of which 16  used pharmacokinetic and 11 pharmacogenetic techniques.  Fifty percent of pharmacokinetic studies met the five predefined quality criteria. Eight of the 16  papers were on antidepressants; the remainder were on antipsychotics. Two of the latter did not find an association with efficacy or safety. None of the  pharmacogenetic studies met the five quality criteria. Only one of the two  studies on antipsychotics found fewer adverse events with genetics-guided  dosing in patients on CYP2D6 substrate antipsychotics. Six of the nine studies  on antidepressants found that pharmacogeneticsbased dosing improved  efficacy.

The evidence available on pharmacokinetics and  harmacodynamics- based personalization of treatment with psychoactive drugs  is scarce. Many existing studies analyze associations between genotypes and response or toxicity but provide few data on the efficacy of  treatment individualization. The results obtained suggest the existence of  significant differences in pharmacokinetic parameters between responding and  nonresponding patients, particularly in the treatment of depression. Given that  the availability of pharmacogenetic information may be useful at the beginning  of treatment, combining both techniques could help optimize pharmacotherapy.  However, clinical trials are needed to establish  their benefits with greater accuracy.