Tools for optimising pharmacotherapy in psychiatry (therapeutic drug monitoring, molecular brain imaging and pharmacogenetic tests): focus on antidepressants

Abstract

Objectives: More than 40 drugs are available to treat affective disorders. Individual selection of the optimal drug and dose is required to attain the highest possible efficacy and acceptable tolerability for every patient. Methods: This review, which includes more than 500 articles selected by 30 experts, combines relevant knowledge on studies investigating the pharmacokinetics, pharmacodynamics and pharmacogenetics of 33 antidepressant drugs and of 4 drugs approved for augmentation in cases of insufficient response to antidepressant monotherapy. Such studies typically measure drug concentrations in blood (i.e. therapeutic drug monitoring) and genotype relevant genetic polymorphisms of enzymes, transporters or receptors involved in drug metabolism or mechanism of action. Imaging studies, primarily positron emission tomography that relates drug concentrations in blood and radioligand binding, are considered to quantify target structure occupancy by the antidepressant drugs in vivo. Results: Evidence is given that in vivo imaging, therapeutic drug monitoring and genotyping and/or phenotyping of drug metabolising enzymes should be an integral part in the development of any new antidepressant drug. Conclusions: To guide antidepressant drug therapy in everyday practice, there are multiple indications such as uncertain adherence, polypharmacy, nonresponse and/or adverse reactions under therapeutically recommended doses, where therapeutic drug monitoring and cytochrome P450 genotyping and/or phenotyping should be applied as valid tools of precision medicine.

Therapeutic Reference Ranges for Psychotropic Drugs: A Protocol for Systematic Reviews

“…Lower and upper limit of a reference range, respectively, should derive from well-designed clinical studies that relate measured drug concentrations to treatment response or specific adverse drug reactions. For many psychotropic drugs relationships between target engagement (TE) and drug blood concentrations on the one hand and clinical effects and side effects on the other hand are well-documented (2)(3)(4). TE by the respective drug (usually occupancy of neuroreceptors or transporters) can be quantified using molecular neuroimaging techniques like positron emission tomography (PET) and single photon emission computed tomography (SPECT).…”

Are higher antidepressant plasma concentrations associated with fall risk in older antidepressant users?

“…However, older adults are more at risk for adverse events due to altered pharmacokinetics and—dynamics [ 25 ]. TDM for TCAs is well-established in clinical practice, both for therapeutic effect and toxicity [ 26 – 29 ]. For SSRIs, the clinical use of TDM is less frequently employed, especially in older adults [ 30 ].…”

Phenotyping Indices of CYP450 and P-Glycoprotein in Human Volunteers and in Patients Treated with Painkillers or Psychotropic Drugs

“…The phenotypic assessment of metabolic pathways has demonstrated its clinical value [ 25 , 32 , 33 ]. Although it is challenging to make a direct comparison between phenotyping and genotyping regarding clinical outcomes, the high phenoconversion rate [ 34 ] leads us to assert that the phenotypic evaluation of CYP and P-gp activity is a more effective tool than genotyping for personalized medicine [ 35 ]. An extensive literature review allowed us to establish tolerance ranges in order to define phenotypic indices for the drugs used in the Geneva cocktail in clinical practice, and it revealed a greater variability of phenotypic indices in our patients.…”