PET imaging for guiding definition of therapeutic reference ranges – new drugs, new guidelines

Positron emission tomography (PET) is now an established tool for assessment of target engagement (TE) of new psychotropic drugs. The relationship between occupancy of a molecular target, drug serum concentrations and clinical efficacy has been documented for many antipsychotics and some but not all antidepressants. This presentation illustrates how PET studies help to establish therapeutic reference ranges for some of the newer psychotropics that have recently reached the market, i.e. lurasidone, nalmefene and vortioxetine. Furthermore, the imaging part of the new World Federation of Societies of Biological Psychiatry (WFSBP) guideline entitled "Tools for Optimising Pharmacotherapy in Psychiatry", which focuses on the class of antidepressants, will be briefly presented. This guideline documents the current knowledge about relationships between antagonism of brain monoamine transporters exerted by antidepressants, the associated serum concentrations and their clinical efficacy. However, while such relationships seem to be well established for (selective) serotonin reuptake inhibitors, TE studies for some other compounds that do not act by blocking the serotonin transporter – such as noradrenaline reuptake inhibitors – obviate the need for further research on and a better understanding of the mechanism of action of psychotropic drugs, which is a prerequisite for rationale therapeutic drug monitoring.