Positron emission tomography for optimizing psychiatric drug treatment: present and future

Imaging techniques, particularly molecular imaging, have contributed significantly to understanding the relationships between target engagement by psychotropic drugs on the one hand and clinical effects and side effects on the other. Especially for antipsychotics, positron emission tomography (PET) studies of target engagement belong to the standard development program of new drugs.

Examples from the fields of antidepressants and antipsychotics will be discussed that illustrate the relationships between receptor (or transporter) occupancy and plasma levels of prototypic drugs from these classes. These relationships are described for each substance by a compound-specific graph. Once this relationship has been determined experimentally, the measurement of a single blood level is sufficient to determine the occupancy of the molecular target with high accuracy.

By relating the "therapeutic window" determined with the help of PET to the associated plasma levels of the respective drug, the method becomes an excellent tool for establishing therapeutic reference ranges for TDM. This will be illustrated for prototypic antipsychotics (e.g., aripiprazole, olanzapine, risperidone). With examples from the group of antidepressants, it will be shown, however, that for targets such as the serotonin and the noradrenaline transporter the relationships are less clear. New drug classes that do not work on the classic monoaminergic targets represent further future challenges for the field. Likewise, drugs that are not administered on a regular basis, specifically psychedelics, will need new methodological approaches to exploit the potential of the method.

Molecular imaging represents a unique method to study not only the mechanisms of action of psychotropic drugs but also to guide routine therapy.

Publication History

Article published online:
12 March 2024