Receptor Occupancy Determined by PET Neuroimaging of [11C]Mirtazapine in Healthy Humans

This project uses a double-blind, placebo-controlled, parallel-group design to determine whether there is a reliable relationship between the level of the antidepressant drug mirtazapine in the bloodstream and the degree of occupancy of neuroreceptors in the brain of healthy human volunteers. The primary data endpoints of the study will be the binding potential of C-11 labelled racemic mirtazapine in the brain under baseline conditions and after 5 days of ingestion of either a placebo tablet or a table containing 7.5 mg or 15 mg of mirtazapine. The degree of receptor occupancy obtained during each experimental condition will be calculated on the basis of the binding potentials in brain regions using data obtained by positron emission tomography (PET scanning). Blood samples will be obtained at the time of PET scanning in order to determine whether there is a reliable correlation between the concentration of mirtazapine in the bloodstream and the degree of receptor occupancy achieved in brain. The study plans to include 24 healthy volunteers with 8 subjects in each of the three groups (placebo, 7.5 mg mirtazapine, and 15 mg mirtazapine). Subjects will be randomized into groups in such a way that each of the three treatments will be used for each of three consecutive subjects that enter the study. This procedure will reduce the possibility that differences in procedures that might occur over time will introduce bias into the results. Radiosynthesis of (C-11)mirtazapine will occur by the authorized and documented procedures currently established at the PET Center of Aarhus University Hospital.