PET Neuroimaging of [11C]Mirtazapine
Condition: Mental Disorders; Mood Disorders; Affective Disorders; Depressive Disorders
MeSH terms: Depressive Disorder; Mental Disorders; Mood Disorders
Study type: Interventional
Phase: Phase 4

Summary: 
      Recent studies show that 25 - 30% of depressed patients never fully recover, resulting in a
      treatment-resistant condition. Thus, depression is a major cause of human suffering. We are
      interested in finding new ways of identifying and alleviating treatment-resistant depression,
      and we believe that recent advances in brain imaging can contribute to achieving that goal.
      In this project, we will use a novel compound ([N-methyl-11C]mirtazapine) that we invented
      for examining the neurochemistry of brain receptors involved in antidepressant actions.

      Our compound, [N-methyl-11C]mirtazapine, is closely related to the clinically effective
      antidepressant drug mirtazapine (Remeron®). It labels several types of noradrenergic
      receptors that have often been implicated in "stress reactions" as well as depressive
      disorders. We believe that our compound can identify specific molecular brain dysfunctions
      that are causally related to treatment-resistant depression.

      The purpose of this study is to determine whether there is a reliable relationship between
      the level of mirtazapine in the bloodstream and the occupancy of neuroreceptors by
      mirtazapine in the brain. We will apply our standard procedures of PET brain scanning and
      region-of-interest data analysis, using healthy volunteers who will receive a daily dose of
      mirtazapine (double-blind design with placebo, 7.5 mg or 15 mg daily for 5 days). We believe
      that this project could provide a procedure for assessing brain function in
      treatment-resistant depression, with the aim of improving the guidelines for successful,
      evidence-based treatment of depression.
    

Detailed description: 
      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.
    

Intervention name(s): Mirtazapine
Intervention type(s): Drug
Intervention MeSH terms: Mirtazapine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Diagnostic
Keywords: Mirtazapine; Antidepressant; Positron Emission Tomography