[11C]Mirtazapine binding in depressed antidepressant nonresponders studied by PET neuroimaging

Rationale Lack of benefit from antidepressant drug therapy is a major source of human suffering, affecting at least 25% of people with major depressive disorder. We want to know whether nonresponse to antidepressants can be linked to aberrant neuroreceptor binding. Objective This study aims to assess the antidepressant binding in brain regions of depressed nonresponders compared with healthy controls. Materials and methods Healthy volunteers and depressed subjects who had failed to benefit from at least 2 antidepressant treatments were recruited by newspaper advertisements. All subjects had received no antidepressant medication for at least 2 months before positron emission tomography (PET) that was carried out with [ 11 C]mirtazapine. Kinetic parameters of [ 11 C]mirtazapine were determined from PET data in selected brain regions by the simplified reference tissue model. Results Binding potentials of [ 11 C]mirtazapine in cerebral cortical regions were lower in depressed nonresponders than in healthy controls. Removal rates of [ 11 C]mirtazapine were higher in diencephalic regions of depressed nonresponders than in healthy controls. Conclusions PET neuroimaging with [ 11 C]mirtazapine showed aberrant neuroreceptor binding in brain regions of depressed subjects who had failed to benefit from treatment with antidepressant drugs.