[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 [11C]mirtazapine. Kinetic parameters of [11C]mirtazapine were determined from PET data in selected brain regions by the simplified reference tissue model.

RESULTS: Binding potentials of [11C]mirtazapine in cerebral cortical regions were lower in depressed nonresponders than in healthy controls. Removal rates of [11C]mirtazapine were higher in diencephalic regions of depressed nonresponders than in healthy controls.

CONCLUSIONS: PET neuroimaging with [11C]mirtazapine showed aberrant neuroreceptor binding in brain regions of depressed subjects who had failed to benefit from treatment with antidepressant drugs.