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

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Abstract

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.

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Acknowledgments

We thank the Danish Medical Research Council, A.P. Møller Foundation for the Advancement of Medical Science, and Max and Inger Woerzner Foundation for financial support and everyone at the PET Center of Aarhus University Hospital for providing a positive research environment.

Authors’ contributions

All authors participated in producing the final written report. D.F.S. designed and performed all experiments, analyzed the data, and wrote the first draft of the manuscript. B.S.S., G.W., and M.A. examined subjects, injected radioligand, and performed clinical duties related to safety and health of volunteers. S.J., D.B., H.A., and K.H.V. produced the radioligand in accordance with quality control requirements. S.B.H. was responsible for technical equipment and data registration. P.V. and R.R. assisted in designing experiments and were responsible for clinical issues as required by the Danish Medicines Agency and the local ethical committee.

Competing interests

The authors declare that they have no competing financial interests related to this report.

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Authors and Affiliations

  1. Center for Psychiatric Research, Psychiatric Hospital of Aarhus University, Risskov, 8240, Denmark

    Donald F. Smith, Bo S. Stork, Gregers Wegener, Poul Videbech & Raben Rosenberg

  2. PET Center, Aarhus University Hospital, 8000, Aarhus, Denmark

    Steen Jakobsen, Dirk Bender, Hélène Audrain, Karina H. Vase & Søren B. Hansen

  3. Neuropsychiatric Clinic, Psychiatric Hospital of Aarhus University, Risskov, 8240, Denmark

    Mahmoud Ashkanian

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  1. Donald F. Smith
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Correspondence to Donald F. Smith.

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Smith, D.F., Stork, B.S., Wegener, G. et al. [11C]Mirtazapine binding in depressed antidepressant nonresponders studied by PET neuroimaging. Psychopharmacology 206, 133–140 (2009). https://doi.org/10.1007/s00213-009-1587-3

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  • DOI: https://doi.org/10.1007/s00213-009-1587-3

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