Secondary Research Project: Monoamine Transporter Occupancy

Emory University, Atlanta GA

Investigators

Linked publications & trials

Abstract

Until now, determining whether patients were receiving an adequate dose of a given antidepressant[unreadable] medication was based almost exclusively upon the experience of the prescribing physician. Recently in[unreadable] vivo imaging technology with PET (positron emission tomography) and SPECT (single photon emission[unreadable] computed tomography) are emerging as new tools for assessment and optimization of pharmacological[unreadable] treatment (e.g. monitor adequacy of dosing), psychiatric medication development, and basic[unreadable] understanding of the pathophysiology of psychiatric illness. However, these techniques are associated[unreadable] with limited availability and significant financial costs that preclude the availability of this technology to the[unreadable] vast majority of clinicians. The goal of this project is to provide a valid and simpler alternative (an assay[unreadable] using a human blood sample) to PET imaging to furnish similar in vivo molecular site occupancy data.[unreadable] Briefly, it now appears that most SSRI antidepressants block approximately 80% of their target serotonin transporters[unreadable] (SERT) at standard clinical doses. This data suggests that appropriate clinical dosing might best be[unreadable] determined by assessing brain SERT occupancy. We have developed a unique method in which we are[unreadable] able to measure the magnitude of 5-HT, NE or dopamine (DA) transporter occupancy in antidepressanttreated[unreadable] patients by exposing cells transfected with the human SERT, NET or DAT to the patients' serum[unreadable] after steady-state is attained. Following validation of this technique using concomitant PET imaging we will determine what magnitude of serotonin and/or norepinephrine uptake blockade is required for an optimal treatment response.[unreadable] Simply stated, if a patient has not responded to a standard dose of an SSRI or SNRI, is it because they[unreadable] have not yet achieved a substantial occupancy of the SERT and/or norepinephrine (NET) transporter?[unreadable] These data may be extremely valuable in monitoring patient compliance, the need for dosage adjustment[unreadable] and, in the case of adequate occupancy without therapeutic response, information that provides a[unreadable] rational decision to switch medication class or initiate other treatment options.