Ketamine Treatment Effects on Synaptic Plasticity in Depression
Status:
Recruiting
Trial end date:
2022-03-01
Target enrollment:
Participant gender:
Summary
Depression is the leading cause of disability globally (1, 2). One-third to one-half of
patients suffering from major depressive disorder (MDD) do not achieve remission even after
multiple antidepressant trials (3). Ketamine is a commonly-used FDA-approved anesthetic
medication that at subanesthetic doses leads to rapid antidepressant and anti-suicidal
ideation effects in hours, rather than weeks, following administration. Despite these
promising findings, a key limitation of ketamine treatment is that it only yields an
antidepressant response in approximately 50% of those treated. The goal of this project is to
A) elucidate ketamine's mechanism of action and B) identify biomarkers predicting treatment
outcome to ketamine which could be used to match patients to treatment based on the
likelihood of effectiveness at the individual level. Data from animal models suggests that
ketamine acts by enhancing the connections between neurons through a process known as
synaptic plasticity (4-7), and that these biological changes are responsible for the
sustained behavioral effects of ketamine (8). A newly available tool allows us to image the
density of these synaptic connections in the living brain using PET (positron emission
tomography) imaging with a radiotracer called [11C]UCB-J, which is a marker of synaptic
density. We propose to directly quantify synaptic density in depressed patients before and
after a course of ketamine, to examine changes in density following treatment. In exploratory
analyses, we will examine synaptic density as a mediator of the sustained antidepressant
effects of ketamine and as a predictor of treatment outcome. To study these questions, we
will quantify synaptic density using PET imaging before and after a course of 4 sequential
intravenous infusions of ketamine administered over a two week period. Study participation
involves an inpatient stay of approximately three weeks at the New York State Psychiatric
Institute at no cost.