Synaptic potentiation and rapid antidepressant response to ketamine in treatment-resistant major depression: A replication study

Abstract

Preclinical and clinical evidence has demonstrated that ketamine has rapid antidepressant effects. Studies using pre-treatment with an AMPA inhibitor suggest that enhancing AMPA throughput is crucial to ketamine's effects, including increases in both basal and evoked gamma power. This study sought to replicate previous findings of increased gamma response to a somatosensory stimulus at 230 min and Day 1 in ketamine responders versus non-responders in 31 depressed subjects and 25 healthy controls. A significant difference in peak gamma power was seen in the depressed ketamine responders versus non-responders. These results implicate AMPA throughput in ketamine's mechanism of antidepressant action.

Trial registration: ClinicalTrials.gov NCT00088699.

Keywords: Depression; Ketamine; Magnetoencephalography (MEG).

Conflict of interest statement

Declaration of interest

All other authors have no conflict of interest to disclose, financial or otherwise.

Copyright © 2018. Published by Elsevier B.V.

Figures

Fig. 1.

A) Evoked gamma power response to a somatosensory stimulus delivered to the hand at t = 0 s. Evoked responses are shown separately for healthy control subjects (HCs), subjects with major depressive disorder (MDD) who did not respond to ketamine infusion (MDD-NR), and subjects with MDD who showed an at least 50% reduction in their Montgomery–Asberg Depression Rating Scale (MADRS) scores at Day 1 post-ketamine infusion (MDD-R). B) The left sensorimotor cortex region of interest (ROI) defined at the time point where the evoked response averaged over all subjects and sessions was maximal (image in radiologic orientation). C) Scatter plot showing the difference in peak gamma power between the ketamine and placebo sessions, plotted versus percent change in MADRS score, parametrized such that a negative percentage indicates a reduction in depressive symptoms.