Background
Major depressive disorder (MDD) is a high risk factor for suicide, with up to 20% of MDD patients attempting suicide during their lifetime. Current treatments for MDD are slow onset of action, low efficiency, and the inability to control suicidal behaviors quickly and effectively. Intravenous ketamine has been shown to have a rapid but transient antidepressant effect, but there is still lack evidence on the efficacy and safety of intravenous esketamine in reducing suicidal ideation and depressive symptoms in MDD patients with suicidal ideation. We designed a study to investigate the effect of short-term repeated intravenous infusion of esketamine three times in MDD patients with suicidal ideation.
Methods
This study features a randomized, double-blind, placebo-controlled trial (RCT) comparing short-term repeated intravenous infusions of esketamine with placebo as a supplement to conventional antidepressants with an intervention period of 6 days and one infusion every other day, followed by 4 weeks of follow-up. These methods support the examination of the efficacy, safety, tolerability, and mechanism of action of short-term repeated intravenous infusions of esketamine in MDD patients with suicidal ideation.
Discussion
This is the first RCT to explore the efficacy and safety of short-term repeated infusion of esketamine on suicidal ideation and depressive symptoms in MDD patients with suicidal ideation. If proven effective and tolerated, it will provide evidence for rapid and effective treatment of suicidal ideation and depressive symptoms in MDD individuals with suicidal ideation.
Trial registration
Chinese Clinical Trial Register, ChiCTR2000041232. Registered 22 December 2020.
Accumulating evidence indicates the presence of structural and functional abnormalities of the posterior cingulate cortex (PCC) in patients with major depressive disorder (MDD) with suicidal ideation (SI). Nevertheless, the subregional-level dynamic functional connectivity (dFC) of the PCC has not been investigated in MDD with SI. We therefore sought to investigate the presence of aberrant dFC variability in PCC subregions in MDD patients with SI. We analyzed resting-state functional magnetic resonance imaging (fMRI) data from 31 unmedicated MDD patients with SI (SI group), 56 unmedicated MDD patients without SI (NSI group), and 48 matched healthy control (HC) subjects. The sliding-window method was applied to characterize the whole-brain dFC of each PCC subregion [the ventral PCC (vPCC) and dorsal PCC (dPCC)]. In addition, we evaluated associations between clinical variables and the aberrant dFC variability of those brain regions showing significant between-group differences. Compared with HCS, the SI and the NSI groups exhibited higher dFC variability between the left dPCC and left fusiform gyrus and between the right vPCC and left inferior frontal gyrus (IFG). The SI group showed higher dFC variability between the left vPCC and left IFG than the NSI group. Furthermore, the dFC variability between the left vPCC and left IFG was positively correlated with Scale for Suicidal Ideation (SSI) score in patients with MDD (i.e., the SI and NSI groups). Our results indicate that aberrant dFC variability between the vPCC and IFG might provide a neural-network explanation for SI and may provide a potential target for future therapeutic interventions in MDD patients with SI.
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