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Ketamine-induced changes in resting state connectivity, 2 h after the drug administration in patients with remitted depression.

Matthew Burrows, Vasileia Kotoula, Ottavia Dipasquale, Argyris Stringaris, Mitul A. Mehta

Journal of Psychopharmacology August 2023 DOI: 10.1177/02698811231189432 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Double-blind, placebo-controlled study Peer reviewed
Sample size 35
Population Volunteers with remitted depression (21 females, mean age 28.5 years)
Interventions Ketamine saline
Dose 0.5 mg/kg
Topics Depression Ketamine Esketamine
Keywords Neuroimaging Resting state connectivity
Key points About 2 hours after ketamine infusion, connectivity between the subgenual anterior cingulate cortex and the amygdala was decreased compared with placebo, and the executive network showed altered connectivity with cortical and subcortical regions, including decreased connectivity of the left hippocampus and right amygdala within the network. The authors propose that these changes may reflect ketamine's effects on brain areas important for cognitive processing and emotional regulation and could indirectly indicate drug-induced plasticity.

Abstract

Resting state connectivity studies link ketamine's antidepressant effects with normalisation of the brain connectivity changes that are observed in depression. These changes, however, usually co-occur with improvement in depressive symptoms, making it difficult to attribute these changes to ketamine's effects per se. Our aim is to examine the effects of ketamine in brain connectivity, 2 h after its administration in a cohort of volunteers with remitted depression. Any significant changes observed in this study could provide insight of ketamine's antidepressant mechanism as they are not accompanied by symptom changes. In total, 35 participants with remitted depression (21 females, mean age = 28.5 years) participated in a double-blind, placebo-controlled study of ketamine (0.5 mg/kg) or saline. Resting state scans were acquired approximately 2 h after the ketamine infusion. Brain connectivity was examined using a seed-based approach (ventral striatum, amygdala, hippocampus, posterior cingulate cortex and subgenual anterior cingulate cortex (sgACC)) and a brain network analysis (independent component analysis). Decreased connectivity between the sgACC and the amygdala was observed approximately 2 h after the ketamine infusion, compared to placebo (pFWE < 0.05). The executive network presented with altered connectivity with different cortical and subcortical regions. Within the network, the left hippocampus and right amygdala had decreased connectivity (pFWE < 0.05). Our findings support a model whereby ketamine would change the connectivity of brain areas and networks that are important for cognitive processing and emotional regulation. These changes could also be an indirect indicator of the plasticity changes induced by the drug.

Comparable studies

Other randomized controlled trials on ketamine for depression, most cited first.

Study Year Design Participants
Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode 2013 Randomized controlled trial n = 73
Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study Adults with moderate to severe nonpsychotic depression and a history of nonresponse to... 2019 Phase 3, double-blind, active-controlled, multicenter randomized controlled trial n = 227
Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression Adults with treatment-resistant depression who achieved stable remission or stable... 2019 Phase 3, multicenter, double-blind, randomized withdrawal study n = 297
Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression Adults with DSM-IV-TR diagnosis of major depressive disorder and history of inadequate... 2017 Phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study n = 67
Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study Depressed patients at imminent risk for suicide 2018 Randomized controlled trial n = 68

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