Ketamine Has Distinct Electrophysiological and Behavioral Effects in Depressed and Healthy Subjects
Allison C. Nugent, Elizabeth D. Ballard, T. Gould, Lawrence T. Park, Ruin Moaddel, Nancy E. Brutsché, Carlos A. Zarate
Molecular Psychiatry February 27, 2018 DOI: 10.1038/s41380-018-0028-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Sample size | 60 |
| Population | Unmedicated subjects with major depressive disorder and healthy controls |
| Intervention | Ketamine |
| Dose | 0.5 mg/kg |
| Topics | Esketamine Ketamine |
| Citations | 254 |
| Key findings | Baseline gamma power moderates the relationship between post-ketamine gamma power and antidepressant response, with opposite associations in MDD subjects depending on their baseline gamma level. |
Abstract
Ketamine’s mechanism of action was assessed using gamma power from magnetoencephalography (MEG) as a proxy measure for homeostatic balance in 35 unmedicated subjects with major depressive disorder (MDD) and 25 healthy controls enrolled in a double-blind, placebo-controlled, randomized cross-over trial of 0.5 mg/kg ketamine. MDD subjects showed significant improvements in depressive symptoms, and healthy control subjects exhibited modest but significant increases in depressive symptoms for up to 1 day after ketamine administration. Both groups showed increased resting gamma power following ketamine. In MDD subjects, gamma power was not associated with the magnitude of the antidepressant effect. However, baseline gamma power was found to moderate the relationship between post-ketamine gamma power and antidepressant response; specifically, higher post-ketamine gamma power was associated with better response in MDD subjects with lower baseline gamma, with an inverted relationship in MDD subjects with higher baseline gamma. This relationship was observed in multiple regions involved in networks hypothesized to be involved in the pathophysiology of MDD. This finding suggests biological subtypes based on the direction of homeostatic dysregulation and has important implications for inferring ketamine’s mechanism of action from studies of healthy controls alone.
Comparable studies
Other randomized controlled trials on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Healthy human subjects recruited from the community | 1994 | Randomized controlled trial | n = 19 |
| 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 |
| Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine Patients undergoing major abdominal surgery | 2005 | Randomized controlled trial | n = 75 |
| Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder Patients with chronic PTSD related to a range of trauma exposures | 2014 | Randomized controlled trial | n = 41 |
| Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers Healthy volunteers | 2000 | Single-blind placebo-controlled study | n = 20 |
Citations in the library
Cited by 109
- Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective Psychiatry and Clinical Neurosciences June 19, 2019
- Blinding and expectancy confounds in psychedelic randomized controlled trials Expert Review of Clinical Pharmacology May 26, 2021
- Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor Molecular Psychiatry May 7, 2021
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
- Molecular and cellular mechanisms underlying the antidepressant effects of ketamine enantiomers and its metabolites Translational Psychiatry November 7, 2019
and 104 more in the library
Cites 20
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
and 15 more in the library