Neural correlates of change in major depressive disorder anhedonia following open-label ketamine
Níall Lally, Allison C. Nugent, David A. Luckenbaugh, Mark J. Niciu, Jonathan P. Roiser, Carlos A. Zarate
Journal of Psychopharmacology February 17, 2015 DOI: 10.1177/0269881114568041 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label investigation with exploratory re-analysis Peer reviewed |
|---|---|
| Population | Medication-free treatment-refractory patients with major depressive disorder |
| Interventions | Ketamine Riluzole Placebo |
| Duration | Up to three days post-infusion |
| Topics | Depression Ketamine Esketamine |
| Keywords | Anhedonia Anterior cingulate cortex Orbitofrontal cortex Hypomania Hippocampus Placebo Antidepressant Anesthesia Riluzole Prefrontal cortex Schizophrenia object-oriented programming Bipolar disorder Glutamate receptor Lithium medication Pathology Cognition |
| Citations | 224 |
| Key points | Anhedonia rapidly decreased following a single ketamine infusion, sustained for up to three days, and correlated with changes in brain glucose metabolism in the hippocampus, dorsal anterior cingulate cortex, and orbitofrontal cortex. |
Abstract
Anhedonia is a cardinal symptom of major depression and is often refractory to standard treatment, yet no approved medication for this specific symptom exists. In this exploratory re-analysis, we assessed whether administration of rapid-acting antidepressant ketamine was associated specifically with reduced anhedonia in medication-free treatment-refractory patients with major depressive disorder in an open-label investigation. Additionally, participants received either oral riluzole or placebo daily beginning 4 hours post-infusion. A subgroup of patients underwent fluorodeoxyglucose positron emission tomography scans at baseline (1-3 days pre-infusion) and 2 hours post-ketamine infusion. Anhedonia rapidly decreased following a single ketamine infusion; this was sustained for up to three days, but was not altered by riluzole. Reduced anhedonia correlated with increased glucose metabolism in the hippocampus and dorsal anterior cingulate cortex (dACC) and decreased metabolism in the inferior frontal gyrus and orbitofrontal cortex (OFC). The tentative relationship between change in anhedonia and glucose metabolism remained significant in dACC and OFC, and at trend level in the hippocampus, a result not anticipated, when controlling for change in total depression score. Results, however, remain tenuous due to the lack of a placebo control for ketamine. In addition to alleviating overall depressive symptoms, ketamine could possess anti-anhedonic potential in major depressive disorder, which speculatively, may be mediated by alterations in metabolic activity in the hippocampus, dACC and OFC.
Comparable studies
Other non-randomized and open-label trials on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Rapid Resolution of Suicidal Ideation After a Single Infusion of anN-Methyl-D-Aspartate Antagonist in Patients With Treatment-Resistant Major Depressive Disorder Subjects with DSM-IV-diagnosed treatment-resistant major depressive disorder | 2010 | Open-label trial | n = 33 |
| Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression Adults (≥ 18 years) with treatment-resistant depression | 2020 | Phase 3, open-label, multicenter, long-term study | n = 802 |
| Intravenous arketamine for treatment-resistant depression: open-label pilot study Humans with treatment-resistant depression | 2020 | Open-label pilot trial | n = 7 |
| A Phase 2 Open Label Study of Efficacy, Safety, and Tolerability of SLS-002 (Intranasal Racemic Ketamine) in Adults with MDD at Imminent Risk of Suicide. Hospitalized patients with Major Depressive Disorder and acute suicidal ideation and... | 2024 | Open label study | n = 17 |
| Ketamine Safety and Tolerability in Clinical Trials for Treatment-Resistant Depression Participants with DSM-IV-defined major depressive disorder and treatment-resistant... | 2014 | Pooled analysis of three clinical trials | n = 97 |