Change in neurocognitive functioning in patients with treatment-resistant depression with serial intravenous ketamine infusions: The Bio-K multicenter trial.
Balwinder Singh, Sagar V Parikh, Jennifer L. Vande Voort, Vanessa K Pazdernik, Eric D Achtyes, Fernando S Goes, Anastasia K Yocum, Louis J Nykamp, Alexis Becerra, LeAnn Smart, John F Greden, William V Bobo, Mark A Frye, Katherine E Burdick, Kelly A Ryan
Psychiatry Research May 1, 2024 DOI: 10.1016/j.psychres.2024.115829 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Nonrandomized, multicenter, open-label clinical trial Peer reviewed |
|---|---|
| Sample size | 74 |
| Population | Adults with treatment-resistant depression |
| Intervention | Intravenous ketamine |
| Duration | Acute phase (three infusions) and continuation phase (four additional infusions for remitters) |
| Topics | Depression Ketamine Esketamine |
| Keywords | Neurocognition Open-label study Rbans Ketamine infusion Mental performance Treatment-resistant depression trd Refractory depression Medical |
| Citations | 18 |
| Registration | NCT03156504 |
| Key findings | Serial intravenous ketamine infusions were associated with cognitive improvement, not deterioration, in adults with treatment-resistant depression, with a 53% remission rate after the acute phase. |
Abstract
This nonrandomized, multicenter, open-label clinical trial explored the impact of intravenous (IV) ketamine on cognitive function in adults (n = 74) with treatment-resistant depression (TRD). Patients received three IV ketamine infusions during the acute phase and, if remitted, four additional infusions in the continuation phase (Mayo site). Cognitive assessments using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were conducted at baseline, end of the acute phase, and end of the continuation phase (Mayo site). Results showed a significant 53 % (39/74) remission rate in depression symptoms after the acute phase. In adjusted models, baseline language domain score was associated with a higher odd of remission (Odds Ratio, 1.09, 95 % CI = 1.03-1.17, p = 0.004) and greater improvement in MADRS at the end of the acute phase (β =-0.97; 95 % CI, -1.74 to -0.20; P = 0.02). The likelihood of remission was not significantly associated with baseline immediate or delayed memory, visuospatial/constructional, or attention scores. In the continuation phase, improvements in immediate and delayed memory and attention persisted, with additional gains in visuospatial and language domains. Limitations included an open-label design, potential practice effects, and ongoing psychotropic medication use. Overall, the study suggests cognitive improvement, not deterioration, associated with serial IV ketamine administrations for TRD. These findings encourage future studies with larger sample sizes and longer follow-up periods to examine any potential for deleterious effect with recurrent ketamine use for TRD. Trial Registration: ClinicalTrials.gov: NCT03156504.
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 |