Association between peripheral biomarkers and clinical response to IV ketamine for unipolar treatment-resistant depression: An open label study.
Melody J Y Kang, Gustavo Vazquez
Journal of Affective Disorders September 1, 2022 DOI: 10.1016/j.jad.2022.08.047 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label observational study Peer reviewed |
|---|---|
| Sample size | 15 |
| Population | Adults diagnosed with treatment-resistant unipolar major depression |
| Intervention | Ketamine |
| Dose | 0.5 mg/kg |
| Duration | Ten infusions over four weeks, with assessments at one and four weeks |
| Measures | MADRS, IL-6, IL-10, TNF-α, BDNF, irisin |
| Topics | Depression Esketamine Ketamine |
| Key findings | Repeated intravenous ketamine infusions significantly reduced depressive symptoms (MADRS) at all timepoints in 15 adults with treatment-resistant depression, with improvements significant at one week and continuing until two weeks, then maintained. Ketamine was generally well tolerated, and BDNF levels inversely correlated with symptom decreases, with higher baseline BDNF predicting mood response at one and four weeks. |
Abstract
Background: Major Depression is the leading cause of disability worldwide. A cohort of patients do not respond adequately to available antidepressants, leading to treatment-resistant depression (TRD). We evaluated the antidepressant efficacy of an acute intravenous ketamine treatment (0.5 mg/kg) for patients with unipolar TRD, and measured peripheral blood-based biomarkers associated with response to treatment.
Methods: Fifteen adults diagnosed with TRD completed an open-label study of ten infusions of subanesthetic ketamine over four weeks. Out of fifteen patients, blood was collected from eleven patients at three timepoints to analyze peripheral biomarkers in isolated plasma, including IL-6, IL-10, TNF-α, BDNF, and irisin. Irisin analysis was completed using an ELISA assay, and the remaining biomarkers were analyzed together simultaneously using a multiplex immunoassay.
Results: Repeated ketamine infusions produced a significant decrease in total average depressive symptoms (MADRS) at all timepoints. Improvements in depressive symptoms were significant at one-week, and continued to significantly decrease until two weeks, where it was maintained. Ketamine was generally well-tolerated, and we observed improvements in functional impairment, anhedonia, and psychiatric symptoms, with no increases in manic symptoms. Levels of BDNF throughout treatment inversely correlated to decreases in MADRS scores, and higher levels of baseline BDNF predicted mood responses at one- and four-weeks.
Limitations: The study was observational and uncontrolled, with a sample size of 15. Outpatients remained on their course of medications, unless they were pharmacological agents that have previously been identified to block ketamine's effects.
Conclusions: Ketamine may be an efficacious and safe pharmacological option for the acute treatment of patients suffering from severe TRD, and BDNF has the potential to function as a prognostic biomarker for predicting response to ketamine treatments.
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 |