Symptomatology and predictors of antidepressant efficacy in extended responders to a single ketamine infusion.
Steven Pennybaker, Mark J. Niciu, David A. Luckenbaugh, Carlos A. Zarate
Journal of Affective Disorders January 15, 2017 DOI: 10.1016/j.jad.2016.10.026 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 93 |
| Population | Treatment-resistant adults with major depressive disorder (unmedicated) or bipolar depression (on therapeutic-dose lithium or valproate) experiencing a major depressive episode of at least moderate severity |
| Intervention | Ketamine |
| Dose | 0.5 mg/kg |
| Duration | Single infusion; assessments at baseline and days 1, 14, and 28 post-infusion |
| Measures | Montgomery-Asberg Depression Rating Scale (MADRS) |
| Topics | Depression Ketamine Esketamine |
| Keywords | Antidepressant Bipolar depression Glutamatergic modulator Nmda receptor antagonist |
| Key findings | A minority of treatment-resistant depressed patients (12.9%, 12 of 93) maintained antidepressant response two weeks after a single ketamine infusion. A positive family history of alcohol use disorder and greater dissociation during infusion were associated with better two-week response, and early improvements in specific depressive symptoms at day one correlated most strongly with two-week antidepressant effects. |
Abstract
Antidepressant response to a single subanesthetic dose infusion of the glutamatergic modulator ketamine is transient in most depressed patients; however, a minority continue to experience an extended response. This study examined depressive symptoms and potential clinical predictors of extended response to ketamine in subjects with mood disorders. Subjects were diagnosed with either major depressive disorder (MDD) or bipolar depression. All subjects were treatment-resistant and experiencing a major depressive episode of at least moderate severity. MDD subjects were unmedicated and those with bipolar depression were receiving therapeutic-dose lithium or valproate. All subjects received a single 0.5mg/kg ketamine infusion. Data were collected pre-infusion (baseline) and at days one, 14, and 28 post-infusion. Twelve of 93 (12.9%) participants continued to meet response criteria (50% reduction in Montgomery-Asberg Depression Rating Scale (MADRS) score) at two weeks. All depressive symptoms assessed by the MADRS were improved at two weeks in ketamine responders except for sleep duration/depth. A positive family history of alcohol use disorder in a first-degree relative (FHP) and greater dissociation during the infusion were associated with better antidepressant response at two weeks. Improved measures of apparent sadness, reported sadness, inability to feel, and difficulty concentrating at day 1 correlated most strongly with antidepressant effects at two weeks. Post-hoc design, small sample size, diagnostic heterogeneity. Static (FHP) and dynamic (improved depressive symptoms) factors may be clinically useful in predicting whether a patient will have an extended response to ketamine.
Comparable studies
Other observational and cohort studies on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder | 2012 | Observational cohort | n = 30 |
| Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Healthy controls and actively depressed patients with treatment-resistant depression... | 2017 | Observational cohort | n = 59 |
| Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression Treatment-resistant inpatients with DSM-IV-TR-diagnosed major depressive disorder or... | 2014 | Post hoc analysis of pooled data from four studies | n = 108 |
| An investigation of amino-acid neurotransmitters as potential predictors of clinical improvement to ketamine in depression Drug-free patients with major depressive disorder | 2011 | Observational cohort | n = 14 |
| Efficacy of ketamine therapy in the treatment of depression Drug-free/naïve men with severe depression, no history of psychotic disorder, head... | 2019 | Observational cohort | n = 25 |
Citations in the library
Cited by 45
- Real-world effectiveness of ketamine in treatment-resistant depression: A systematic review & meta-analysis. Journal of Psychiatric Research May 1, 2022
- Randomized trial of ketamine masked by surgical anesthesia in patients with depression Nature Mental Health October 19, 2023
- International pooled patient-level meta-analysis of ketamine infusion for depression: In search of clinical moderators Molecular Psychiatry September 7, 2022
- At-home, sublingual ketamine telehealth is a safe and effective treatment for moderate to severe anxiety and depression: Findings from a large, prospective, open-label effectiveness trial. Journal of Affective Disorders July 1, 2022
- Prolonged ketamine infusion modulates limbic connectivity and induces sustained remission of treatment-resistant depression Psychopharmacology January 22, 2021
and 40 more in the library
Cites 29
- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
- Measurement of dissociative states with the Clinician‐Administered Dissociative States Scale (CADSS) Journal of Traumatic Stress 1998
- Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression American Journal of Psychiatry October 1, 2015
- Rapid Resolution of Suicidal Ideation After a Single Infusion of anN-Methyl-D-Aspartate Antagonist in Patients With Treatment-Resistant Major Depressive Disorder The Journal of Clinical Psychiatry July 13, 2010
- Intravenous Esketamine in Adult Treatment-Resistant Depression: A Double-Blind, Double-Randomization, Placebo-Controlled Study Biological Psychiatry November 4, 2015
and 24 more in the library