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Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression
Open accessAbstract
OBJECTIVE: The N-methyl-D-aspartate receptor antagonist ketamine has rapid antidepressant effects in treatment-resistant major depressive disorder (MDD) and bipolar depression. Clinical predictors may identify those more likely to benefit from ketamine within clinically heterogeneous populations. METHOD: Data were analyzed from 4 studies of treatment-resistant inpatients with DSM-IV-TR-diagnosed MDD or bipolar I or II depression. Patients who were currently experiencing a moderate-to-severe major depressive episode were enrolled between November 2004 and March 2013. All subjects received a single subanesthetic (0.5 mg/kg) ketamine infusion over 40 minutes. Patients were analyzed at the 230-minute postinfusion time point (n = 108), at day 1 (n = 82), and at day 7 (n = 71). Univariate Pearson correlations were performed for each variable with percent change from baseline in the 17-item Hamilton Depression Rating Scale (HDRS). Multivariate linear regression was then conducted for statistically significant predictors (P ≤ .05, 2-tailed). RESULTS: Higher body mass index correlated with greater HDRS improvement at 230 minutes (standardized β = -0.30, P = .004) and at day 1 (standardized β = -0.37, P = .001), but not at day 7 (standardized β = -0.18, P = .10). Family history of an alcohol use disorder in a first-degree relative was associated with greater HDRS improvement at day 1 (standardized β = -0.27, P = .014) and day 7 (standardized β = -0.41, P < .001). No prior history of suicide attempt(s) was associated with greater improvement only at day 7 (standardized β = 0.28, P = .01). The overall statistical model explained 13%, 23%, and 36% of HDRS percent change variance at 230 minutes, day 1, and day 7, respectively. CONCLUSIONS: Despite its post hoc nature, this study identified several clinical correlates of ketamine's rapid and durable antidepressant effects. Further investigation of these relationships is critical for individualized treatment of depression.
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“Elevated body mass index (BMI) has been found to be a predictor of response to ketamine,196 but in another study197 elevated BMI was not correlated with ketamine response, and presence of metabolic syndrome was negatively correlated with ketamine response.”
From Ketamine as an antidepressant: Overview of its mechanisms of action and potential predictive biomarkers (2020) · cites this paper as [196]
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A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression.
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Self-citationKrystal, J. H. (1994) · Archives of General Psychiatry · doi:10.1001/archpsyc.1994.03950030035004 · Cited by 3,330
mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists
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Metadata
- Authors
- Niciu, M. J., Luckenbaugh, D. A., Ionescu, D. F., Guevara, S., Machado-Vieira, R., Richards, E. M., Brutsche, N. E., Nolan, N. M., & Zarate, C. A.
- Affiliations
- National Institutes of Health (US)
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2014-05-15
- Volume
- 75
- Issue
- 05
- Pages
- e417-e423
- ISSN
- 0160-6689 (ISSN-L)
- PMC
- PMC4310499
- OpenAlex
- W2005055479
- Cited by
- 165
- References
- 41
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 13 · 2023: 12 · 2022: 12 · 2021: 21 · 2020: 21 · 2019: 7 · 2018: 12 · 2017: 8 · 2016: 10 · 2015: 16 · 2014: 7
- FWCI
- 9.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health (Z99 MH999999)
- National Institute of Mental Health
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- ketamine, treatment-resistant depression, major depressive disorder, bipolar depression, antidepressant response, predictors of treatment response, body mass index, family history of alcoholism, suicide attempt history, NMDA receptor antagonists, rapid antidepressant effects, personalized treatment
- MeSH terms
- Adult, Bipolar Disorder, Major Depressive Disorder, Depressive Disorder, Major, Female, Follow-Up Studies, Humans, Infusions, Intravenous, Ketamine, Male, Middle Aged, Psychiatric Status Rating Scales, Severity of Illness Index, Time Factors, Body Mass Index, Receptors, N-Methyl-D-Aspartate, Treatment Outcome, Excitatory Amino Acid Antagonists, Depressive Disorder, Treatment-Resistant
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