Brain-Derived Neurotrophic Factor and Initial Antidepressant Response to an N-Methyl-D-Aspartate Antagonist
Open accessAbstract
OBJECTIVE: A model has been proposed to explain the pathophysiology of mood disorders based on decreased neurotrophin levels during mood episodes; treatment with antidepressants and mood stabilizers is associated with clinical improvement. This study investigated whether changes in brain-derived neurotrophic factor (BDNF) levels are associated with the initial antidepressant effects of ketamine, a high-affinity N-methyl-D-aspartate (NMDA) antagonist. METHOD: Twenty-three subjects aged 18 to 65 years with DSM-IV major depressive disorder (treatment resistant) participated in this study, which was conducted between October 2006 and May 2008. The subjects were given an open-label intravenous infusion of ketamine hydrochloride (0.5 mg/kg) and rated using various depression scales at baseline and at 40, 80, 120, and 230 minutes postinfusion. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale score. BDNF levels were obtained at the same time points as depression rating scale scores. RESULTS: Despite a significant (P <. 001) improvement in MADRS scores after subjects received ketamine treatment, no changes in BDNF levels were observed in subjects after they received ketamine compared to baseline. Also, no association was found between antidepressant response and BDNF levels. CONCLUSIONS: This study demonstrates that ketamine's rapid initial antidepressant effects are not mediated by BDNF. Further studies are necessary to shed light on the neurobiological basis of these effects. TRIAL REGISTRATION: clinicaltrials.gov Identifiers: NCT00024635 and NCT00088699.
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Conflicting clinical results have also been reported.
“However, conflicting clinical results have also been reported (Machado-Vieira et al., 2009).”
From BDNF - a key transducer of antidepressant effects (2016) · cites this paper as Machado-Vieira et al., 2009
In 23 TRD patients who received open-label IV ketamine 0.5 mg/kg, there was no increase in plasma BDNF levels.
“one study of 23 TRD patients who received open-label intravenous ketamine (0.5 mg/kg) reported no increase in plasma BDNF levels [97].”
From Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review (2024) · cites this paper as [97]
Ketamine responders with treatment-resistant depression demonstrated rapid elevations in plasma BDNF levels, although another study did not support this finding.
“Ketamine responders with TRD demonstrated rapid elevations in plasma BDNF levels112,113; however, another study did not support this finding.114”
From Ketamine as an antidepressant: Overview of its mechanisms of action and potential predictive biomarkers (2020) · cites this paper as [114]
Higher levels of BDNF were correlated with lower severity of depressive symptoms on rating scales.
“In the aforementioned investigations, higher levels of BDNF were correlated with lower severity of depressive symptoms on rating scales.”
From Ketamine as an antidepressant: Overview of its mechanisms of action and potential predictive biomarkers (2020) · cites this paper as [114]
TRD is associated with prolonged mental and physical dysfunction, increased healthcare spending, worse clinical outcomes, and a higher risk of suicide.
“Overall, Treatment Resistant Depression (TRD) is associated with several comorbid features, including prolonged mental and physical dysfunction, increased healthcare spending, worse clinical outcomes, and a higher risk of suicide [4,6,7,8,9].”
From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [7]
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References 33 · Cited by 155
Research works printed but not linked: 3
- [29]Beck AT Beamesderfer A Assessment of depression: the depression inventory Mod Probl Pharmacopsychiatry 1974 7 0 151 169 4412100
- [30]Hedlund JL Vieweg BW The Brief Psychiatric Rating Scale (BPRS): a comprehensive review J Oper Psychiatr 1980 11 48 65
- [34]Marano CM Phatak P Vemulapalli UR Increased plasma concentration of brain-derived neurotrophic factor with electroconvulsive therapy: a pilot study in patients with major depression J Clin Psychiatry 2007 68 4 512 517 17474805
- Authors
- Machado-Vieira, R., Yuan, P., Brutsche, N., DiazGranados, N., Luckenbaugh, D., Manji, H. K., & Zarate, C. A.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Zarate, Carlos A.
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2009-09-08
- Volume
- 70
- Issue
- 12
- Pages
- 1662-1666
- ISSN
- 0160-6689 (ISSN-L)
- PMC
- PMC2819547
- OpenAlex
- W2044063521
- Cited by
- 155
- References
- 33
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 6 · 2023: 3 · 2022: 8 · 2021: 7 · 2020: 9 · 2019: 5 · 2018: 7 · 2017: 5 · 2016: 11 · 2015: 14 · 2014: 15 · 2013: 12 · 2012: 20
- FWCI
- 10.10
- 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 Institutes of Health
- National Institute of Mental Health (Z01MH002857, ZIAMH002857)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- brain-derived neurotrophic factor, ketamine, NMDA receptor antagonists, antidepressant response, major depressive disorder, treatment-resistant depression, rapid antidepressant effects, neurotrophins, mood disorders
- MeSH terms
- Adult, Antidepressive Agents, Depressive Disorder, Major, Major Depressive Disorder, Double-Blind Method, Drug Resistance, Female, Humans, Infusions, Intravenous, Ketamine, Male, Placebos, Psychiatric Status Rating Scales, Receptors, N-Methyl-D-Aspartate, Treatment Outcome, Excitatory Amino Acid Antagonists, Brain-Derived Neurotrophic Factor
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