Brain-Derived Neurotrophic Factor and Initial Antidepressant Response to anN-Methyl-D-Aspartate Antagonist
Rodrigo Machado‐Vieira, Peixiong Yuan, Nancy E. Brutsché, Nancy Diazgranados, David A. Luckenbaugh, Husseini Manji, Carlos A. Zarate
The Journal of Clinical Psychiatry September 8, 2009 DOI: 10.4088/jcp.08m04659 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label trial Peer reviewed |
|---|---|
| Sample size | 23 |
| Population | Adults aged 18 to 65 years with DSM-IV major depressive disorder (treatment resistant) |
| Intervention | Ketamine hydrochloride |
| Dose | 0.5 mg/kg |
| Duration | 230 minutes postinfusion |
| Topics | Anxiety Depression Ketamine |
| Keywords | Brain-derived neurotrophic factor Antidepressant Mood Neurotrophic factors Antagonist Rating scale Depression economics Developmental psychology Receptor |
| Citations | 154 |
| Registration | NCT00024635 NCT00088699 |
| Key findings | Ketamine's rapid initial antidepressant effects are not mediated by changes in BDNF levels. |
Abstract
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.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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MADRS scores improved significantly after ketamine, but BDNF levels did not change and were not associated with antidepressant response.
Synthesized
Comparable studies
Other non-randomized and open-label trials on ketamine for anxiety, most cited first.
Citations in the library
Cited by 60
- Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression American Journal of Psychiatry October 1, 2015
- Better Biomarkers, Faster Drugs, Stronger Models: Progress Towards Precision Psychiatry. Missouri medicine 2023
- Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics Annual Review of Medicine October 23, 2014
- Single-dose infusion ketamine and non-ketamine N-methyl-D-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories Psychological Medicine February 12, 2016
- Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder The International Journal of Neuropsychopharmacology June 7, 2012
and 55 more in the library
Cites 3
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Cellular mechanisms underlying the antidepressant effects of ketamine: role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biological Psychiatry February 15, 2008
- Acute administration of ketamine induces antidepressant-like effects in the forced swimming test and increases BDNF levels in the rat hippocampus. Progress in Neuro-Psychopharmacology and Biological Psychiatry January 1, 2008