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Brain-derived neurotrophic factor serum levels following ketamine and esketamine intervention for treatment-resistant depression: secondary analysis from a randomized trial.

Ana Teresa Caliman-Fontes, Gustavo C Leal, Fernanda S Correia-Melo, Camilla S Paixão, Michelle S Carvalho, Ana Paula Jesus-Nunes, Flávia Vieira, Guilherme Magnavita, Igor D Bandeira, Rodrigo P Mello, Graziele Beanes, Samantha S Silva, Mariana Echegaray, Lucas P Carvalho, Paulo Machado, Aline S Sampaio, Taiane de A Cardoso, Flávio Kapczinski, Acioly L T Lacerda, Lucas C Quarantini

Trends in Psychiatry and Psychotherapy March 7, 2023 DOI: 10.47626/2237-6089-2021-0298 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Randomized, double-blind clinical trial Peer reviewed
Sample size 53
Population Participants with treatment-resistant depression
Interventions Ketamine Esketamine
Dose ketamine 0.5 mg/kg; esketamine 0.25 mg/kg
Duration Single-dose intervention with assessments before and 24 hours, 72 hours, and 7 days after infusion; blood samples collected before infusion, 24 hours, and 7 days afterwards
Measures Montgomery-Åsberg Depression Rating Scale (MADRS), serum BDNF levels
Topics Depression Ketamine Esketamine
Keywords Humans Brain-derived neurotrophic factor Depressive disorder, treatment-resistant Bdnf Biochemical markers Neurotrophins Nmda antagonists
Key findings Neither ketamine nor esketamine produced significant changes in serum BDNF levels at 24 hours or 7 days after a single infusion, and BDNF levels did not differ between the two drugs or correlate with treatment response or depression severity, despite both drugs showing similar therapeutic effects.

Abstract

Objectives: Evidence suggests that ketamine's influence on brain-derived neurotrophic factor (BDNF) might be involved in its mechanism of rapid antidepressant action. We aimed to evaluate the differential impact of ketamine and esketamine on serum BDNF levels and its association with response patterns in treatment-resistant depression (TRD).

Methods: Participants (n = 53) are from a randomized, double-blind clinical trial comparing the efficacy of single-dose ketamine (0.5mg/kg, n = 27) and esketamine (0.25mg/kg, n = 26) in TRD. Depression severity was assessed before and 24 hours, 72 hours, and 7 days after the intervention, using the Montgomery-Åsberg Depression Rating Scale (MADRS). Blood samples were collected before infusion, 24 hours, and 7 days afterwards.

Results: There were no significant changes in BDNF levels at post-infusion evaluation points, and no difference in BDNF levels comparing ketamine and esketamine. Both drugs exhibited similar therapeutic effect. There was no association between BDNF levels and response to treatment or severity of depressive symptoms.

Conclusion: There was no significant treatment impact on BDNF serum levels - neither with ketamine nor esketamine - despite therapeutic response. These results suggest that ketamine or esketamine intervention for TRD has no impact on BDNF levels measured at 24 hours and 7 days after the infusion.

Comparable studies

Other randomized controlled trials on esketamine for depression, most cited first.

Study Year Design Participants
Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study Adults with moderate to severe nonpsychotic depression and a history of nonresponse to... 2019 Phase 3, double-blind, active-controlled, multicenter randomized controlled trial n = 227
Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression Adults with treatment-resistant depression who achieved stable remission or stable... 2019 Phase 3, multicenter, double-blind, randomized withdrawal study n = 297
Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression Adults with DSM-IV-TR diagnosis of major depressive disorder and history of inadequate... 2017 Phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study n = 67
Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study Depressed patients at imminent risk for suicide 2018 Randomized controlled trial n = 68
Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1) Adults with moderate-to-severe depression and nonresponse to at least two... 2019 Randomized controlled trial n = 346

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