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

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. This clinical trial is registered on the Japan Primary Registries Network: UMIN000032355.

Ketamine in the Treatment of Obsessive-Compulsive Disorder: A Systematic Review

“…Additionally, regarding the neurobiological basis for ketamine’s rapid antidepressant effects, some studies point to a neurotrophic hypothesis, in which increased expression of brain-derived neurotrophic factor in the medial prefrontal cortex and hippocampus lead to increased synaptic activity in these areas 65 . Data about BDNF and ketamine in humans is still controversial, however 66 . It is worth noting that early evidence points to similar mechanisms for the rapid antidepressant effects of serotonergic psychedelics, such as psilocybin and LSD 67 …”

“…65 Data about BDNF and ketamine in humans is still controversial, however. 66 It is worth noting that early evidence points to similar mechanisms for the rapid antidepressant effects of serotonergic psychedelics, such as psilocybin and LSD. 67…”

The Mechanisms Behind Rapid Antidepressant Effects of Ketamine: A Systematic Review With a Focus on Molecular Neuroplasticity

“…Ketamine-induced increases in BDNF are observed in serum after 1 week ( 126 ) and plasma after 230–240 min ( 127 , 128 ). Depressive symptoms of patients correlated with BDNF plasma levels for up to 72 h ( 128 ), while one found no correlation with mood responses ( 129 ). Other studies have found no differences in BDNF levels in plasma at the same time points despite significant improvements in mood ( 129 – 133 ).…”

“…Depressive symptoms of patients correlated with BDNF plasma levels for up to 72 h ( 128 ), while one found no correlation with mood responses ( 129 ). Other studies have found no differences in BDNF levels in plasma at the same time points despite significant improvements in mood ( 129 – 133 ). In a genome-wide association study, single nucleotide polymorphisms as well as whole genes involved in BDNF-TrkB signaling were shown to be associated with rapid and sustained antidepressant effects in patients with TRD ( 134 ).…”

Plasma Brain-Derived Neurotrophic Factor Levels in First-Episode and Recurrent Major Depression and before and after Bright Light Therapy in Treatment-Resistant Depression

“…The results showing lower BDNF levels in TRD are slightly intriguing, given that all our patients were medicated, and antidepressants were expected to normalize BDNF levels [ 53 ]. However, no significant differences in serum BDNF levels in TRD patients treated with esketamine or ketamine were reported [ 54 ].…”