This open-label study (n=94) finds that baseline plasma BDNF concentrations (a protein related to nerve growth) correlate with ketamine (6 infusions, 35mg/70kg) antidepressant effects (MADRS).

Abstract

“Objectives Accumulating evidence has implicated that brain derived neurotrophic factor (BDNF) is thought to be involved in the pathophysiology of depression, but its correlation with ketamine’s antidepressant efficacy focusing on Chinese individuals with depression is not known. This study was aim to determine the correlation of plasma BDNF (pBDNF) concentrations and ketamine’s antidepressant efficacy.

Methods Ninety-four individuals with depression received six intravenous infusions ketamine (0.5 mg/kg). Remission and response were defined as Montgomery-Asberg Depression Rating Scale (MADRS) scores less than 10 and a reduction of 50% or more in MADRS scores, respectively. Plasma was collected at baseline and at 24 h and 2 weeks after completing six ketamine infusions (baseline, 13 d and 26 d).

Results A significant improvement in MADRS scores and pBDNF concentrations was found after completing six ketamine infusions compared to baseline (all ps < 0.05). Higher baseline pBDNF concentrations were found in ketamine responders/remitters (11.0 ± 6.2/10.1 ± 5.8 ng/ml) than nonresponders/nonremitters (8.0 ± 5.5/9.2 ± 6.4 ng/ml) (all ps < 0.05). Baseline pBDNF concentrations were correlated with MADRS scores at 13 d (t = − 2.011, p = 0.047) or 26 d (t = − 2.398, p = 0.019) in depressed patients (all ps < 0.05). Subgroup analyses found similar results in individuals suffering from treatment refractory depression.

Conclusion This preliminary study suggests that baseline pBDNF concentrations appeared to be correlated with ketamine’s antidepressant efficacy in Chinese patients with depression.”

Authors: Wei Zheng, Yan-Ling Zhou, Cheng-Yu Wang, Xiao-Feng Lan, Bin Zhang, Su-Miao Zhou, Su Yan & Yu-Ping Ning

Summary

ABSTRACT

This study was conducted on Chinese individuals with depression to determine the correlation between plasma BDNF concentrations and ketamine’s antidepressant efficacy.

Ninety-four individuals with depression received six intravenous infusions ketamine. Plasma was collected at baseline, 24 h and 2 weeks after completing six infusions.

After completing six ketamine infusions, depressed patients showed significant improvement in MADRS scores and pBDNF concentrations compared to baseline. Higher baseline pBDNF concentrations were found in ketamine responders/remitters than nonresponders/nonremitters.

INTRODUCTION

Ketamine, an antagonist of glutamatergic N-methyl-D-aspartate (NMDA) receptors, has been consistently reported to have fast-acting and sustained antidepressant effects in individuals suffering from unipolar and bipolar depression.

Subanesthetic intravenous ketamine’s antidepressant actions are still incompletely understood, but recent evidence implicates neurotrophic factors in the pathophysiology of mood disorders, and BDNF may be a critical component in subanesthetic intravenous ketamine’s antidepressant actions.

BDNF plays a role in the pathophysiology of schizophrenia and mood disorders. For example, depressed patients have lower serum BDNF concentrations and pBDNF concentrations than healthy subjects, and recover after successful antidepressant therapy.

Several studies have investigated BDNF as a predictor of ketamine’s antidepressant efficacy in individuals suffering from treatment-refractory depression, but with inconsistent findings. The present study examined the relationship between pBDNF concentrations and six subanesthetic intravenous ketamine’s antidepressant efficacy in Chinese individuals suffering from depression.

Study sample

Data of the current study were collected from an open-label clinical study that examined serial intravenous subanesthetic ketamine’s antidepressant and antisuicidal efficacy in individuals suffering from depression.

All subjects were recruited based on the following inclusion criteria: age between 18 and 65 years, no psychotic symptoms, diagnosis of unipolar or bipolar depression, TRD, negative urine toxicology, and no unstable medical illness.

Treatment

All patients received thrice-weekly ketamine infusions for 2 weeks, with a follow-up period of two weeks. They continued taking psychotropic agents.

Response and remission

A MADRS score less than 10 and a reduction of 50% or more in MADRS scores were used to assess remission and response to ketamine.

Statistical analysis

The Mann – Whitney U test, independent t tests, Fisher’s exact test, and Chi-squared test were used to analyze the data. Bivariate correlation analysis and multiple linear regression analysis were also performed on the data in order to determine the independent association between baseline pBDNF concentrations and MADRS scores.

Treatment outcome and BDNF

After six ketamine infusions, 68.1% of patients with MADRS and 51.9% of patients with TRD had a response or remission, respectively. Higher baseline pBDNF concentrations were found in ketamine responders/remitters than nonresponders/nonremitters.

Correlation of BDNF and MADRS scores

Correlation analyses showed that pBDNF concentrations at baseline were associated with MADRS scores in depressed patients and TRD patients.

DISCUSSION

This study found that pBDNF concentrations increased after six subanesthetic intravenous ketamine in Chinese individuals suffering from unipolar and bipolar depression, and that pBDNF concentrations were related with MADRS scores.

After six ketamine infusions, pBDNF concentrations were significantly increased in responders/remitters compared to nonresponders/nonremitters, but repeated ketamine infusions failed to significantly increase pBDNF concentrations in responders/remitters when compared to nonresponders/nonremitters. Therefore, these findings should be confirmed by randomized controlled trials.

Several animal studies reported that increased hippocampal and cortical BDNF expression can partly accounting for ketamine’s antidepressant-like efficacy. BDNF is implicated in the regulation of synaptic plasticity, including the synaptic recruitment of AMPA receptors.

The following limitations should be acknowledged: the sample size was small, subjective evaluation was inevitable, and brain BDNF concentrations were not directly measured. However, baseline pBDNF concentrations appeared to be correlated with ketamine’s antidepressant efficacy in Chinese patients with depression.

Author Contributions

Wei Zheng performed the experiments, Yan-Ling Zhou designed the experiments, Cheng-Yu Wang performed the experiments, Xiao-Feng Lan and Bin Zhang performed the experiments, Su-Miao Zhou and Su Yan analyzed the data, and Yu-Ping Ning approved the final draft.