Effects of subanesthetic repeated esketamine infusions on memory function and NGF in patients with depression: An open-label study

J Affect Disord. 2025 Jan 15:369:1183-1189. doi: 10.1016/j.jad.2024.09.162. Epub 2024 Sep 24.

Abstract

Background: Subanesthetic ketamine is a rapidly acting antidepressant, yet the effects of ketamine on cognitive function are inconsistent. The primary objective of this study was to explore the effects of esketamine on memory function and plasma levels of nerve growth factor (NGF) in patients with depression.

Methods: A total of 132 patients with depression completed six intravenous esketamine infusions (0.4 mg/kg) over 11 days. Depressive symptoms and neurocognitive function were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Plasma NGF levels were assayed by enzyme-linked immunosorbent assay (ELISA).

Results: The mean MADRS score of depressed patients decreased from 32.11 ± 10.06 to 15.10 ± 8.62 after six infusions. Significant improvement in immediate memory, language, attention, and delayed memory were observed. NGF plasma levels increased from 226.13 ± 61.73 to 384.37 ± 56.89. Pearson's correlation analysis showed a positive correlation between memory function and NGF levels at baseline. The baseline memory function was negatively associated with the changes in NGF levels.

Limitation: The major limitation of this study is the open-label design.

Conclusions: Subanesthetic esketamine infusions could improve depressive symptoms and neurocognitive function. Our study showed increased plasma NGF levels in depressed patients after treatment, suggesting that NGF may play a role in the improvement of memory function by esketamine.

Keywords: Antidepressant; Cognition; Ketamine; Major depressive disorder; Nerve growth factor.

MeSH terms

  • Adult
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / pharmacology
  • Depression / blood
  • Depression / drug therapy
  • Female
  • Humans
  • Infusions, Intravenous
  • Ketamine* / administration & dosage
  • Ketamine* / pharmacology
  • Male
  • Memory* / drug effects
  • Middle Aged
  • Nerve Growth Factor* / blood
  • Neuropsychological Tests
  • Psychiatric Status Rating Scales

Substances

  • Ketamine
  • Nerve Growth Factor
  • Esketamine
  • Antidepressive Agents
  • NGF protein, human