Ketamine is an antidepressant agent that is efficacious in 20-50% of the patients with depression who do not respond to conventional treatment. Evidence suggests that brain derived neurotrophic factor (BDNF) represents a neuroplastic marker of antidepressant response. This is based on studies investigating high-dose intravenous single administration. It remains unclear whether low-dose oral repeated administration produces a similar effect.

The present study aims to investigate whether prolonged low-dose oral esketamine treatment influences BDNF levels in patients with treatment resistant major depression (TRD). Increases in BDNF levels, including a positive association with antidepressant efficacy, are anticipated.

Data and biomaterials were obtained from a randomised placebo-controlled trial evaluating the efficacy of oral esketamine (1.25 mg/kg) in TRD. Patients (N = 111) were monitored for depression severity (Hamilton Depression Rating Scale, HDRS) and serum BDNF levels (enzyme-linked immunosorbent assay, ELISA) at baseline and after 6 weeks of treatment. Repeated measures analysis of variance (ANOVA) will be performed to evaluate the change in BDNF levels in the esketamine relative to the placebo group. Correlational analyses will be conducted to investigate the association between changes in BDNF levels and depression severity.

The results will provide insight in the effect of dosage, frequency, and route of administration in the influence of esketamine on BDNF levels.

The effect of esketamine on BDNF levels might vary depending on treatment protocol. Future research could utilise this knowledge to improve treatment efficacy for TRD patients.