The effect of recombinant erythropoietin on plasma brain derived neurotrophic factor levels in patients with affective disorders: a randomised controlled study

PLoS One. 2015 May 26;10(5):e0127629. doi: 10.1371/journal.pone.0127629. eCollection 2015.


The study aims to investigate the effect of repeated infusions of recombinant erythropoietin (EPO) on plasma brain derived neurotrophic factor (BDNF) levels in patients with affective disorders. In total, 83 patients were recruited: 40 currently depressed patients with treatment-resistant depression (TRD) (Hamilton Depression Rating Scale-17 items (HDRS-17) score >17) (study 1) and 43 patients with bipolar disorder (BD) in partial remission (HDRS-17 and Young Mania Rating Scale (YMRS) ≤ 14) (study 2). In both studies, patients were randomised to receive eight weekly EPO (Eprex; 40,000 IU) or saline (0.9% NaCl) infusions in a double-blind, placebo-controlled, parallel--group design. Plasma BDNF levels were measured at baseline and at weeks 5, 9 and at follow up, week 14. In contrast with our hypothesis, EPO down regulated plasma BDNF levels in patients with TRD (mean reduction at week 9 (95% CI): EPO 10.94 ng/l (4.51-21.41 ng/l); mean increase at week 9: Saline 0.52 ng/l, p=0.04 (-5.88-4.48 ng/l) p=0.04, partial ŋ2=0.12). No significant effects were found on BDNF levels in partially remitted patients with BD (p=0.35). The present effects of EPO on BDNF levels in patients with TRD point to a role of neurotrophic factors in the potential effects of EPO seen in TRD and BD. The neurobiological mechanisms underlying these effects and the interaction between EPO and peripheral levels on BDNF need to be further elucidated in human studies including a broad range of biomarkers.

Trial registration: NCT00916552.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain-Derived Neurotrophic Factor / blood*
  • Depressive Disorder, Treatment-Resistant / blood
  • Depressive Disorder, Treatment-Resistant / drug therapy
  • Erythropoietin / therapeutic use*
  • Female
  • Humans
  • Male
  • Mood Disorders / blood*
  • Mood Disorders / drug therapy*
  • Recombinant Proteins / therapeutic use*
  • Remission Induction


  • Brain-Derived Neurotrophic Factor
  • Recombinant Proteins
  • Erythropoietin
  • BDNF protein, human

Associated data


Grant support

The study was funded by the Danish Ministry of Science, Innovation and Higher Education, Novo Nordisk Foundation, Beckett Fonden, Savværksejer Juhl’s Mindefond, and the Augustinus Foundation. The funding source had no role in the study design, in the collection, analyses, and interpretation of data, in writing the manuscript, or in the decision to submit the paper for publication.