Clinical impact of melatonin on breast cancer patients undergoing chemotherapy; effects on cognition, sleep and depressive symptoms: A randomized, double-blind, placebo-controlled trial

PLoS One. 2020 Apr 17;15(4):e0231379. doi: 10.1371/journal.pone.0231379. eCollection 2020.


This randomized, double-blinded, placebo-controlled trial tested the hypothesis that 20mg of melatonin before and during the first cycle of adjuvant chemotherapy for breast cancer (ACBC) reduced the side effects associated with cognitive impairment. We evaluated the effects of melatonin on cognition, depressive symptoms and sleep quality, and whether these effects were related to serum levels of Brain Derived Neurotrophic Factor (BDNF) and its receptor, tropomyosin kinase B (TrkB). Thirty-six women were randomly assigned to receive melatonin or placebo for 10 days. To evaluate cognitive performance, we used the Trail-Making-Test Parts A and B (A-B), Rey Auditory-Verbal Learning Test (RAVLT), Controlled Oral Word Association Test (COWAT) and an inhibitory task type Go / No-Go. Our results revealed that melatonin improved executive function on TMT scores, enhanced episodic memory (immediate and delayed) and recognition on RAVLT, and increased verbal fluency in the orthographic COWAT. The TMT-A-B(A-B) were negatively correlated with baseline levels of TrkB and BDNF, respectively. At the end of treatment, changes in TrkB and BDNF were inversely associated with depressive symptoms and sleep quality, but not with the TMT scores. These results suggest a neuroprotective effect of melatonin to counteract the adverse effects of ACBC on cognitive function, sleep quality and depressive symptoms.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Biomarkers / blood
  • Brain-Derived Neurotrophic Factor / blood
  • Breast Neoplasms / complications
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology*
  • Cognitive Dysfunction / prevention & control*
  • Depression / drug therapy*
  • Depression / etiology
  • Double-Blind Method
  • Female
  • Humans
  • Melatonin / pharmacology
  • Melatonin / therapeutic use*
  • Membrane Glycoproteins / blood
  • Middle Aged
  • Neuropsychological Tests
  • Placebo Effect
  • Receptor, trkB / blood
  • Sleep* / drug effects
  • Treatment Outcome


  • Antineoplastic Agents
  • Biomarkers
  • Brain-Derived Neurotrophic Factor
  • Membrane Glycoproteins
  • BDNF protein, human
  • Receptor, trkB
  • tropomyosin-related kinase-B, human
  • Melatonin

Grants and funding

The present research was funded via the following Brazilian agencies: (i) Committee for the Development of Higher Education Personnel (CAPES) (PNPD Grant no. 1509885 MZ). (ii) National Council for Scientific and Technological Development [(CNPq (Research grant: IT 302345/2011-6 and WC 30 1256/ 201 3-6)]. (iii) Hospital de Clínicas de Porto Alegre (HCPA) Research Incentive Funding (FIPE: 14-0701). (iv) Foundation for Research of the State of Rio Grande do Sul (FAPERGS). (v) Studies and Projects Financing Agency (FINEP: 1245/13). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.