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

Ana Claudia Souza Palmer,Maxciel Zortea,Jorge Villanova Biazús,Wolnei Caumo,Iraci L S Torres,Andressa Souza,Vinicius Santos,Felipe Fregni,Pasquale F Innominato

doi:10.1371/journal.pone.0231379

Abstract

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.

Highlights

Cognitive impairment in patients receiving chemotherapy for breast cancer can manifest with acute and/or delayed complications[1,2]
The sample comprised of 36 women scheduled for Variables Age Formal education Body Mass Index Visual Analogue Scale (0–100) Brain-Derived Neurotrophic Factor Tropomyosin receptor kinase B Protein S100 Beta Pittsburgh Sleep Quality Index Beck Depression Inventory II Chronic disease Hypertension Hypothyroidism Diabetes mellitus Asthma Psychotropic medication Selective serotonin reuptake inhibitors Tricyclics Benzodiazepines Antipsychotics Chemotherapy regimens ACT 1 AC 1 ACTH 1 TAC 2 TC 2
In the placebo group we did not observe a correlation with Δ-Tyrosine Kinase receptor-B (TrkB), Pittsburgh Sleep Quality Index (PSQI), nor with BDI-II. These findings confirm the benefits of melatonin use compared to placebo prior to adjuvant chemotherapy for breast cancer (ACBC) in reducing performance time on the Trail Making Test Parts A and B (TMT-A-B), increasing the score in immediate and delayed recall, and improving recognition in the Rey Auditory-Verbal Learning Test (RAVLT) and increasing words recited during the orthographic Controlled Oral Word Association Test (COWAT)

Summary

Introduction

Cognitive impairment in patients receiving chemotherapy for breast cancer can manifest with acute and/or delayed complications[1,2]. According to Jansen et al.[3], 23% of women with breast cancer had experienced cognitive impairment before chemotherapy. This increased to 52% during chemotherapy[3]. The neurotoxicity associated with chemotherapy for breast cancer is substantiated by the persistent cognitive deficits related to volume reduction in the hippocampal gray matter one year after treatment completion[7]. There is evidence that the reduction in hippocampal volume is associated with a decrease in cognitive function in patients with major depression[8]. The mechanisms underpinning these symptoms need to be further investigated

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Conclusion