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

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.

Pathogenesis, Assessments, and Management of Chemotherapy-Related Cognitive Impairment (CRCI): An Updated Literature Review

“…A randomized, double-blinded, placebo-controlled trial demonstrated the neuroprotective effect of melatonin on the neuroplasticity process. It may offset the cognitive function decline, impaired sleep quality, and depression symptoms of breast cancer patients during adjuvant chemotherapy [ 111 ]. Antioxidant N -acetylcysteine alters the cognitive deficits mainly by reversing mitochondrial dysfunction, preventing free radical production, reducing hippocampal neuron apoptosis, and dendritic spine loss [ 112 ].…”

Antioxidants for the Treatment of Breast Cancer: Are We There Yet?

“…Melatonin also exhibits neuroprotective abilities by counteracting the adverse effects of adjuvant chemotherapy on cognitive function, sleep quality and depressive symptoms. Hence, it could be a novel adjuvant therapy to improve the existing breast cancer treatments [ 39 , 40 , 41 , 42 ]. Furthermore, melatonin can increase the efficacy of chemotherapeutics in combinatory treatments [ 40 ].…”

“…First of all, they are all randomized, double-blinded, placebo-controlled trials, which agree that the administration of melatonin results in an improvement in sleep quality and expected effect since regulation of sleep/wake rhythm is one of its qualities. Nevertheless, these trials do not coincide with dosage nor patients’ situation [ 41 , 49 , 50 , 51 , 52 , 53 ]. NCT01355523 included post-surgery patients with a dose of 6 mg of melatonin.…”

Microbial production of beneficial indoleamines (serotonin and melatonin) with potential application to biotechnological products for human health

“…Moreover, several clinical studies demonstrated that the ingestion of melatonin produces a reduction in the toxicity of chemotherapeutic agents in cancer patients (Palmer et al 2020). On the other hand, experimental models on rats showed that melatonin delays tumorigenesis initiation since interactions with DNA-bound carcinogens prevent the accumulation of mutations inside cells and the initiation of cancer (Kumar et al 2017).…”