The effect of MELatOnin on Depression, anxietY, cognitive function and sleep disturbances in patients with breast cancer. The MELODY trial: protocol for a randomised, placebo-controlled, double-blinded trial

Abstract

IntroductionBreast cancer represents about one-third of all cancer diagnoses and accounts for about 15% of cancer deaths in women. Many of these patients experience depression, anxiety, sleep disturbances and cognitive dysfunction. This may adversely affect quality of life and also contribute to morbidity and mortality. Melatonin is a regulatory circadian hormone having, among others, a hypnotic and an antidepressive effect. It has very low toxicity and very few adverse effects compared with the more commonly used antidepressants and hypnotics.Methods and analysisThe objective of this double-blind, randomised, placebo-controlled trial is to investigate whether treatment with oral melatonin has a prophylactic or ameliorating effect on depressive symptoms, anxiety, sleep disturbances and cognitive dysfunction in women with breast cancer. Furthermore, the authors will examine whether a specific clock-gene, PER3, is correlated with an increased risk of depressive symptoms, sleep disturbances or cognitive dysfunction. The MELODY trial is a prospective double-blinded, randomised, placebo-controlled trial in which the authors intend to include 260 patients. The primary outcome is depressive symptoms measured by the Major Depression Inventory. The secondary outcomes are anxiety measured by a Visual Analogue Scale, total sleep time, sleep efficiency, sleep latency and periods awake measured by actigraphy and changes in cognitive function measured by a neuropsychological test battery. Tertiary outcomes are fatigue, pain, well-being and sleep quality/quantity measured by Visual Analogue Scale and sleep diary and sleepiness measured by the Karolinska Sleepiness Scale. The PER3 genotype is also to be determined in blood samples.

Melatonin-Induced Oncostasis, Mechanisms and Clinical Relevance

“…In a randomized controlled double-blind clinical trial on 50 patients referred for liver surgery a single preoperative enteral dose of 50 mg/kg melatonin was safe and well tolerated [215]. This underlines the urgent need for large clinical trials in the field of melatonin and cancer [216,217]. …”

Variação longitudinal da qualidade do sono em mulheres com câncer de mama

“…Among factors negatively affecting their quality of life, patients with breast cancer live with depression, anxiety, fatigue, pain, and sleep disorders, which may contribute to an increase in mortality. (6) In addition to a positive correlation between poor sleep quality and depression, there was a negative correlation between hope and poor sleep quality scores and, similarly, between hope and depression, in all stages of this study. Furthermore, health status, family support, and self-esteem of women with breast cancer have been shown to indirectly affect depression through hope.…”

“…(4,5) A complex relationship -under the influence of several factors -can be distinguished between depression and breast cancer, despite the former often being undiagnosed and untreated. (6) Depression and mood swings may present throughout treatment or even after its conclusion. (7,8) Depressive symptoms are predictors of subjective sleep quality in women with breast cancer before, during and after radiation therapy.…”

Assessment of the intake of tryptophan-enriched cereals in the elderly and its influence on the sleep-wake circadian rhythm

“…On the other hand, it has been reported that melatonin has a possible anti-depressive, anxiolytic, analgesic or sedative effects, among others, probably based on its effect on the circadian functions regulation (Hansen et al, 2011).…”