Effect of Melatonin on Cognitive Function and Sleep in relation to Breast Cancer Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Background. Sleep disturbances and cognitive dysfunction are common in patients with breast cancer. Disturbed sleep leads to poor cognitive performance and exogenous melatonin may improve sleep and attenuate cognitive dysfunction. We hypothesized that melatonin would improve sleep and cognitive function after surgery. Methods. This study reports secondary endpoints from a randomized, double-blind, placebo-controlled trial. Women, 30–75 years, were randomized to 6mg oral melatonin/placebo for 3 months. We assessed postoperative cognitive dysfunction (POCD) with a neuropsychological test battery, sleep with a diary, and sleep quality with VAS. Results. 54 patients were randomized to melatonin (n = 28) or placebo (n = 26); 11 withdrew (10 placebo, 1 melatonin, P = 0.002). The incidence of POCD was 0% (0/20) [95% CI 0.0%; 16.8%] in the placebo group and 0% (0/26) [95% CI 0.0%; 13.2%] in the melatonin group 2 weeks postoperatively (P = 1.00) and 6.3% (1/16) [95% CI 0.0%; 30.2%] in the placebo group and 0% (0/26) [95% CI 0.0%; 13.2%] in the melatonin group 12 weeks postoperatively (P = 0.38). Sleep efficiency was significantly greater in the melatonin group; mean difference was 4.28% [95% CI 0.57; 7.82] (P = 0.02). The total sleep period was significantly longer in the melatonin group; mean difference was 37.0 min [95% CI 3.6; 69.7] (P = 0.03). Conclusion. Melatonin increased sleep efficiency and total sleep time but did not affect cognitive function. The dropout rate was significantly lower in the melatonin group. This trial is registered with Clinicaltrials.gov NCT01355523.

Effect of Melatonin on Sleep in the Perioperative Period after Breast Cancer Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial

“…However, our study did not administer a pre-surgery (60 min before surgery) dose of melatonin and in this way differed from the other studies. 4,5,7 We, however, found a similar increase in SE which was also reported in the sleep diary 24 from the same study population. Overall, subjective and objective sleep outcomes seem to describe two different dimensions of sleep.…”

“…21 Other secondary outcomes on postoperative cognitive dysfunction (POCD), sleep diary and VAS data have also been reported previously. 24 Subjective sleep outcomes (sleep diary and VAS) were reported as summarized data in 2 periods (perioperative period and long-term postoperative period), which is different from the current paper. The study was approved by the Local Ethics Committee (H-4-2011-007), the Danish Medicines Agency (EudraCT nr.…”

“…The VAS data in the current publication represent a detailed analysis of VAS data measured in the perioperative period which has previously been published. 24…”

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

“…This study extended data that use of 20mg of melatonin prior to the first cycle of ACBC has a neuroprotective effect on cognitive functions evaluated by a set of tests that measures several PLOS ONE dimensions of cognitive flexibility allied to attention. However, a study that used 6mg of melatonin prior and post ACBC did not find a similar benefit in cognitive function [19]. In fact, our results are in the sense of most clinical studies that demonstrated a benefit of 20mg of melatonin use in cancer patients on clinical outcomes (i.e.…”

“…Therefore, it can be considered a physiological sleep regulator, reaching higher plasma levels during the night. According to several studies, exogenous melatonin has demonstrated a positive influence on depressive symptoms and sleep quality in breast cancer patients [19][20][21]. However, its neuroprotective effect to contra-regulate the neurotoxicity induced by ACBC on cognitive function needs further exploration.…”