Madsen, M.T., Hansen, M.V., Andersen, L.T., Hageman, I., Rasmussen, L.S., Bokmand, S., . . . Gogenur, I. (2015). Effect of melatonin on sleep in the perioperative period after breast cancer surgery: A randomized, double-blind, placebo-controlled trial. Journal of Clinical Sleep Medicine, 12, 225–233. 

To conduct a secondary data analysis from the MELODY trial to determine if 6 mg of oral melatonin administered at bedtime pre- and postsurgery would improve objective and subjective sleep outcomes in patients with breast cancer

The original study design was a randomized, double-blind, placebo-controlled trial to test the effect of melatonin on depressive symptoms. Participants randomized to melatonin or placebo taken at bedtime for three days prior to surgery and continued until 12 weeks postoperative. Secondary data points for sleep are described in this article. No baseline sleep assessment was reported, and time points of subjective and objective data collection were preoperative night 2/3, preoperative night 1, postoperative night 1/2/3, postoperative night 4/5/6, and night before histology information, normally two weeks postoperative.

• N = 48  
• MEAN AGE = 55 years
• AGE RANGE = 34–74 years 
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Nonmetastatic breast cancer 
• OTHER KEY SAMPLE CHARACTERISTICS: All participants were surgical patients scheduled for mastectomy or lumpectomy with sentinel node dissection with and without axillary dissection.

• SITE: Single site    
• SETTING TYPE: Not specified    
• LOCATION: Herlev Hospital, Copenhagen, Denmark

• PHASE OF CARE: Active antitumor treatment

• Secondary analysis of effect of melatonin on subjective and objective sleep  pre- and postsurgery

Subjective measures included visual analog scale for subjective sleep quality (0 mm = best possible sleep and 100 mm = worst sleep). The Karolinska sleepiness scale (KS) was used to assess level of sleepiness using nine-point scale (1 = very alert, 10 = very sleepy). No psychometric properties were provided. Objective sleep actigraphy data were guided with a sleep diary for parameters of efficiency, time in bed, total sleep time, wake after sleep onset (WASO), latency, and awakenings. Actigraphy was recorded for the entire study period.

Evaluation of objective sleep outcomes from actigraphy revealed no significant differences for preoperative sleep or wake outcome variables postoperatively and prehistology. Sleep efficiency was higher in the treatment group (p < 0.03). WASO was significantly lower in the postoperative times of 1/2/3 and 4/5/6 in the melatonin group (p < 0.03). No significant differences were found in the subjective measurements (sleep, pain, KSS) preoperatively and postoperatively.

Use of oral 6 mg of melatonin one hour before bed significantly increased efficiency in the three postoperative time points, and WASO decreased during the postoperative time points. However, subjective sleep and pain did not improve. Melatonin use needs to be further evaluated as this study had several limitations.

• Small sample (less than 100)
• Measurement validity/reliability questionable
• Findings not generalizable
• Questionable protocol fidelity
• Subject withdrawals of 10% or greater
• Appropriateness of study statistical plan is questionable.
• The active and placebo groups differed on the duration of surgery and anesthesia; since one of the three-day sleep periods included postoperative nights one, two, and three, the duration of anesthesia may have affected sleep and other outcomes in the first postoperative night, which should have been accounted for or addressed in the Limitations section.
• The rationale for 6 mg dose is missing.

Nurses need to inquire about pre- and postoperative use of any medications to understand and counsel patients and family members on evidence that would support the use of the medication. Melatonin may be helpful to improve sleep, but additional studies are needed.