Hansen, M.V., Andersen, L.T., Madsen, M.T., Hageman, I., Rasmussen, L.S., Bokmand, S., . . . Gogenur, I. (2014). Effect of melatonin on depressive symptoms and anxiety in patients undergoing breast cancer surgery: A randomized, double-blind, placebo-controlled trial. Breast Cancer Research and Treatment, 145, 683–695. 

To investigate whether melatonin could lower the risk of depressive symptoms in women with breast cancer in a three-month period after surgery with a secondary aim of assessing the effect of melatonin on anxiety, sleep, general well-being, fatigue, pain, and sleepiness in the immediate and long-term postoperative period

This study compared 6 mg oral melatonin versus a placebo daily one hour before bedtime for one week preoperatively and 12 weeks postoperatively (or a placebo administered on the same schedule).

• N = 54 intention to treat (28 intervention, 26 placebo); 43 analyzed per protocol (27 intervention, 16 placebo)
• MEAN AGE = 51 years (melatonin), 60 years (placebo) (SD = 46–68 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Breast cancer; majority lumpectomy plus sentinel lymph node; majority received chemotherapy; majority did not receive antihormone therapy 

• SETTING TYPE: Outpatient    
• LOCATION: Denmark, Department of Breast Surgery

• PHASE OF CARE: Active antitumor treatment

Randomized, double-blinded, placebo-controlled trial

• Major Depression Inventory (MDI)
• Visual Analog Scale (VAS) and Karolinska Sleepiness Scale (KSS) for anxiety, sleep, general well-being, fatigue, and pain
• ActiGraph
• Sleep diary

The incidence of depressive symptoms (MDI = 21) at one point in the study period was significantly different between groups, as 45% (9/20) of patients had depressive symptoms in the placebo group versus 11% (3/27) in the melatonin group (p =  0.008); relative risk 0.25 (95%, CI: 0.076–0.80). The area under the curve for VAS data on anxiety, sleep, general well-being, fatigue, and pain and KSS for sleepiness in the short-term perioperative period showed no significant differences between the two groups.

This study demonstrated no effects of melatonin on fatigue; it may be useful for the prevention of depression in women with breast cancer.

• Small sample (< 100)
• Key sample group differences that could influence results
• Other limitations/explanation: A large number of patients assessed for eligibility did not meet criteria; depression, not fatigue, was the primary endpoint; and there were more participants in the placebo group ineligible for analysis than the experimental group.

Melatonin is not effective in treating cancer-related fatigue; it may be useful in preventing depression.