Melatonin

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.

To determine if oral melatonin administered at night would reduce fatigue and improve sleep in patients with advanced cancer treated in a palliative care facility

This was a two-part trial. In part one, patients received either melatonin (20 mg) or placebo followed by a washout of two days, then crossed over and received the opposite of the first week of treatment. Part two was an open-label study of patients who completed part one and chose to continue melatonin. Study questionnaires were completed at the beginning and end of each treatment period (days 1, 7 ,10, and 17). In part two, study measures were obtained weekly. Patients were randomly assigned to the order in which they received melatonin or placebo.

• N = 34 by ITT analysis  
• MEAN AGE = 64.5 years
• AGE RANGE = 35–84 years
• MALES: 38%, FEMALES: 62%
• KEY DISEASE CHARACTERISTICS: Breast and lung cancer were most common. All had advanced disease.

• SITE: Single site  
• SETTING TYPE: Inpatient  
• LOCATION: Denmark

• PHASE OF CARE: Active antitumor treatment

• Randomized, placebo-controlled, crossover trial

• Multidimensional Fatigue Inventory (MFI)
• EORTC Cancer Quality of Life Core 15 for palliative care patients (EORTC-QLQ-C15-PAL)

No significant differences were noted in patient outcomes between the placebo and melatonin groups.

Melatonin administration did not improve fatigue, insomnia, or other symptoms in patients with advanced cancer.

• Small sample (less than 100)
• Subject withdrawals 10% or greater
• Multiple and frequent use of the same measurement tools

This study did not show any improvement in fatigue or sleep as a result of melatonin.