Melatonin

To evaluate the impact of melatonin on survivors of breast cancer with data analysis of secondary quality-of-life outcomes (sleep, mood, hot flashes)

Participants were randomized using 1:1 randomization format and received four months of 3 mg melatonin or placebo nightly at 9 pm.

• N = 85
• MEAN AGE: 59 years
• RANGE: 38-81 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Stage I-III primary nonmetastatic breast cancer, ductal carcinoma in situ, lobular carcinoma in situ, completed with active treatment (surgery, radiation, chemotherapy, and hormonal therapy) 60 days prior to enrollment.
• OTHER KEY SAMPLE CHARACTERISTICS: There was no history of other cancers except nonmelanoma skin cancer; no night-shift work; no active seizures with medication; and no beta-blocker, warfarin, hormonal therapy, black cohosh, flaxseed, soy, or sleep-aid use. There was also no melatonin use 30 days prior to enrollment.

• SITE: Single site
• SETTING TYPE: Outpatient
• LOCATION: Dana-Farber/Harvard Cancer Center, Boston, MA

PHASE OF CARE: Transition phase after active treatment

• Secondary analysis of the effect of melatonin on sleep, mood, and hot flashes
• Original study was a double-blind, placebo-controlled, randomized trial

• Subjective measures included Pittsburgh Sleep Quality Index (PSQI) (19-item scale)
• Center for Epidemiologic Studies Depression (CES-D) (20-item scale)
• North Center Cancer Treatment Group hot flash diary (frequency and intensity of hot flashes over seven days, and severity [1 = mild to 4 = very severe]).
• Diary data summed but number of and severity of hot flashes per day, calculation of hot flash score using frequency and severity

No baseline differences in characteristics were noted between groups (n = 48 melatonin; n = 46 placebo). Sleep outcomes included significant improvement in sleep quality, daytime dysfunction, and PSQI total scores in treatment versus placebo. Overall change of sleep over time using all time points, which was adjusted for multiple comparisons, showed overall high PSQI global scores in placebo group (1.67) (95% CI [0.67, 2.66]), indicating worse sleep quality. CES-D scores did not change over time. Hot flash frequency decreased over time for both treatment groups. Only grade 1-2 toxicities were reported.

The use of oral 3 mg of melatonin showed minimal side effects with possible impact on the improvement of subjective sleep quality. There was no exclusion for prior sleep disorders, limiting understanding of MOA of melatonin and preexisting sleep disorders. Sleep was a secondary outcome of this study and needs larger RCT trials to verify results.

• Small sample (less than 100)
• Details of randomization process are missing.
• Melatonin dose is often started low and increased as needed; yet the rationale for a stable 3 mg dose of melatonin in this study is unclear
• Underpowered for evaluation of effect on hot flashes

Oral 3 mg melatonin is potentially a safe and effective treatment for sleep disturbances in survivors of breast cancer with baseline poor sleep quality. However, additional larger scale-studies in which sleep is the primary variable outcome are needed using objective and subjective measures of sleep.

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.