Effectiveness Not Established

Melatonin

for Cognitive Impairment

Melatonin is a naturally occurring hormone produced by the pineal gland that has numerous biologic effects, including antioxidant properties and potential effects on the sleep-wake cycle and immune system functions. Melatonin is available as a dietary supplement. Long-term effects of supplementation are not known. Melatonin has been studied for its effect on anorexia, depression, fatigue, sleep-wake disturbances, and cognitive impairment in people with cancer.

Research Evidence Summaries

Hansen, M.V., Madsen, M.T., Andersen, L.T., Hageman, I., Rasmussen, L.S., Bokmand, S., . . . Gogenur, I. (2014). Effect of melatonin on cognitive function and sleep in relation to breast cancer surgery: A randomized, double-blind, placebo-controlled trial. International Journal of Breast Cancer, 2014, 416531. 

Study Purpose

To determine the effectiveness of melatonin on postoperative cognitive function and sleep quality in women who underwent breast cancer surgery

Intervention Characteristics/Basic Study Process

The intervention group received 6 mg of melatonin orally one hour before bedtime one week prior to surgery through 12 weeks postoperatively. The control group received a placebo medication packaged by the hospital pharmacy with the same instructions. Both the placebo and melatonin were labeled and administered identically. Neuropsychological testing was conducted within one week preoperatively and after two and 12 weeks postoperatively. Sleep assessments were collected three days preoperatively to eight days postoperatively (short-term) and 2–12 weeks postoperatively (long-term).

Sample Characteristics

  • N = 54 (intervention 28, placebo 26)  
  • MEAN AGE = 51 years (intervention), 60 years (placebo)
  • FEMALES: 100%
  • KEY DISEASE CHARACTERISTICS: Women who were 30–75 years old undergoing a lumpectomy or mastectomy and were American Society of Anesthesiologists classes I–III
  • OTHER KEY SAMPLE CHARACTERISTICS: Exclusions included patients who were pregnant; depression as indicated by the Major Depression Inventory; current chemotherapy; patients taking SSRIs, antithrombotic agents, MAO inhibitors, calcium channel blockers, or insulin; patients with pre-existing neurologic diseases, sleep apnea, another sleep disorder, kidney disease, autoimmune disorders, or an allergy to melatonin

Setting

  • SITE: Single-site    
  • SETTING TYPE: Multiple settings    
  • LOCATION: Herlev Hospital Department of Breast Surgery, Copenhagen, Denmark

Phase of Care and Clinical Applications

  • PHASE OF CARE: Active antitumor treatment

Study Design

Double-blinded, randomized, controlled study

Measurement Instruments/Methods

  • Mini-Mental State Examination (MMSE)
  • International Studies of Postoperative Cognitive Dysfunction (ISPOCD) Test Battery
    • Visual verbal learning test 
    • Concept shifting task
    • Letter-digit coding test 
    • Stroop color-word test
  • Sleep diary (sleep latency, number of awakenings, total sleep, sleep efficiency) 
  • Sleep Visual Analog Scale (VAS)
  • Major Depression Scale (MDS)

Results

There were no statistically significant differences between group characteristics. There was no evidence of cognitive impairment two weeks postoperatively in either group; however, there was a decline in cognitive performance (as a composite z-score) in the placebo group, 6.3%, compared to no decline in the intervention group (p = .38). Perioperative sleep efficiency was significantly greater for the intervention group (p = .02). Postoperative total sleep time was greater in the intervention group (p = .03). Side-effect frequency was similar for both groups; however, there was a difference in types of effects reported. Intervention side effects included dizziness (14%), headache (10%), and paresthesias (10%), and the placebo group experienced headache (27%), difficulty falling asleep (13%), and nausea (13%).

Conclusions

Although cognitive impairment was not found to be a significant problem in this sample, subjects who received melatonin had greater sleep efficiency and total sleep time postoperatively than those in the placebo group. In addition, subjects who received melatonin tended to have less cognitive decline although it was not statistically significant.

Limitations

  • Small sample (< 100)
  • Subject withdrawals ≥ 10%
  • Other limitations/explanation: More subjects in the placebo group withdrew (n = 10) than in the intervention group (n = 1).

Nursing Implications

Melatonin may be useful as an intervention to reduce cognitive difficulties and improve sleep, but further study is warranted.

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