Home

Survivorship

Melatonin

Melatonin is used in naturopathic practice to resolve sleep disturbances, but is also used because of its immune-active properties. The effect of melatonin on insomnia has been reported in different patient populations, including medically ill patients, critically ill patients, patient with schizophrenia, elder patients and healthy people. However, no RCTs of melatonin in insomnia have been reported in oncology populations.

A study of 40 schizophrenic outpatients with initial insomnia of at least 2 weeks' duration randomly assigned patients to an increase in their current medications with either flexibly dosed melatonin (3-12 mg/night; N = 20) or placebo (N = 20). By use of a questionnaire, double-blind assessments of aspects of sleep functioning were obtained daily across the next 15 days. The modal stable dose of melatonin was 3 mg. Relative to placebo, melatonin significantly improved the quality and depth of nighttime sleep, reduced the number of nighttime awakenings, and increased the duration of sleep without producing a morning hangover (p < .05). Subjectively, melatonin also significantly reduced sleep-onset latency, heightened freshness on awakening, improved mood, and improved daytime functioning (p < .05).

In another study, 33 medically ill persons with initial insomnia were randomly assigned to receive either melatonin (N = 18) or placebo (N = 15) in a flexible-dose regimen. Double-blind assessments of aspects of sleep functioning were obtained daily across the next 8 to 16 days. The mean stable dose of melatonin was found to be 5.4 mg. Relative to placebo, melatonin significantly hastened sleep onset, improved quality and depth of sleep, and increased sleep duration without producing drowsiness, early-morning "hangover" symptoms, or daytime adverse effects (p < .05). Melatonin also contributed to freshness in the morning and during the day and improved overall daytime functioning. Benefits were most apparent during the first week of treatment.

Another study reported on the efficacy and safety of a prolonged release melatonin formulation (PR-melatonin; Circadin* 2 mg) in insomnia patients aged 55 years and older. A total of 354 males and females aged 55-80 years were admitted to the study, 177 to active medication and 177 to placebo. The study consisted of a 2-week, single blind, placebo run-in period followed by a 3-week double blind treatment period with PR-melatonin or placebo, one tablet per day at 2 hours before bedtime. Significant differences in favor of PR-melatonin vs. placebo treatment were found in improvements in quality of sleep, morning alertness, shortening of sleep latency (similar to that of most frequently used sleep medications) and quality of life.

Melatonin use has also been reported in critically ill patients who had undergone a tracheostomy to aid weaning from mechanical ventilation. In a randomized double-blind placebo-controlled trial involving 24 patients, oral melatonin 10 mg or placebo was administered at 9 p.m. for four nights. Melatonin use was associated with a 1-hour increase in nocturnal sleep and 'better' sleep.

In addition to its use for sleep disturbances, melatonin has also been studied in some trials because for its anti-proliferative effects on cancer cells. There is some evidence from RCTs that melatonin may improve quality of life and survival either used by itself or in combination with other substances (such as a low dose interleukin-2 and tamoxifen) in patients with a variety of solid tumors and hematological malignancies.

Safety

Doses between 0.3 to 5mg are usually recommended in naturopathic practice for the treatment of insomnia. However, doses of up to 40 mg a day have been used safely when prescribed for anti-proliferative effects.

Recommendations

Melatonin is used in medical practice by naturopathic physicians in patients with insomnia during cancer. Although evidence is clear that melatonin has a positive effect on insomnia in critically ill patients, no RCTs have been reported until now that have tested the effect in oncology populations.

Show/Hide References

References - Hide References

  • Andrade C, Srihari BS, Reddy KP, Chandramma L. Melatonin in medically ill patients with insomnia: a double-blind, placebo-controlled study. J Clin Psychiatry. 2001 Jan;62(1):41-5.
  • Blask DE, Sauer LA, Dauchy RT. Melatonin as a chronobiotic/anticancer agent: cellular, biochemical, and molecular mechanisms of action and their implications for circadian-based cancer therapy. Curr Top Med Chem. 2002 Feb;2(2):113-32.
  • Bourne RS, Mills GH, Minelli C. Melatonin therapy to improve nocturnal sleep in critically ill patients: encouraging results from a small randomised controlled trial. Crit Care. 2008;12(2):R52. Epub 2008 Apr 18.
  • Cos S, Garcia-Bolado A, Sanchez-Barcelo EJ. Direct antiproliferative effects of melatonin on two metastatic cell sublines of mouse melanoma (B18BL6 and PG19). Melanoma Res 2001;11:197-201. Prostate 2001;46:52-61.
  • Lissoni P, et al. A randomized study with the pineal hormone melatonin versus supportive care alone in patients with brain metastases due to solid neoplasms. Cancer 1994;73:699-701.
  • Lissoni P, et al. A phase II study of tamoxifen plus melatonin in metastatic solid tumour patients. Br J Cancer 1996:74:1466-8.
  • Lissoni P, Chilelli M, Villa S, Cerizza L, Tancini G. Five years survival in metastatic non-small cell lung cancer patients treated with chemotherapy alone or chemotherapy and melatonin: a randomized trial. J Pineal Res. 2003 Aug;35(1):12-5.
  • Lissoni P, Brivio F, Fumagalli L, Messina G, Vigore L, Parolini D, Colciago M, Rovelli F. Neuroimmunomodulation in medical oncology: application of psychoneuroimmunology with subcutaneous low-dose IL-2 and the pineal hormone melatonin in patients with untreatable metastatic solid tumors. Anticancer Res. 2008 Mar-Apr;28(2B):1377-81.
  • Moselhy SS, Al Mslmani MA. Chemopreventive effect of lycopene alone or with melatonin against the genesis of oxidative stress and mammary tumors induced by 7,12 dimethyl(a)benzanthracene in sprague dawely female rats. Mol Cell Biochem. 2008 Aug 6. [Epub ahead of print]
  • Suresh Kumar PN, Andrade C, Bhakta SG, Singh NM. Melatonin in schizophrenic outpatients with insomnia: a double-blind, placebo-controlled study. J Clin Psychiatry. 2007 Feb;68(2):237-41.
  • Wade AG, Ford I, Crawford G, McMahon AD, Nir T, Laudon M, Zisapel N. Efficacy of prolonged release melatonin in insomnia patients aged 55-80 years: quality of sleep and next-day alertness outcomes. Curr Med Res Opin. 2007 Oct;23(10):2597-605.
  • Xi SC, Siu SW, Fong SW, Shiu SY.Inhibition of androgen-sensitive LNCaP prostate cancer growth in vivo by melatonin: association of antiproliferative action of the pineal hormone with mt1receptor protein expression. Prostate. 2001 Jan 1;46(1):52-61.