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Effect of melatonin on depressive symptoms and anxiety in patients undergoing breast cancer surgery: a randomized, double-blind, placebo-controlled trial

Abstract

Depression, anxiety and sleep disturbances are known problems in patients with breast cancer. The effect of melatonin as an antidepressant in humans with cancer has not been investigated. We investigated whether melatonin could lower the risk of depressive symptoms in women with breast cancer in a three-month period after surgery and assessed the effect of melatonin on subjective parameters: anxiety, sleep, general well-being, fatigue, pain and sleepiness. Randomized, double-blind, placebo-controlled trial undertaken from July 2011 to December 2012 at a department of breast surgery in Copenhagen, Denmark. Women, 30–75 years, undergoing surgery for breast cancer and without signs of depression on Major Depression Inventory (MDI) were included 1 week before surgery and received 6 mg oral melatonin or placebo for 3 months. The primary outcome was the incidence of depressive symptoms measured by MDI. The secondary outcomes were area under the curve (AUC) for the subjective parameters. 54 patients were randomized to melatonin (n = 28) or placebo (n = 26) and 11 withdrew from the study (10 placebo group and 1 melatonin group, P = 0.002). The risk of developing depressive symptoms was significantly lower with melatonin than with placebo (3 [11 %] of 27 vs. 9 [45 %] of 20; relative risk 0.25 [95 % CI 0.077–0.80]), giving a NNT of 3.0 [95 % CI 1.7–11.0]. No significant differences were found between AUC for the subjective parameters. No differences in side effects were found (P = 0.78). Melatonin significantly reduced the risk of depressive symptoms in women with breast cancer during a three-month period after surgery.

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Acknowledgments

This work was supported by grants from the University of Copenhagen, The Aase and Ejnar Danielsens Foundation, The A.P. Møller Foundation for the Advancement of Medical Science, The Else and Mogens Wedell Wedellborgs Foundation, The Beckett Foundation, The Hede Nielsen Family Foundation, The Dagmar Marshalls Foundation and Manufacturer Einar Willumsen’s Memorial Scholarship. These abovementioned funders have had no influence on the design and conduct of the study; collection, management analysis, and interpretation of data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. All these activities are done by the authors. Pharma Nord provided the melatonin and placebo tablets but had no influence on the design and conduct of the study; collection, managementanalysis and interpretation of data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. The study received no financial support from the industry. The authors would also like to thank Rikke Søby Andersen, research nurse, for her help with the study and the patients for their time and participation.

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The authors declare that they have no conflicts of interest.

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The experiments comply with the current laws in Denmark.

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Correspondence to Melissa V. Hansen.

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Hansen, M.V., Andersen, L.T., Madsen, M.T. et al. Effect of melatonin on depressive symptoms and anxiety in patients undergoing breast cancer surgery: a randomized, double-blind, placebo-controlled trial. Breast Cancer Res Treat 145, 683–695 (2014). https://doi.org/10.1007/s10549-014-2962-2

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  • DOI: https://doi.org/10.1007/s10549-014-2962-2

Keywords

  • Breast cancer
  • Depression
  • Anxiety
  • Surgery
  • Melatonin