The Effect of Melatonin on Depression, Anxiety, Cognitive Function and Sleep Disturbances in Breast Cancer Patients (MELODY)

• Major Depression Inventory (MDI) [ Time Frame: App. 1 week pre-operatively = day -7 ] [ Designated as safety issue: No ]
  MDI is a self-rating depression scale with 12 questions. MDI has previously been investigated in a Danish population. On a six-point Likert scale, the items measure how much time the symptoms have been present during the last 14 days. MDI is scored according to specific guidelines and can be used as a rating scale/diagnostic instrument. When used as a diagnostic instrument patients are classified as mild, moderate or severe depression or no depression.
  
  
• MDI [ Time Frame: App. 2 weeks postoperatively = day 14 ] [ Designated as safety issue: No ]
  MDI is a self-rating depression scale with 12 questions. MDI has previously been investigated in a Danish population. On a six-point Likert scale, the items measure how much time the symptoms have been present during the last 14 days. MDI is scored according to specific guidelines and can be used as a rating scale/diagnostic instrument. When used as a diagnostic instrument patients are classified as mild, moderate or severe depression or no depression.
  
  
• MDI [ Time Frame: App. 4 weeks postoperatively = day 28 ] [ Designated as safety issue: No ]
  MDI is a self-rating depression scale with 12 questions. MDI has previously been investigated in a Danish population. On a six-point Likert scale, the items measure how much time the symptoms have been present during the last 14 days. MDI is scored according to specific guidelines and can be used as a rating scale/diagnostic instrument. When used as a diagnostic instrument patients are classified as mild, moderate or severe depression or no depression.
  
  
• MDI [ Time Frame: App. 8 weeks postoperatively = day 56 ] [ Designated as safety issue: No ]
  MDI is a self-rating depression scale with 12 questions. MDI has previously been investigated in a Danish population. On a six-point Likert scale, the items measure how much time the symptoms have been present during the last 14 days. MDI is scored according to specific guidelines and can be used as a rating scale/diagnostic instrument. When used as a diagnostic instrument patients are classified as mild, moderate or severe depression or no depression.
  
  
• MDI [ Time Frame: App. 12 weeks postoperatively = day 84 ] [ Designated as safety issue: No ]
  MDI is a self-rating depression scale with 12 questions. MDI has previously been investigated in a Danish population. On a six-point Likert scale, the items measure how much time the symptoms have been present during the last 14 days. MDI is scored according to specific guidelines and can be used as a rating scale/diagnostic instrument. When used as a diagnostic instrument patients are classified as mild, moderate or severe depression or no depression.
  
  

• Anxiety [ Time Frame: Daily - from inclusion till 14 days postoperatively ] [ Designated as safety issue: No ]
  Anxiety measured by VAS (visual analog scale)
  
  
• Sleep architecture [ Time Frame: From inclusion till 14 days postoperatively ] [ Designated as safety issue: No ]
  Actigraphy (total minutes asleep, sleep effectiveness, sleep latency, awakenings). A wrist actigraph will be worn from inclusion till 14 days postoperatively.
  
  
• Cognitive function [ Time Frame: App. 1 week preoperatively = day-7 ] [ Designated as safety issue: No ]
  Domaine specific changes in cognitive function measured by ISPOCD (International Study of Post-Operative Cognitive Dysfunction) neuropsychological test-battery.
  
  
• Cognitive function [ Time Frame: App. 2 weeks postoperatively = day 14 ] [ Designated as safety issue: No ]
  Domaine specific changes in cognitive function measured by ISPOCD (International Study of Post-Operative Cognitive Dysfunction) neuropsychological test-battery.
  
  
• Cognitive function [ Time Frame: App. 12 weeks postoperatively = day 84 ] [ Designated as safety issue: No ]
  Domaine specific changes in cognitive function measured by ISPOCD (International Study of Post-Operative Cognitive Dysfunction) neuropsychological test-battery.
  
  
• HPER3 genotype [ Time Frame: At inclusion = day-7 ] [ Designated as safety issue: No ]
  A blood sample will be taken at inclusion and analysed for HPER3 genotype (4/4, 4/5, 5/5) and this will be investigated for a correlation with sleep, cognitive function and depressive symptoms
  
  
• Sleep [ Time Frame: Daily from inclusion till 14 days postoperatively ] [ Designated as safety issue: No ]
  Subjective sleep score on Visual Analog Scale. Sleepiness measured by Karolinska Sleepiness Scale. A sleep-diary recording sleep quantity of day and night sleep. Completed daily.
  
  
• Sleep [ Time Frame: App. 14 days postoperatively till 12 weeks postoperatively ] [ Designated as safety issue: No ]
  Subjective sleep on a Visual Analog Scale. Sleepiness measured by Karolinska Sleepiness Scale. A sleep-diary recording sleep quantity of day and night sleep. Completed every 14th day.
  
  
• Fatigue [ Time Frame: Daily from inclusion till 14 days postoperatively ] [ Designated as safety issue: No ]
  Fatigue on a Visual Analog Scale - filled out daily.
  
  
• Fatigue [ Time Frame: App. 14 days postoperatively till 12 weeks postoperatively ] [ Designated as safety issue: No ]
  Fatigue on a Visual Analog Scale - filled out every 14th day.
  
  
• General well-being [ Time Frame: Daily from inclusion till 14 days postoperatively ] [ Designated as safety issue: No ]
  Generel well-being on a Visual Analog Scale - filled out daily.
  
  
• General well-being [ Time Frame: App. 14 days postoperatively till 12 weeks postoperatively ] [ Designated as safety issue: No ]
  General well-being on a Visual Analog Scale - filled out every 14th day.
  
  
• Pain [ Time Frame: Daily from inclusion till 14 days postoperatively ] [ Designated as safety issue: No ]
  Pain on a Visual Analog Scale - filled out daily.
  
  
• Pain [ Time Frame: App. 14 days postoperatively till 12 weeks postoperatively ] [ Designated as safety issue: No ]
  Pain on a Visual Analog Scale - filled out every 14th day.
  
  
• Anxiety [ Time Frame: App. 14 days postoperatively till 12 weeks postoperatively ] [ Designated as safety issue: No ]
  Anxiety measured by VAS (visual analog scale). Completed every 14th day.
  
  

About 1.4 million women are diagnosed with breast cancer every year. Breast cancer is the most common malignancy among women worldwide constituting about 1/5 of all cancer types. Breast cancer diagnosis and treatment, and the months following primary therapy are stressful times for most women. Aside from the actual "cancer threat" many women experience various degrees of depression, anxiety, sleep disturbances and memory/concentration problems (cognitive dysfunction). Naturally these factors influence the quality of life but also contribute to morbidity and mortality.

Melatonin is a regulatory circadian hormone having, among others, hypnotic, sedative, anxiolytic and possibly anti-depressive effects. It has very low toxicity and very few adverse effects.

The purpose of this project is to test melatonin (6 mg daily for 1 week preoperatively to 12 weeks postoperatively) on breast cancer patients and hopefully hereby be able to prevent depression, anxiety, sleep disturbances and cognitive dysfunction. On an overall perspective this will hopefully contribute to improving the quality of life for these patients and extend their lifetime. Furthermore the investigators will be examining whether a specific gene called a clock-gene (HPER3) is correlated with an increased risk of depression, sleep disturbances or cognitive dysfunction. If this is the case it could become possible to identify women with an increased risk and provide prophylactic treatment for those with a risk of developing a depression, sleep disturbances or cognitive disturbances.

Sample size calculations were based on our primary outcome parameter. Using a conservative estimate for the incidence of depression, the investigators expect to find a reduction from 30% to 15% with melatonin treatment. Sample size is sufficient to include our secondary and tertiary outcome parameters as well. The sample size calculations were calculated with a power of 80%, a type I error of 5% and a type II error of 20%.