Abstract
Background
Sleep disturbance is a major issue for patients with chronic pain. Melatonin has been shown to improve symptoms of fibromyalgia, but its efficacy in other chronic non-malignant pain conditions is not fully known. Hence, we determined the effect of melatonin in patients with severe noncancer chronic pain.
Methods
This was a randomised double-blinded crossover trial of modified-release melatonin as Circadin™ compared with placebo. Sixty male and female subjects with chronic severe pain were randomised to receive either 2 mg of Circadin™ or placebo before sleep for 6 weeks, followed by a >4 week washout, then crossing over to the other treatment. Sleep disturbance, quality, and latency were measured using three different validated sleep assessment tools. The primary outcome measure was self-reported sleep disturbance after 6 weeks of treatment. Adverse events were also recorded.
Results
Sleep disturbance after 6 weeks was not significantly altered by melatonin treatment, but differences between melatonin and placebo treatment periods after 3 weeks were seen: sleep disturbance (P=0.014), latency (P=0.04), overall sleep quality (P=0.004), and effect of pain on sleep (P=0.032). Pain intensity scores improved during both treatment periods (both P<0.001). There were no differences in adverse events between treatment periods.
Conclusions
Circadin™ treatment did not improve sleep disturbance in patients with severe chronic pain compared with placebo at 6 weeks, but there were consistent improvements in aspects of sleep in the shorter term. Given its favourable safety profile, it could be beneficial for some patients with chronic pain.
Sleep disturbance is a major issue for patients with chronic pain. Melatonin has been shown to improve symptoms of fibromyalgia, but its efficacy in other chronic non-malignant pain conditions is not fully known. Hence, we determined the effect of melatonin in patients with severe noncancer chronic pain.
Methods
This was a randomised double-blinded crossover trial of modified-release melatonin as Circadin™ compared with placebo. Sixty male and female subjects with chronic severe pain were randomised to receive either 2 mg of Circadin™ or placebo before sleep for 6 weeks, followed by a >4 week washout, then crossing over to the other treatment. Sleep disturbance, quality, and latency were measured using three different validated sleep assessment tools. The primary outcome measure was self-reported sleep disturbance after 6 weeks of treatment. Adverse events were also recorded.
Results
Sleep disturbance after 6 weeks was not significantly altered by melatonin treatment, but differences between melatonin and placebo treatment periods after 3 weeks were seen: sleep disturbance (P=0.014), latency (P=0.04), overall sleep quality (P=0.004), and effect of pain on sleep (P=0.032). Pain intensity scores improved during both treatment periods (both P<0.001). There were no differences in adverse events between treatment periods.
Conclusions
Circadin™ treatment did not improve sleep disturbance in patients with severe chronic pain compared with placebo at 6 weeks, but there were consistent improvements in aspects of sleep in the shorter term. Given its favourable safety profile, it could be beneficial for some patients with chronic pain.
| Original language | English |
|---|---|
| Pages (from-to) | 725-734 |
| Number of pages | 10 |
| Journal | British Journal of Anaesthesia |
| Volume | 132 |
| Issue number | 4 |
| Early online date | 14 Feb 2024 |
| DOIs | |
| Publication status | Published - Apr 2024 |
Bibliographical note
AcknowledgementsWe are very grateful to Flynn Pharma Ltd. for the provision of Circadin™ and placebo tablets for this trial. We acknowledge the members of the Trial Steering Group and the Data and Safety Monitoring Committee and the trial participants.
Funding:
British Journal of Anaesthesia/Royal College of Anaesthetists, grant reference WKR0-2017-0043.
Data Availability Statement
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Keywords
- chronic pain
- clinical trial
- crossover
- melatonin
- sleep