Melatonin treatment has consistent but transient beneficial effects on sleep measures and pain in patients with severe chronic pain: the DREAM-CP randomised controlled trial

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 TM compared with placebo. Sixty male and female subjects with chronic severe pain were randomised to receive either 2 mg of Circadin TM 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 TM 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.