Project 442962

Chronic pain affects 20-30% of Canadians, costs >$650 billion/year in North America and is recognized as a disease in its own right. Current therapies have limited efficacy and tolerability. Rational, carefully supervised, combination therapy with different treatments may provide improvements in pain relief and quality of life and potentially fewer anti-inflammatory drug-related and opioid-related mortalities. Over half of pain sufferers receive 2 or more analgesic drugs, but evidence for combination therapy is limited and more research is needed. Our previous CIHR-funded trials have shown improved patient outcomes with combination therapy and provided a framework to evaluate novel combinations for chronic pain. We now propose a double-blind, randomized, placebo-controlled, 4-period crossover trial to compare a pregabalin (PGB) + melatonin (MLT) combination versus monotherapy for chronic pain (fibromyalgia). The anticonvulsant, PGB, has been shown to reduce pain, and also improve sleep maintenance in multiple trials. The pineal hormone, MLT, has shown evidence of pain reduction in both laboratory and clinical settings and multiple clinical trials demonstrating efficacy for primary insomnia and delayed sleep phase syndrome. We hypothesize that a PGB+MLT combination has superior efficacy versus monotherapy for chronic pain, because of: 1) favourable interactions between these agents; 2) evidence of superior efficacy of other PGB-containing, and MLT-containing combinations; and 3) compounded benefits of concurrently reducing both pain and sleep disturbance. We will evaluate pain, and also sleep, function, mood, and adverse effects in patients taking these agents. Expected results will guide improvements in therapy by advancing knowledge about rational combination therapy for chronic pain. Our Canadian Chronic Pain Network will provide opportunities for subsequent confirmatory trials and related knowledge translation efforts across Canada and beyond.