The use of nonopioid pharmacologic agents for noncancer chronic pain was associated with small to moderate improvements in pain and function in the short term, according to an evidence report published by the Agency for Healthcare Research and Quality (AHRQ).

The report aimed to evaluate the effectiveness of nonopioid drugs in patients with specific types of chronic pain. “Given the complexity of treating chronic pain and concerns regarding the safety and long term effectiveness of opioids, there is a need for a comprehensive understanding of the benefits and harms of nonopioid pharmacologic treatments,” the authors explained. The benefits and harms of nonopioid agents were evaluated by considering their effect on pain, function, quality of life, and adverse events.

Various electronic databases were accessed to obtain randomized controlled trials (RCTs) evaluating nonopioid agents in chronic pain patients. The review focused on 7 chronic pain conditions, including neuropathic pain, fibromyalgia, osteoarthritis, inflammatory arthritis, low back pain, chronic headache, and sickle cell disease. Short term (1 to <6 months after completion of treatment), intermediate term (≥6 to <12 months), and long term (≥12 months) effects were assessed for each drug. Additionally, the magnitude of each effect was categorized as small, moderate, or large based on previously defined criteria. 

A total of 185 RCTs were included in the review. In the short term, findings of the analysis revealed small to moderate improvements (ie, 5-20 points on a 0-100 point scale) in pain with pregabalin, gabapentin, oxcarbazepine, and duloxetine for neuropathic pain; pregabalin, gabapentin, duloxetine, and milnacipran for fibromyalgia; duloxetine and nonsteroidal anti-inflammatory drugs (NSAIDs) for osteoarthritis; duloxetine for low back pain, and NSAIDs for inflammatory arthritis. Treatment was also associated with small improvements in function, apart from duloxetine for low back pain and gabapentin/pregabalin for neuropathic pain. Quality of life improvements were noted with duloxetine for neuropathic pain and osteoarthritis, however, evidence was limited for the other agents. 

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Studies evaluating nonopioid agents for intermediate and long term term outcomes, however, were limited. There was some evidence indicating  that memantine improved pain, function, and quality of life in fibromyalgia patients in the intermediate term; improvements in pain were also found to be maintained with duloxetine and milnacipran. 

Findings of the analysis also showed that increases in withdrawal due to adverse events were small to moderate and dose dependent for some agents (duloxetine, milnacipran, pregabalin, gabapentin, NSAIDs) and large for others (oxcarbazepine). 

“Our report reviewed evidence that may help inform decisions regarding prioritization of nonopioid drug therapies by clinicians and patients when selecting therapy,” the authors concluded. They added that “The evidence reviewed here may also help inform healthcare policy (including reimbursement policy) related to coverage of these nonopioid treatments, and inform policy decisions regarding funding priorities for future research.”


McDonagh MS, Selph SS, Buckley DI, et al. Nonopioid Pharmacologic Treatments for Chronic Pain. [published online April 16, 2020]. Agency for Healthcare Research and Quality. doi: 10.23970/AHRQEPCCER228.