Nonopioid Pharmacologic Treatments for Chronic Pain

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Systematic Review

Source: Agency for Healthcare Research and Quality

Last Reviewed: June 2022

In this systematic review, the Agency for Healthcare Research and Quality (AHRQ) evaluated the benefits and harms of non-opioid drugs in randomized controlled trials of patients with specific types of chronic pain, considering the effects on pain, function, quality of life, and adverse events. 

Researchers found that:

  • In the short term, improvement in pain and function was small with specific anticonvulsants, moderate with specific antidepressants in diabetic peripheral neuropathy/post-herpetic neuralgia and fibromyalgia, and small with nonsteroidal anti-inflammatory drugs (NSAIDs) in osteoarthritis and inflammatory arthritis.
  • In the intermediate term, evidence was limited — with evidence of benefit for memantine in fibromyalgia and for serotonin norepinephrine reuptake inhibitor (SNRI) antidepressants in low back pain and fibromyalgia.
  • In the long term, evidence was too limited to draw conclusions. In general, evidence on quality of life was limited and no treatment achieved a large improvement in pain or function.
  • Small to moderate, dose-dependent increases in withdrawal due to adverse events were found with the SNRIs duloxetine and milnacipran, the anticonvulsants pregabalin and gabapentin, and NSAIDs. Large increases were seen with oxcarbazepine. NSAIDs have increased risk of serious gastrointestinal, liver dysfunction, and cardiovascular adverse events.

Increased incidence of drug class-specific adverse events led to withdrawal from treatment in some patients, suggesting that careful consideration of patient characteristics is needed in selecting non-opioid drug treatments.

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Suggested Citation


McDonagh MS, Selph SS, Buckley DI, et al. (2022). Nonopioid Pharmacologic Treatments for Chronic Pain. Retrieved from