Study Finds Limited Evidence to Support Use of Non-Opioid Drugs for Chronic Pain

By Pat Anson, PNN Editor

A new study by federal researchers has found limited evidence to support the use of non-opioid medications in treating chronic pain conditions such as fibromyalgia, neuropathy, rheumatoid arthritis and low back pain.

Only small improvements in pain and function were found in the use of anti-convulsants and non-steroidal anti-inflammatory drugs (NSAIDs), while moderate improvement was found in the use of some antidepressants.

Researchers noted that evidence was “too limited to draw conclusions” on long-term use of non-opioid drugs, and “no treatment achieved a large improvement in pain or function.” They also cautioned that “careful consideration of patient characteristics is needed in selecting nonopioid drug treatments” because of the risk of side effects.

The report was prepared for the Agency for Healthcare Research and Quality (AHRQ) by the Pacific Northwest Evidence-based Practice Center (EPC) at Oregon Health & Science University. The EPC has recently finalized two other studies on the use of opioids and nonpharmacological treatments for chronic pain.

Unlike their report on opioids, EPC researchers did not consult with technical experts and peer reviewers associated with Physicians for Responsible Opioid Prescribing (PROP), an anti-opioid activist group.

The researchers analyzed nearly 200 clinical studies and systematic reviews of non-opioid medication. Only 25 of the studies were rated as good quality and only 8 lasted a year or more. The pharamceutical industry funded 82 percent of them.

The EPC report is more cautious than other federal studies on the use of non-opioids such as pregabalin (Lyrica) and gabapentin (Neurontin).  Side effects from those drugs were often so severe that some patients stopped taking them and dropped out of clinical studies.

“Large increases in risk of adverse events were seen with pregabalin (blurred vision, cognitive effects, dizziness, peripheral edema, sedation, and weight gain), gabapentin (blurred vision, cognitive effects, sedation, weight gain), and cannabis (nausea, dizziness),” EPC researchers found. “Dose reductions reduced the risk of some adverse events with SNRI antidepressants. In the short term small increases in risk of major coronary events and moderate increases in serious gastrointestinal events (both short and long term) were found with NSAIDs.”

The EPC study is in marked contrast to the 2016 CDC opioid guideline, which recommends pregabalin, gabapentin and NSAIDs as alternatives to opioids with little to no mention of their side effects.

Other researchers have also warned that the effectiveness of gabapentin and pregabalin, which belong to a class of anti-convulsant drugs known as gabapentinoids, is often exaggerated in prescribing guidelines.

“Gabapentinoids have become frequent first-line alternatives in patients with chronic pain from whom opioids are being withheld or withdrawn, as well as in patients with acute pain who traditionally received short courses of low-dose opioid,” researchers at the University of South Carolina School of Medicine warned in a 2019 study.

“The evidence to support off-label gabapentinoid use for most painful clinical conditions is limited. For some conditions, no well-performed controlled trials exist.”

The EPC’s trio of studies on opioids, non-opioid drugs and non-pharmacological treatments are expected to help guide the CDC as it prepares an update and expansion of its 2016 opioid guideline, which is expected in late 2021. The update is likely to include new guidelines for treating short term, acute pain.  

How will CDC interpret the EPC findings on opioids and non-opioids? One outcome is suggested in the opioid study.

“Findings support the recommendation in the 2016 CDC guideline that opioids are not first-line therapy and to preferentially use nonopioid alternatives,” researchers said.