Gabapentinoids Ineffective for Pain Relief After Surgery

By Pat Anson, PNN Editor

Would you want to take Lyrica (pregabalin) or Neurontin (gabapentin) for pain relief after a major surgery? Both drugs belong to a class of nerve medication called gabapentinoids that are increasingly being prescribed to patients perioperatively (after surgery) as an alternative to opioid medication.

But gabapentinoids also have risks and there is little evidence to support their use for postoperative pain relief, according to a large new study by a team of Canadian researchers.  

“No clinically significant analgesic effect for the perioperative use of gabapentinoids was observed. There was also no effect on the prevention of postoperative chronic pain and a greater risk of adverse events. These results do not support the routine use of pregabalin or gabapentin for the management of postoperative pain in adult patients,” wrote lead author Michael Verret, MD, a resident at Laval University in Quebec City.  

Verret and his colleagues conducted a meta-analysis of 281 clinical trials involving nearly 25,000 patients undergoing a wide range of surgeries, including orthopedic, spinal and abdominal operations.

Their findings, recently published in the journal Anesthesiology, indicate that the analgesic benefits of pregabalin and gabapentin after surgery are negligible, regardless of the dose or type of operation. Gabapentinoids were also ineffective in preventing chronic pain from developing after surgery, one of the primary justifications for using the drugs postoperatively.

“Gabapentinoids were also associated with a greater incidence of adverse events, namely dizziness and visual disturbance, while other major adverse events such as respiratory depression and addiction are not reported or are underreported,” said Verret.

The findings contradict guidelines published by the American Pain Society (APS) in 2016,  which advocate “around the clock” use of gabapentin, pregabalin and other nonopioid drugs both before and after surgery.

“The panel recommends use of gabapentin or pregabalin as part of a multimodal regimen in patients who undergo surgery. Both medications are associated with reduced opioid requirements after major or minor surgical procedures, and some studies reported lower postoperative pain scores,” the APS guideline states.

“The panel suggests that clinicians consider a preoperative dose of gabapentin or pregabalin, particularly in patients who undergo major surgery or other surgeries associated with substantial pain, or as part of multimodal therapy for highly opioid-tolerant patients.”

‘Evidence of Harm’

Although opioid addiction is relatively rare after surgery, dozens of U.S. hospitals followed the lead of the APS and other medical guidelines by stopping the use of opioids for certain surgeries.

Cleveland Clinic Akron General Hospital, for example, adopted a policy of only using gabapentin and other non-opioid analgesics for colorectal operations.

It is now clear that over the past two decades, evidence of benefit from routine perioperative administration of gabapentinoids has diminished, while evidence of harm has increased.
— Dr. Evan Kharasch

Critics say gabapentinoids have become a trendy alternative for post-surgical pain relief, even though evidence supporting their use is minimal.

“It is now clear that over the past two decades, evidence of benefit from routine perioperative administration of gabapentinoids has diminished, while evidence of harm has increased. If any potential benefits exist in ‘special populations,’ published reports have yet to identify the benefits or the populations,” lead author Evan Kharasch, MD, Editor-in-Chief of Anesthesiology, wrote in an editorial.

“The good intentions that led to routine gabapentinoid use should be redirected to lead the way out. The French Society of Anesthesia and Intensive Care Medicine now states that gabapentinoids should not be used systematically or in outpatient surgery. Other societies should follow. As the weight of evidence has shifted and the risk–benefit balance tilted away from benefit, evidence-based practice impels revising if not eliminating the routine use of perioperative gabapentinoids in adults.”

It's too late for the APS to change its guideline. The organization filed for bankruptcy in 2019, ironically because of the high cost of legal fees in defending itself against opioid litigation.

While the CDC’s controversial opioid guideline does not advocate using gabapentinoids for post-surgical pain, it does recommend their use in treating chronic pain -- with little to no mention of their side effects.

One of the co-authors of the CDC guideline, Dr. Roger Chou, also played a significant role in drafting the APS guideline. Chou is currently heading much of the research being conducted by the CDC as it prepares to update and possibly expand its 2016 guideline.