Access to the PPM Journal and newsletters is FREE for clinicians.

Gabapentinoids for Chronic Low Back Pain? Not So Fast

August 16, 2017
Treatment has significant risk of adverse effects, with no proven benefits for pain relief in patients with chronic low back pain, meta-analysis shows

Interviews with Michael J. Brennan, MD, and Harsha Shanthanna, MD.

Chronic low back pain (CLBP) has a lifetime prevalence between 51% and 80%, and it can leave patients and their physicians desperate for relief.

In recent years—especially as concern over the opioid epidemic has increased—doctors have turned to prescribing the gabapentinoids pregabalin (Lyrica) and gabapentin (Neurontin, others), which have demonstrated benefit for neuropathic pain conditions but not for nonspecific CLBP.

Gabapentinoids are anticonvulsant medications that have shown benefit as antispasticity agents in studies in involving patients with spinal cord injuries. Both gabapentin and pregabalin inhibit the α2δ subunit of L-type voltage-gated Ca2+ channels, which are thought to inhibit glutamate release. Both agents have demonstrated efficacy in treatment of neuropathic pain and spasticity in patients with MS, noted Jeffrey Fudin, PharmD, a member of the Practical Pain Management editorial board.

Now, a new report published in PLOS Medicine urges caution in prescribing these drugs for CLBP, citing a lack of efficacy, risks, and costs.1

"The most important finding is that the widespread use of pregabalin or gabapentin for chronic non-specific low back pain, which is the most common chronic pain ailment today, is not supported by evidence," said study author Harsha Shanthanna, MD, MBBS, MSc, PhD, associate professor of anesthesiology and a chronic pain physician at St. Joseph's Healthcare, McMaster University, Hamilton, Canada.

Dr. Shanthanna and his colleagues are not the only ones concerned about the increase in prescribing of these drugs. In recent guidelines, the National Health Service (NHS) in England addressed its concerns about the off-label use and the risk of misuse of these drugs.2 In addition, the American College of Physicians released new guidelines for low back pain in February, 2017.

Details on Systematic Review, Meta-Analysis

Dr. Shanthanna's team searched MEDLINE, EMBASE and Cochrane from inception until December 20, 2016. They evaluated 8 randomized control studies that met their criteria.  Another 21 studies were excluded. The researchers examined the strength of evidence to determine how useful either drug was in reducing pain and improving functions, while looking at the potential adverse effects of the drug in those with predominant CLBP.

Three studies looked at gabapentin compared to placebo, while the other 5 evaluated pregabalin.

Compared to placebo, many adverse events were more common with the medications, including:

  • Dizziness (RR 1.99, 95% CI, 1.94 to 3.37)
  • Fatigue (RR 1.85, 95% CI, 1.12 to 3.05)
  • Mentation difficulties (RR 3.34, 95% CI, 1.54 to 7.25)
  • Visual disturbances (RR 5.72, 95% CI, 1.94 to 16.91)

The researchers used GRADE (Grading of Recommendations Assessment, Development, and Evaluation) to assess the quality of evidence. Evidence quality was found to be very low for dizziness and fatigue and for mentation problems and moderate for visual problems. Few studies reported functional and emotional improvement, with no significant improvements found.

The researchers pooled the studies on both drugs to look at pain relief. Compared to placebo, the gabapentinoid group had a small pain reduction (MD=022 units, 95% CI -0.51 to 0.07, I2 =0%).  No studies compared pregabalin to placebo, but rather to an active comparator in three studies. That analysis found an improvement in the active comparator group (MD= 0.42 units, 95% CI 0.20 to 0.64). No hospitalizations or deaths were reported.

Pain Specialist Weighs In

The findings are not a surprise, said Michael J. Brennan, MD, senior attending physician at Bridgeport Hospital and consulting physician at St. Vincent's Hospital in Connecticut and a member of the Practical Pain Management editorial board. Nor should the findings surprise clinicians familiar with the mechanism of action of gabapentinoids, he noted.

"One must remember that gabapentin is an anti-epileptic class drug. Its mechanism of action is presumptively at a specific calcium channel where there is dysfunctional regulation of calcium influx. This leads to abnormal firing and release of potentially pain mediating neurotransmitters," he said. Gabapentinoids work, theoretically, by modulating these channels and stabilizing the calcium influx, decreasing the inappropriate release of pain-related neurotransmitters or stabilizing the hyperirritable nerve membranes to reduce their firing, he said.

"CLBP is a heterogeneous group of conditions whose common denominator is pain emanating from the spine or its related structures," he said. "Not all back pain is due to nerve-related problems. In fact, the opposite is likely the case.'' Typically, he noted, there is no evidence of acute or chronic nerve pathology; musculoskeletal injury is the most likely common etiology of CLBP, along with osteoarthritis.

Dr. Brennan said the worsening concerns of opioid misuse, coupled with the limited effectiveness of other pain-relievers, is probably driving the increased use of gabapentinoids. It also underscores the lack of options for clinicians when patients are seeking pain relief, he said. And, whatever the medications, he added, ''all medications need caution and monitoring."

Researchers' Perspective

"There are no easy solutions to CLBP," Dr. Shanthanna told Practical Pain Management. He also acknowledged that the study had some limitations. For instance, the review did not focus on the effectiveness of the medication when radicular leg pain is associated with, or predominant with, CLBP.

His best advice? "Physicians should consider multimodal treatment, including physical and psychological therapy," he says. They should optimize medication for individual patient response. Many patients are kept on the drugs for a long time without appropriate assessment of effectiveness, he said.

More Perspectives

Physicians are increasingly prescribing both gabapentin and pregabalin for almost any type of pain, according to a perspective published in the New England Journal of Medicine.3 That is true despite the fact that the FDA only has approved both drugs for postherpetic neuralgia, pregabalin for fibromyalgia and for neuropathic pain linked with diabetes or spinal cord injuries, wrote Christopher Goodman, MD, and Allan Brett, MD, of the University of South Carolina School of Medicine.

They note that in 2016, gabapentin was the 10th most frequently prescribed medication in the US. Prescriptions jumped from 39 million in 2012 to 64 million in 2016.

Lyrica had sales of $4.4 billion in 2016, more than double the 2012 sales, they said.

Their bottom line? "Although gabapentinoids offer an alternative that is potentially safer than opioid (and presumably more effective in selected patients), additional research is needed to more clearly define their role in pain management."

Last updated on: August 16, 2017
Continue Reading:
Can Yoga and Stretching Exercises Relieve Chronic Low Back Pain?

Join The Conversation

Register or Log-in to Join the Conversation
close X