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Published On January 24, 2018

BASIC RESEARCH

The Not-an-Opioid Epidemic

More physicians are prescribing a class of drugs called gabapentinoids to manage pain. Should we be worried?

The opioid epidemic has left physicians desperate for alternatives that will effectively treat chronic pain without the risk of addiction. While new classes of safer analgesics may be on their way (“Build a Better Painkiller,” Winter 2017), clinicians need other options now, and many appear to be turning to gabapentinoids, including Neurontin (gabapentin) and Lyrica (pregabalin).

The number of prescriptions for gabapentin jumped 64% between 2012 and 2016, making it by some accounts the 10th most commonly prescribed medication in the United States at that time. Last June doctors in Ohio wrote more prescriptions for gabapentin than for any other drug.

The recent popularity of gabapentinoids has raised two major concerns. First, evidence suggests that these drugs just aren’t very good at treating many common forms of pain, thus putting patients at risk of unnecessary costs and side effects. Second, emerging data suggests that some patients who receive gabapentinoid prescriptions misuse or sell the pills, which are becoming an increasingly popular street drug.

Neurontin was approved by the Food and Drug Administration as an antiseizure medication in 1993, and later it gained approval for treating postherpetic neuralgia, which results from nerve damage caused by shingles. The chemically similar Lyrica, which arrived in 2004, was approved for the same uses, and to treat fibromyalgia as well as pain associated with nerve damage from diabetes.

The precise mechanism of gabapentinoids is unknown, though they can dampen pain signals sent to the brain by damaged nerves, says Harsha Shanthanna, an anesthesiologist at St. Joseph’s Healthcare at McMaster University in Hamilton, Ontario. Yet damaged nerves don’t play a role in most common kinds of pain, he adds. In a 2017 review of eight randomized trials published in PLOS Medicine, Shanthanna and several colleagues found little evidence that gabapentinoids relieve chronic low-back pain. Moreover, while gabapentinoids may reduce acute pain immediately following an operation, a separate review last year also found them ineffective for managing long-term pain after surgery.

Yet physicians continue to prescribe the drugs off label for treating other forms of pain, including chronic pain. Gabapentinoids not only fail to help in many cases, says Shanthanna, but they also put patients at risk for adverse side effects that include dizziness, fatigue, visual disturbances, and what some users describe as a zombie-like mental state.

Meanwhile, gabapentinoids’ popularity as a recreational drug is on the rise. The drugs can induce mild euphoria, and heavy users report feeling more relaxed, sociable or uninhibited. Moreover, some surveys have found that gabapentinoid abuse is more prevalent among those who also misuse opioids.

“Gabbies” cost just a dollar or two per 800-milligram pill on the street, says Thomas Sherba, principal investigator for the Ohio Substance Abuse Monitoring Network, which tracks drug addiction trends in that state. The pills may be swallowed whole, crushed and snorted, combined with heroin or an opioid to intensify that drug’s high, or ingested in other ways. There have been reports of patients obtaining the medications by doctor shopping and faking symptoms. Those in treatment for opioid misuse who are on opioid-replacement therapies such as Suboxone or Vivitrol often receive gabapentin to ease withdrawal symptoms (which can include pain). Some users have reported, however, that combining opioid replacement with extra-large doses of gabapentin produces a heroin-like high, says Sherba.

The Drug Enforcement Administration classifies one of the two gabapentinoids—pregabalin—as a Schedule V drug, which means that the medication has a low risk for abuse, but there are few limits on how it can be prescribed. While the DEA currently has no plans to do the same for gabapentin, the state of Kentucky recently classified it as a controlled substance.

Deflating gabapentinoids’ hype as an opioid alternative will leave many physicians back where they started—with an immediate need for drugs that treat pain without the addiction risks of opioids. Shanthanna notes that some antidepressants show promise for treating pain, and he is optimistic about research into nonpharmacological approaches, such as exercise or cognitive behavioral therapy. “We need to do more for our patients and not just prescribe something indiscriminately that we think will work,” he says.