Doctors prescribe the drug gabapentin to treat an array of symptoms and conditions, ranging from the burning pain of nerve damage to long-lasting coughs, making it one of the most widely prescribed medications in the United States. Many of those prescriptions are written off-label, which means that a drug is prescribed for a purpose other than the one the FDA approved it for.
An array of uses
Some experts are questioning gabapentin’s off-label versatility in light of the lack of robust evidence showing that the drug is effective for nonapproved purposes, especially given its possible side effects, which include dizziness, problems walking, and sedation—potentially troublesome for older adults.
Gabapentin is currently approved to treat seizures and postherpetic neuralgia, which is shingles-related nerve pain that persists for longer than three months. Gabapentin is thought to work similarly to a brain chemical called gamma-aminobutyric acid (GABA), which helps tamp down nerve activity, including the body’s response to nerve pain.
Gabapentin was first approved as an anticonvulsant drug in 1993 under the brand name Neurontin. It was approved for post-shingles pain in 2002. Gabapentin belongs to a class of drugs called gabapentinoids, which also includes pregabalin (Lyrica). Pregabalin is approved to treat seizures, postherpetic neuralgia, neuropathic (nerve) pain associated with diabetic neuropathy or spinal cord injury, and fibromyalgia.
A significant difference between generic gabapentin and non-generic pregabalin is cost. Gabapentin can cost a few dollars a month, whereas pregabalin can cost hundreds of dollars a month. This price discrepancy might change soon, though: Lyrica was due to lose its patent protection in summer 2019; however, no generic version has yet been approved by the FDA.
Should off-label be off-limits?
In a review published in the May 2019 issue of JAMA Internal Medicine, researchers at the University of South Carolina Medical School expressed concern about the recent rise in gabapentin prescriptions in the United States, which increased from 44 million in 2013 to 68 million in 2017. The surge likely reflects the willingness of more and more doctors to prescribe gabapentin for off-label purposes.
Many doctors might have been influenced by early, aggressive marketing of Neurontin as an alternative treatment for many conditions beyond those for which it received FDA approval. The FDA later deemed the marketing was improper after it was revealed that the manufacturer, Parke-Davis, manipulated results of the clinical trials to magnify the drug’s effectiveness. Parke-Davis paid a penalty for its misleading advertising in 2004, the same year the drug became available in generic form.
Today, gabapentin is most commonly used off-label to relieve neuropathic pain—possibly because doctors are looking for either a safer alternative to opioids or a cheaper substitute for pregabalin. The problem with this, the researchers say, is that few, if any, well-designed clinical trials have been performed to study whether the drug is effective for its off-label uses (see inset). What’s more, the dosages of gabapentin used vary from trial to trial, so it’s difficult to reach a well-informed consensus about what works and what doesn’t.
Off-Label Gabapentin: What the Science Says
The anticonvulsant drug gabapentin is prescribed to treat numerous symptoms and conditions beyond those for which it's approved by the FDA. Here are some common off-label uses and how the evidence stacks up for each.
Beware of adverse effects
As many as one in three people taking a high dose of gabapentin will experience sleepiness or dizziness, putting them at risk for falls, especially when these symptoms are combined with the drug’s effect on gait. Water retention, weight gain, muscle tremors, and rashes occur in some patients. Some people find that gabapentin affects their ability to remember, process information, and concentrate.
In rare cases, gabapentin (but more so pregabalin) has been associated with an elevated risk of suicide. As a precaution, the lowest possible dose should be used and increased as needed to reduce the possibility of side effects.
You should also avoid mixing moderate to high doses of gabapentin with opioids. Both drugs share overlapping side effects—drowsiness, respiratory depression (slow, shallow breathing), and respiratory failure that can be enhanced when they’re combined. That combination can be deadly, especially for older adults.
What’s more, gabapentin has been flagged as a drug that has the potential for abuse or misuse by people seeking euphoric effects, especially when mixed with opioids. The potential for abuse is increased in people who have used or currently use benzodiazepines and opioids.
Gabapentin can be a useful drug when used for the FDA-approved treatment of seizures and shingles-induced nerve pain. If you and your doctor are considering gabapentin for off-label use, you should fully understand that the drug might not improve your symptoms. But because there’s no way to predict who’ll benefit from gabapentin, a short course of the drug might be worth trying if other treatments have failed.
If you’re already using gabapentin for off-label reasons, and it doesn’t seem to be working, ask your doctor if he or she can recommend a more effective replacement. But if it’s working for you as an off-label remedy, there’s probably no reason to discontinue the drug unless the side effects are troublesome. But do be sure to see your doctor for periodic assessments of gabapentin’s benefits and risks.
This article first appeared in the September 2019 issue of UC Berkeley Health After 50.
Published September 11, 2019