Gabapentin and Pregabalin Only ‘Modestly Effective’ for Pain
/By Pat Anson, PNN Editor
A new review of clinical studies on the use of gabapentin (Neurontin) and pregabalin (Lyrica) in pain management found the drugs are only “modestly effective” and could be risky for some pain patients.
Gabapentin and pregabalin belong to a class of nerve medication called gabapentinoids, which were originally developed as anticonvulsants to treat epileptic seizures. In recent years, however, they have been increasingly prescribed off-label as an alternative to opioids in managing pain. About one in five U.S. adults with chronic pain are prescribed a gabapentinoid.
"Treating pain has been problematic for a long time, and we're still dealing with the fallout from opioid overuse," says lead author Craig Williams, PharmD, a clinical professor at Oregon State University College of Pharmacy. "Gabapentinoids are modestly effective for certain patients; they are rarely extremely effective, and they are not effective at all for some patients because the mechanisms of the pain don't match up with the mechanisms of the drug.
"Doctors who prescribe gabapentinoids for pain should do so with their eyes wide open and be prepared to stop them if they are ineffective or cause too many side effects."
The study findings, published in the journal Drugs, found that many of the clinical trials for gabapentin and pregabalin were of short duration, had a small number of participants, and performed only slightly better than placebos in reducing pain. Many patients who take the medications also report side effects such as dizziness, confusion, drowsiness, mood swings and weight gain.
"Treating pain is about making patients more functional so they can live their lives better, and if they have to deal with adverse effects for a little pain relief, their lives may not be improving," said Williams.
Pregabalin has been approved by the Food and Drug Administration for four pain conditions: post-herpetic neuralgia (shingles), diabetic peripheral neuropathy, spinal cord injury, and fibromyalgia. Gabapentin has only been approved by the FDA for post-herpetic neuralgia.
Despite the limits on their uses, many doctors legally prescribe the drugs “off-label” for pain conditions such as migraines, back pain, post-operative pain and even dental pain. Gabapentin was once derisively referred to as “snake oil” by a pharmaceutical executive because it is so widely prescribed for so many different pain conditions, despite weak evidence.
"In addition, we found that the trials used by the FDA to approve gabepentinoids for pain indications had a couple of key structural weaknesses," Williams said. "The trials tended to be short, typically lasting one to three months, and the trials typically excluded the simultaneous use of other medications that affect the central nervous system. That's important because patients taking gabepentinoids are rarely taking them exclusively; they're often prescribed in conjunction with opioids, muscle relaxants or other epilepsy drugs."
Gabapentin can cause euphoria and feelings of intoxication, and make the effect of opioids and other drugs seem stronger. A 2019 study linked gabapentin to a growing number of attempted suicides.
That same year, the FDA warned that gabapentin and pregabalin may cause serious breathing problems and respiratory depression, especially in older adults. A recent study found that gabapentin raises the risk of delirium in older adults recovering from surgery.
