Written by Clay Smith
Gabapentinoids play a limited role for specific types of neuropathic pain, and pain reduction is modest at best. Side effects of dizziness, somnolence, and gait problems occur frequently.
Why does this matter?
Gabapentin was initially intended and marketed as an anticonvulsant. It is now mainly used for pain, but the only FDA approved use is post-herpetic neuralgia (PHN). Pregabalin has broader FDA approved uses that include PHN or neuropathic pain from diabetes, spinal cord injury, or fibromyalgia. Pfizer, the manufacturer of gabapentin and pregabalin, has been fined repeatedly for improper marketing of off-label uses. The history of gabapentin trials leading to approval for pain control is sordid and showed questionable tactics including, “planning to suppress unfavorable study results” and selective outcome reporting. See the NEJM exposé, which found that in, “8 of the 12 reported trials, the primary outcome defined in the published report differed from that described in the protocol.” Both these drugs are frequently used off-label. What is the evidence for such use?
Considering gabapentin for diabetic neuropathy, there were 5 RCTs reviewed, 2 of which showed no benefit. Three showed a decrease on a 0-10 pain scale by 1.1 to 1.9; a decrease in pain by at least 1 is considered clinically significant. A Cochrane review found the NNT was 6 for diabetic neuropathy pain. For other types of neuropathic pain (other than post-herpetic neuralgia or diabetic neuropathy), there is little evidence that gabapentin produces clinically significant pain reduction, except perhaps spinal cord injury (a single RCT with 20 total patients). Use of either gabapentinoid for sciatica doesn’t reduce pain. Evidence for pregabalin showed no benefit for these off-label painful conditions: central neuropathic pain, HIV neuropathy, unspecified neuropathy, acute zoster, chronic prostatitis, burns, or sickle cell pain. Pregabalin for chronic pancreatitis or traumatic nerve injury showed statistically but not clinically significant decreases in pain (i.e. <1 on a 0-10 scale).
Given that the primary evidence is not very compelling, it’s unfortunate that meta-analyses and guidelines tend to generalize and even overstate the effectiveness of gabapentinoids. Finally, these drugs are not benign — dizziness, somnolence, and gait disturbance are common. “The number needed to harm for each adverse effect has ranged from roughly 3 to 11.” This is especially important among the elderly and those on other sedating medications. Also, there is growing recognition of abuse potential with gabapentinoids. Opioid-related deaths increase when patients are taking concomitant gabapentinoids.
These drugs have a limited role, but their effectiveness at reducing specific neuropathic pain syndromes is modest at best. Consider the side effects, cost, and likelihood of effectiveness when using them.
A Clinical Overview of Off-label Use of Gabapentinoid Drugs. JAMA Intern Med. 2019 Mar 25. doi: 10.1001/jamainternmed.2019.0086. [Epub ahead of print]
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Reviewed by Thomas Davis