Gabapentin and Pregabalin for Pain

An interesting recent article in JAMA Internal Medicine was critical of off-label use of gabapentin (Neurontin, and generics) and pregabalin (Lyrica) for treatment of pain,¹ a subject The Medical Letter has reviewed with varying degrees of skepticism for many years.^2-5

Goodman and Brett point out that both drugs were originally approved as anticonvulsants, but most of their clinical trials, marketing, and sales have been for pain syndromes. Both are manufactured by the same company (Pfizer), but only gabapentin is available generically. Probably for that reason, gabapentin is often used instead of pregabalin. The use of both drugs, according to the article, has tripled over the past 15 years, perhaps mainly as substitutes for opioid treatment of pain syndromes.

The only pain syndrome for which gabapentin is FDA-approved is postherpetic neuralgia. Pregabalin is approved for postherpetic neuralgia, diabetic neuropathy, and most recently for pain associated with spinal cord injury. And how effective are they for their approved indications and off-label uses? In a large randomized trial of pregabalin for treatment of sciatica published recently in The New England Journal of Medicine, the drug was not significantly more effective than placebo.⁶ Goodman and Brett make several interesting observations about other clinical trials evaluating the efficacy of gabapentin and pregabalin for treatment of pain. For example, among 5 trials of gabapentin for painful diabetic neuropathy, 2 (including the largest) showed no benefit and 2 others showed improvement in pain of only 1 point on a 0 to 10 scale.

And there’s more about the muddy definition of neuropathy, troubling adverse effects, and possible interactions with the opioid epidemic. We all know what skillful advertising can do, but sometimes we need a good reminder. Read the article.

1. CW Goodman and AS Brett. A clinical overview of off-label use of gabapentinoid drugs. JAMA Intern Med 2019 March 25 (epub).
2. Gabapentin (Neurontin) for chronic pain. 2004; 46:29.
3. Pregabalin (Lyrica) for neuropathic pain and epilepsy. 2005; 47:75.
4. Pregabalin (Lyrica) for fibromyalgia. 2007; 49:77.
5. Nonopioid drugs for pain. 2018; 60:24.
6. S Mathieson et al. Trial of pregabalin for acute and chronic sciatica. N Engl J Med 2017; 376:1111.

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