As part of current efforts to reduce unnecessary opioid consumption, clinicians have increasingly prescribed gabapentinoids for a range of pain disorders.1 The use of these agents more than tripled between 2002 and 2015, although they have received US Food and Drug Administration (FDA) approval for pain syndromes that may not account for this trend.2 Gabapentin is approved for the treatment of postherpetic neuralgia, and pregabalin is approved for the treatment of postherpetic neuralgia, diabetic neuropathy, neuropathic pain from spinal cord injury, and fibromyalgia.1

In a special communication article published in March 2019 in JAMA Internal Medicine, Christopher W. Goodman and Allan S. Brett of the University of South Carolina School of Medicine caution against off-label use of gabapentinoids without clear clinical justification because evidence for their use is weak for most conditions other than those approved by the FDA.1

The authors note that Pfizer was previously penalized for deceptive marketing practices promoting off-label uses for both gabapentin and pregabalin, and they suggest that these practices may have contributed to the current misconception that gabapentinoids may be prescribed for the treatment of several pain conditions. In addition, professional guidelines — including those from the Centers for Disease Control and Prevention and the American Academy of Neurology — may exaggerate the effectiveness of gabapentinoids for off-label uses, despite the lack of supporting evidence, according to the authors.3,4

“To prescribe gabapentinoids responsibly, clinicians should be familiar with the published evidence that addresses off-label use of these drugs,” the authors wrote.1 To that end, they reviewed relevant findings from double-blind randomized trials, as summarized below.

●       For gabapentin, evidence is mixed regarding its effectiveness for the treatment of diabetic neuropathy, with 4 of 5 trials showing minimal or no benefit compared with placebo.

●   There is minimal or no evidence for the use of gabapentin as an off-label therapy for other types of neuropathic pain, low-back pain, radiculopathy, or fibromyalgia.

●       Although pregabalin and gabapentin are approved therapies for postherpetic neuralgia, neither medication was found to be effective for the treatment of acute herpes zoster pain in 2 placebo-controlled trials.

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In addition, clinicians often assume that gabapentin is interchangeable with pregabalin, as the two molecules have structural similarity, but they have distinct pharmacokinetic profiles. Substituting pregabalin with gabapentin may be tempting, as the cost of pregabalin is high compared with that of generic gabapentin — a difference of up to several hundred dollars for a month’s treatment. “Given the differences in cost, substitution of gabapentin for pregabalin when only pregabalin is FDA approved for a given disorder is understandable and often reasonable; however, clinicians should be aware that the evidence to support interchangeability is limited,” noted the authors.1