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A recent article in JAMA by Drs. Goodman and Brett reviews the increasing off label use of gabapentinoid drugs, originally developed as antiseizure drugs that are now increasingly prescribed for painful conditions.
The only FDA approved pain-related indication for gabapentin (Neurontin) is for the treatment of postherpetic neuralgia. Similarly, pregabalin (Lyrica) has FDA-approved indications for postherpetic neuralgia, neuropathic pain associated with diabetic neuropathy or spinal cord injury, and fibromyalgia.
Their review examined the limited published evidence to support off-label gabapentinoid uses, primarily noting that much of the literature and guidelines tend to overstate gabapentinoid effectiveness.
Clinicians should be aware of the limited evidence supporting the off-label use of gabapentinoid drugs.
Some of the highlights from this review article includes:
- Gabapentin was approved by the FDA in 1993 for treatment of seizures. Early on the manufacturer began marketing the drug for off-label treatment of pain, but only had one pain indication (postherpetic neuralgia) There were clinical trials in neuropathic pain, bipolar disorder, and migraine prophylaxis, that tended to magnify the drug’s perceived effectiveness.
- In 2004, gabapentin became available as a generic drug.
- Pregabalin was approved in 2004 for treatment of seizures and postherpetic neuralgia and diabetic neuropathy.
- Despite limited indications, gabapentinoid used has tripled over the past 15 years.
- From 2013 to 2017, gabapentin prescriptions increased from 44 million to 68 million annually, and gabapentin was the 10th most commonly prescribed medication in 2017 in the USA.
- Pregabalin ranked sixth best selling brand-name drug in 2017; between 2013 and 2017, pregabalin sales increased from $2.4 billion to $4.9 billion.
- Gabapentins efficacy in diabetic neuropathy finds, at best, mixed results in 5 trials.
- There are few studies of gabapentinoids in nondiabetic neuropathies.
- Gabapentinoid therapy was shown to be ineffective for low back pain or radiculopathy.
- Pregabalin is approved for fibromyalgia, but the only placebo-controlled trial of gabapentin for fibromyalgia, showed a mean difference in pain of 0.9, on a 0 to 10 scale.
- Both drugs have been shown to be ineffective in acute zoster pain.
- Gabapentin and pregabablin are not proven to be interchangeable with pregabalin. They have structural similarity, but have different mechanisms of action and pharmacokinetics. There are no published direct comparisons between the 2 drugs.
- Adverse risks show a dose related increase in dizziness, somnolence, and gait disturbance. The number needed to harm for each adverse effect has ranged from roughly 3 to 11; as many as 1 in 3 recipients of higher-dose gabapentinoids will experience somnolence or dizziness.
- There appears to be a growing misuse of gabapentinoids related to the opioid epidemic.