#25 Gabapentin & Chronic Pain: Missing Evidence and Real Effect?
CLINICAL QUESTION
What is the evidence to support gabapentin (or pregabalin) in chronic peripheral neuropathic pain?
BOTTOM LINE
The apparent benefit of gabapentin in chronic pain was exaggerated by publication and reporting biases. In carefully selected patients with peripheral neuropathic pain, gabapentin may offer moderate or more pain relief for 1 in every 6-8 patients but causes adverse events in a similar number. There is no trial evidence pregabalin is superior to gabapentin.
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EVIDENCE
Review of 20 Randomized Controlled Trials (RCTs) of gabapentin for off-label use (primarily 17/20 for pain).1
- Eight were never published (40%).
- Reporting of outcomes in 12 published studies:
- Only four used the planned primary outcome.
- Of 180 predefined secondary, 122 (68%) not reported.
- Moderate-marked improvement in pain occurs in 13-17.5% more patients than placebo.
- Number Needed to Treat (NNT) = 6-8 (two weeks).
- Efficacy greatest in post-herpetic neuralgia.
- No benefit for acute pain or in dose escalation beyond 900mg (but more adverse events).
- Adverse events: NNH 8 (dizziness, somnolence, gait disturbance, peripheral edema, etc.).
- NNT for moderate benefit was 5-7 and for substantial benefit was 6-7.
- An older Cochrane review4 (of published studies only) reported a more optimistic estimate of pain relief in chronic pain, NNT 3-4.
- Another review5 found similar.
- Pregabalin best case: Effective peripheral chronic pain relief is NNT ~8 based on published plus unpublished studies.6
- Common Drug Review7 reported pregabalin was intermittently (but not consistently) better than placebo.
- No direct clinical trial evidence for superiority over gabapentin.
- One trial had an active comparator: Pregabalin not superior to placebo but a tricyclic antidepressant was.
- Common Drug Review7 reported pregabalin was intermittently (but not consistently) better than placebo.
- Other reviews suggest tricyclic antidepressants are similar8 or perhaps superior8,9 to gabapentin or pregabalin. This evidence may be biased by time and trial quality.8
- While publication bias and selective reporting likely occur more in industry funded research, non-profit funded RCTs also selectively report outcomes.10
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