#404 From Nerve Pain to Knee Pain: Gabapentinoids for osteoarthritis
CLINICAL QUESTION
Are gabapentinoids effective for the treatment of osteoarthritis?
BOTTOM LINE
Based on a few small, short, randomized controlled trials (RCTs), gabapentinoids are likely superior to placebo. On a 0-to-10 point scale (lower=less pain, baseline=6), gabapentinoids decreased pain to 3.4 versus 5.4 (placebo) at 13 weeks, but the percentage of patients who respond to therapy is unknown. Efficacy appears similar to duloxetine. Gabapentinoids can cause dizziness, peripheral edema and weight gain.
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EVIDENCE
- Results statistically significant unless indicated.
- One systematic review without meta-analysis:1 RCTs (plus one additional)2 reported individually. Knee osteoarthritis unless indicated. Pain usually measured on visual analog scale, range 0-10, lower=less pain.
- Versus placebo:
- 44 patients (hand osteoarthritis); pregabalin 300mg or placebo. At 13 weeks:3
- Pain (baseline ~6): decreased to 3.4 (pregabalin) versus 5.4 (placebo).
- Function (scale with range 0-900, lower=better, baseline ~595): Decreased to 362 (pregabalin) versus 509 (placebo).
- Days using rescue medications: 9 (pregabalin) versus 56 (placebo) (statistics not reported).
- 44 patients (hand osteoarthritis); pregabalin 300mg or placebo. At 13 weeks:3
- Versus acetaminophen:
- 100 patients; gabapentin 600mg or acetaminophen 2000mg. At 12 weeks:4
- Pain, PEER estimation (baseline ~8.5): Decreased to ~3 (gabapentin) versus ~5 (acetaminophen).
- Function, PEER estimation (scale with range: 0-68, lower=better, baseline ~55): Decreased to ~17 (gabapentin) versus ~35 (acetaminophen).
- 100 patients; gabapentin 600mg or acetaminophen 2000mg. At 12 weeks:4
- Versus duloxetine:
- 60 patients; 300mg pregabalin versus 60mg duloxetine. At 12 weeks:2
- Pain (baseline ~7): Decreased to 2.1 (pregabalin) versus 2.7 (duloxetine), not statistically different.
- Function (scale with range: 0-68, lower=better, baseline ~39): Decreased to 15 (pregabalin) versus 23 (duloxetine).
- Additional RCTs, pain:3,4 Pregabalin 300mg and gabapentin 600mg similar to duloxetine.
- 60 patients; 300mg pregabalin versus 60mg duloxetine. At 12 weeks:2
- Versus oral NSAID:
- 59 patients: Pregabalin 25mg versus meloxicam 10mg.5 At 4 weeks:
- Pain, function: Similar between groups.
- Limitations: Small trials with short duration may inflate benefit, limited harms reported, underpowered,2-4 lack of blinding,2,5 no responder analyses.2-4
- 59 patients: Pregabalin 25mg versus meloxicam 10mg.5 At 4 weeks:
CONTEXT
- For chronic pain, 12% patients stop gabapentinoids due to adverse effects (dizziness, peripheral edema, weight gain).6
- Osteoarthritis Guideline: 6
- Physical activity foundational.
- Pharmacologic options: Reduction on 11-point visual analog scale over placebo of ~1-1.5 for oral/topical NSAIDS, intra-articular corticosteroids and duloxetine.7-8
- Acetaminophen: No effect.
- Pregabalin/gabapentin: Not discussed.
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No direct head-to-head randomized controlled trials compare pregabalin 300 mg daily versus gabapentin 600–900 mg daily specifically for pain reduction and functional improvement in chronic knee osteoarthritis (OA)
As someone who uses the gabapentinoids frequently for neuropathic pain, it is refreshing to see evidence of its use in OA. One thing that is not clear is how the ideal dosage is confirmed. eg one study had 300 mg of pregabalin and another study had 25 mg. To minimize the side effects, it might be prudent to start low and build up the dosage until you hit the target dosage.
Not reflective of the diversity of management strategies in actual continuity of care