Prednisone is NOT Recommended for Neuropathic Pain
Prednisone has no established role in the treatment of neuropathic pain and should not be prescribed for this indication. There is no evidence supporting the benefit of glucocorticoids, including prednisone, for neuropathic pain management 1.
Why Prednisone is Ineffective
Lack of efficacy evidence: Multiple high-quality guidelines explicitly state that NSAIDs and glucocorticoids have no data supporting their benefit in neuropathic pain settings 1.
Wrong mechanism of action: Neuropathic pain arises from nerve damage and altered pain processing, not from inflammation that would respond to corticosteroids 2, 3.
Exception for acute inflammatory neuropathy: The only scenario where steroids may help is acute steroid-responsive small-fiber sensory neuropathy, an extremely rare entity where prednisone 1 mg/kg/day produces dramatic improvement within 1-2 weeks 4. This represents a distinct inflammatory condition, not typical neuropathic pain.
What You Should Prescribe Instead
First-Line Options (Choose One to Start)
Gabapentinoids:
- Pregabalin: Start 75 mg twice daily (150 mg/day total), increase to 150 mg twice daily (300 mg/day) after 1 week, maximum 300 mg twice daily (600 mg/day) 2, 5.
- Gabapentin: Start 100-300 mg at bedtime, increase by 300 mg every 3-7 days to target 1800-3600 mg/day in 2-3 divided doses 1, 2.
Antidepressants:
- Duloxetine (SNRI): Start 30 mg once daily for 1 week to minimize nausea, then increase to 60 mg once daily (target dose), maximum 120 mg/day 1, 2.
- Nortriptyline (TCA): Start 10-25 mg at bedtime, increase every 3-7 days to 25-100 mg at bedtime. Requires ECG screening if patient >40 years old 1, 2.
Topical Agents for Localized Pain
- 5% Lidocaine patches: Apply daily to painful area, minimal systemic absorption, excellent for elderly patients with localized peripheral neuropathic pain 1, 2.
- 8% Capsaicin patches: Single 30-60 minute application provides relief for up to 90 days in localized neuropathic pain 1.
Second-Line Options (After First-Line Failure)
- Tramadol: Start 50 mg once or twice daily, maximum 400 mg/day. Has dual mechanism (weak opioid + SNRI effects). Caution: serotonin syndrome risk when combined with SNRIs/SSRIs 2, 6.
Treatment Algorithm
Start with either a gabapentinoid OR an antidepressant based on patient factors:
Allow adequate trial period: Maintain therapeutic dose for at least 2-4 weeks before declaring treatment failure 1, 2.
If partial response: Add a medication from a different class (e.g., gabapentinoid + antidepressant combination provides superior relief) 2, 5.
If inadequate response to first-line agents: Switch to alternative first-line agent from different class, or add tramadol as second-line 2, 6.
Refractory cases: Consider referral to pain specialist for multimodal therapy including physical therapy, which provides anti-inflammatory effects and improves pain perception 1, 2.
Critical Pitfalls to Avoid
Underdosing: Most patients require full therapeutic doses (pregabalin 300 mg/day, gabapentin 1800-3600 mg/day, duloxetine 60 mg/day) for efficacy 1, 2, 5.
Premature discontinuation: Allow minimum 2-4 weeks at therapeutic dose before switching medications 1, 2.
Ignoring renal function: Gabapentinoids require dose adjustment in renal impairment (reduce by 50% if CrCl 30-60 mL/min, 75% if CrCl 15-30 mL/min) 5.
Cardiac screening neglect: TCAs require ECG in patients >40 years; contraindicated in recent MI, arrhythmias, heart block 2.
Expected Outcomes
- First-line medications achieve 30-50% pain reduction in approximately 50% of patients 3, 7.
- Number needed to treat (NNT) ranges from 3.5-7.7 for 50% pain reduction with first-line agents 7, 6.
- Lumbosacral radiculopathy is notably more refractory to all neuropathic pain medications compared to other neuropathic conditions 2, 6.