What is the recommended treatment for a patient with painful small fibre neuropathy?

Management of Painful Small Fibre Neuropathy

Start with either duloxetine 60 mg daily or pregabalin 150 mg daily as first-line therapy, as these are the only FDA-approved medications with the strongest evidence for neuropathic pain and have superior efficacy compared to other agents. 1

First-Line Treatment Selection

Choose between two evidence-based options based on patient-specific factors:

Option 1: Duloxetine (Preferred for most patients)

• Start at 30 mg once daily for 1 week to minimize nausea, then increase to target dose of 60 mg once daily 2
• Maximum dose can be increased to 120 mg/day if needed after 2-4 weeks at 60 mg 2
• Number needed to treat (NNT) is 5.2 for 60 mg/day and 4.9 for 120 mg/day 1
• Major advantages: Fewer anticholinergic effects than tricyclics, no ECG monitoring required, and once-daily dosing 2, 1
• Allow at least 4 weeks at therapeutic dose to properly assess efficacy 2

Option 2: Pregabalin (Preferred if duloxetine contraindicated)

• Start at 75 mg twice daily (150 mg/day) for the first week 2, 3
• Increase to 150 mg twice daily (300 mg/day) after 1 week based on response 2, 3
• Maximum dose is 300 mg twice daily (600 mg/day) for patients not responding to 300 mg/day after 2-4 weeks 3
• NNT is 5.99 for 300 mg/day and 4.04 for 600 mg/day 1
• Use "asymmetric dosing" with larger dose in evening to minimize daytime sedation 4

Alternative First-Line: Gabapentin (if cost is a concern)

• Start at 100-300 mg at bedtime, titrate gradually to 900-3600 mg/day in 2-3 divided doses 2
• Requires scheduled daily dosing at therapeutic levels (1800-3600 mg/day) for at least 2-4 weeks to achieve efficacy 2
• NNT is 5.9-8.0 for neuropathic pain conditions 2

Combination Therapy for Partial Response

If first-line monotherapy provides only partial relief (less than 50% pain reduction), add a medication from a different class rather than switching. 2

• Combine gabapentinoid (pregabalin or gabapentin) with duloxetine for superior pain relief compared to either agent alone 2, 5
• A fixed-dose combination of pregabalin 75 mg plus duloxetine 30 mg twice daily achieved similar analgesia to pregabalin 150 mg twice daily with comparable side effects 5
• Continue combination therapy for at least 2-4 weeks before assessing combined efficacy 2

Second-Line Treatment (After First-Line Failure)

Tramadol

• Start at 50 mg once or twice daily, maximum 400 mg/day 2, 1
• Dual mechanism: weak μ-opioid agonist and inhibits serotonin/norepinephrine reuptake 2
• Critical warning: Risk of serotonin syndrome when combined with SNRIs/SSRIs—use with extreme caution 2

Tricyclic Antidepressants (TCAs)

• Use secondary amines (nortriptyline, desipramine) over tertiary amines due to fewer anticholinergic effects 2
• Start at 10-25 mg at bedtime, titrate slowly to 75-150 mg/day over 2-4 weeks 2
• Mandatory ECG screening for patients over 40 years before starting 2
• Contraindications: recent MI, arrhythmias, heart block, cardiac disease 2

Topical Agents for Localized Pain

• 5% lidocaine patches: Apply daily to painful area, minimal systemic absorption, excellent for elderly patients 2
• 8% capsaicin patches: Single 30-minute application provides pain relief for at least 12 weeks 2

Special Population Considerations

Older Adults

• Start with lower doses and titrate more slowly 2
• Prioritize topical agents (lidocaine or capsaicin) due to minimal systemic effects 1
• Avoid TCAs or use with extreme caution due to anticholinergic burden and cardiac risks 2

Renal Impairment

• Adjust gabapentin and pregabalin doses based on creatinine clearance 1, 3
• Duloxetine does not require dose adjustment 2

Cardiac Disease

• Avoid TCAs entirely or limit to less than 100 mg/day with ECG monitoring 2, 1
• Prefer duloxetine, pregabalin, or gabapentin as safer alternatives 1

COPD Patients

• Gabapentin is first-line choice as it lacks anticholinergic effects and does not cause respiratory depression 6
• Duloxetine is acceptable as second-line with moderate anticholinergic burden 6
• Avoid amitriptyline entirely due to thickened bronchial secretions and respiratory depression 6

Critical Treatment Principles

• Allow adequate trial duration: Minimum 2-4 weeks at therapeutic dose before declaring treatment failure 2
• Ensure target doses are reached before switching medications—many patients are undertreated with suboptimal doses 7, 4
• Higher doses of pregabalin (450-600 mg/day) are significantly more effective than lower doses for patients who tolerate them 7
• Avoid strong opioids for long-term management due to risks of dependence, cognitive impairment, respiratory depression, and pronociception 2

When to Refer to Pain Specialist

• Failure of first-line medications alone and in combination 2
• Consideration of spinal cord stimulation for refractory cases 8
• Need for intravenous immunoglobulin (IVIg) or anti-TNF therapy if underlying sarcoidosis or autoimmune etiology suspected 8

Common Pitfalls to Avoid

• Premature discontinuation: Patients often discontinue before reaching therapeutic dose or adequate trial duration 4
• Suboptimal dosing: Many patients remain on starting doses without appropriate titration to effective levels 7, 4
• Ignoring dose escalation: Patients who don't respond to lower doses often respond with notable improvements when dose is escalated 7
• Using "as needed" dosing for gabapentinoids: These require scheduled daily dosing at therapeutic levels to achieve efficacy 2