What is the first-line treatment for postherpetic neuralgia (PHN)?

First-Line Treatment for Postherpetic Neuralgia

Gabapentin is the recommended first-line oral pharmacological treatment for postherpetic neuralgia, initiated at 300 mg on day 1,600 mg on day 2 (300 mg twice daily), and 900 mg on day 3 (300 mg three times daily), with subsequent titration to 1800-3600 mg/day in three divided doses as needed for pain relief. 1, 2

Oral First-Line Options

Gabapentin (Primary Recommendation)

• The American College of Physicians specifically recommends gabapentin as first-line oral therapy, with FDA approval supporting its use for postherpetic neuralgia 1, 2
• Target maintenance dose is 1800 mg/day (600 mg three times daily), with maximum of 3600 mg/day if needed 1, 3, 2
• Clinical trials demonstrate no additional benefit above 1800 mg/day, though higher doses may increase adverse effects 3, 2
• An adequate trial requires 3-8 weeks for titration plus 2 weeks at maximum tolerated dose (total of 2+ months to properly assess efficacy) 3
• Divided dosing throughout the day is mandatory due to saturable absorption in the proximal small intestine 3

Tricyclic Antidepressants (Equally Effective Alternative)

• Nortriptyline is preferred over amitriptyline with excellent efficacy (NNT = 2.64), offering equivalent analgesic benefit but better tolerability 1
• Start at 10-25 mg at bedtime, increase every 3-7 days to final dose of 25-100 mg at bedtime as tolerated 1
• TCAs represent the most comprehensively studied medications for PHN with approximately 50% of patients experiencing effective analgesia 4
• Caution: TCAs are frequently contraindicated or poorly tolerated in elderly patients due to anticholinergic effects, cardiac conduction abnormalities, and orthostatic hypotension 4

Topical First-Line Options

Lidocaine 5% Patches (Preferred for Localized Pain)

• Excellent efficacy (NNT = 2) with minimal systemic absorption, making them particularly suitable for elderly patients or those with comorbidities 5, 1
• Can be worn for 12-24 hours on affected areas, delivering medication gradually over hours 1
• Especially valuable in older adults due to minimal systemic effects and lack of drug interactions 5, 1

High-Concentration Capsaicin (8% Patch)

• Provides moderate-quality evidence for efficacy in postherpetic neuralgia with pain relief lasting at least 12 weeks 5, 1
• Apply 4% lidocaine for 60 minutes before capsaicin application to mitigate erythema and pain side effects 1
• Works through desensitization of pain receptors 1

Critical Dosing Adjustments

Renal Impairment (Gabapentin)

• Dosage reduction is mandatory in renal insufficiency to prevent toxicity 3, 2
• For creatinine clearance 30-59 mL/min: 200-700 mg twice daily 2
• For creatinine clearance 15-29 mL/min: 200-700 mg once daily 2
• For creatinine clearance <15 mL/min: 100-300 mg once daily 2
• Hemodialysis patients require supplemental post-dialysis dosing of 125-350 mg after each 4-hour session 2

Elderly Patients

• Start with lower doses and titrate more slowly due to decreased renal function and increased risk of adverse effects 5, 3
• For gabapentin in elderly: consider starting at 100-200 mg/day rather than standard 300 mg 5
• Topical treatments are particularly valuable in this population due to minimal systemic effects 5, 1

Common Pitfalls to Avoid

• Undertitration and premature assessment of efficacy: Allow adequate time (2+ months) for gabapentin titration and evaluation before declaring treatment failure 3
• Failure to adjust for renal function: This is crucial to prevent toxicity, especially in elderly patients 3, 2
• Somnolence, dizziness, and mental clouding are common with gabapentinoids and can be very problematic in older patients—start low and go slow 5
• Do not use lamotrigine for PHN: Lack of convincing efficacy evidence and risk of serious rash 1

Second-Line Considerations (When First-Line Inadequate)

• Pregabalin (NNT = 4.93) if inadequate response to gabapentin, with effective doses typically 150-600 mg/day in two divided doses 1, 6
• Opioids (oxycodone, extended-release morphine, methadone) show efficacy (NNT = 2.67) but should not be first-line due to risks of pronociception, cognitive impairment, respiratory depression, and addiction potential 1
• Combination therapy (e.g., morphine with gabapentin) may be more effective when single agents fail, allowing lower doses of each medication 1