What is the recommended treatment for a patient with postherpetic neuralgia (PHN)?

Treatment for Herpetic Neuralgia (Postherpetic Neuralgia)

Start with gabapentin as first-line oral therapy, beginning at 300 mg on day 1,600 mg on day 2, and 900 mg on day 3, then titrate to 1800-3600 mg/day in three divided doses, or use topical lidocaine 5% patches for localized pain, particularly in elderly patients or those with multiple comorbidities. 1, 2

First-Line Treatment Options

Oral Gabapentin

• The American College of Physicians recommends gabapentin as first-line oral pharmacological treatment, with FDA-approved dosing starting at 300 mg on day 1,600 mg on day 2, and 900 mg on day 3, then titrating to 1800-3600 mg/day in three divided doses as needed for pain relief 1, 2
• Efficacy is demonstrated across the 1800-3600 mg/day dose range, with no additional benefit shown above 1800 mg/day, and the maximum time between doses should not exceed 12 hours 1, 2
• Pain reduction may be seen as early as Week 1 and is maintained throughout treatment 2

Topical Lidocaine 5% Patches

• The American College of Physicians and American Geriatrics Society recommend lidocaine 5% patches as first-line therapy with excellent efficacy (NNT = 2) and minimal systemic absorption 1, 3
• Patches can be worn for 12-24 hours on affected areas, providing sustained pain relief with minimal systemic side effects, making them particularly suitable for elderly patients or those with comorbidities who cannot tolerate oral medications 1, 3
• This is definitively standard of care and FDA-approved for postherpetic neuralgia, with no drug-drug interactions due to minimal systemic absorption 3
• Critical caveat: Patches must be applied to intact skin only—contraindicated on broken or inflamed skin, and work best for localized pain areas rather than widespread or diffuse pain 3

Tricyclic Antidepressants (TCAs)

• Nortriptyline has excellent efficacy (NNT = 2.64) and is preferred over amitriptyline due to better tolerability with equivalent analgesic benefit 1, 4
• Start at 10-25 mg at bedtime and increase every 3-7 days to a final dose of 25-100 mg at bedtime as tolerated, minimizing daytime sedation effects 1, 4
• In elderly patients, start with lower doses (10 mg) and titrate more slowly to minimize side effects 4
• Important consideration: Anticholinergic side effects may be dose-limiting, particularly in patients ≥65 years 1

Second-Line Treatment Options

Pregabalin

• Consider pregabalin if patients have inadequate response to gabapentin, with an NNT of 4.93 and effective doses typically ranging from 150-600 mg/day in two divided doses 1, 5
• FDA-approved for postherpetic neuralgia, with pain reduction seen as early as Week 1 in clinical trials 5
• Monitor for somnolence, dizziness, and mental clouding, especially in older patients 1

Topical Capsaicin

• Capsaicin 8% dermal patch can provide pain relief for at least 12 weeks from a single application 1
• Low-concentration capsaicin 0.075% cream can be applied 3-4 times daily for 6 weeks 1
• Key strategy to minimize side effects: Apply 4% lidocaine for 60 minutes before capsaicin application to mitigate erythema and pain 1

SNRIs (Duloxetine, Venlafaxine)

• Duloxetine is supported by two high-quality studies and five medium-quality studies for neuropathic pain 1
• Venlafaxine is supported by one high-quality study for neuropathic pain 1
• Start with lower doses and titrate slowly to minimize adverse effects in older adults 1

Opioids

• Oxycodone, extended-release morphine, and methadone show efficacy (NNT = 2.67) but should not be used as first-line agents due to risks of pronociception, cognitive impairment, respiratory depression, endocrine/immunological changes, and potential for misuse and addiction 1
• Tramadol shows efficacy with an NNT of 4.76 1
• Consider combination therapy (morphine with gabapentin) when single agents provide inadequate relief, allowing for lower doses of each medication while providing additive effects 1

Dosage Adjustments for Renal Impairment

Gabapentin Renal Dosing

• For creatinine clearance ≥60 mL/min: 900-3600 mg/day in three divided doses 2
• For creatinine clearance 30-59 mL/min: 400-1400 mg/day in two divided doses 2
• For creatinine clearance 15-29 mL/min: 200-700 mg/day as single daily dose 2
• For creatinine clearance <15 mL/min: 100-300 mg/day as single daily dose, with supplemental post-hemodialysis doses of 125-350 mg after each 4 hours of hemodialysis 2

Treatment Duration and Monitoring

• Continue treatment indefinitely until pain relief is achieved, as postherpetic neuralgia may persist for months to years 4
• Periodic reassessment of continued therapy is recommended, as postherpetic neuralgia may improve over time 1
• The probability of pain relief correlates strongly with the brevity of the interval between rash onset and treatment initiation, highlighting the importance of early treatment 4

What NOT to Use

• Lamotrigine is not recommended for PHN due to lack of convincing evidence of efficacy and risk of lamotrigine-associated rash 1
• Corticosteroids provide no benefit for established postherpetic neuralgia and expose patients to unnecessary adverse effects including hyperglycemia, osteoporosis, hypertension, and immunosuppression 1

Non-Pharmacological Adjuncts

• Cognitive behavioral therapy (CBT), hypnosis, and physical and occupational therapy may be beneficial as adjunctive treatments 1
• Alpha lipoic acid (ALA) has a potential role in multimodal therapy, though studies specifically in PHN are limited 1