What alternative treatment options are available for post-herpetic neuralgia (PHN) in adult or elderly patients who cannot tolerate gabapentin or have not responded adequately to it?

Alternative Treatments for Post-Herpetic Neuralgia Beyond Gabapentin

For patients who cannot tolerate or have failed gabapentin, tricyclic antidepressants (specifically nortriptyline) should be your first alternative choice, offering the best efficacy with an NNT of 2.64, followed by topical lidocaine patches for localized pain. 1

First-Line Alternatives

Tricyclic Antidepressants (TCAs)

• Nortriptyline is preferred over amitriptyline due to equivalent analgesic benefit but superior tolerability, particularly important in elderly patients who comprise the majority of PHN sufferers 1
• Start at 10-25 mg at bedtime and increase every 3-7 days to a target dose of 25-100 mg at bedtime as tolerated 1, 2
• TCAs demonstrate excellent efficacy with an NNT of 2.64, making them among the most effective treatments available for PHN 1
• Anticholinergic side effects may be dose-limiting, especially in patients ≥65 years, so monitor for dry mouth, constipation, urinary retention, and cognitive effects 1

Topical Lidocaine 5% Patches

• Provide excellent pain relief (NNT = 2) with minimal systemic absorption, making them particularly suitable for elderly patients or those with multiple comorbidities 1, 2
• Can be worn for 12-24 hours on affected areas, delivering medication gradually over hours 1
• Especially effective for localized pain areas and allodynia 1
• Minimal drug interactions and systemic side effects make this an ideal option for patients on multiple medications 1

Second-Line Alternatives

Pregabalin

• Consider if the patient failed gabapentin specifically, as it is another gabapentinoid with similar but not identical mechanisms 1
• Effective dose ranges from 150-600 mg/day in two divided doses, with an NNT of 4.93 1
• Start at 25-50 mg/day and titrate to effective dose 1
• Monitor for somnolence, dizziness, and mental clouding, especially in older patients - these side effects led to 14% discontinuation in premarketing trials compared to 7% with placebo 3
• In PHN trials specifically, dizziness (26% vs 9% placebo) and somnolence (16% vs 5% placebo) were the most common adverse effects 3

Capsaicin

• Available as 8% dermal patch or lower concentration (0.075%) cream applied 3-4 times daily for 6 weeks 1
• Can provide pain relief for at least 12 weeks after application 1, 2
• Apply 4% lidocaine for 60 minutes before capsaicin application to minimize the burning sensation and erythema that commonly occur 1, 2
• Effective for some patients but poorly tolerated by many due to initial burning 1

SNRIs (Duloxetine and 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 1
• Start with lower doses and titrate slowly to minimize adverse effects, particularly in older adults 1

Third-Line Options (Use with Caution)

Opioids

• Oxycodone, extended-release morphine, and methadone show efficacy with an NNT of 2.67 1
• Should NOT be used as first-line agents due to significant risks including pronociception, cognitive impairment, respiratory depression, endocrine/immunological changes, and potential for misuse and addiction 1
• Tramadol shows efficacy with an NNT of 4.76 and may be considered as a safer opioid option 1

Combination Therapy

• When single agents provide inadequate relief, combining medications (such as morphine with gabapentin, or nortriptyline with gabapentin) may be more effective 1, 2
• Combination therapy allows for lower doses of each medication while providing additive effects 1

Treatments to AVOID

Lamotrigine

• Not recommended for PHN due to lack of convincing evidence of efficacy and risk of lamotrigine-associated rash 1

Corticosteroids

• Avoid corticosteroids for established PHN - they provide no benefit and expose patients to unnecessary adverse effects including hyperglycemia, osteoporosis, hypertension, and immunosuppression 1

Non-Pharmacological Approaches

• Cognitive behavioral therapy (CBT), hypnosis, and physical/occupational therapy may be beneficial as adjunctive treatments 1
• These approaches can be particularly valuable for patients who cannot tolerate multiple medications 1

Special Considerations for Elderly Patients

• Start with lower doses and titrate more slowly in elderly patients 1
• Topical treatments (lidocaine patches, capsaicin) are particularly valuable due to minimal systemic effects 1
• Monitor carefully for anticholinergic effects with TCAs and sedation with pregabalin 1, 3

Treatment Algorithm

1. First choice: Nortriptyline 10-25 mg at bedtime, titrate to 25-100 mg OR topical lidocaine 5% patches for localized pain 1
2. If inadequate response: Add or switch to pregabalin 150-600 mg/day in divided doses 1
3. For persistent localized pain: Add capsaicin 8% patch (with lidocaine pre-treatment) 1
4. If still inadequate: Consider combination therapy or SNRI (duloxetine/venlafaxine) 1
5. Refractory cases only: Opioids as last resort, with careful risk-benefit assessment 1