What is the treatment for postherpetic neuralgia (PHN) following shingles?

Treatment of Postherpetic Neuralgia

Gabapentin is the first-line oral pharmacological treatment for postherpetic neuralgia, starting at 300 mg on day 1,600 mg on day 2, and 900 mg on day 3, then titrating up to 1800-3600 mg/day in three divided doses, with no additional benefit shown above 1800 mg/day. 1, 2

First-Line Treatment Options

Oral Medications

• Gabapentin demonstrates efficacy with a number needed to treat (NNT) of 4.39 for postherpetic neuralgia, making it the preferred initial oral agent as recommended by the American Academy of Neurology 1, 3, 2
• Tricyclic antidepressants (TCAs) have excellent efficacy with an NNT of 2.64, making them highly effective for PHN, with nortriptyline preferred over amitriptyline due to better tolerability with equivalent analgesic benefit 1, 3
• Nortriptyline should be started at 10-25 mg at bedtime and increased every 3-7 days to a final dose of 25-100 mg at bedtime as tolerated 1
• Early initiation of TCAs is critical: the probability of pain relief correlates very strongly with the brevity of the interval between rash onset and commencement of treatment with an adrenergically active antidepressant 4

Topical Medications

• Topical lidocaine 5% patches provide excellent efficacy (NNT = 2) with minimal systemic absorption, making them particularly suitable for elderly patients or those with comorbidities, and can be worn for 12-24 hours on affected areas 1, 3
• Capsaicin 8% dermal patch provides pain relief for at least 12 weeks after a single 30-minute application, though erythema and pain are common side effects 1, 3
• Pre-treat with 4% lidocaine for 60 minutes before capsaicin application to minimize erythema and pain 1, 3

Second-Line Treatment Options

• Pregabalin should be considered if patients have an 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, 3, 5
• Tramadol shows efficacy with an NNT of 4.76 1
• Opioids (oxycodone, extended-release morphine, methadone) show efficacy with an NNT of 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, 3
• Combination therapy, such as morphine with gabapentin, may be more effective when single agents provide inadequate relief, allowing for lower doses of each medication while providing additive effects 1, 3

Non-Pharmacological Approaches

• Cognitive behavioral therapy, hypnosis, and physical and occupational therapy are beneficial adjuncts for PHN management 1, 3
• Hypnosis is specifically recommended for neuropathic pain 1, 3

Special Populations

• For elderly patients, start with lower doses and titrate more slowly, with topical treatments being particularly valuable due to minimal systemic effects 1
• Patients with creatinine clearance between 30-60 mL/min require dose adjustments for pregabalin 5

Critical Pitfalls to Avoid

• Lamotrigine is not recommended for PHN due to lack of convincing evidence of efficacy and risk of lamotrigine-associated rash 1
• Carbamazepine and conventional analgesics are of little or no value in treating established postherpetic neuralgia 6
• Sympathetic blockade was found to be without value in most cases 4
• Monitor for medication side effects, particularly somnolence, dizziness, and mental clouding with gabapentinoids, especially in elderly patients 1
• More than 90% of PHN patients experience allodynia with clinically evident sensory deficit, but the presence or absence of allodynia has no predictive significance for treatment response 4

Treatment Algorithm

1. Initiate gabapentin as first-line oral agent, titrating to 1800-3600 mg/day in divided doses 1, 2
2. Consider topical lidocaine patches concurrently, especially in elderly patients or those with localized pain 1, 3
3. If inadequate response after 8 weeks, switch to or add nortriptyline 25-100 mg at bedtime 1, 4
4. If still inadequate response, consider pregabalin 150-600 mg/day or capsaicin 8% patch 1, 3
5. Reserve opioids for refractory cases only after failure of first and second-line agents 1, 3
6. Incorporate non-pharmacological approaches throughout treatment 1, 3

Important Clinical Context

• Antiviral treatment (acyclovir) during acute herpes zoster does not significantly reduce the incidence of PHN at 4 or 6 months, though there is some evidence for reduction in pain at 4 weeks 7
• Once PHN is established (pain persisting ≥3 months after rash onset), antiviral therapy has little or no effect on the clinical course 8
• At least half of shingles sufferers over age 65 develop postherpetic neuralgia, making aggressive early treatment essential 6