What are the treatment options for refractory postherpetic neuralgia (PHN)?

Treatment of Refractory Post-Herpetic Neuralgia

For refractory post-herpetic neuralgia (PHN) that has failed first-line therapies, combination therapy with gabapentin plus low-dose opioids (morphine or oxycodone) provides superior pain relief compared to monotherapy, allowing lower doses of each medication while achieving additive analgesic effects. 1

Defining Refractory PHN

Refractory PHN is defined as persistent neuropathic pain despite adequate trials of at least 3-6 months of first-line pharmacological treatments including gabapentin (up to 3600 mg/day), tricyclic antidepressants, pregabalin, or topical lidocaine patches. 2, 3

Pharmacological Approach for Refractory Cases

Combination Therapy (Preferred Strategy)

• Gabapentin plus opioids (morphine extended-release or oxycodone) demonstrates superior efficacy when single agents fail, with an NNT of 2.67 for opioids in PHN, allowing dose reduction of each medication while maintaining analgesic benefit. 1

• Pregabalin should be tried if gabapentin response is inadequate, with effective doses of 150-600 mg/day in two divided doses (NNT = 4.93), as it has a different pharmacokinetic profile despite similar mechanism of action. 1, 4

• Nortriptyline (preferred over amitriptyline) provides excellent efficacy (NNT = 2.64) and can be combined with gabapentinoids, starting at 10-25 mg at bedtime and titrating every 3-7 days to 25-100 mg as tolerated. 1, 2

Topical Therapies for Localized Pain

• High-concentration capsaicin 8% patch provides pain relief lasting up to 90 days from a single 30-minute application, with pretreatment using 4% lidocaine for 60 minutes to reduce application discomfort. 1, 2

• Lidocaine 5% patches remain effective even in refractory cases when pain is localized, with minimal systemic absorption and no drug interactions, particularly valuable in elderly patients with multiple comorbidities. 5, 6

Interventional Treatments

Interventional procedures should only be considered after documented failure of at least 3-6 months of optimized pharmacological therapy, including combination regimens. 2, 3

Recommended Interventional Sequence

1. First-tier interventions (least invasive):

   • Subcutaneous botulinum toxin A injection into affected dermatomes 3, 7
   • Transcutaneous electrical nerve stimulation (TENS) 3
   • Stellate ganglion block for cervical/upper thoracic distribution 3, 7

2. Second-tier interventions (moderate invasiveness):

   • Pulsed radiofrequency (PRF) therapy shows the most durable long-term efficacy among interventional options 3, 7
   • Peripheral nerve stimulation for localized refractory pain 3
   • Paravertebral nerve blocks 3

3. Third-tier interventions (most invasive, reserved for severe refractory cases):

   • Spinal cord stimulation for severe, widespread refractory pain 3, 7
   • Avoid dorsal root ganglion radiofrequency ablation - this destructive procedure should be used with extreme caution due to permanent nerve damage risk 3

Critical Warnings About Interventional Approaches

• Do NOT use intrathecal methylprednisolone despite some historical use - significant adverse events and lack of high-quality evidence make this approach inadvisable. 5, 3

• Radiofrequency ablation of the dorsal root ganglion should NOT be used routinely due to its destructive nature and potential for worsening neuropathic pain. 2, 3

• Intrathecal steroid injections may be considered for intractable PHN, but evidence is limited to observational studies showing benefit for 1 week to 2 years. 5

Combination Interventional + Pharmacological Strategy

• PRF combined with nerve block represents the most effective combination intervention, superior to either treatment alone. 7

• Subcutaneous injection + nerve block + ozone therapy shows promise as a second-line combination intervention. 7

• Continue optimized pharmacological therapy (gabapentin or pregabalin plus tricyclic antidepressants) even when pursuing interventional treatments. 8

Alternative and Adjunctive Therapies

• Electroacupuncture and osteopathic manipulative treatment show efficacy in some refractory cases and may be considered as adjunctive therapies, particularly when patients cannot tolerate or refuse invasive procedures. 8

• Physical therapy, cognitive behavioral therapy, and sleep hygiene optimization should continue throughout treatment as these address functional impairment and quality of life. 5

Common Pitfalls to Avoid

• Do not use lamotrigine - it lacks convincing efficacy evidence for PHN and carries risk of serious rash including Stevens-Johnson syndrome. 1

• Do not prescribe opioids as monotherapy for long-term management - they should only be used in combination with gabapentinoids or tricyclic antidepressants to allow lower opioid doses and reduce risks of tolerance, dependence, and adverse effects. 1, 2

• Do not abandon topical therapies even in refractory cases - the lidocaine patch and high-dose capsaicin patch can provide meaningful relief with minimal systemic effects and should be continued alongside systemic therapies. 1, 6

• Monitor elderly patients closely for cognitive impairment, falls, and sedation when using combination therapy with gabapentinoids and tricyclic antidepressants. 5, 1

• Reassess treatment goals regularly - some patients with refractory PHN may require acceptance of partial pain relief rather than complete resolution, with focus shifting to functional improvement and quality of life. 5