• Neuro-Ophthalmology/Orbit

    Postherpetic neuralgia (PHN) is defined as neuropathic pain, which may be lancinating or burning, with associated itching or allodynia (a painful response to a usually nonpainful stimulus) following resolution of the herpes zoster rash. The pain often lasts years and is not only physically disabling to the patient, but also serves as a challenging treatment dilemma to the practitioner. Recent recommendations regarding administration of the zoster vaccine to adults age 60 years and older should greatly reduce the burden of a disease most commonly seen in the elderly, however PHN continues to cause a significant reduction in quality of life and a burden on the health care system.

    Introduction

    As the ophthalmic branch of the trigeminal ganglion is affected in 10 to 20% of cases of herpes zoster, ophthalmologists are often familiar with the treatment of acute herpes zoster ophthalmicus, but less accustomed to treating the resulting PHN. While some studies have shown a reduction in PHN after the administration of antivirals during the acute phase, significant symptoms remain in many patients. Additionally, when evaluating periocular pain, ophthalmologists must consider a diagnosis of PHN, which can also occur in the absence of skin involvement (zoster sine herpete). Many patients have comorbid conditions such as depression, anxiety, and sleep disturbances related to their PHN. Medications are often prescribed in suboptimal dosages or even incorrect medications are given, leading to inadequate pain control and frustration for both the patient and physician. This article reviews the current recommendations for treatment of PHN.

    Treatment

    Treatment of PHN can be divided into oral medications, topical medications, and invasive therapies. The approved oral medications consist of tricyclic antidepressants (TCAs), anticonvulsants, and opioids.

    Oral Medications
    TCAs block the re-uptake of norepinephrine and serotonin. Amitriptyline and nortriptyline are examples, with the latter generally having fewer side effects. Both are started at 25 to 50 mg at bedtime or divided twice daily, increasing the dose by 10 to 25 mg every 7 days until reduction in pain is achieved, with a maximum dose of 150 mg per day. The most common side effects are anticholinergic effects such as dry mouth, urinary retention, constipation, along with sedation and blurred vision. Background and paroxysmal pain seem to be more receptive to TCAs than allodynia and burning pain are. There is also an additive benefit when combined with narcotics or anticonvulsants.

    Approved anticonvulsants include gabapentin and pregabalin. The mechanism of action of these medications is thought to be multifactorial, and they have been shown to be particularly effective in the treatment of allodynia. Current guidelines recommend a starting dose of gabapentin of 100 to 300 mg. However recent evidence has shown no increase in adverse effects (dizziness, somnolence) with an initial dose of 600 mg. Doses can be titrated quickly, increasing by 300 mg every 3 days up to 3600 mg per day in 3 divided doses. Pregabalin should be started at 150 mg divided 2 to 3 times daily and titrated to a maximum dose of 300 to 600 mg per day. Use of anticonvulsants has been shown to provide a reduction in need for opioids. Additionally, valproic acid has recently been shown to provide significant pain relief for PHN.

    The use of opioids has been controversial in the treatment of neuropathic pain such as PHN. However, the administration of slow-release opioids such as controlled-release oxycodone may improve symptoms from constant or paroxysmal pain and allodynia safely in the elderly without risk of addiction. Sustained-release tramadol, a weak opioid agonist, has been shown to reduce pain and improve quality of life at doses of 100 to 400 mg per day. When combined with TCAs and/or anticonvulsants, opioids may have an additive effect.

    Topical Therapies
    Topical therapies for PHN include lidocaine creams and ointments, lidocaine patch and capsaicin. Topical lidocaine can be particularly effective in treating allodynia, itching, and lancinating pain. The lidocaine patch is not very practical for facial pain, but 5% lidocaine ointment and lidocaine-prilocaine cream are easily applied to the affected area and can be used every 4 to 6 hours as needed. Capsaicin, derived from chili peppers, depletes substance P from sensory neurons. The medicine is often not well tolerated due to burning and redness, but pretreatment with topical lidocaine cream may reduce unwanted side effects. Patients should avoid contact with the eyes and mucosa. The recommended dosage for capsaicin cream is 0.025 to 0.075% cream applied 3 to 4 times daily to the affected area.

    Invasive Therapies
    Patients with intractable pain from PHN may benefit from more invasive therapies, however there are limited controlled investigations or guidelines regarding these treatments. Some of the therapeutic options include botulinum map injections, trigeminal neurectomy, and trigeminal or occipital peripheral nerve stimulation.

    Summary

    Current treatment guidelines provide first-, second-, and third-line options for the management of PHN. First-line therapeutic options include TCAs, antiepileptics, and topical lidocaine. Second-line treatments are opioids and tramadol. Capsaicin and valproic acid are considered third-line therapies. Most medicines can be combined for an additive or even synergistic effect. Treatment regimens should be tailored to each patient's quality and quantity of pain, other comorbid conditions, and tolerance of side effects. Attention should be paid to a patient's response to treatment, with regular reassessment of pain and adverse effects of therapies to optimize medical management and reduce the significant burden of disease.

    References

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    Author Disclosure

    Drs. Braswell and Flanagan state that they have no financial relationship with the manufacturer of any product discussed in this article or with the manufacturer of any competing product.