Prevention of postherpetic neuralgia

An elderly patient is admitted to the internal medicine service with a diagnosis of herpes zoster infection in the typical dermatomal distribution.  The patient’s rash is currently not very painful (2/10) but she is concerned about long-lasting pain as her friend had pain from zoster that lasted for months.  What can we use to prevent the development of postherpetic neuralgia?

Postherpetic neuralgia is a common complication of herpes zoster infection and can be challenging to treat.  Drugs approved by the FDA to treat postherpetic neuralgia include pregabalin (Lyrica), gabapentin (Neurontin), and capsaicin patch (high-concentration patch - Qutenza).  Other medications that have been shown in randomized controlled trials to also reduce pain from postherpetic neuralgia include topical lidocaine, tricyclic antidepressants (eg. nortriptyline), opioids, and tramadol¹. 

No medication has been approved for the prevention of postherpetic neuralgia but here is the data on several agents that have been studied:

Gabapentin

One study administered gabapentin to patients with acute herpes zoster infection in addition to standard treatment of valacyclovir 1000 mg three times a day².  This was done at a single center with no control group and the resultant rate of postherpetic neuralgia at six months was 9.8%.  The authors claim that this intervention reduced the rates of postherpetic neuralgia but compared to historic controls, the results are comparable to treatment without gabapentin³.  Furthermore, one commentator points out that if all 1 million patients estimated to develop shingles in a given year were to receive the goal dose of 3,600 mg per day of gabapentin for 1 month, it would cost nearly $500 million⁴.  (It depends on what pricing you use but my math still puts it somewhere in the hundreds of millions per month of treatment).

Tricyclic antidepressants

One study enrolled 80 patients to receive either amitriptyline 25 mg at bedtime or placebo for three months at presentation with acute zoster infection.  Patients were treated with antivirals at the providers’ discretion and the majority actually did not receive antiviral therapy for the acute infection.  The study found that the rate of patients with postherpetic neuralgia was reduced by half in the amitriptyline group versus placebo group (35.3% versus 15.8%)⁵.

Corticosteroids

A recent Cochrane review was done that identified two randomized controlled trials of patients that received either a corticosteroid or placebo in the first seven days of acute herpes zoster infection.  The outcome was presence of postherpetic neuralgia six months after the acute infection.  The conclusion was that there was no significant reduction in postherpetic neuralgia (RR 0.95, 95% CI 0.45 to 1.99)⁶.  Remember, corticosteroids have a litany of side effects and will place the patient in an immunocompromised state.

In summary, no medication or class of medications has demonstrated robust evidence for preventing postherpetic neuralgia, starting from the acute infection.  One intervention with clear evidence to preventing postherpetic neuralgia is to prevent the development of acute zoster infection itself with the zoster vaccine.  The CDC ACIP recommends that a single dose of zoster vaccine be given to adults 60 years old or older, whether or not the patient reported a prior episode of shingles.  Even if the patient reports a negative history for chickenpox, the vaccine can be given without serologic testing.  Patients should not receive the vaccine if they have a history of anaphylactic-type reaction to any of the components (such as gelatin or neomycin) or if they are immunocompromised (from disease or from medications such as high-dose steroids) since the vaccine is live⁷.

Antiviral therapy

Antiviral therapy is recommended for all immunocompromised patients with acute zoster and in those nonimmunocompromised patients who are at least 50 years old, have moderate or severe pain, severe rash, involvement of the face/eye, or have other complications of zoster.  These agents [acyclovir (Zovirax), valacyclovir (Valtrex), or famciclovir (Famvir)] should be initiated as soon as possible as they have been shown to reduce the formation of new lesions, reduce viral shedding, and decrease the severity of acute pain.  A meta-analysis has shown that they did not reduce the incidence of postherpetic neuralgia, however.  Studies have shown that valacyclovir and famciclovir are superior to acyclovir for the acute pain of zoster, likely because they have higher and prolonged antiviral concentrations in the blood (even though they’re dosed three times a day versus acyclovir which is dosed five times a day).  Intravenous acyclovir is recommended for immunocompromised patients and those with neurologic complications¹.

Back to the patient case

The best intervention for the above vignette would be to start appropriate antiviral therapy as it is recommended for anyone over 50.  Gabapentin, tricyclic antidepressants, and steroids do not have convincing evidence for routine use and considering her pain score of only 2/10, their many known side effects may outweigh their benefit.  Remember to dose these antivirals renally and ensure the patient remains hydrated as they can all precipitate in the kidneys if they exceed maximum solubility.  For mild pain, acetaminophen and NSAIDs can also be used.

Take home pearls:

• Many agents are somewhat effective in treating postherpetic neuralgia once it is established as a chronic problem but there is not much to support the use of gabapentin, tricyclic antidepressants, or steroids in the acute phase for pain.
• Preventing the acute infection itself with the vaccine is an effective way to reduce postherpetic neuralgia across the population.
• In New York State, the zoster vaccine can be administered by immunizing pharmacists following a valid prescription, even in the community setting.
• Early antiviral treatment (valacyclovir and famciclovir preferred) is an effective way to reduce the acute neuralgia from zoster infection.

References:

1.  Cohen JI.  Herpes zoster.  N Engl J Med  2013;369:255-63.

2.  Lapolla W, DiGiorgio C, Haitz K, et al.  Incidence of postherpetic neuralgia after combination treatment with gabapentin and valacyclovir in patients with acute herpes zoster.  Arch Dermatol  2011;147(8):901-7.

3.  Schmader KE, Oxman MN. Chapter 194. Varicella and Herpes Zoster. In:Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K. eds.Fitzpatrick's Dermatology in General Medicine, 8e. New York: McGraw-Hill; 2012

4.  Fett N.  Gabapentin Not Shown to Prevent Postherpetic Neuralgia. Arch Dermato. 2012;148(3):400-1. 

5.  Bowsher D.  The effects of pre-emptive treatment of postherpetic neuralgia with amitriptyline: a randomized double-blind placebo-controlled trial.  J Pain Symptom Manage.  1997;13(6):327-31.

6.  Han Y, Zhang J, Chen N, He L, Zhou M, Zhu C. Corticosteroids for preventing postherpetic neuralgia. Cochrane Database of Systematic Reviews 2013, Issue 3. 

7.  Herpes Zoster Vaccination Information for Health Care Professionals.  Available at: http://www.cdc.gov/Vaccines/vpd-vac/shingles/hcp-vaccination.htm#recommendations.  Accessed January, 2014.

photo by AJC1