Postherpetic Neuralgia

TIM LANCASTER, University of Oxford, Oxford, United Kingdom

DAVID W. WAREHAM, M.B., B.S., M.Sc., Queen Mary University of London & Barts & The London NHS Trust

JOHN YAPHE, Rabin Medical Centre, Petach Tikvah, Israel

What are the effects of interventions to prevent postherpetic neuralgia?

LIKELY TO BE BENEFICIAL

Oral antiviral agents (acyclovir, famciclovir, valacyclovir, netivudine). One systematic review of randomized controlled trials (RCTs) has found limited evidence that acyclovir given for seven to 10 days reduces pain at one to three months. One RCT found that famciclovir versus placebo significantly reduced pain duration after acute herpes zoster. One RCT has found that valacyclovir versus acyclovir significantly reduced the prevalence of postherpetic neuralgia at six months. One RCT found no significant difference in outcomes between netivudine and acyclovir. One RCT found no significant difference in the resolution of postherpetic neuralgia between valacyclovir and famciclovir.

UNKNOWN EFFECTIVENESS

Amitriptyline. One small RCT found that amitriptyline versus placebo started within 48 hours of rash onset and continued for 90 days reduced the prevalence of postherpetic neuralgia at six months, but the difference did not reach significance.

Adenosine monophosphate; amantadine; cimetidine; inosine pranobex; levodopa. RCTs found insufficient evidence on the effects of these interventions.

UNLIKELY TO BE BENEFICIAL

Topical antiviral agents (idoxuridine). One systematic review has found that idoxuridine versus placebo or versus oral acyclovir increases short-term pain relief in acute herpes zoster, but found no significant difference in pain at six months.

LIKELY TO BE INEFFECTIVE OR HARMFUL

Corticosteroids. Systematic reviews have found conflicting evidence about the effects of corticosteroids alone on postherpetic neuralgia. One RCT found limited evidence that high-dose steroids added to antiviral agents may be of short-term benefit in acute herpes zoster, but found no significant effect on pain at six months. There is concern that corticosteroids may cause dissemination of herpes zoster.

What are the effects of treatments in established postherpetic neuralgia?

BENEFICAL

Gabapentin. One systematic review identified one RCT, which found that gabapentin versus placebo significantly relieves pain after eight weeks of treatment. One subsequent RCT found similar results.

Tricyclic antidepressants. Two systematic reviews have found that tricyclic antidepressants versus placebo significantly increase pain relief in postherpetic neuralgia after six weeks.

UNKNOWN EFFECTIVENESS

Oxycodone (oral opioid). One systematic review found limited evidence that oral oxycodone versus placebo may reduce pain after four to eight weeks, but may be associated with more adverse effects.

Topical anesthesia. We found insufficient evidence from three RCTs about the effects of lidocaine.

Topical counterirritants. Two systematic reviews and one small RCT found limited evidence that capsaicin versus placebo may improve pain relief, but also causes painful skin reactions in some people.

Tramadol. One systematic review found limited evidence from one small RCT that tramadol reduced pain more than clomipramine after six weeks.

LIKELY TO BE INEFFECTIVE OR HARMFUL

Dextromethorphan. One systematic review and one subsequent RCT found no evidence that dextromethorphan was more effective than placebo or lorazepam after three to six weeks.

Epidural morphine. One small RCT found that epidural morphine versus placebo reduced pain by more than 50 percent, but the reduction was not maintained beyond 36 hours. Epidural morphine caused intolerable opioid effects in 75 percent of people.

Definition

Postherpetic neuralgia is pain that sometimes follows resolution of acute herpes zoster and healing of the zoster rash. It can be severe, accompanied by itching, and follows the distribution of the original infection. Herpes zoster is an acute infection caused by activation of latent varicella zoster virus (human herpes virus 3) in people who have been rendered partially immune by a previous attack of chickenpox. Herpes zoster infects the sensory ganglia and their areas of innervation. It is characterized by pain along the distribution of the affected nerve and crops of clustered vesicles over the area.

Incidence/Prevalence

In a United Kingdom general practice survey of 3,600 to 3,800 people, the annual incidence of herpes zoster was 3.4 per 1,000.¹ Incidence varied with age. Herpes zoster was relatively uncommon in people younger than 50 years (less than two per 1,000 a year), but rose to five to seven per 1,000 a year in people 50 to 79 years of age, and 11 per 1,000 in people 80 years or older. In a population-based study of 590 cases in Rochester, Minn., United States, the overall incidence was lower (1.5 per 1,000), but there were similar increases in incidence with age.² Prevalence of postherpetic neuralgia depends on when it is measured after acute infection, and there is no agreed time point for diagnosis.

Etiology/Risk Factors

The main risk factor for postherpetic neuralgia is increasing age. In a United Kingdom general practice study (involving 3,600 to 3,800 people, 321 cases of acute herpes zoster), there was little risk in those younger than 50 years, but postherpetic neuralgia developed in more than 20 percent of people who had had acute herpes zoster between 60 and 65 years age and in 34 percent in those older than 80 years.¹ No other risk factor has been found to predict consistently which people with herpes zoster will experience continued pain. In a general practice study in Iceland (421 people followed for up to seven years after an initial episode of herpes zoster), the risk of postherpetic neuralgia was 1.8 percent (95 percent confidence interval [CI], 0.6 to 4.2 percent) for people younger than 60 years, and the pain was mild in all cases.² The risk of severe pain after three months in people older than 60 years was 1.7 percent (95 percent CI, 0 to 6.2 percent).

Prognosis

About 2 percent of people with acute herpes zoster in the United Kingdom general practice survey had pain for more than five years.¹ Prevalence of pain falls as time elapses after the initial episode. Among 183 people older than 60 years in the placebo arm of a United Kingdom trial, the prevalence of pain was 61 percent at one month, 24 percent at three months, and 13 percent at six months after acute infection.³ In a more recent RCT, the prevalence of postherpetic pain in the placebo arm at six months was 35 percent in 72 people older than 60 years.⁴

SEARCH DATE: September 2002

EDITOR'S NOTE: Netivudine and inosine pranobex are not available in the United States.

Adapted with permission from Lancaster T, Wareham D, Yaphe J. Postherpetic neuralgia. Clin Evid Concise 2003;9:In press.

REFERENCES

1. Hope-Simpson RE. Postherpetic neuralgia. J R Coll Gen Pract 1975;25:571-5.
2. Ragozzino MW, Melton J III, Kurland LT, et al. Population based study of herpes zoster and its sequelae. Medicine 1982;61:310-6.
3. Mckendrick MW, McGill JI, Wood MJ. Lack of effect of aciclovir on postherpetic neuralgia. BMJ 1989;298:431.
4. Bowsher D. The effects of pre-emptive treatment of postherpetic neuralgia with amitriptyline: a randomised, double-blind, placebo-controlled trial. J Pain Symptom Manage 1997;13:327-31.

This is one in a series of chapters excerpted from Clinical Evidence Concise, published by the BMJ Publishing Group, Tavistock Square, London, United Kingdom. Clinical Evidence is published in print twice a year and is updated monthly online. Each topic is revised every eight months, and users should view the most up-to-date version at www.clinicalevidence.com. If you are interested in contributing to Clinical Evidence Concise, please contact Claire Folkes (cfolkes@bmj group.com). This series is part of the AFP's CME. See "Clinical Quiz" on page 1433.