Antiviral Medications for the Prevention of Postherpetic Neuralgia After Herpes Zoster Infection

No benefit over placebo

Benefits in NNT

None were helped
None were helped (0%)

Harms in NNT

None were harmed
None were harmed (0%)
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Chen N, Li Q, Yang J, Zhou M, He L. Antiviral treatment for preventing postherpetic neuralgia. Cochrane Database Syst Rev 2014;(2):CD006866.

Study Population: 1,211 patients with herpes zoster (shingles) infection randomized to treatment with antiviral medication or placebo in six trials

Efficacy Endpoints

Incidence of postherpetic neuralgia at 6 months after a first attack of shingles

Harm Endpoints

“Serious” (life-threatening, those leading to death) and “nonserious” adverse events during or within 2 weeks of treatment


Postherpetic neuralgia (PHN) is a condition of persistent, refractory pain in an area previously affected by an acute herpes zoster infection. Age remains an important risk factor for the development of PHN, with 40% of patients older than 50 years and 75% of patients 75 years and older developing PHN after an initial episode of shingles.1 Persistent pain can lead to significant long-term problems such as depression, altered activities of daily living, and anorexia.1 Prior systematic reviews have suggested that treatment with antivirals within 72 hours of the onset of rash may reduce the incidence or duration of PHN.1

The Cochrane systematic review discussed here is an update of a previous Cochrane review from 2009 and draws no new conclusions compared to the earlier review. The current review included six double-blind randomized placebo-controlled trials and a total of 1,211 patients. Five of these trials evaluated oral acyclovir, and the sixth trial evaluated famciclovir. Fifteen other studies were excluded for reasons such as a short follow-up interval, lack of placebo control, or initiation of treatment beyond 72 hours from the onset of rash.

This review found no significant difference between acyclovir and placebo in the incidence of PHN at 4 months (risk ratio [RR] = 0.75, 95% confidence interval [CI] = 0.51–1.11) or at 6 months (RR = 1.05, 95% CI = 0.87–1.27). The single study that evaluated famciclovir also failed to show reduced incidence compared to placebo. One trial comparing placebo and acyclovir with 46 participants reported statistically significant lower mean pain scores between 2 and 6 months using the visual analog scale–validated pain scale. The most common adverse drug events included nausea, vomiting, and headache, but these were not significantly different than in patients who received placebo.

The Cochrane review concludes that there is high-quality evidence that acyclovir does not reduce the incidence of PHN and suggests that further trials should focus on famciclovir and other antiviral agents since there is currently insufficient evidence to determine their efficacy.


The results of prior studies may have been affected by how PHN was defined. This review defined PHN as pain persisting at least 120 days from the onset of rash. Four trials recorded data on herpetic neuralgia 1 month after rash onset, and this was analyzed in the review as an additional outcome measure not specified in the protocol. It found a statistically significant reduction in pain in the acyclovir group at 1 month after rash onset when compared to placebo (153/347 [44.1%] and 184/345 [53.3%], respectively; RR = 0.83, 95% CI = 0.71–0.96; p = 0.01).

Only a few trials have examined pain and quality of life. Then Cochrane review suggests that these endpoints may be more useful measures in determining treatment efficacy rather than focusing only on the presence of symptoms. Only one of the trials included in this review was rated to be of good quality (based on design and avoidance of biases); the remaining studies were rated as fair because of unclear risk of bias. Biases identified included problems with blinding, allocation concealment, and random sequence generation. It appears that future research should adopt improved methods of data reporting so as to increase the likelihood of arriving at more clinically useful conclusions.

In conclusion, the existing evidence does not support the use of antiviral medication to prevent postherpetic neuralgia at 6 months. There are some data that suggest the benefit of antivirals on acute symptoms of zoster, but since this review focuses on antivirals for PHN prevention we have assigned a color rating of red (no benefit) to this treatment.

The original manuscript was published in Academic Emergency Medicine as part of the partnership between and AEM.

See's previous reviews of this topic:
Antivirals for Preventing Post-Herpetic Neuralgia, November 23, 2010


Daniel S. Kowalsky, MD; Allan B. Wolfson, MD


March 4, 2019