Antiviral treatment for preventing postherpetic neuralgia

Cochrane Database Syst Rev. 2014 Feb 6;(2):CD006866. doi: 10.1002/14651858.CD006866.pub3.


Background: Postherpetic neuralgia (PHN) is a painful and refractory complication of herpes zoster. Treatments are either partially or totally ineffective for many people with PHN. Antiviral agents, used at the time of the rash, have been proposed as an intervention to prevent the development of PHN. This is the first update since the first publication of the review in 2009.

Objectives: To assess the effectiveness of antiviral agents in preventing PHN.

Search methods: On 26 April 2013, we updated the searches in the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, and the Chinese Biomedical Retrieval System. We checked the references of published studies to identify additional trials, and contacted authors to obtain additional data. We searched other databases in The Cochrane Library for information for the Discussion and two clinical trials registries for ongoing trials.

Selection criteria: We considered all randomised controlled trials (RCTs) of antiviral treatment given within 72 hours after the onset of herpes zoster for preventing PHN. There were no language restrictions.

Data collection and analysis: Two authors independently selected trials, evaluated the risk of bias in included trials, and extracted and analysed data.

Main results: Six RCTs with a total of 1211 participants were eligible; five trials evaluated oral aciclovir, and one, with 419 participants, evaluated oral famciclovir. We were able to conduct meta-analyses as there were sufficient similarities in the included studies, such as the reporting of the presence of PHN, duration of rash before treatment initiation and treatment regimen. For our primary outcome, based on three trials (609 participants) we found no significant difference between the aciclovir and control groups in the incidence of PHN four months after the onset of the acute herpetic rash (risk ratio (RR) 0.75, 95% confidence interval (CI) 0.51 to 1.11), nor was there a significant difference at six months (RR 1.05, 95% CI 0.87 to 1.27, two trials, 476 participants). In four of the trials (692 participants), there was some evidence for a reduction in the incidence of pain four weeks after the onset of rash. In the trial of famciclovir versus placebo, neither 500 mg nor 750 mg doses of famciclovir reduced the incidence of herpetic neuralgia significantly. The most commonly reported adverse events were nausea, vomiting, diarrhoea and headache for aciclovir, and headache and nausea for famciclovir. For neither treatment was the incidence of adverse events significantly different from placebo. None of the studies were at high risk of bias, although the risk of bias was unclear in at least one domain for all but one study. We found no new RCTs when we updated the searches in April 2013.

Authors' conclusions: There is high quality evidence that oral aciclovir does not reduce the incidence of PHN significantly. In addition, there is insufficient evidence to determine the effect of other antiviral treatments; therefore, further well-designed RCTs are needed to investigate famciclovir or other new antiviral agents in preventing PHN. Future trials should pay more attention to the severity of pain and quality of life of participants, and should be conducted among different subgroups of people, such as people who are immunocompromised.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • 2-Aminopurine / analogs & derivatives*
  • 2-Aminopurine / therapeutic use
  • Acyclovir / therapeutic use*
  • Antiviral Agents / therapeutic use*
  • Famciclovir
  • Humans
  • Neuralgia, Postherpetic / prevention & control*
  • Randomized Controlled Trials as Topic


  • Antiviral Agents
  • 2-Aminopurine
  • Famciclovir
  • Acyclovir