Antiviral treatment for preventing postherpetic neuralgia: Cochrane systematic review
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.
To assess the effectiveness of antiviral agents in preventing PHN.
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.
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.
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.
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.
Chen Ning, Li Qifu, Yang Jie, Zhou Muke, Zhou Dong, He Li
Antiviral treatment for preventing nerve pain after shingles (postherpetic neuralgia)
We reviewed the evidence about the effect of antiviral medicines for preventing postherpetic neuralgia (PHN).
PHN is a painful condition that can occur after shingles (herpes zoster) in the area where the rash occurred. Many people with PHN find that treatments work only a little or not at all. Attention has therefore turned to stopping the development of PHN. Some people suggested that medicines that target the virus that causes shingles (antiviral medicines), given at the time of the rash, might prevent PHN. The aim of this review was to assess the whether antiviral medicines are able to prevent PHN.
We identified six clinical trials that met our standards for inclusion in the review. They included a total of 1319 participants. We decided that our main measure of whether antiviral medicines work in preventing PHN would be whether or not PHN had developed six months after a first attack of shingles (some of the studies we included of aciclovir measured PHN at four months).
Key results and quality of the evidence
Aciclovir, which is an antiviral medicine, was used in five trials (900 participants) and was not better than a placebo (dummy pill) in preventing PHN. In the other trial (419 participants), famciclovir, which is another antiviral drug, was no better than placebo in preventing pain following healing of the shingles rash. The number of side effects with aciclovir and famciclovir was not very different from the number with placebo. The trials did not have any major problems of design or conduct that put the results in doubt, although most of the reports did not provide enough information to fully assess every aspect. We conclude that according to high quality evidence, oral aciclovir was ineffective in reducing the incidence of PHN and there is not enough evidence on other antiviral treatments. There need to be further well-designed trials of famciclovir or other new antiviral agents with a greater number of participants. Future trials should pay more attention to the severity of pain and quality of life of participants, and should include different groups of people, such as those who have lowered immunity.
The evidence is current to April 2013, when the searches were last updated. Because new evidence on this topic is slow to emerge, we have scheduled the next update of this review for 2017.
Implications for practice
There is high quality evidence that oral aciclovir does not significantly reduce the incidence of postherpetic neuralgia, defined as pain lasting 120 days or longer from rash onset. There was some evidence for a reduction in the incidence of pain in the short term, that is four weeks after the onset of rash. There was insufficient evidence to support the use of other antiviral agents for preventing PHN.
Implications for research
Further trials of aciclovir would be inappropriate, but well-designed, randomised controlled trials of famciclovir or other new antiviral agents, comparing them to aciclovir and with a greater number of participants, are needed to evaluate the efficacy of these antiviral agents in preventing postherpetic neuralgia. Future investigators should pay more attention to the severity of pain and quality of life, and should consider different subgroups, such as the immunocompromised. The effects of antiviral treatment started sooner rather than later after herpes zoster onset should be stratified for assessment. Moreover, the quality of reporting should be improved, so that more useful data can be obtained.