Medline ® Abstracts for References 5-8

Meta-analysis of four double-blind, randomized, placebo-controlled trials of oral acyclovir (800 mg five times daily) for the treatment of herpes zoster was conducted to provide definitive assessments of the effect of acyclovir on the resolution of zoster-associated pain. The studies involved a total of 691 patients, and the analysis was performed on an intent-to-treat basis. A range of milestones of pain cessation were evaluated by means of Cox regression models with adjustment for relevant prognostic factors. The proportion of patients with postherpetic neuralgia at 3 and 6 months was also determined. Advancing age and more severe pain at presentation were associated with more prolonged pain. Acyclovir was clearly shown to accelerate pain resolution by all of the measures employed. Benefit was especially evident in patients 50 years of age or older. Fewer acyclovir recipients had postherpetic neuralgia at 3 or 6 months. Overall, the reductions of pain duration and prevalence were approximately twofold.

BACKGROUND: Herpes zoster is a common affliction in older patients, with up to 15% experiencing some residual pain in the distribution of the rash several months after healing. Despite numerous randomized clinical trials, the effect of treating herpes zoster with oral acyclovir in preventing postherpetic neuralgia remains uncertain because of conflicting results.

METHODS: Meta-analysis of published randomized clinical trials on the use of acyclovir to prevent postherpetic neuralgia using the fixed-effects model of Peto.

RESULTS: Thirty clinical trials of treatment with oral acyclovir in immunocompetent adults were identified. After excluding studies with duplicate data, suboptimal and topical dosing, non-placebo-controlled or nonrandomized designs, and those using intravenous acyclovir, 5 trials were found to be homogeneous and were combined for analysis. From these trials, the summary odds ratio for the incidence of "any pain" in the distribution of rash at 6 months in adults treated with acyclovir was 0.54 (95% confidence interval, 0.36-0.81).

CONCLUSION: Treatment of herpes zoster with 800 mg/d of oral acyclovir within 72 hours of rash onset may reduce the incidence of residual pain at 6 months by 46% in immunocompetent adults.

An overview of all the available placebo-controlled trial data for oral acyclovir in acute herpes zoster infection has confirmed that a dose of 800 mg five times daily for seven to ten days is effective in reducing the incidence of post-herpetic neuralgia and the duration of pain. Although one study failed to demonstrate such an effect, three other studies and a combined analysis, using the log rank test, did so. The duration of pain was shortened from an average of 86 to 49 days (p less than 0.001). Future studies will need to take account of these findings since oral acyclovir is most likely to be used as the standard reference therapy.

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, are one of the best-established approaches that may prevent the development of PHN.

OBJECTIVES: To investigate the effectiveness of antiviral agents in preventing PHN.

SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Trials Register (January 13 2009), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2008, Issue 4), MEDLINE (January 1966 to November Week 3 2008), EMBASE (January 1980 to Week 02 2009), LILACS (January 1982 to 13 January 2009), and the Chinese Biomedical Retrieval System (January 1978 to 13 January 2009). We checked the references of published studies to identify additional trials.

SELECTION CRITERIA: All randomised and quasi-randomised controlled trials for antiviral treatment given within 72 hours after the onset of herpes zoster forpreventing PHN irrespective of any language restrictions.

DATA COLLECTION AND ANALYSIS: Two authors independently selected trials and evaluated the methodological quality, then extracted and analysed data from the included trials.

MAIN RESULTS: Twenty trials were identified. Twelve trials were excluded and two trials are awaiting classification. Six randomised controlled trials, with a total of 1211 participants were eligible; five trials evaluated oral acyclovir, and one trial with 419 participants evaluated oral famciclovir. There was no significant difference between the oral acyclovir and control groups on the incidence of PHN four months (risk ratio (RR), 0.75; 95% CI 0.51 to 1.11; P = 0.15) or six months (RR 1.05, 95% CI 0.87 to 1.27; P = 0.62) after the onset of the acute herpetic rash. 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 and 750 mg doses of famciclovir reduced the incidence of herpetic neuralgia significantly.

AUTHORS' CONCLUSIONS: Oral acyclovir did not reduce the incidence of PHN significantly. There is insufficient evidence from randomised controlled trials to determine whether other antiviral treatments prevent PHN. Additional well-designed, randomised controlled trials of famciclovir or other new antiviral agents, with a greater number of participants are needed. 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.