Medline ® Abstracts for References 5-7

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.