Does Treatment of Acute Herpes Zoster Prevent or Shorten Postherpetic Neuralgia? A Systematic Review of the Literature
In the most recent meta-analysis,30 Jackson and colleagues included a fifth trial31 and reported an absolute risk reduction of 16% for the incidence of any pain at 6 months (P <.05; number needed to treat [NNT] = 6.3). Multiple methodologic flaws in that meta-analysis, detailed in the Cochrane Review Database,32 make application of the results unclear.
Additional oral acyclovir trials are summarized in Table 1.* Extending the duration of treatment to 14 or 21 days did not provide benefit over 7 days.33,34 Lower doses of acyclovir had no effect on incidence, severity, or duration of PHN.17,35,36 There is no evidence to support use of intravenous or topical acyclovir for prevention of PHN.*
Marginal evidence exists to suggest that oral acyclovir 800 mg 5 times daily may reduce the incidence of pain at 1 to 3 months. Information regarding effects on quality of life were generally lacking.
Newer Antivirals
Famciclovir, a prodrug of penciclovir, did not affect the incidence of PHN measured at the time of cutaneous healing in a placebo-controlled trial of 419 patients6 (Table 2). Among the 186 patients (44%) who developed PHN, famciclovir significantly reduced its duration by a median of 2 months, 3.5 months in patients older than 50 years. No dose-response difference was noted. In a subsequent publication presenting monthly prevalence data,37 pain 6 months after enrollment was reported in 15% of patients assigned famciclovir 500 mg and 23.8% of the patients assigned placebo (NNT = 11.4). Similar results were stated for the 750-mg group. Results were reported as statistically significant but P values were not given.
Valacyclovir, a prodrug of acyclovir, has not been studied in a placebo-controlled trial in patients older than 50 years, based on published reports. In a comparison trial with acyclovir,7 valacyclovir for 7 or 14 days did not reduce the incidence of PHN (pain after rash healing) but did accelerate its resolution by 1 to 2 weeks. Pain persisting for 6 months was found in 25.7% of the acyclovir group and 18.6% of the combined valacyclovir group (P = .02; NNT = 15.6). The actual benefit of valacyclovir cannot be determined, since the evidence for acyclovir is inconclusive.
Steroids
Inflammation of peripheral nervous system structures has been identified in specimens from patients with PHN.38 Because of this, corticosteroids have been used in the treatment of herpes zoster in hopes of preventing PHN. Trials evaluating steroids are heterogeneous, involving different drugs, doses, routes, durations, and follow-up methods, thus hampering pooling of trial data (Table 3).
Esmann and coworkers39 compared a 21-day oral prednisolone treatment with placebo in 84 patients, all of whom received acyclovir for the first 7 days. Pretrial calculation demonstrated that 324 patients would be required to detect an 80% change in incidence of PHN at 6 months with statistical significance. Enrollment was stopped early when an interim analysis did not show any treatment effect at 3 months at the P <.10 level. No benefit was seen at 6 months. Data points before 6 months were not reported. This is the methodologically strongest of the 4 early steroid trials.
Clemmensen and Andersen40 randomized 60 patients to adrenocorticotropic hormone, prednisone, or placebo. No benefit was found for prednisone, and both active treatments may have increased pain at 1 month. No data were reported beyond 6 weeks.
Keczkes and Basheer41 randomized 40 patients with “severe, painful” zoster to prednisolone or carbamazepine for 4 weeks. A decreased incidence in pain was reported with prednisolone at 8 weeks, but statistics were not reported. Of the 4 early steroid trials, this shows the greatest benefit but is methodologically the weakest study. Without a placebo group, the purported benefit of prednisolone due to a detrimental effect of carbamazepine cannot be excluded.
Eaglstein and colleagues42 randomized 35 patients with “severely painful” zoster to triamcinolone versus placebo. No patients younger than 60 years developed neuralgia. Pain reduction with triamcinolone was reported at 8 weeks but not at 6 months for the 24 patients who developed neuralgia. Statistics were not reported.
These 4 trials have undergone several reviews. In a meta-analysis, Lycka10 reported statistically significant reductions in pain at 6 and 12 weeks after zoster onset but not at 6 months. That meta-analysis incorporated unpublished data obtained from the original investigators. NNTs of 4.5 to prevent pain at 6 weeks and 3.5 to prevent pain at 12 weeks were reported, although an intention-to-treat analysis was not performed. The authors of 2 other reviews4,11 concluded that there was insufficient evidence to support a benefit from steroids, finding the trials too heterogeneous to appropriately combine in meta-analysis.4
