Does Treatment of Acute Herpes Zoster Prevent or Shorten Postherpetic Neuralgia? A Systematic Review of the Literature

A later placebo-controlled trial³¹ randomized 201 patients to acyclovir, prednisone, both, or neither for 21 days. That trial had good methodology and may have been large enough to provide the evidence to support or refute the benefit of steroids. No differences in pain incidence were found at 3 or 6 months. Benefit during the first month was found, but results were reported only as risk reductions.With no incidence or duration data reported, these results are not clinically applicable. Follow-up commentary⁴³ pointed out the need for actual data instead of risk ratios. The authors’ response provided limited data showing reductions in median time to cessation of analgesic use (from 28 to 14 days), return to normal activity (from 21 to 3 days), and uninterrupted sleep (from 26 to 5 days) for the combined acyclovir and prednisone treatment group compared with the placebo group. No data were provided for the acyclovir-only or prednisone-only groups.

Wood and colleagues³⁴ randomized 400 patients to prednisolone or placebo for 21 days. Patients were also randomized to acyclovir for 7 days or 21 days, so there was no placebo-only group. There was no benefit to extending acyclovir to 21 days or to adding prednisolone with respect to incidence or duration of PHN.

A recent review⁴⁴ incorporating these newer trials concluded that steroids can reduce acute herpes zoster pain and improve short-term (1-month) quality of life and suggested that steroids are reasonable to use in patients older than 50 years. No effect, however, was demonstrated on the incidence, severity, or duration of PHN.

Tricyclic Antidepressants

Amitriptyline exerts a pain-modulating effect separate from its antidepressant properties⁴⁵ and has been widely used in neuropathic and other chronic pain states. Amitriptyline (25 mg nightly) used preemptively for 90 days starting within 48 hours of rash onset showed a statistically significant reduction in pain incidence at 6 months in a single placebo-controlled trial of fair quality.⁸ Blinding may have been inadequate, because patients were warned of potential dry mouth. Follow-up was a single contact by telephone or mail at 6 to 8 months. Acyclovir given by general practitioners was not controlled. Twenty-four percent of the amitriptyline group and 50% of the placebo group received acyclovir. Among amitriptyline-treated patients, there was a nonsignificant trend toward reduced pain with acyclovir use, while placebo patients who received acyclovir experienced a nonsignificant trend toward increased pain.

Percutaneous Electrical Nerve Stimulation

Percutaneous electrical nerve stimulation (PENS) compared favorably with famciclovir in a single blind randomized trial of 50 adults with zoster.⁴⁶ A 12% absolute risk reduction in pain was reported at 3 and 6 months (but not at 9 months), but no statistical analysis was reported for this measure. Statistically significant reductions in severity of pain were found at 3 and 6 months. Costs and availability of PENS were not reported.

Discussion

There are limited data from randomized controlled trials that indicate that early treatment of acute herpes zoster decreases the incidence or duration of PHN. Acyclovir was the most-studied agent, but there is no convincing evidence that acyclovir alters the course of PHN. There is some evidence that oral acyclovir 800 mg 5 times daily for 7 to 10 days reduces the incidence of pain in the short term (1 to 3 months). Valacyclovir was somewhat more effective than acyclovir in the single largest antiviral trial, but without a placebo control, the actual efficacy of either drug is indeterminate. Famciclovir did not alter the incidence of PHN (at the time of rash healing) but did significantly reduce the duration of PHN in a single placebo-controlled trial of good methodology.

Randomized antiviral trials have been limited totrials including patients presenting within 72 hours of rash onset. No data are available to address the use of antivirals initiated more than 72 hours after rash onset. In the largest prospective study of patients presenting to general practitioners with zoster,¹ only 44% presented within 72 hours of rash onset.

For immunocompetent subjects, oral acyclovir, famciclovir, and valacyclovir were free of major toxicities and demonstrated side effects comparable with placebo in the clinical trials presented. According to the package inserts, posttrial case reports of more serious reactions, including anaphylaxis and renal failure, have been cited. These medications require dose adjustment in patients with compromised renal function.

Steroids, like antivirals, are widely prescribed for the treatment of acute herpes zoster. Although useful for reduction of early pain, there is no evidence that systemic steroids prevent or shorten the course of PHN. No further trials are needed in this regard. The largest and best designed trial involving corticosteroids for the treatment of zoster is rendered clinically inapplicable by the presentation of relative risk reduction rather than incidence and duration data for placebo and treatment groups.