Medline ® Abstracts for References 18-20

Although acute pain in patients with herpes zoster can be severe and has a substantial impact on health-related quality of life, there have been no randomized clinical trials of oral medications specifically for its ongoing treatment. A randomized clinical trial was conducted in which 87 subjects>or=50 years of age with herpes zoster within 6 calendar days of rash onset and with worst pain in the past 24h>or=3 on a 0-10 rating scale initiated 7 days of treatment with famciclovir in combination with 28 days of treatment with either controlled-release (CR) oxycodone, gabapentin, or placebo. Subjects were evaluated for adverse effects of treatment, acute pain, and health-related quality of life. The results showed that CR-oxycodone and gabapentin were generally safe and were associated with adverse events that reflect well-known effects of these medications. Discontinuing participation in the trial, primarily associated with constipation, occurred more frequently in subjects randomized to CR-oxycodone (27.6%) compared with placebo (6.9%). Treatment with CR-oxycodone reduced the mean worst pain over days 1-8 (p=0.01) and days 1-14 (p=0.02) relative to placebo but not throughout theentire 28-day treatment period as pain resolved in most subjects. Gabapentin did not provide significantly greater pain relief than placebo, although the data for the first week were consistent with a modest benefit. By demonstrating that CR-oxycodone is safe, generally adequately tolerated, and appears to have efficacy for relieving acute pain, the results of this clinical trial provide a foundation for evidence-based treatment for acute pain in herpes zoster.

BACKGROUND: Postherpetic neuralgia is a common serious complication of herpes zoster. Corticosteroids are anti-inflammatory and might be beneficial.

OBJECTIVES: To examine the efficacy of corticosteroids in preventing postherpetic neuralgia.

SEARCH STRATEGY: Search for randomised or quasi-randomised controlled trials for corticosteroids for preventing postherpetic neuralgia in MEDLINE (1950 to 2006), EMBASE (1980 to 2006), LILACS (1982 to 2005), the Chinese Biomedical Retrieval System (1978 to 2006) and the Cochrane Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 3, 2006). Date of most recent search: September 2006.

SELECTION CRITERIA: Types of studies: quasi-randomised or randomised controlled trials.

TYPES OF PARTICIPANTS: people of all ages with herpes zoster of all degrees of severity within seven days after onset. Types of interventions: all kinds of corticosteroids given by oral, intramuscular or intravenous routes during the acute stage (starting within one week of onset of the rash) compared with no treatment or placebo, but not with other treatments. We also included trials which compared corticosteroids plus routine treatment with placebo plus routine treatment. Types of outcome measures: Primary: the presence of postherpetic neuralgia six months after the onset of the acute herpetic rash. Secondary: pain severity measured by a validated visual analogue scale or numerical descriptive scale after three, six and 12 months; quality of life measured with the short form 36 questionnaire after six months; adverse events during or within two weeks after stopping treatment.

DATA COLLECTION AND ANALYSIS: Data were extracted by two independent reviewers.

MAIN RESULTS: Five trials were included with altogether 787 participants. All were randomised, double-blind, placebo-controlled parallel group studies. Our primary outcome measure was the presence of postherpetic neuralgia six months after the onset of the acute herpetic rash. There was no significant difference between the corticosteroid and control groups for the primary outcome (RR 1.27, 95% CI 0.20 to 7.97). There was also no significant difference between the corticosteroid plus antiviral agents and placebo plus antiviral agents groups for the primary outcome (RR 0.90, 95% CI 0.40 to 2.03). No included trials evaluated pain severity with a validated visual analogue scale or numerical descriptive scale and also no trials measured quality of life with the Short Form 36 questionnaire. Adverse events during or within two weeks after stopping treatment were reported by all five included trials, but after meta-analysis, there was no significant difference in any serious adverse event (death, acute cardiac insufficiency, rash dissemination, bacterial pneumonia or haematemesis) or non serious adverse event (dizziness, nausea, vomiting, hypertension or hyperglycaemia).

AUTHORS' CONCLUSIONS: There was insufficient evidence to conclude that corticosteroids are safe or effective in the prevention of postherpetic neuralgia. More randomised controlled trials with a greater number of participants are needed to determine reliably whether there is real benefit (or harm) from the use of corticosteroid therapy to prevent postherpetic neuralgia. Future trials should measure function and quality of life.

Seventy-two patients older than 60 years of age who received a diagnosis of herpes zoster (HZ) were entered into a randomized, double-blind, placebo-controlled trial of daily amitriptyline 25 mg. Treatment with either amitriptyline or placebo continued for 90 days after diagnosis. Pain prevalence at 6 months was the primary outcome. Results showed that early treatment with low-dose amitriptyline reduced pain prevalence by more than one-half (p<0.05; odds ratio, 2.9:1) This finding makes a strong case for the pre-emptive administration of amitriptyline, in combination with an antiviral drug, to elderly patients with acute herpes zoster.