ABSTRACT
OBJECTIVES: We wanted to determine whether any treatment had been shown to reduce pain or disability from postherpetic neuralgia (PHN), a common sequela of herpes zoster in elderly patients.
STUDY DESIGN: We undertook a systematic review of English-language randomized controlled trials (RCTs) of treatments of PHN with evaluation periods longer than 24 hours.
DATA SOURCES: We systematically searched MEDLINE, Current Contents, and the Cochrane Library. We also searched reference lists of identified trials and reviews and contacted content experts.
OUTCOMES MEASURED: Two reviewers independently evaluated RCTs for methodologic quality and data extraction. Outcomes of primary focus were pain and quality of life.
RESULTS: Twenty-seven RCTs met inclusion criteria and were reviewed. Six trials of tricyclic antidepressants found evidence for clinically meaningful effects over 6 weeks. All other treatments were evaluated in no more than 2 trials meeting our inclusion criteria. Topical capsaicin 0.075%, gabapentin, and controlled-release oxycodone were shown to be effective, but the clinically meaningful benefit is difficult to quantify. Intrathecal methylprednisolone and possibly bupivacaine sympathetic blocks are helpful in refractory cases. Other treatments evaluated, including topical lidocaine, had no evidence or inconsistent evidence of benefit.
CONCLUSIONS: No single best treatment for PHN is known. Tricyclic antidepressants, topical capsaicin, gabapentin, and oxycodone are effective for alleviating PHN; however, long-term, clinically meaningful benefits are uncertain and side effects are common. Patients with PHN refractory to these therapies may benefit from intrathecal methylprednisolone. Little evidence is available regarding treatment of PHN of less than 6 months’ duration.
KEY POINTS FOR CLINICIANS
- Spontaneous resolution is common in patients whose postherpetic neuralgia (PHN) has lasted for less than 6 months; treatment decisions are largely empiric and not evidence based.
- For PHN of longer duration, treatments shown to be more effective than placebo include tricyclic antidepressants, topical capsaicin 0.075%, gabapentin, and controlled-release oxycodone. Benefits should be weighed against adverse effects and costs.
- Patients with PHN refractory to currently available and studied topical and oral agents should be considered for intrathecal steroid therapy.
Postherpetic neuralgia (PHN), the most common complication of herpes zoster, is much more prevalent among adults older than 50 years than in younger people.1,2 The largest English-language prospective study of patients presenting with zoster suggests that the average family physician can expect to see 4 cases of zoster per year and 1 case of PHN lasting more than 3 months every 3 years.3 Among placebo cohorts from randomized controlled trials (RCTs) of acute zoster treatment, the incidence of pain at 3 months has been reported as 17% to 60%; at 6 months, 5% to 39%.4 There is limited evidence that therapies for acute zoster have an impact on PHN.4
This review addresses therapies to reduce pain or improve quality of life in patients with PHN. The condition has been variously defined in terms of timing (either following resolution of acute zoster [rash healing] or a defined time after onset of zoster), duration (any time after zoster or a minimum of 6 months after zoster), and type of pain (such as lancinating pain or allodynia [pain caused by a stimulus that does not nor mally provoke pain]).5,6 PHN may include a spectrum of presentations, from brief intermittent mild pain that resolves spontaneously to chronic persistent disabling pain recalcitrant to multiple therapies. To avoid missing potentially relevant findings, we defined PHN broadly as any pain after cutaneous healing of zoster.
Methods
Search strategy
Medline (1966 to present) was searched on October 19, 2000. The search combined the terms “post-herpetic or postherpetic” and “neuralgia or neuropathy or pain” and publication type “clinical trial (including phases I to IV) or controlled clinical trial or randomized controlled trial.” The Cochrane Controlled Trials Registry 2000, Issue 3, was searched with the same terms. Current Contents was searched to identify more recent references. We also identified trials through article reference lists (from included trials and 40 reviews), contact of authors and content experts, and the Food and Drug Administration (FDA) Web site.
Selection criteria
Inclusion criteria for this review were RCTs that enrolled patients with PHN (history of zoster, pain in the dermatomal distribution of the zoster rash, and pain persisting or occurring after resolution of the zoster rash), addressed relevant end points (pain resolution, pain severity, effect on quality of life), and had full reports available in English. Since responses to initial therapy may change over time, we included only trials with evaluation periods lasting more than 24 hours.
The authors independently evaluated trials meeting these inclusion criteria for quality and independently extracted data. Quality was evaluated using the Jadad scale,7 which addresses selected criteria (randomization technique, allocation concealment, blinding, accounting of dropouts) and rates methodologic quality on a 5-point scale, with 5 representing the highest score. Differences were resolved through discussion. Trials scoring only 1 point were excluded except for 2 instances noted in our discussion.