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Treating herpes zoster and postherpetic neuralgia: An evidence-based approach

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When are corticosteroids appropriate for patients with herpes zoster? Which tricyclics are best for frail and elderly patients with PHN pain? And when should you consider opioids? Read on.


Postherpetic neuralgia (PHN) is a management challenge—because of its severity, long duration, and potential for debilitation, often in the highly vulnerable elderly population. And, as the most common complication of an acute episode of herpes zoster (shingles) in an immunocompetent person, PHN is likely no stranger to your practice.

Herpes zoster is one of the most common neurological problems, with an incidence of up to 1 million new cases per year in the United States.1 Although the precise number for the prevalence of PHN in the United States is unknown, investigators estimate it at 500,000 to 1 million.2

Major risk factors for development of PHN after an episode of herpes zoster include:

  • older age

  • greater acute pain during herpes zoster

  • greater severity of rash.3,4

PHN is commonly defined as “dermatomal pain that persists 120 days or more after the onset of rash.”5 The pain of PHN has been characterized as a stimulus-dependent continuous burning, throbbing, or episodic sharp electric shock-like sensation6 and as a stimulus-dependent tactile allodynia (ie, pain after normally nonpainful stimulus) and hyperalgesia (exaggerated response to a painful stimulus). In addition, some patients experience myofascial pain secondary to excessive muscle guarding. Chronic pruritus can be present.

More than 90% of patients who have PHN have allodynia,7 which tends to occur in areas where sensation is relatively preserved. Patients also feel spontaneous pain in areas where sensation is lost or impaired.

In this article, we review the evidence for the range of treatments for acute herpes zoster and PHN, as well offer preventive strategies for herpes zoster.

Acute herpes zoster: Start antivirals early

Evidence-based treatment of acute herpes zoster includes antiviral drugs and analgesics.

Antiviral agents suppress viral replication and have a beneficial effect on acute and chronic pain. Acyclovir (800 mg, 5 times a day), valacyclovir (1000 mg, every 8 hours), and famciclovir (500 mg, every 8 hours) are antivirals commonly used to treat herpes zoster. All 3 drugs have comparable efficacy and safety profiles.

In a meta-analysis of patients older than 50 years who were treated with acyclovir or placebo, pain persisted in 15% of the acyclovir-treated group, compared with 35% of the placebo group.8 In terms of duration, a study comparing famciclovir treatment with placebo showed that subjects in the placebo group had persistent pain for 163 days, whereas famciclovir-treated patients had pain for 63 days.9

Based on this evidence, antiviral medications are strongly recommended for treating herpes zoster, especially for patients at increased risk of developing PHN. Antiviral treatment should be started within 72 hours of the onset of the rash.

No good evidence supports the efficacy of antiviral treatment administered 72 hours after the onset of rash. One uncontrolled trial, however, examined the effectiveness of acyclovir started before vs after 72 hours; the difference in pain persistence was not significant between the groups, suggesting acyclovir has benefit even when given after 72 hours.10

In clinical practice, the diagnosis of herpes zoster is often not made within 72 hours of symptom onset; nevertheless, it is important to identify patients who could still benefit from antiviral medication even when treatment is started relatively late in the disease course. This is especially true in ocular zoster, because viral shedding may continue beyond 72 hours.11

Analgesics are part of a practical approach for managing herpes zoster–associated pain that begins with a short-acting opioid in combination with acetaminophen or a nonsteroidal anti-inflammatory (NSAID) agent. Gabapentin or pregabalin, followed by a tricyclic antidepressant, can be added if conventional analgesics are not entirely effective. The analgesic regimen should be tailored to the patient’s needs and tolerance of adverse effects. If pain control is inadequate or adverse effects are intolerable, consider referring the patient to a pain management center for possible interventional modalities.

Key Point

Gabapentin or pregabalin, followed by a tricyclic antidepressant, can be added if conventional analgesics are not effective for herpes zoster pain.

Corticosteroids are not recommended routinely for treatment of herpes zoster; you can try them in otherwise healthy older adults, however, if antiviral therapy and analgesics do not relieve pain. In 2 double-blind controlled trials, a combination of acyclovir and corticosteroids for 21 days did not decrease the incidence of PHN—although some benefit was seen in terms of patients’ return to normal activities, cessation of analgesic therapy, and improved sleep.12,13

Evidence-based treatment options for PHN

Pharmacotherapy for PHN includes anticonvulsants, tricyclic antidepressants, opioids, and topical agents. Invasive interventions have a limited but important role in the management of PHN pain in clinical practice.


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