Incidence of Postherpetic Neuralgia After Combination Treatment With Gabapentin and Valacyclovir in Patients With Acute Herpes Zoster

Abstract

Objective: To evaluate the efficacy of treatment with gabapentin plus valacyclovir hydrochloride for the prevention of postherpetic neuralgia in patients with acute herpes zoster. Design:Uncontrolled, open-label study.Setting: A private dermatology clinic.Participants: Consecutive immunocompetent adults (age, Ն50 years) who presented with herpes zoster within 72 hours of vesicle formation with moderate to severe pain (Ն4 on the 10-point Likert scale) were recruited for study participation.Intervention: The patients received 1000 mg of valacylovir hydrochloride 3 times a day for 7 days plus gabapentin at an initial dose of 300 mg/d, titrated up to a maximum of 3600 mg/d, side effects permitting. Main Outcome Measures:Proportion of patients with zoster pain (pain Ͼ0) at 3, 4, and 6 months as well as average pain severity, the proportion of patients with sleep disturbance, and quality-of-life measures (determined by the MedicalOutcomeStudyShortForm36-ItemHealthSurvey).Results: A total of 133 patients (mean age, 64.6 years) were enrolled in the study. The overall incidence of zoster pain at 6 months was 9.8%. Conclusion:The combination of gabapentin and valacyclovir administered acutely in patients with herpes zoster reduces the incidence of postherpetic neuralgia.Trial Registration: clinicaltrials.gov Identifier: NCT01250561. P OSTHERPETIC NEURALGIA (PHN) is the painful sequelae of acute herpes zoster virus infection described as burning or throbbing pain, sharp stabs, electric shocks, and allodynia. 1 The time threshold after the clinical eruption of zoster for pain to be classified as PHN is variable (30, 90, or 120 days or 6 months) across researchers; however, recent models support 90 days as the most appropriate time point definition. 2,3 Risk factors for PHN development include herpes zoster infection at older age, worse acute pain, more severe rash, and the presence of a painful prodrome. [3][4][5][6] The cause of PHN is presumably nerve damage resulting from herpes zoster in-fection. Pathologic findings include primary afferent neuronal body and axon degeneration, atrophy of the spinal cord, scarring of the dorsal root ganglion, and loss of epidermal innervations. 7,8 Postherpetic neuralgia is exceedingly difficult to treat and has been shown to cause severe impairment in quality of life similar to many other systemic diseases. 9-12 Current therapies include tricyclic antidepressants, anticonvulsant agents, and a variety of oral and topical analgesics; however, these therapies are only partially effective in relieving pain. 2 The primary goal for PHN management is to develop more effective treatment geared toward disease prevention rather than palliation. 2 Several studies have demonstrated the efficacy of gabapentin for PHN. [13][14][15][16][17] Ani- CME available online at

Post-herpetic neuralgia

“…Five systematic reviews, 47–51 three RCTs7,35,52 and one cohort study12 contained evidence pertaining to the prevention of PHN; no meta-analyses did.…”

“…In a recent study,52 133 consecutive patients with acute HZ were enrolled in a private dermatology clinic and treated with valacyclovir and gabapentin at currently recommended dosages, with a lower incidence of PHN at 6 months.…”

Efficacy of gabapentin for prevention of postherpetic neuralgia: study protocol for a randomized controlled clinical trial

“…Researchers in an uncontrolled open-label study concluded that the combination of gabapentin and valacyclovir reduces the incidence of PHN [8]; however, although the gabapentin dose could be titrated up to 3600 mg/day, only a few patients reached that dose, and the median dose was 1085 mg/day for 34 days. This study was criticized because there was no control group; instead, the authors compared the incidence of PHN with historic control subjects described in a meta-analysis of six RCTs of antiviral agents used to treat acute zoster infection [27].…”

“…Researchers in a previous nonrandomized, noncontrolled experimental study reported the incidence of PHN was 20% [8]. Thus, we estimated a 45% incidence of PHN in the placebo group, based on its incidence in patients older than 50 years old with an average VAS pain score of 4 or more reported in a longitudinal study [20].…”

“…However, gabapentin used for the prevention of PHN has shown contradictory results. Researchers in an uncontrolled, open-label study reported that administration of gabapentin plus valacyclovir during the acute phase of HZ infection reduced the incidence of PHN [8]. A more recent prospective, controlled, two-armed study using low doses of gabapentin and valacyclovir showed no statistical differences between the two groups regarding PHN prevention [9].…”