Research Article: Efficacy of gabapentin for the prevention of postherpetic neuralgia in patients with acute herpes zoster: A double blind, randomized controlled trial

Date Published: June 5, 2019

Publisher: Public Library of Science

Author(s): Oana Bulilete, Alfonso Leiva, Manuel Rullán, Antonia Roca, Joan Llobera, Vera Bril.


Postherpetic neuralgia (PHN) is the most common complication of herpes zoster (HZ). Previous trials have reported that gabapentin can relieve chronic neuropathic pain, but its effect on prevention of PHN is unclear.

To assess the efficacy of a 5-week course of gabapentin on acute herpetic pain and on the prevention of PHN at 12 weeks in patients with acute HZ.

This was a randomized, double blind, placebo-controlled trial conducted in 17 primary care health centers in Mallorca, Spain. All patients were older than 50 years, presented with HZ within 72 h of rash onset, and had moderate-severe pain (≥4 on a 10-point visual analogue scale [VAS]). Ninety-eight patients were randomized to receive gabapentin or placebo. All patients received valaciclovir for 7 days and analgesia if needed. The treatment period was 5 weeks, followed by 7 weeks of follow-up. Gabapentin was initiated at 300 mg/day and gradually titrated to a maximum of 1800 mg/day. The main outcome measure was pain at 12 weeks.

Seventy-five patients completed the study, 33 in the gabapentin group and 42 in the control group. A total of 18.2% of patients in the gabapentin group and 9.5% in the control group reported pain at 12 weeks (p = 0.144). Four patients in the gabapentin group (12.1%), but no patients in the placebo group, reported pain of 4 or more on a 10-point VAS. Patients taking gabapentin reported worse health-related quality of life and poorer sleep quality. Three patients discontinued the trial due to adverse effects from gabapentin.

Addition of gabapentin to the usual treatment of HZ within 72 h of rash onset provided no significant relief from acute herpetic pain or prevention of PHN.

ISRCTN Registry identifier: ISRCTN79871784

Partial Text

The most common chronic complication of herpes zoster (HZ; shingles) is postherpetic neuralgia (PHN), a persistent neuropathic pain that occurs after the acute HZ infection. HZ is considered a significant public health problem, due to its increasing incidence along with the ageing population[1] and its substantial impact on patient quality of life, in the acute and chronic phases[2]. Moreover, HZ was recently associated with greater risk for cerebrovascular and cardiac events shortly after the acute infection occurs[3].

The 29 participating GPs initially screened 128 eligible patients (Fig 1). Ninety-eight consenting patients were ultimately randomized, 50 to the intervention group and 48 to the placebo group. After randomization, 15 patients (15.3%) were loss to follow up (10 in the gabapentin group and 5 in the placebo group) and 7 patients (7.14%) withdrew consent (6 in the gabapentin group and 1 in the placebo group). One patient randomized to the gabapentin group was excluded from the analysis, for not meeting inclusion criteria. Adverse effects from gabapentin were responsible for 3.1% of the patient losses (3 of 6 patients who withdrew consent).

We found no evidence that gabapentin prevented PHN when added to the usual treatment for HZ. Some evidence suggests that attenuation of pain during the acute phase of HZ might prevent PHN[31], and that gabapentin attenuates neuropathic pain by acting on the central and peripheral nervous system[32], both of which are damaged by the HZ infection. Therefore, we hypothesized that addition of gabapentin to the usual HZ treatment might provide better control of pain and reduce the incidence of PHN. Our results are inconsistent with this hypothesis.

Our results provide no evidence that gabapentin prevented PHN. However, further studies with larger sample sizes are needed to confirm the effect of gabapentin on prevention of PHN.




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