NEW ORLEANS - Gabapentin given in combination with valacyclovir in patients with acute herpes zoster reduces the incidence of postherpetic neuralgia, based on the results of an open-label study.
Of 133 consecutive patients who started the dual therapy within 72 hours after developing their first vesicle, only 9.8% had postherpetic neuralgia (PHN), as defined by any zoster pain 6 months after rash onset, Dr. Whitney Lapolla reported at the annual meeting of the American Academy of Dermatology.
Dr. Whitney Lapolla
This was a study without a placebo arm, so it's necessary to turn to the published literature for historical controls. A recent review of eight clinical trials of antiviral therapy for herpes zoster showed a PHN rate of 11%-33% at 6 months, with an average of about 19%, convincingly higher than with gabapentin plus valacyclovir, said Dr. Lapolla of the center for clinical studies at the University of Texas at Houston.
"Why is this important? Postherpetic neuralgia is a devastating illness causing extremely poor quality of life, and it’s difficult to treat once established," she said. "The available treatments include tricyclic antidepressants, the anticonvulsants gabapentin and pregabalin, and systemic and topical analgesics. Unfortunately, if you add all these up, the result is very poor symptom control, so the goal needs to be to prevent postherpetic neuralgia from developing in the first place."
The prevention of PHN takes on added importance in light of several recent reports suggesting the incidence of PHN may be increasing. Proposed explanations for the upward trend include the aging of the baby boomers, increased use of immunosuppressive therapies, and varicella vaccination in childhood, Dr. Lapolla continued.
Of course, the herpes zoster vaccine has been shown to reduce the incidence of zoster by 51% and, more importantly, reduce the risk of PHN by 67%, but patients have been slow to adopt this vaccine.
Dr. Lapolla said one of the key implications of her prevention study is that it’s particularly important to offer the gabapentin-valacyclovir regimen to patients at highest risk for PHN, namely those over age 70 and/or with severe acute zoster pain, as defined by a pain score of 7 or more on a 10-point Likert pain scale at presentation.
Of the 133 participants in the study, 40 were aged 70 or older, 47 were aged 50-59 years, and 46 were aged 60-69. Two-thirds were women. Sixty-two percent had severe zoster pain at presentation, and the rest had moderate pain, as defined by a score of 4-6 on the 10-point scale.
At follow-up evaluations conducted at 3, 4, and 6 months, a higher proportion of the 70-plus age group had pain compared with younger patients. Among the 70-plus population, a pain score greater than 0 was present in 22.5% at 3 months, 25% at 4 months, and 17.5% at 6 months. Among 50- to 59-year-olds, the rates at the same time points were 12.8%, 12.8%, and 4.3%. Pain rates were intermediate in the 60-69 age group.
Among patients with severe pain at presentation with zoster, the prevalence of late PHN at 6 months’ follow-up was 13.4%, compared with a 3.9% rate among those who presented with moderate pain.
The treatment regimen consisted of 1,000 mg of valacyclovir three times daily for 7 days along with escalating doses of gabapentin (Neurontin). Patients took 300 mg of gabapentin daily for the first week, 300 mg three times daily during the second week, 600 mg three times daily the third week, and 1,200 mg three times daily the fourth week, side effects permitting. If a patient complained of intolerable dizziness, the gabapentin dose was dropped back down to the last tolerated dose.
After 4 weeks of therapy, patients who still had a pain score of 4 or more on the 10-point scale continued on their maximum tolerated dose of gabapentin for another 4 weeks. However, if their pain score was less than 4, gabapentin was tapered over the course of 1 week. No one in the trial received gabapentin for more than 8 weeks.
Gabapentin is approved for the treatment of PHN, but Dr. Lapolla and her coinvestigators under the direction of Dr. Steven K. Tyring said that on the basis of animal studies, gabapentin might be more effective when given at the acute zoster stage to prevent PHN. Consistent with this hypothesis were several surgical pain studies showing that patients had less postsurgical pain and used fewer analgesics when gabapentin was started preoperatively.
Dr. Lapolla said she and her collaborators plan to redo this study using pregabalin (Lyrica) instead of gabapentin.