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Gabapentin slashes risk of postherpetic neuralgia.

WAIKOLOA, HAWAII -- A week oral antiviral therapy combined with 4-8 weeks of gabapentin markedly reduces the postherpetic neuralgia rate in patients with herpes zoster, Dr. Stephen K. Tyring reported.

"We've followed 138 patients out to 6 months. [It's] the most dramatic reduction I've seen in my 24 years of doing shingles research: a 77% reduction in postherpetic neuralgia by using the combination," said Dr. Tyring at the annual Hawaii dermatology seminar sponsored by Skin Disease Education Foundation.

He reported on 138 patients with acute, blister-stage shingles. All were at least 50 years old, with vesicles of less than 72 hours' duration and self-reported pain scores of 4 or more on a 0-10 scale, an indicator of increased postherpetic neuralgia risk. All participants were placed on 1 week of valacy-clovir, analgesics as needed, and 4-8 weeks of gabapentin.

The comparator group consisted of historical controls meeting the same entry criteria who received 1 week of valacyclovir, plus analgesics as needed.

The cumulative rate of postherpetic neuralgia at 6 months was 33% in the control arm, compared with 9% in the combined therapy group.

Dr. Tyring, a dermatologist at the University of Texas, Houston, indicated that he is confident that the substitution of acyclovir or famciclovir for valacyclovir, and pregabalin for gabapentin, would yield similarly favorable outcomes.

Dr. Tyring was prompted to study gabapentin's potential as prophylaxis against postherpetic neuralgia in patients with acute herpes zoster because the scientific literature indicates that gabapentin is far more effective as a neuroprotective agent than as a therapeutic one.

"This leads to the question, why would you want to wait until someone gets postherpetic neuralgia to use gabapentin or pregabalin?" he observed.

In response to an audience question regarding the point at which the acute zoster lesions become too old to initiate effective therapy, Dr. Tyring said the conventional cutoff in clinical trials of antiviral agents is 72 hours.

However, "in real life I give antivirals on the 7th day all the time,"he explained. "My philosophy is, if there are vesicles and they're not completely crusted, I'll give [patients] the antiviral because it may benefit them. I'd rather treat them and not have them benefit than not treat them until 6 months later when they're having postherpetic neuralgia."

His dosing of gabapentin is 300 mg once daily for the first week, while the patients are also on valacyclovir.

"The reason is that if you give 300 mg t.i.d. or higher during the week of antiviral therapy and they start getting drowsy or dizzy, they may stop both drugs and lose the benefit of the antiviral. After that, it's 300 mg t.i.d. for a week. If they tolerate that, 600 mg t.i.d. for a week. Then if they tolerate that, 900 mg t.i.d. for a week. At some point they're going to start getting drowsy or perhaps a little disoriented. I certainly don't want these senior citizens to fall and break anything, so as soon as they start getting side effects, I stop at that dose or go back one step in order to maintain the highest tolerated dosage during that first month," he said.

If, at 1 month, the pain score has fallen below 4 for the Past week, Dr. Tyring tapers the gabapentin over the next 3-4 days, and treatment is over. Those who have a pain score of 4 or more can stay on the highest tolerated dose through the 8th week before tapering.

Dr. Tyring observed that physicians now have three ways to intervene in order to prevent postherpetic neuralgia, which affected individuals consistently describe as the most painful experience in their life. One is to vaccinate children against chicken pox. Although the definitive answer on this approach is not in, the Japanese experience over the last 30 years suggests that it results in less shingles and postherpetic neuralgia in later life than with wild-type infection.

The second approach is to prevent shingles by vaccinating patients aged 60 and older. This, however, has problems, noted Dr. Tyring, because the average age at which shingles occurs is in the mid-50s, so by the time patients reach eligibility for reimbursement for the costly vaccine, their chance of ever developing shingles has already been reduced by more than 50%. Also, the vaccine is contraindicated in individuals who are immunocompromised, as are many elderly.

These shortcomings may account for the vaccine's limited popularity: To date, only 2% of people aged 60 years and older have received it.

Building upon the observation in the landmark 38,000-patient study that led to marketing approval--that the vaccine's benefit appeared to be greatest in younger participants, which is logical, because younger patients have stronger immune systems--studies are underway that may eventually result in lowering the vaccination threshold to age 50 years.

And now, Dr. Tyring concluded, there is a third means of preventing postherpetic neuralgia: Combine any of three oral antivirals with gabapentin or pregabalin and analgesics.

He disclosed receiving research funding, consulting fees, or honoraria from Astellas Pharma Inc., Catalyst Pharmaceutical Research LLC, GlaxoSmithKline Inc., Merck & Co., and Novartis.

SDEF and this news organization are wholly owned subsidiaries of Elsevier.

Why would you want to wait until someone gets postherpetic neuralgia to use gabaprntin or pregablin?


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Article Details
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Title Annotation:Dermatology
Author:Jancin, Bruce
Publication:Internal Medicine News
Article Type:Clinical report
Geographic Code:1USA
Date:Jun 15, 2008
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