Nancy A. Melville

September 26, 2011

September 26, 2011 (Las Vegas, Nevada) — The anticonvulsant gabapentin can be a highly effective treatment for postherpetic neuralgia, but new research suggests that very few patients achieve the optimal dose recommended by the US Food and Drug Administration (FDA), new research shows.

According to a retrospective study presented here at the American Academy of Pain Management (AAPM) 22nd Annual Clinical Meeting, only 14% of patients actually achieve the FDA-approved gabapentin dose of 1800 mg.

"We found that only about 14% of patients get up to the FDA-approved dose: Most are either discontinued or receive much lower doses. In fact, the average dose is only about 900 mg, or half of the FDA-approved dose. So we think that gabapentin doesn't reach its potential," lead author Michael Sweeney, MD, chief medical officer and vice president of research and development for Depomed Inc, told Medscape Medical News.

The drug is usually given 3 to 4 times daily, and titration to the 1800-mg level is expected to take several weeks. However, a study of 939 patients from a large US health plan who initiated treatment between July 2005 and February 2010 showed that only 134 patients, or just 14.3%, reached the full dose.

For those who did achieve an optimal dose, the titration period took an average of 69 days, and patients stayed on gabapentin for an average of 73 days before any interruptions in therapy of more than 30 days. Patients received an average of 3.08 prescriptions, but only 494 patients, or 52.9%, filled a single prescription during the follow-up period.

Patients Choose to Switch

Because the study was retrospective, the authors could not confirm the actual reasons for the failure to increase the dose, but Dr. Sweeney said that anecdotal evidence derived from conversations with physicians suggests adverse events were the reason.

"It's essentially the adverse events of dizziness and somnolence that cause patients not to titrate aggressively," he said. "The events were seen in the clinical trials at a rate of between about 20% and 30% with the immediate-release gabapentin."

An extended-release, once-daily, 1800-mg formulation of the drug (Gralise, Depomed) was approved by the FDA in February for the treatment of postherpetic neuralgia. That formulation, which is due to launch in the United States in October, was not evaluated in the study.

Dr. Sweeney noted that although gabapentin taken 3 times a day usually takes 6 or more weeks to titrate to an effective dose, Gralise's titration to an effective dose will only take 2 weeks.

If patients are unable to reach the effective dosage level, physicians may have a tough time convincing them to stick with the therapy through the adverse events until it becomes fully effective, said Dr. Sweeney.

"When a patient is in pain, they want their pain relieved now, so if the doctor tries to go slow, the patient may strongly request something that works better, and in this study, about 60% switched to something else."

Among those who switched, 35% switched to opioids, 19% switched to antidepressants, and 9% switched to another anticonvulsant.

There are some sound arguments physicians can make in favor of trying to stick with the regimen, Dr. Sweeney said. "For one thing, the drug is effective when used at the appropriate dose. Apart from the nuisance of dizziness and somnolence, gabapentin is an incredibly safe drug. It doesn't cause various adverse events to any extent," he noted.

"[I]mportantly, it is not an opioid," he added. "When you're dealing with an elderly population, as we are with postherpetic neuralgia, it has virtually no drug interactions, whereas you do with the other drugs."

Too Much Too Soon?

Although the study confirms previous research, it is striking just how few patients reached the optimal dose and refilled a second prescription for the drug, and more questions remain, said Gary M. Reisfield, MD, assistant professor and director of the Division of Pain and Palliative Medicine at the University of Florida College of Medicine's Department of Community Health & Family Medicine in Jacksonville.

"One of the limitations of this type of study is that it is unable tell us why so few patients were titrated to a potentially effective dose, and why nearly half of the patients never filled a second prescription for gabapentin. In my experience, gabapentin is often titrated too quickly, or not titrated at all, with patients being started immediately on 900 mg daily," said Dr. Reisfield.

The approach may exacerbate the adverse events of dizziness and sleepiness, hence undermining efficacy, particularly among elderly patients, he said.

"The mantra in treating older patients is to start low and go slow. It is also imperative for clinicians to counsel patients that, unlike most pain medications, gabapentin does not work immediately, or even quickly, and even with an excellent clinical response, it will not eliminate all of their pain."

"By establishing realistic expectations, patients may be more likely to be adherent with therapy," he said.

The study was supported by Depomed. Dr. Reisfield has disclosed no relevant financial relationships.

American Academy of Pain Management (AAPM) 22nd Annual Clinical Meeting: Abstract 20. Presented September 21, 2011.


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