In a clinical trial of a new type of drug to relieve severe, chronic pain caused by nerve damage, the anti-convulsant medicine gabapentin has provided significant relief from the aching, burning, tearing pain that some shingles patients suffer for years after other symptoms subside.
Shingles, caused by the virus Herpes zoster, results from the reactivation of the chickenpox virus and attacks more than a million people in the United States each year. While the shingles rash and pain eventually subside in most people, about 10 to 15 percent experience continued severe pain known as postherpetic neuralgia, or PHN, which can last years, and often the rest of an older patient's life.
The shingles clinical trial was reported in the December 2 issue of the Journal of the American Medical Association (JAMA) by University of California San Francisco neurologist Michael Rowbotham, MD, and colleagues at the Rehabilitation Institute of Chicago, Oregon Health Sciences University, and Parke-Davis Pharmaceutical Research, which funded the study.
Soon after gabapentin came into use in 1995 to treat epilepsy, physicians noted its pain-relieving powers. The shingles study reported in the Dec. 2 issue of JAMA is one of two multi-center studies to test the drug's ability to control severe pain associated with nerve damage. A report on its ability to relieve pain from diabetic neuropathy is also published in the Dec. 2 JAMA issue. An editorial on the promising findings, written by Mayo Clinic neurologist Phillip Low, appears in the same issue.
Tricyclic antidepressants are the principal drug used to treat PHN pain, but they don't work for more than half of those who try them, and many cannot tolerate their side effects, which include decreased blood pressure, constipation and forgetfulness, Rowbotham said. Most PHN sufferers are elderly, making these side effects particularly unacceptable. In contrast, gabapentin appears to be at least as effective as tricyclic antidepressants, and gabapentin's side effects are often better tolerated, the researchers found.
"Gabapentin appears to affect a completely different aspect of the nerve cell circuitry involved in chronic pain than do opioids (morphine-like drugs) and tricyclic antidepressants, the main drugs currently used to treat severe nerve damage pain," Rowbotham said. "This report should help physicians become more aware of the effective treatments available for chronic neuropathic pain. It will give more choice in what can be used to relieve pain, particularly for the elderly. And it should also inspire pharmaceutical companies to look for new treatments that are effective and well tolerated."
The eight-week clinical trial involved a total of 229 PHN sufferers. Patients were asked to rate the effect of gabapentin or a matching placebo on their pain, mood and level of sleep interference. Adverse side effects were also monitored. On a self-reporting ten-point "pain scale," patients treated with gabapentin reported an average drop in pain of about one third -- 6.3 to 4.2 points, while the patients treated with placebo noted almost no change in their pain. Adverse effects were "minor and well tolerated," consisting mainly of sleepiness and dizziness. Particularly important, serious cardiovascular side effects were not found.
Although the mechanism of action of gabapentin remains uncertain, evidence suggests that it affects a particular type of calcium channel in pain-transmitting nerve cells of the spinal cord, Rowbotham said. What is already apparent is that gabapentin does not affect the same nerve pathways that opioids or tricyclics do, making it a new kind of drug for pain.
"This is the first non-opioid medication in at least a decade to be proven a first-line therapy for neuropathic pain," he said. "This is exciting, and an important step forward in allowing people with chronic pain to choose from a broad range of medications that each have a potential to control their pain."
Rowbotham, lead author of the JAMA paper, is associate professor of clinical neurology at UCSF and director of UCSF's Pain Clinical Research Center. Collaborating with him on the gabapentin study were Norman Harden, MD, of the Rehabilitation Institute of Chicago, Brett Stacey, MD, assistant professor of anesthesiology at Oregon Health Sciences University, and physicians from 12 other centers around the U.S. The study was organized by Leslie Magnus-Miller, MD, and statistician Paula Podolnick, both of Parke-Davis Pharamaceutical Research, which developed gabapentin for epilepsy and funded the shingles study.