Two drugs may give relief from neuropathic pain

New uses for old drugs

Physicians may soon have two new weapons available in their arsenal against the sometimes excruciating pain of diabetic neuropathy that affects an estimated 45% of all diabetic patients during the course of their disease:

1. The effectiveness of gabapentin, long used to control seizures, has been established in a study from the University of Wisconsin Medical School at the University of Wisconsin at Madison, which was reported in the Journal of the American Medical Association.

2. Phase IIb human clinical trials are now under way in the use of Memantine, a drug used in Germany for AIDS dementia syndrome for the past 10 years.

Researchers studying the drugs believe they offer relief from the chronic and often debilitating pain suffered by an estimated 800,000 diabetics in the United States. Of particular concern is the night pain that disturbs sleep and extracts an enormous price in terms of quality of life.

The University of Wisconsin study shows gabapentin, an anticonvulsive drug available in the United States for four years, can be a first-line agent for diabetic peripheral neuropathy because its action is "more rapid" than tricyclic antidepressants, says Miroslav Backonja, MD, associate professor of medicine at the University of Wisconsin and lead author of the Gabapentin study.

Backonja’s double-blind study included 165 diabetic patients at 20 medical centers, average age 53, who had experienced neuropathy for one to five years and had an average pain score of 4 or more on an 11-point scale.

His results were as follows:

• Gabapentin significantly reduced pain and reduced sleep disturbances, improved mood and improved the patients’ quality of life.

• At least 60% of patients on gabapentin reported at least a moderate improvement in pain, compared to 33% of the placebo group.

"This is the first time in more than a decade we’ve found another promising agent for treatment of nerve pain from diabetes, Backonja says. "Gabapentin is a welcome addition to our options for pain control. It is well-tolerated by most patients and doesn’t interact negatively with other medications."

Gabapentin is likely to be used as an "off-label" medication as a result of the study, he says, since the new use is not likely to be presented for U.S. Food and Drug Administration (FDA) approval. "This is proven, but not FDA approved," Backonja says.

Researchers at the Neurobiological Technol-ogies Inc. of Richmond, CA, say they hope to find similar results in its trial of Memantine. Lisa Carr, MD, PhD, Neurobiological Technologies’ director of medical affairs, says earlier animal and laboratory evidence showed "trends toward efficacy, particularly in the reduction of nocturnal pain."

The eight-week double-blind placebo-controlled study includes 375 patients at 22 sites.

Memantine is an oral medication researchers theorize restores the function of impaired neurons by modulating activity of the NMDA receptors. "Memantine is an excellent NMDA receptor modulator," Carr says.

By restoring function, Carr says, injured or damaged neurons may be inhibited from firing abnormally. That process is linked to a number of neurological conditions, including neuropathy, Alzheimer’s disease, shingles, herpes zoster, and a variety of types of dementia.

There have been no known serious complications from the use of Memantine. "There’s a long body of knowledge we can draw on because it has been in use in Europe for a long time," Carr says.

While Memantine is believed to have analgesic effects on neuropathy, she cautions, "The drug does not act directly on vessels. It would not repair vessels. It should not replace adequate sugar control, which is still paramount."

For more information, contact: Miroslav Backonja, MD, Associate Professor of Medicine at the University of Wisconsin at Madison. Telephone: (608) 263-5420. Lisa Carr, MD, PhD, Director of Medical Affairs, Neurobiological Technologies. Telephone: (510) 215-8000.