Drug aids care of diabetic peripheral neuropathy

Case study coincides with Wyeth clinical trials

Eleven patients with diabetic peripheral neuropathy treated with Wyeth-Ayerst’s antidepressant venlafaxine (Effexor) experienced nearly 100% pain reduction by 14 days, according to endocrinologists in private practice in Oklahoma.

Wyeth has been testing the drug for this indication and recently has begun Phase II trials, although no trial results are being disclosed, according to a company spokesperson. The drug was approved for depression in 1997. An indication for generalized anxiety disorder was added a year later.

The physicians report no side effects among the small population treated. Side effects have hampered effective treatment with traditional tricyclic antidepressive agents, says Marion Parrott, MD, vice president for clinical affairs for the American Diabetes Association.

"Neuropathy is very difficult to treat. At this point, treatment is trial and error," she says. "In the common foot pain, it can lead to foot ulcers and, in some cases, amputation. It can be extremely painful."

Endocrinologist Jonathan Davis, MD, in private practice in Edmond, OK, says one of his patients, a 41-year-old male with mild nocturia being treated with glipizide, developed severe burning paresthesia not relieved by codeine, acetaminophen, or amitriptyline. At five days on 75 mg of venlafaxine, 95% relief was reported.

Success leads to further study

Following the initial patient’s success, Davis put four other patients (all men, ages 35 to 71) on 37.5 mg to 75 mg daily, resulting in 75% to 100% relief by 14 days.

"They had been [unsuccessfully] treated with oral agents . . . that are commonly used for neuropathy. It’s unlikely pain relief was due to spontaneous remissions or placebo effect because neuropathy recurred when medication was stopped in two patients. It is also unlikely that the relief was due to mood alterations because the relief occurred too rapidly," says Davis.

Venlafaxine inhibits the reuptake of serotonin and norepinephrine and, to a small extent, dopamine. Unlike the tricyclics, the drug does not block muscarinic, histaminergic, or andrenergic receptors, which Parrott says lead to side effects such as dry mouth, hypertension, and dizziness, hampering treatment for neuropathy.

Topical pain medications and anti-seizure drugs also have been used for diabetic neuropathy.

Parrott says up to 60% of diabetics experience neuropathy due to elevated blood sugar, which is most commonly manifested as foot pain but also can result in unregulated blood pressure or heart rate, muscle weakness, tingling sensations in the extremities, stomach or bladder disorders, or sexual dysfunction. "The most important thing in the long run is to control the blood sugar," she says. "But that can be difficult. We know the bonding of glucose to the nerve tissue causes the pain and that antidepressants can raise the pain threshold."

Venlafaxine is cautioned for use in patients with high blood pressure, heart, liver, or kidney disease, and in patients with a history of seizures.