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DULOXETIN REPORTED TO BE EFFECTIVE TREATMENT FOR DIABETIC NEUROPATHIC PAIN

MIAMI BEACH—Duloxetine, a drug already approved for the treatment of depression, was reported to be safe and effective for diabetic neuropathic pain in a multicenter, randomized, parallel, double-blind, placebo-controlled trial. The results of the study – which was sponsored by the drug's manufacturer, Lilly Research Laboratories – were presented here in April at the AAN Annual Meeting.

Why would a drug for depression be studied for neuropathy? Presenting the study findings, F. Wernicke, PhD, MD, Associate Director of Global Product Safety- Neuroscience at Lilly Research Laboratories, said investigators were interested in duloxetine for pain because of its dual inhibition of serotonin and norepinephrine reuptake.

Studies have shown that duloxetine can relieve pain in animal models, he said. He added that duloxetine does not affect the underlying neuropathy in type I or type II diabetes, “but only the pain component.”

PROTOCOL MODELED ON APPROACH TO DEPRESSION

The study used the same doses of duloxetine that are used to treat major depression – 60 mg to 120 mg per day – enrolling 358 patients with pain due to bilateral peripheral diabetic neuropathy in patients with type 1 and type II diabetes mellitus. Patients were randomized in a 1:1:1 fashion to receive duloxetine 60 mg/day, duloxetine 60 mg b.i.d., or placebo for 12 weeks.

IMPROVEMENTS IN PAIN MEASURES

Compared with placebo, both duloxetine treatment groups achieved significantly more improvement on the 24-hour average pain severity score using a 10-point scale (0=no pain, 10=worst possible pain imaginable). At entry, patients had a pain score of 4, and the average score at baseline was 6.

At 24 hours, 43 percent of the placebo group experienced at least a 30 percent reduction in pain (defined as response), as did 68 percent in the duloxetine 60 mg/day group, and 64 percent in the duloxetine 120 mg/day group. Thirty percent of the placebo arm – 50 percent of those who took 60 mg of duloxetine daily, and 39 percent of those who took 120 mg of duloxetine daily – experienced at least a 50 percent reduction in pain.

Nausea (19 percent) and somnolence (12.1 percent) were the two most frequently reported duloxetine-related adverse events. Other adverse events included hyperhidrosis (14 percent) and anorexia, vomiting, and constipation (all three, less than 10 percent). These effects were transient, Dr. Wernicke said. More patients discontinued treatment due to adverse events in the duloxetine 60 mg b.i.d. group (12.1 percent) than the placebo group (2.6 percent).

No adverse effects on blood sugar, lipid profiles, or electrophysiological tests were seen with duloxetine, and both doses of duloxetine were safe and well tolerated.

Figure

Dr. F. Wernicke said investigators were interested in duloxetine for pain because of its dual inhibition of serotonin and norepinephrine reuptake.

STUDY IMPLICATIONS

Discussing the paper, Michael Polydefkis, MD, Assistant Professor of Neurology at the Johns Hopkins Hospital in Baltimore, emphasized the magnitude of the problem of diabetic neuropathy, noting that 30-to 60-percent of patients with type I and type II diabetes experience pain related to this condition. Many drugs have been tested, and carbamazepine and oxcarbazepine are currently the most widely used to treat diabetic neuropathic pain, he said.

The accepted clinical outcome is a 50 percent reduction in a 24-hour pain score, Dr. Polydefkins noted. The number needed to treat (NNT) is also used to determine the usefulness of a drug; that number reflects the number of patients needed to be treated so that one patient can achieve an end point – in this case, 50 percent reduction in 24-hour pain score.

On this measure, he noted duloxetine did not score better than other therapies. For example, the NNT is 2.7 for anticonvulsants, 3.4 for antidepressants, 2.6 for tricyclic antidepressants, and 5 for duloxetine.

But he said among its advantages, duloxetine is easy to dose, with a single pill providing benefit. He added that it also does not cause weight gain or loss, which is not true of other medications and is important for people with diabetes.

He concluded that “duloxetine is an important advance as an addition to the armamentarium that neurologists have for the treatment of diabetic pain and neuropathy.”

MAJOR ADVANCE?

But not all experts agreed with that assessment. Part of the problem, they say, is that there have been no head-to-head trials comparing duloxetine with other therapies for neuropathic pain. For example, pregabalin, an antiepileptic drug related to gabapentin, has also been found to be useful for the treatment of peripheral neuropathy. In a study presented here at the AAN Annual Meeting, pregabalin was reported to be effective as adjunctive therapy in patients with neuropathic pain due to spinal cord injury.

Jonathan Katz, MD, Associate Professor of Neurology at the Forbes Norris ALS/MDA Center in San Francisco, said “at best, duloxetine is on a par with current drugs. When prescribing drugs to treat neuropathic pain, physicians have to take costs and side effects into account,” he continued.

When asked whether head-to-head trials would be conducted to compare therapies for diabetic peripheral neuropathic pain, Dr. Wernicke said no direct comparative trials are presently planned.

ARTICLE IN BRIEF

  • ✓ Duloxetine, a drug already approved for the treatment of depression, was reported to be safe and effective for diabetic neuropathic pain in a multicenter, randomized, parallel, double-blind, placebo-controlled trial.