Robert Tanenberg, MD, of East Carolina University in Greenville, N.C., reported at the American Academy of Pain Medicine that, adding duloxetine to gabapentin also produced similar pain relief as monotherapy,
On the 11-point Likert pain severity scale, 12-week treatment with duloxetine monotherapy reduced severity 2.62 points, which proved to be noninferior to a 2.12-point reduction with pregabalin. It was also noninferior to the combination of duloxetine and gabapentin, which registered a 2.39-point decline in pain severity.
Tanenberg said that five different analyses of the results, including intention-to-treat and per protocol methodology came up with noninferiority conclusion for both the primary and secondary endpoints.
Tanenberg mentioned that, “It makes more sense to substitute a monotherapy approach rather than adding another drug to treatment.”
At his poster presentation he said that, “Duloxetine and pregabalin are both good drugs for reducing neuropathic pain in these patients who are no longer responding to gabapentin.”
“I’m not surprised at these results,” said Mike W. Hooten, MD, of the Mayo Clinic in Rochester, Minn. “The efficacy of all these drugs is similar in patients with peripheral neuropathy.”
Hooten, who did not participate in the study, noted that, “The results of the study show that we have additional options for our patients.”
“Historically,” Tanenberg reported, “diabetic peripheral neuropathy has been treated with tricyclic antidepressants, certain anticonvulsants such as gabapentin and opioid analgesics. However, the use of these agents is often limited by lack of efficacy or significant side effects.”
“Pain due to diabetic neuropathy is commonly experienced in the feet or ankles, and if inadequately treated, it is often associated with mood and sleep disturbances.”
Tanenberg said doctors should select those options on the basis of the adverse event profile of the drugs and how individual patients are likely to respond to therapy.
For example, he noted that weight increased with pregabalin treatment and decreased with duloxetine and the duloxetine-gabapentin combination. Nausea and insomnia were seen less often with pregabalin than with the duloxetine treatments. Peripheral edema, however, was more common with pregabalin.
In the open-label, randomized study, Tanenberg and his team enrolled 134 patients to receive pregabalin, 135 to receive the combination of duloxetine and gabapentin, and 138 patients to receive duloxetine. There were 96 patients on pregabalin who completed the 12-week study compared with 96 patients on the combination treatment and 87 patients taking duloxetine.
Tanenberg acknowledged that the open-label nature of the study limits generalization of the results. “The lack of blinding may have influenced the evaluation of efficacy and adverse events for both the patients and the investigators,” he said.
And “without a gabapentin monotherapy control group, a conclusion drawn from the differences observed between duloxetine monotherapy and duloxetine-gabapentin must be viewed with caution,” Tanenberg said.
He also noted that the 12-week length of the study makes it unable to address long-term outcomes.
The patients in the study had a mean age of about 61; about 80% were Caucasian; about 60% were men. Nine out of 10 of the patients were Type 2 diabetes patients. They had been diagnosed with diabetic peripheral neuropathy for least four years. At baseline, the average pain severity score was about 5.8.
- Note that in a randomized open label study, sponsored by the makers of duloxetine, duloxetine and pregabalin were equivalent in reducing pain in patients who no longer respond to gabapentin for peripheral diabetic neuropathy.
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
Tanenberg R, et al “An open-label, randomized comparison of duloxetine, pregabalin, and the combination of duloxetine and gabapentin among patients with inadequate response to gabapentin for the management of diabetic peripheral neuropathic pain” AAPM 2011; Abstract 263