NEW YORK -- September 29, 2009 -- Combination treatment using gabapentin and nortriptyline reduces neuropathic pain more than either drug alone, and thus could be used in patients that only partially respond to one drug or the other, according to a study published early online and in an upcoming edition of The Lancet.
Gabapentin and nortriptyline are 2 of several first line drugs with the most favourable therapeutic profiles. However, when given as monotherapy, the maximum tolerated doses of these drugs rarely reduce pain by more than 60% and provide relief in only 40% to 60% of patients because of incomplete efficacy and dose-limiting side-effects.
Ian Gilron, Clinical Pain Research, Queen's University, and Kingston General Hospital, Kingston, Ontario, and colleagues assessed the efficacy and tolerability of combined nortriptyline and gabapentin compared with each drug given alone.
The randomised controlled trial included 56 patients with diabetic polyneuropathy or postherpetic neuralgia, and who had a daily pain score of at least 4 on a scale of zero to 10.
Patients were assigned in a 1:1:1 ratio to 1 of 3 sequences of daily oral gabapentin, nortriptyline, and their combination. In sequence, a different drug was given to each randomised group in 3 treatment periods. A crossover design was used and all patients were able to try all 3 treatments and each patient serves as his/her own control.
During each of three 6-week treatment periods, drug doses were titrated towards maximum tolerated dose. The primary outcome was mean daily pain at maximum tolerated dose.
The researchers found that 45 patients completed all 3 treatment periods; 47 patients completed at least 2 treatment periods and were analysed for the primary outcome. Mean daily pain was 5.4 at baseline, and at maximum tolerated dose, pain was 3.2 for gabapentin, 2.9 for nortriptyline, and 2.3 for combination treatment.
Pain with combination treatment was significantly lower than with gabapentin (-0.9) or nortriptyline alone (-0.6).
At maximum tolerated dose, the most common adverse event was dry mouth, which was significantly less frequent in patients on gabapentin than on nortriptyline or combination treatment. No serious adverse events were recorded for any patients during the trial.
"This trial shows that combination of an antidepressant and an anticonvulsant drug seems to be superior to monotherapy for neuropathic pain... Although development of more effective and better tolerated monotherapies is much anticipated, our findings suggest that drug combinations represent the most effective strategy for many patients with neuropathic pain," the authors wrote. "On the basis of our results, we recommend combined gabapentin and nortriptyline for patients who have a partial response to either drug alone and seek additional pain relief."
SOURCE: The Lancet
E-Mail this DGNews to a colleague
