Promising Results In Reducing Neuropathic Pain With Combined Drug Treatment, Tha

[Guest guest]

Promising Results In Reducing Neuropathic Pain With Combined Drug Treatment,

Than With Either Drug Alone

http://www.medicalnewstoday.com/articles/165647.php

An article published Online First and in a future edition of The Lancet reports

that combination treatment using gabapentin and nortriptyline reduces

neuropathic pain more than either drug alone. This treatment could be used in

patients that only partly respond to one drug or the other. The article is the

work of Professor Ian Gilron, Director of Clinical Pain Research, Queen's

University, and Kingston General Hospital, Kingston, Ontario, Canada, and

colleagues.

Neuropathic pain has been defined as pain " initiated or caused by a primary

lesion or dysfunction in the nervous system. " It affects more than 2 to 3

percent of the general population. Disorders causing neuropathic pain include

nerve problems in the spine; diabetic polyneuropathy, in which damage to blood

vessels in diabetes also causes damage to nerves; and postherpetic neuralgia

(PHN) which is a nerve pain caused by the varicella zoster virus which can

follow an outbreak of shingles. Gabapentin is an anticonvulsant and

nortriptyline is an antidepressant. They are two of several first line drugs

with the most positive therapeutic profiles. However, when given as monotherapy,

the maximum tolerated doses of these drugs hardly ever reduce pain by more than

60 percent. In addition, they provide relief in only 40 to 60 percent of

patients because of partial efficacy and dose-limiting side-effects. The authors

in this study evaluated the efficacy and tolerability of combined nortriptyline

and gabapentin compared with each drug given alone.

A total of 56 patients with diabetic polyneuropathy or postherpetic neuralgia

were included in this randomised controlled trial. They had a daily pain score

of at least 4 (scale 0 to 10) and were enrolled and treated at one site in

Canada between November 2004 and December 2007. Patients were assigned in a

1:1:1 ratio to one of three sequences of daily oral gabapentin, nortriptyline,

and their combination. In series, a different drug was given to each randomised

group in three treatment periods. This trial is referred to as a 'crossover'

design. All patients get to try all three treatments and each patient serves as

his/her own control. During each of three six-week treatment periods, drug doses

were gradually increased towards maximum tolerated dose. The primary outcome was

an average daily pain at maximum tolerated dose.

Results indicated that 45 patients completed all three treatment periods; 47

patients completed at least two 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 considerably lower

than with gabapentin (-0•9) or nortriptyline alone (-0•6). At maximum tolerated

dose, the most frequent adverse event was dry mouth, which was significantly

less frequent in patients on gabapentin than on nortriptyline or combination

treatment. During the trial, there were no serious adverse events recorded for

any patients.

The authors write in conclusion: " 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. 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. "

In an associated note, Dr Troels Staehelin Jensen, Department of Neurology,

Aarhus University Hospital, and Dr Nanna Brix Finnerup, Danish Pain Research

Center, Aarhus University Hospital, Denmark, define Gilron and colleagues'

proposal to use the two drugs in this way as 'a logical step forward'.

" Nortriptyline and gabapentin, alone and in combination for neuropathic pain: a

double-blind, randomised controlled crossover trial "

Ian Gilron, Joan M , Dongsheng Tu, R Holden, Alan C , Robyn

L Houlden

DOI: 10.1016/S0140-6736(09)61081-3

The Lancet