Mix of drugs better for chronic pain

The combination of an antidepressant and anti-seizure medication may help relieve pain and improve sleep in people suffering from a type of chronic pain, a Canadian trial suggests.

The combination of an antidepressant and anti-seizure medication may help relieve pain and improve sleep in people suffering from a type of chronic pain.

Neuropathic pain is caused by nerve damage or disease in the nervous system and affects more than two per cent of the general population.

When people suffering from neuropathic pain were given both an anti-seizure drug (gabapentin) and an antidepressant (nortriptyline), they experienced less pain than when they took one of the drugs individually, Dr. Ian Gilron, director of clinical pain research at Queen's University in Kingston, Ont., and his colleagues reported in Wednesday's online issue of The Lancet.

It's important to understand how drugs interact since 45 per cent of Canadians being treated for neuropathic pain take two or more drugs for pain, Gilron said.

The study was a randomized controlled trial of 56 people who were enrolled and treated at one site in Canada between 2004 and 2007.

2 ailments studied

Participants had either diabetic polyneuropathy, in which damage to blood vessels in diabetes also causes damage to nerves, or postherpetic neuralgia, nerve pain that can follow a case of shingles.

All the patients tried each drug and the combination during six-week treatment periods, with each patient serving as his or her own control.

The average daily pain measurement on a 10-point scale was 5.4 at the start of the study.

Among 47 people who completed at least two treatment periods, "pain scores" at the maximum tolerated dose were:

  • 3.2 for the anti-seizure drug.
  • 2.9 for the antidepressant.
  • 2.3 for the combination.

The combination also seemed to improve sleep interference, with people rating sleep interference as 1.0 for the combination, compared with 2.2 when the drugs were taken individually, the researchers found.

"That's a very important issue for this group of patients, whose debilitating, unrelenting pain often interferes with normal sleep," Gilron said in a release.

Caught in cycle

The finding is interesting and important since many chronic pain sufferers get caught in a vicious cycle in which less sleep equals more pain, added Dr. Jane Aubin, Scientific Director of Canadian Institutes of Health Research Institute of Musculoskeletal Health and Arthritis. The institute funded the research.

"Combined gabapentin and nortriptyline seems to be more efficacious than either drug given alone for neuropathic pain, therefore we recommend use of this combination in patients who show a partial response to either drug given alone and seek additional pain relief," the study's authors concluded.

The idea of combining the two drugs is a "logical step forward," neurologist Dr. Troels Staehelin Jensen of Aarhus University Hospital in Denmark and Dr. Nanna Brix Finnerup of the Danish Pain Research Center, said in a journal commentary.

"The trial did not establish superiority of nortriptyline versus gabapentin, and only slight differences were reported in side-effect profiles, which supports the recommendation that both drug classes be used as first-line treatments," the pair wrote.

The drugmakers provided the medications used in the study. The commentators said they have received research funding or honoraria from pharmaceutical companies.