Drug Combo Spells Relief for Neuropathic Pain Sufferers

The combination of nortriptyline and morphine appears to offer superior efficacy in providing relief from chronic neuropathic pain than monotherapy with either agent.

The combination of nortriptyline and morphine appears to offer superior efficacy in providing pain relief than monotherapy with either agent, according to research from Queen’s University in Kingston, Canada published ahead of print in Pain. Nearly 90% of participants in the study achieved successful relief from chronic neuropathic pain with the narcotic-antidepressant combination, a success rate that was significantly better than observed with either drug alone.

“Chronic pain is an increasingly common problem and can exert disastrous personal, societal, and socio-economic impacts on patients, their families, and their communities,”said lead author Ian Gilron, MD MSc, Director of Clinical Pain Research and Professor, Departments of Anesthesiology & Perioperative Medicine and Biomedical & Molecular Sciences, Queen's University. “Current neuropathic pain treatments are ineffective or intolerable for many sufferers so this new evidence supporting the morphine—nortriptyline combination is important news for patients.”

For the randomized, double-blind, crossover trial, patients with neuropathic pain were enrolled at one site between January 25, 2010 and May 22, 2014 and then randomized in a 1:1:1 ratio using a Latin Square design to receive oral nortriptyline, morphine, or a combination of both drugs. Participants were able to try each of the three treatment options (morphine or nortriptyline alone or the combination of both) in each of three 6-week treatment periods. During each treatment period, study participants’ pain levels and side effects were recorded as part of follow-up assessments.

Doses were titrated toward the maximal tolerated dose is each of the three 6-week periods, with average daily pain at the maximal tolerated dose as the primary outcome of the study. Secondary outcomes included other pain, mood and quality of life measures, and adverse effects. Among 62 patients screened, 52 enrolled in the study and 39 completed at least two treatment periods.

Average daily pain was measured during the study using participants’ numerical ratings of pain on a validated 0-10 scale. At baseline, average daily pain was 5.3, compared with 3.1 for the maximal tolerated dose of nortriptyline monotherapy, 3.4 for the maximal tolerated dose of morphine alone, and just 2.6 for the maximal tolerated dose of the morphine—nortriptyline combination. Brief Pain Inventory scores for both average and present pain were significantly lower for combination users when compared with monotherapy users.

The research team also found constipation, dry mouth, and somnolence to be the most frequent adverse effects with combination treatment. However, rates of these side effects were not substantially worse with the combination when compared with either drug alone. Moderate-severe constipation occurred in 43% of combination users, compared with 46% of morphine users. Moderate-severe dry mouth occurred in 58% of combination users, compared with 49% of nortriptyline.

“It's important to remember that we don't want to completely eliminate patients' ability to sense pain as it's a warning system for us, but we do want to find the right balance of pain relief and drug side effects,” said Gilron, who is also an anesthesiologist at Kingston General Hospital. “Morphine and nortriptyline are excellent candidates for pain management because of the extensive research conducted on them, their low cost, and widespread availability all over the world.”