Oral Opioid Therapy for Chronic Peripheral and Central Neuropathic Pain
N Engl J Med 2003; 348:1223-1232March 27, 2003DOI: 10.1056/NEJMoa021420
Although opioids are commonly used to treat chronic neuropathic pain, there are limited data to guide their use. Few controlled trials have been performed, and many types of neuropathic pain remain unstudied.
Adults with neuropathic pain that was refractory to treatment were randomly assigned to receive either high-strength (0.75-mg) or low-strength (0.15-mg) capsules of the potent μ-opioid agonist levorphanol for eight weeks under double-blind conditions. Intake was titrated by the patient to a maximum of 21 capsules of either strength per day. Outcome measures included the intensity of pain as recorded in a diary, the degree of pain relief, quality of life, psychological and cognitive function, the number of capsules taken daily, and blood levorphanol levels.
Among the 81 patients exposed to the study drug, high-strength levorphanol capsules reduced pain by 36 percent, as compared with a 21 percent reduction in pain in the low-strength group (P=0.02). On average, patients in the high-strength group took 11.9 capsules per day (8.9 mg per day) and patients in the low-strength group took close to the 21 allowed (18.3 capsules per day; 2.7 mg per day). Affective distress and interference with functioning were reduced, and sleep was improved, but there were no differences between the high-strength group and the low-strength group in terms of these variables. Noncompletion of the study was primarily due to side effects of the opioid. Patients with central pain after stroke were the least likely to report benefit.
The reduction in the intensity of neuropathic pain was significantly greater during treatment with higher doses of opioids than with lower doses. Higher doses produced more side effects without significant additional benefit in terms of other outcome measures.