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Levorphanol Effective in Neuropathic Pain

March 26, 2003
Laurie Barclay, MD

The mu agonist levorphanol is effective for neuropathic pain, according to the results of a randomized, double-blind study published in the March 27 issue of the New England Journal of Medicine. Higher doses reduced pain more than lower doses but had greater adverse effects limiting the additional benefit. An editorialist puts this into perspective, suggesting that this adds to the evidence countering the opinion that neuropathic pain is opioid-resistant.

"Although opioids are commonly used to treat chronic neuropathic pain, there are limited data to guide their use," write Michael C. Rowbotham, MD, and colleagues from the University of California at San Francisco. "Studies in animals and some studies in humans have suggested that chronic neuropathic pain may respond poorly to opioid therapy, but placebo-controlled studies of brief intravenous infusions have demonstrated analgesia."

In this eight-week study, 81 adults with refractory neuropathic pain received either high-dose (0.75 mg) or low-dose (0.15 mg) capsules of levorphanol titrated by the patient to a maximum of 21 capsules daily. Those in the low-dose group took close to the maximum number of capsules allowed (18.3 capsules; 2.7 mg daily), with a mean reduction in pain of 21%. Patients in the high-dose group took an average of 11.9 capsules daily (8.9 mg) with a mean reduction in pain of 36% (P = .02 compared with low-dose group).

In the high-dose group, 66% of patients who completed the study had moderate or better pain relief. Study dropouts were mostly because of opioid adverse effects. Both groups had similar improvements in affective distress, interference with functioning, and sleep disturbance. Levorphanol was least effective in patients with central pain after stroke.

"The magnitude of the reduction in neuropathic pain achieved with high-strength levorphanol capsules is similar to that reported in placebo-controlled studies of tricyclic antidepressants and the anticonvulsant gabapentin," the authors write. "Higher doses of the opioid levorphanol are more effective than low doses in reducing the intensity of chronic neuropathic pain originating in the central or peripheral nervous system, but in many patients, pain relief is not achieved or there are intolerable side effects."

In an accompanying editorial, Kathleen M. Foley, MD, from the Memorial Sloan-Kettering Cancer Center in New York, N.Y., notes that this study supports the concept of opioid responsiveness in neuropathic pain syndromes, but that it does not address the long-term efficacy of opioids. She suggests tailoring the choice of opioid for each patient to the intensity of pain and rotating various opioids to maximize analgesia and minimize adverse effects.

"This study adds to the expanding literature of randomized, placebo-controlled trials of opioids in patients with central or peripheral neuropathic pain that show opioids work," she writes. "Together, these studies challenge the traditional view that neuropathic pain is opioid-resistant and now provide the scientific basis for developing a rational approach to the opioid treatment of neuropathic pain."

N Engl J Med. 2003;348:1223-1232, 1279-1281

Reviewed by Gary D. Vogin, MD
Laurie Barclay, MD Writer for Medscape Medical News

© 2003 Medscape