Levorphanol research for neuropathic pain

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Levorphanol Effective in Neuropathic Pain - Laurie Barclay, MD

from the New Englang Journal of Medicine 2003;348:1223-1232, 1279-1281

March 26, 2003 — 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 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. "

Reviewed by D. Vogin, MD