Opioid Agonists forTreatment of Neuropathic Pain: New Research

[Guest guest]

Efficacy and Safety of Opioid Agonists in the Treatment of

Neuropathic Pain of Nonmalignant Origin

Systematic Review and Meta-analysis of Randomized Controlled Trials

Elon Eisenberg, MD; Ewan D. McNicol, RPh; B. Carr, MD

JAMA. 2005;293:3043-3052. Vol. 293 No. 24, June 22/29, 2005

Context: In the United States, an estimated 2 million persons have

neuropathic pain that is often resistant to therapy. The use of

opioids for neuropathic pain remains controversial, in part because

studies have been small, have yielded equivocal results, and have not

established the long-term risk-benefit ratio of this treatment.

Objective: To assess the efficacy and safety of opioid agonists for

the treatment of neuropathic pain based on published randomized

controlled trials (RCTs).

Data Sources: We searched MEDLINE (1966 to December 2004) and the

Cochrane Central Register of Controlled Trials (fourth quarter, 2004)

for articles in any language, along with reference lists of reviews

and retrieved articles, using a combination of 9 search terms for

RCTs with 32 terms for opioids and 15 terms for neuropathic pain.

Study Selection: Trials were included in which opioid agonists were

given to treat central or peripheral neuropathic pain of any

etiology, pain was assessed using validated instruments, and adverse

events were reported. Studies in which drugs other than opioid

agonists were combined with opioids or opioids were administered

epidurally or intrathecally were excluded.

Data Extraction: Data were extracted by 2 independent investigators

and included demographic variables, diagnoses, interventions,

efficacy, and adverse effects.

Data Synthesis: Twenty-two articles met inclusion criteria and were

classified as short-term (less than 24 hours; n = 14) or intermediate-

term (median = 28 days; range = 8-56 days; n = 8) trials. The short-

term trials had contradictory results. In contrast, all 8

intermediate-term trials demonstrated opioid efficacy for spontaneous

neuropathic pain. A fixed-effects model meta-analysis of 6

intermediate-term studies showed mean posttreatment visual analog

scale scores of pain intensity after opioids to be 14 units lower on

a scale from 0 to 100 than after placebo (95% confidence interval

[CI], –18 to –10; P<.001). According to number needed to harm (NNH),

the most common adverse event was nausea (NNH, 3.6; 95% CI, 2.9-4.8),

followed by constipation (NNH, 4.6; 95% CI, 3.4-7.1), drowsiness

(NNH, 5.3; 95% CI, 3.7-8.3), vomiting (NNH, 6.2; 95% CI, 4.6-11.1),

and dizziness (NNH, 6.7; 95% CI, 4.8-10.0).

Conclusions: Short-term studies provide only equivocal evidence

regarding the efficacy of opioids in reducing the intensity of

neuropathic pain. Intermediate-term studies demonstrate significant

efficacy of opioids over placebo for neuropathic pain, which is

likely to be clinically important. Reported adverse events of opioids

are common but not life-threatening. Further RCTs are needed to

establish their long-term efficacy, safety (including addiction

potential), and effects on quality of life.

Author Affiliations: Pain Relief Unit, Rambam Medical Center, and

Haifa Pain Research Group, the Technion-Israel Institute of

Technology, Haifa, Israel (Dr Eisenberg); Department of Anesthesia

(Mr McNicol and Dr Carr), Pharmacy Department (Mr McNicol), and

Division of Clinical Care Research (Dr Carr), Tufts–New England

Medical Center and Tufts University School of Medicine, Boston, Mass.

Dr Carr is now with Innovative Drug Delivery Systems Inc, New York,

NY.