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.
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
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.
Eisenberg E, McNicol ED, Carr DB. Efficacy and Safety of Opioid Agonists in the Treatment of Neuropathic Pain of Nonmalignant OriginSystematic Review and Meta-analysis of Randomized Controlled Trials. JAMA. 2005;293(24):3043-3052. doi:10.1001/jama.293.24.3043