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Meta-Analysis
. 2013 Aug 29;2013(8):CD006146.
doi: 10.1002/14651858.CD006146.pub2.

Opioids for neuropathic pain

Ewan D McNicol  1 , Ayelet Midbari, Elon Eisenberg
Affiliations
Meta-Analysis

Opioids for neuropathic pain

Ewan D McNicol et al. Cochrane Database Syst Rev. .

Abstract

Background: This is an updated version of the original Cochrane review published in Issue 3, 2006, which included 23 trials. The use of opioids for neuropathic pain remains controversial. Studies have been small, have yielded equivocal results, and have not established the long-term profile of benefits and risks for people with neuropathic pain.

Objectives: To reassess the efficacy and safety of opioid agonists for the treatment of neuropathic pain.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (to 24th October 2012), MEDLINE (1966 to 24th October 2012 ), and EMBASE (1980 to 24th October 2012) for articles in any language, and reference lists of reviews and retrieved articles.

Selection criteria: We included randomized controlled trials (RCTs) 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. We excluded studies in which drugs other than opioid agonists were combined with opioids or opioids were administered epidurally or intrathecally.

Data collection and analysis: Two review authors independently extracted data and included demographic variables, diagnoses, interventions, efficacy, and adverse effects.

Main results: Thirty-one trials met our inclusion criteria, studying 10 different opioids: 23 studies from the original 2006 review and eight additional studies from this updated review.Seventeen studies (392 participants with neuropathic pain, average 22 participants per study) provided efficacy data for acute exposure to opioids over less than 24 hours. Sixteen reported pain outcomes, with contradictory results; 8/16 reported less pain with opioids than placebo, 2/16 reported that some but not all participants benefited, 5/16 reported no difference, and 1/16 reported equivocal results. Six studies with about 170 participants indicated that mean pain scores with opioid were about 15/100 points less than placebo.Fourteen studies (845 participants, average 60 participants per study) were of intermediate duration lasting 12 weeks or less; most studies lasted less than six weeks. Most studies used imputation methods for participant withdrawal known to be associated with considerable bias; none used a method known not to be associated with bias. The evidence, therefore, derives from studies predominantly with features likely to overestimate treatment effects, i.e. small size, short duration, and potentially inadequate handling of dropouts. All demonstrated opioid efficacy for spontaneous neuropathic pain. Meta-analysis demonstrated at least 33% pain relief in 57% of participants receiving an opioid versus 34% of those receiving placebo. The overall point estimate of risk difference was 0.25 (95% confidence interval (CI) 0.13 to 0.37, P < 0.0001), translating to a number needed to treat for an additional beneficial outcome (NNTB) of 4.0 (95% CI 2.7 to 7.7). When the number of participants achieving at least 50% pain relief was analyzed, the overall point estimate of risk difference between opioids (47%) and placebo (30%) was 0.17 (95% CI 0.02 to 0.33, P = 0.03), translating to an NNTB of 5.9 (3.0 to 50.0). In the updated review, opioids did not demonstrate improvement in many aspects of emotional or physical functioning, as measured by various validated questionnaires. Constipation was the most common adverse event (34% opioid versus 9% placebo: number needed to treat for an additional harmful outcome (NNTH) 4.0; 95% CI 3.0 to 5.6), followed by drowsiness (29% opioid versus 14% placebo: NNTH 7.1; 95% CI 4.0 to 33.3), nausea (27% opioid versus 9% placebo: NNTH 6.3; 95% CI 4.0 to 12.5), dizziness (22% opioid versus 8% placebo: NNTH 7.1; 95% CI 5.6 to 10.0), and vomiting (12% opioid versus 4% placebo: NNTH 12.5; 95% CI 6.7 to 100.0). More participants withdrew from opioid treatment due to adverse events (13%) than from placebo (4%) (NNTH 12.5; 95% CI 8.3 to 25.0). Conversely, more participants receiving placebo withdrew due to lack of efficacy (12%) versus (2%) receiving opioids (NNTH -11.1; 95% CI -20.0 to -8.3).

Authors' conclusions: Since the last version of this review, new studies were found providing additional information. Data were reanalyzed but the results did not alter any of our previously published conclusions. Short-term studies provide only equivocal evidence regarding the efficacy of opioids in reducing the intensity of neuropathic pain. Intermediate-term studies demonstrated significant efficacy of opioids over placebo, but these results are likely to be subject to significant bias because of small size, short duration, and potentially inadequate handling of dropouts. Analgesic efficacy of opioids in chronic neuropathic pain is subject to considerable uncertainty. Reported adverse events of opioids were common but not life-threatening. Further randomized controlled trials are needed to establish unbiased estimates of long-term efficacy, safety (including addiction potential), and effects on quality of life.

PubMed Disclaimer

Conflict of interest statement

EE has received research support from government and industry sources at various times, and consulted for and received lecture fees from various pharmaceutical companies related to analgesics and other healthcare interventions.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Short‐term Efficacy Studies: opioid vs placebo, Outcome 1 Pain intensity post‐opioid/placebo.
1.2
1.2. Analysis
Comparison 1 Short‐term Efficacy Studies: opioid vs placebo, Outcome 2 % Pain reduction post‐opioid/placebo.
2.1
2.1. Analysis
Comparison 2 Intermediate‐term Efficacy Studies: Opioid vs. Placebo, Outcome 1 Number of participants with at least 33% pain relief.
2.2
2.2. Analysis
Comparison 2 Intermediate‐term Efficacy Studies: Opioid vs. Placebo, Outcome 2 Number of participants with at least 50% pain relief.
2.3
2.3. Analysis
Comparison 2 Intermediate‐term Efficacy Studies: Opioid vs. Placebo, Outcome 3 Pain intensity post‐opioid/placebo.
2.4
2.4. Analysis
Comparison 2 Intermediate‐term Efficacy Studies: Opioid vs. Placebo, Outcome 4 Evoked pain intensity post‐opioid/placebo.
2.5
2.5. Analysis
Comparison 2 Intermediate‐term Efficacy Studies: Opioid vs. Placebo, Outcome 5 SF‐36 Health Survey.
2.6
2.6. Analysis
Comparison 2 Intermediate‐term Efficacy Studies: Opioid vs. Placebo, Outcome 6 Brief Pain Inventory: Pain Interference items.
2.7
2.7. Analysis
Comparison 2 Intermediate‐term Efficacy Studies: Opioid vs. Placebo, Outcome 7 Beck Depression Inventory.
3.1
3.1. Analysis
Comparison 3 Intermediate‐term Efficacy Studies: opioid vs active control, Outcome 1 Number of participants with at least 33% pain relief.
3.2
3.2. Analysis
Comparison 3 Intermediate‐term Efficacy Studies: opioid vs active control, Outcome 2 Number of participants with at least 50% pain relief.
3.3
3.3. Analysis
Comparison 3 Intermediate‐term Efficacy Studies: opioid vs active control, Outcome 3 Pain intensity post‐opioid/active control.
3.4
3.4. Analysis
Comparison 3 Intermediate‐term Efficacy Studies: opioid vs active control, Outcome 4 SF‐36 Health Survey.
3.5
3.5. Analysis
Comparison 3 Intermediate‐term Efficacy Studies: opioid vs active control, Outcome 5 Beck Depression Inventory.
4.1
4.1. Analysis
Comparison 4 Adverse Events from Intermediate‐term Studies: opioid vs placebo, Outcome 1 Participants reporting constipation.
4.2
4.2. Analysis
Comparison 4 Adverse Events from Intermediate‐term Studies: opioid vs placebo, Outcome 2 Participants reporting dizziness.
4.3
4.3. Analysis
Comparison 4 Adverse Events from Intermediate‐term Studies: opioid vs placebo, Outcome 3 Participants reporting drowsiness/somnolence.
4.4
4.4. Analysis
Comparison 4 Adverse Events from Intermediate‐term Studies: opioid vs placebo, Outcome 4 Participants reporting nausea.
4.5
4.5. Analysis
Comparison 4 Adverse Events from Intermediate‐term Studies: opioid vs placebo, Outcome 5 Participants reporting vomiting.
4.6
4.6. Analysis
Comparison 4 Adverse Events from Intermediate‐term Studies: opioid vs placebo, Outcome 6 Particpants withdrawing due to adverse events.
4.7
4.7. Analysis
Comparison 4 Adverse Events from Intermediate‐term Studies: opioid vs placebo, Outcome 7 Participants withdrawing due to lack of efficacy.
5.1
5.1. Analysis
Comparison 5 Adverse Events from Intermediate‐term Studies: opioid vs active control, Outcome 1 Participants reporting constipation.
5.2
5.2. Analysis
Comparison 5 Adverse Events from Intermediate‐term Studies: opioid vs active control, Outcome 2 Participants reporting dizziness.
5.3
5.3. Analysis
Comparison 5 Adverse Events from Intermediate‐term Studies: opioid vs active control, Outcome 3 Participants reporting drowsiness/somnolence.
5.4
5.4. Analysis
Comparison 5 Adverse Events from Intermediate‐term Studies: opioid vs active control, Outcome 4 Participants reporting nausea.
5.5
5.5. Analysis
Comparison 5 Adverse Events from Intermediate‐term Studies: opioid vs active control, Outcome 5 Participants reporting vomiting.
5.6
5.6. Analysis
Comparison 5 Adverse Events from Intermediate‐term Studies: opioid vs active control, Outcome 6 Participants withdrawing due to adverse events.
5.7
5.7. Analysis
Comparison 5 Adverse Events from Intermediate‐term Studies: opioid vs active control, Outcome 7 Participants withdrawing due to lack of efficacy.
See this image and copyright information in PMC

Update of

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References to other published versions of this review

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