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Meta-Analysis
. 2013 Aug 27;2013(8):CD004959.
doi: 10.1002/14651858.CD004959.pub4.

Opioids compared to placebo or other treatments for chronic low-back pain

Luis Enrique Chaparro  1 , Andrea D Furlan, Amol Deshpande, Angela Mailis-Gagnon, Steven Atlas, Dennis C Turk
Affiliations
Meta-Analysis

Opioids compared to placebo or other treatments for chronic low-back pain

Luis Enrique Chaparro et al. Cochrane Database Syst Rev. .

Abstract

Background: The use of opioids in the long-term management of chronic low-back pain (CLBP) has increased dramatically. Despite this trend, the benefits and risks of these medications remain unclear. This review is an update of a Cochrane review first published in 2007.

Objectives: To determine the efficacy of opioids in adults with CLBP.

Search methods: We electronically searched the Cochrane Back Review Group's Specialized Register, CENTRAL, CINAHL and PsycINFO, MEDLINE, and EMBASE from January 2006 to October 2012. We checked the reference lists of these trials and other relevant systematic reviews for potential trials for inclusion.

Selection criteria: We included randomized controlled trials (RCTs) that assessed the use of opioids (as monotherapy or in combination with other therapies) in adults with CLBP that were at least four weeks in duration. We included trials that compared non-injectable opioids to placebo or other treatments. We excluded trials that compared different opioids only.

Data collection and analysis: Two authors independently assessed the risk of bias and extracted data onto a pre-designed form. We pooled results using Review Manager (RevMan) 5.2. We reported on pain and function outcomes using standardized mean difference (SMD) or risk ratios with 95% confidence intervals (95% CI). We used absolute risk difference (RD) with 95% CI to report adverse effects.

Main results: We included 15 trials (5540 participants). Tramadol was examined in five trials (1378 participants); it was found to be better than placebo for pain (SMD -0.55, 95% CI -0.66 to -0.44; low quality evidence) and function (SMD -0.18, 95% CI -0.29 to -0.07; moderate quality evidence). Transdermal buprenorphine (two trials, 653 participants) may make little difference for pain (SMD -2.47, 95%CI -2.69 to -2.25; very low quality evidence), but no difference compared to placebo for function (SMD -0.14, 95%CI -0.53 to 0.25; very low quality evidence). Strong opioids (morphine, hydromorphone, oxycodone, oxymorphone, and tapentadol), examined in six trials (1887 participants), were better than placebo for pain (SMD -0.43, 95%CI -0.52 to -0.33; moderate quality evidence) and function (SMD -0.26, 95% CI -0.37 to -0.15; moderate quality evidence). One trial (1583 participants) demonstrated that tramadol may make little difference compared to celecoxib (RR 0.82, 95% CI 0.76 to 0.90; very low quality evidence) for pain relief. Two trials (272 participants) found no difference between opioids and antidepressants for either pain (SMD 0.21, 95% CI -0.03 to 0.45; very low quality evidence), or function (SMD -0.11, 95% -0.63 to 0.42; very low quality evidence). The included trials in this review had high drop-out rates, were of short duration, and had limited interpretability of functional improvement. They did not report any serious adverse effects, risks (addiction or overdose), or complications (sleep apnea, opioid-induced hyperalgesia, hypogonadism). In general, the effect sizes were medium for pain and small for function.

Authors' conclusions: There is some evidence (very low to moderate quality) for short-term efficacy (for both pain and function) of opioids to treat CLBP compared to placebo. The very few trials that compared opioids to non-steroidal anti-inflammatory drugs (NSAIDs) or antidepressants did not show any differences regarding pain and function. The initiation of a trial of opioids for long-term management should be done with extreme caution, especially after a comprehensive assessment of potential risks. There are no placebo-RCTs supporting the effectiveness and safety of long-term opioid therapy for treatment of CLBP.

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Conflict of interest statement

None

Figures

1
1
Funnel plot of comparison: 3 Strong opioids compared to placebo, outcome: 1.3 Mean pain intensity.
2
2
Funnel plot of comparison: 3 Strong opioids compared to placebo, outcome: 3.4 Disability.
3
3
Study flow diagram.
4
4
Summary of risk of bias of included studies.
5
5
Funnel plot of comparison: 1 Tramadol compared to placebo, outcome: 1.1 Pain intensity (higher score means worse pain levels).
6
6
Funnel plot of comparison: 1 Tramadol compared to placebo, outcome: 1.2 Disability (higher ratings mean greater disability).
1.1
1.1. Analysis
Comparison 1 Tramadol compared to placebo, Outcome 1 Pain intensity (higher score means worse pain levels).
1.2
1.2. Analysis
Comparison 1 Tramadol compared to placebo, Outcome 2 Disability (higher ratings mean greater disability).
1.3
1.3. Analysis
Comparison 1 Tramadol compared to placebo, Outcome 3 Side effects.
2.1
2.1. Analysis
Comparison 2 Buprenorphine compared to placebo, Outcome 1 Mean pain intensity.
2.2
2.2. Analysis
Comparison 2 Buprenorphine compared to placebo, Outcome 2 At least 30% of pain relief or moderate improvement.
2.3
2.3. Analysis
Comparison 2 Buprenorphine compared to placebo, Outcome 3 At least 50% of pain relief.
2.4
2.4. Analysis
Comparison 2 Buprenorphine compared to placebo, Outcome 4 Disability (higher ratings mean greater disability).
3.1
3.1. Analysis
Comparison 3 Strong opioids compared to placebo, Outcome 1 Mean pain intensity.
3.2
3.2. Analysis
Comparison 3 Strong opioids compared to placebo, Outcome 2 At least 30% of pain relief or moderate relief.
3.3
3.3. Analysis
Comparison 3 Strong opioids compared to placebo, Outcome 3 At least 50% of pain relief.
3.4
3.4. Analysis
Comparison 3 Strong opioids compared to placebo, Outcome 4 Disability.
3.5
3.5. Analysis
Comparison 3 Strong opioids compared to placebo, Outcome 5 Side effects.
4.1
4.1. Analysis
Comparison 4 Opioids (all types) compared to placebo, Outcome 1 Mean change in pain intensity in enriched design trials (higher changes indicate less favourable scores).
4.2
4.2. Analysis
Comparison 4 Opioids (all types) compared to placebo, Outcome 2 Side effects.
5.1
5.1. Analysis
Comparison 5 Tramadol compared to celecoxib, Outcome 1 At least 30% of pain relief or moderate improvement.
6.1
6.1. Analysis
Comparison 6 Opioids (all types) compared to antidepressants, Outcome 1 Pain (higher score means worse pain level).
6.2
6.2. Analysis
Comparison 6 Opioids (all types) compared to antidepressants, Outcome 2 Disability (higher ratings mean greater disability).
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References

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References to ongoing studies

NCT01081912 {unpublished data only}
    1. A randomized double‐blind, placebo‐controlled Trial to evaluate the efficacy, tolerability and safety of hydrocodone bitartrate controlled‐release capsules in opioid‐experienced subjects with moderate to severe CLBP.. Ongoing study March 4, 2010..
NCT01358526 {unpublished data only}
    1. A Randomized, double‐blind, placebo‐controlled, multicentre trial with an enriched study design to assess the efficacy and safety of oxycodone/naloxone controlled‐release tablets (OXN) compared to placebo in opioid‐experienced subjects with moderate to severe pain due to chronic low back pain who require around‐the‐clock opioid therapy. Ongoing study May 2011..
NCT01455519 {unpublished data only}
    1. True functional restoration and analgesia in non‐radicular low back pain: a prospective double blind, placebo‐controlled study of hydromorphone ER.. Ongoing study October 2011..
NCT01571362 {unpublished data only}
    1. A multicentre, 12 week, double‐blind, placebo‐controlled, randomized withdrawal study to determine the efficacy and safety of ALO‐02 (oxycodone hydrochloride and naltrexone hydrochloride) extended‐release capsules in subjects with moderate to severe CLBP.. Ongoing study June 2012..
NCT01789970 {unpublished data only}
    1. A 12 week, randomized, double‐blind, placebo‐controlled, randomized‐withdrawal study to evaluate the efficacy and safety of hydrocodone bitartrate extended‐release tablets (CEP‐33237) at 30 to 90 mg every 12 hours for relief of CLBP who require opioid treatment for an extended period of time.. Ongoing study March 2013..

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