Opioids in chronic low back pain. A systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least 4 weeks duration

Abstract

The efficacy and safety of opioid therapy in chronic low back pain (CLBP) is under debate. We updated a recent systematic review on the efficacy and safety of opioids in CLBP. We screened MEDLINE, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL) up until October 2013, as well as reference sections of original studies and systematic reviews of randomized controlled trials (RCTs) of opioids in CLBP. We included double-blind randomized placebo-controlled studies of at least 4 weeks duration. Using a random effects model, absolute risk differences (RD) were calculated for categorical data and standardized mean differences (SMD) for continuous variables. We included 12 RCTs with 17 treatment arms and 4375 participants. Median study duration was 12 (4-16) weeks. Of the 17 treatment arms, seven (41.2 %) used oxycodone; four (23.6 %) tramadol; buprenorphine and oxymorphone were each used in two (11.8 %) and hydromorphone and tapentadol each in one (5.8 %). The results for studies with parallel/cross-over design were as follows (with 95 % confidence interval, CI): opioids were superior to placebo in reducing pain intensity (SMD -aEuro parts per thousand 0.29 [-aEuro parts per thousand 0.37, -aEuro parts per thousand 0.21], p < 0.0001; six studies with 2896 participants). Opioids were superior to placebo in 50 % pain reduction (RD 0.05 [0.01, 0.10], p = 0.01; two studies with 1492 participants; number needed to benefit (NNTB) 19 [95 % CI 10-107]). Opioids were not superior to placebo in reports of much or very much improved pain (RD 0.16 [-aEuro parts per thousand 0.01, 0.34], p = 0.07; two studies with 1153 participants). Opioids were superior to placebo in improving physical functioning (SMD -aEuro parts per thousand 0.22 [-aEuro parts per thousand 0.31, -aEuro parts per thousand 0.12], p < 0.0001; four studies with 1895 participants). Patients dropped out less frequently with opioids than with placebo due to lack of efficacy (RD -aEuro parts per thousand 0.10 [-aEuro parts per thousand 0.16, -aEuro parts per thousand 0.04], p = 0.001; five studies with 3168 participants; NNTB 10 [8-13]). Patients dropped out more frequently with opioids than with placebo due to adverse events (RD 0.12 [0.05, 0.19], p = 0.0007; six studies with 2910 participants; number needed to harm (NNTH) 7 [95 % CI 6-8]). There was no significant difference between opioids and placebo in terms of the frequency of serious adverse events or deaths. Opioids were superior to placebo in terms of efficacy and inferior in terms of tolerability. Opioids and placebo did not differ in terms of safety during the study period. The conclusion on the safety of opioids compared to placebo is limited by the low number of serious adverse events and deaths. Short-term and intermediate-term opioid therapy may be considered in selected CLBP patients. The English full-text version of this article is freely available at SpringerLink (under "Supplemental").