Opioids for chronic low back pain: An updated systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least 4 weeks of double-blind duration

Abstract

Background and objective: This updated systematic review evaluated the efficacy, tolerability and safety of opioids compared to placebo in non-malignant chronic low back pain.

Databases and data treatment: Clinicaltrials.gov, CENTRAL, MEDLINE and PsycINFO were searched from October 2013 to May 2019. Randomized controlled trials comparing opioids with placebo and at least 4 weeks of double-blinded duration were analysed. Primary outcomes were pain relief of 50% or greater, disability, tolerability and safety. Effects were summarized by a random effects model using risk differences or standardized mean differences. We added nine new studies with 2,980 participants for a total of 21 studies with 7,650 participants. Study duration ranged between 4 and 15 weeks. Studies with a parallel and cross-over design: Based on very low to low-quality evidence, opioids provided no clinically relevant pain relief of 50% or greater, but a clinically relevant reduction of disability compared to placebo. Enriched enrolment randomized withdrawal (EERW) design: Based on very low to low-quality evidence, opioids provided a clinically relevant pain relief of 50% or greater, but not a clinically relevant reduction of disability compared to placebo. There was no clinically relevant harm with regard to serious adverse events by opioids compared to placebo in studies with parallel/cross-over and EERW design. There was a relevant harm with regard to drop out rates due to adverse events in studies with parallel/cross-over, but not in studies with EERW design.

Conclusions: Opioids may provide a safe and clinically relevant pain relief for 4-15 weeks in highly selected patients.

Significance: Within the context of randomized controlled trials of 4-15 weeks, opioids provided a clinically relevant pain relief of 30% or greater and a clinically relevant reduction of disability compared to placebo in non-malignant chronic low back pain. Number needed to treat for an additional drop out due to side effects was 11 (95% confidence interval: 6-33). Assessment of abuse and addiction was incomplete. The frequency of serious adverse events including deaths did not differ from placebo.