Efficacy and harms of long-term opioid therapy in chronic non-cancer pain: Systematic review and meta-analysis of open-label extension trials with a study duration ≥26 weeks

Abstract

Background and objective: This updated systematic review evaluated the efficacy, acceptability and safety of long-term opioid therapy (LTOT) for chronic non-cancer pain (CNCP).

Databases and data treatment: Clinicaltrials.gov, CENTRAL and MEDLINE until June 2019. We included open-label extension trials with a study duration ≥26 weeks of RCTs with ≥2 weeks duration. Pooled estimates of event rates of categorical data and standardized mean differences (SMD) of continuous variables were calculated using a random effects model.

Results: We added four new studies with 1,154 participants for a total of 15 studies with 3,590 participants. Study duration ranged between 26 and 156 weeks. Studies included patients with low back, osteoarthritis and neuropathic pain. The quality of evidence for every outcome was very low. 31.1% (95% Confidence interval [CI] 23.0%-40.7%) of patients randomized at baseline finished the open label period. 14.1% (95% CI 10.9%-19.4%) of patients dropped out to due adverse events. In 6.3% (95 CI 3.9%-10.1%) of patients serious adverse events and in 2.7% (95% CI 1.5%-4.7%) aberrant drug behaviour were noted. 0.5% (95% CI 0.2%-1.4%) of patients died.

Conclusions: Within the context of open-label extension studies, opioids maintain reduction of pain and disability and are rather well tolerated and safe. LTOT can be considered in carefully selected and monitored patients with low back, osteoarthritis and neuropathic pain who experience a clinically meaningful pain reduction with at least tolerable adverse events in short-term opioid therapy.

Significance: There is very low quality evidence of the long-term efficacy, tolerability and safety of opioids for chronic low back, osteoarthritis and diabetic polyneuropathic pain within the context of open-label extension studies of randomized controlled trials. Drop out rate due to adverse events and deaths increase with study duration. One-third of patients profit from LTOT. Long-term opioid therapy can be considered in some carefully selected and monitored patients.