Efficacy and safety of strong opioids for chronic noncancer pain and chronic low back pain: a systematic review and meta-analyses

Abstract

In recent years, long-term prescribing and use of strong opioids for chronic noncancer pain (CNCP) has increased in high-income countries. Yet existing uncertainties, controversies, and differing recommendations make the rationale for prolonged opioid use in CNCP unclear. This systematic review and meta-analyses compared the efficacy, safety, and tolerability of strong opioids with placebo or nonopioid therapy in CNCP, with a special focus on chronic low back pain (CLBP). Systematic literature searches were performed in 4 electronic databases (MEDLINE, Web of Science, Cochrane Library, and CINAHL) in July 2019 and updated by regular alerts until December 2020. We included 16 placebo-controlled randomized controlled trials for CLBP and 5 studies (2 randomized controlled trials and 3 nonrandomized studies) of opioids vs nonopioids for CNCP in the quantitative and qualitative synthesis. Random effects pairwise meta-analyses were performed for efficacy, safety, and tolerability outcomes and subgroup analyses for treatment duration, study design, and opioid experience status. Very low to low certainty findings suggest that 4 to 15 weeks (short or intermediate term) opioid therapy in CLBP (compared with placebo) may cause clinically relevant reductions in pain but also more gastrointestinal and nervous system adverse events, with likely no effect on disability. By contrast, long-term opioid therapy ($6 months) in CNCP may not be superior to nonopioids in improving pain or disability or pain-related function but seems to be associated with more adverse events, opioid abuse or dependence, and possibly an increase in all-cause mortality. Our findings also underline the importance and need for well-designed trials assessing long-term efficacy and safety of opioids for CNCP and CLBP.

Patients’ self‐reported physical and psychological effects of opioid use in chronic noncancer pain—A retrospective cross‐sectional analysis

“…Considering physical effects, the frequencies reported here are higher than in the literature. 'Dizziness' was reported to be experienced in 57% of this patient cohort, whereas estimates emerging from meta-analyses and the scientific literature suggest a range of 8% to 33% (Furlan et al, 2006;Moore & McQuay, 2005;Nury et al, 2021). This pattern was also observed for 'nausea/vomiting' (57% vs. 15%-21%), 'pruritus' (19% vs. 4%-13%) 'constipation' (53% vs. 15%-27%; Furlan et al, 2006;Moore & McQuay, 2005;Nury et al, 2021).…”

“…'Dizziness' was reported to be experienced in 57% of this patient cohort, whereas estimates emerging from meta-analyses and the scientific literature suggest a range of 8% to 33% (Furlan et al, 2006;Moore & McQuay, 2005;Nury et al, 2021). This pattern was also observed for 'nausea/vomiting' (57% vs. 15%-21%), 'pruritus' (19% vs. 4%-13%) 'constipation' (53% vs. 15%-27%; Furlan et al, 2006;Moore & McQuay, 2005;Nury et al, 2021). The main reason for the high physical side effect rates in this study could be our direct enquiry about these effects, whereas the side effect data from clinical studies often arise as spontaneous ad hoc reports (unless the primary study outcome parameter included the side effect).…”

“…The use of opioids for non-cancer pain has a long history; but since its use was described in case reports before the 1990s (Portenoy & Foley, 1986), it has nowadays become common to prescribe opioids for chronic non-cancer pain (CNCP; Häuser et al, 2020). Although there is some lowquality evidence of long-term effectiveness of opioids for subgroups within this patient population (Nury et al, 2021;Petzke et al, 2020;Sommer et al, 2020;Welsch et al, 2020), knowledge about the long-term effects of opioids in CNCP is limited.…”

Buprenorphine/naloxone versus methadone opioid rotation in patients with prescription opioid use disorder and chronic pain: study protocol for a randomized controlled trial

“…While opioids are potent analgesics on the short-term, evidence to support long-term analgesic efficacy of opioids is weak [ 1 , 2 ]. Long-term opioid use can result in development of tolerance and therefore reduced effectivity of the medication, requiring increasing doses to sustain the initial level of analgesia [ 3 ].…”

Pattern of Self-Administered Vapor Fentanyl Exposure Determines Long-term Behavior Consequences, in Mice with or without Neuropathic Pain

“…However, chronic opioid use has several side effects, including the risk of addiction [6]. This is especially true for long-term opioid use in chronic pain [7]. Approximately 21-29% of chronic pain patients who are on opioids misuse them, and rates of addiction are estimated to be between 8-12% [8].…”