Opioids for chronic non‐cancer neuropathic pain. An updated systematic review and meta‐analysis of efficacy, tolerability and safety in randomized placebo‐controlled studies of at least 4 weeks duration

Abstract

Background and Objective This updated systematic review evaluated the efficacy, tolerability and safety of opioids compared to placebo in chronic non‐cancer neuropathic pain. Databases and Data Treatment Clinicaltrials.gov, CENTRAL, PubMed and PsycINFO were searched from October 2013 to June 2019. Randomized controlled trials comparing opioids with placebo and at least 4 weeks 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 (RD) or standardized mean differences (SMD). We added four new studies with 662 participants for a total of 16 included studies with 2,199 participants. Study duration ranged between 4 and 12 weeks. Studies with a parallel and cross‐over design: Based on low to moderate quality evidence, opioids (buprenorphine, hydromorphone, morphine, oxycodone, tramadol) provided a clinically relevant pain relief of 50% or greater and reduction of disability compared to placebo. There was no clinically relevant harm with regards to the drop out rate due to adverse and serious adverse events by opioids compared to placebo. Enriched enrolment randomized withdrawal design: Based on low to moderate quality evidence, tapentadol provided a clinically relevant pain relief of 50% or greater and reduction of disability compared to placebo in diabetic polyneuropathy. There was no clinically relevant harm with regards to the drop out rate due to adverse and serious adverse events by tapentadol compared to placebo. Conclusions Some opioids provided a short‐term substantial pain relief in highly selected patients in some neuropathic pain syndromes. Significance Some opioids (buprenorphine, morphine, oxycodone, tramadol, tapentadol) provide substantial pain relief compared to placebo in postherpetic neuralgia and peripheral neuropathies of different aetiologies for 4–12 weeks. There is insufficient evidence to support or refute the suggestion that these drugs are effective in other neuropathic pain conditions. The safety of opioids with regards to abuse and deaths in the studies analysed cannot be extrapolated to routine clinical care.

Pain trends among American adults 2002-2018: Patterns, disparities, and correlates

“…One potential mechanism which we were unable to assess is the rise in use of prescription opioid analgesics. Disturbingly, there is no evidence that long-term use of opioid "painkillers" is effective in treating chronic pain (Chou et al 2015;Kissin 2013;Sommer et al 2020). A recent randomized year-long trial actually found that opioids reduced pain less than nonopioids like Tylenol (Krebs et al 2018), and other studies have found that prescription opioids predict more intense pain, lower functioning, higher disability, and higher health care utilization among chronic pain patients (Eriksen et al 2006;Morasco et al 2017).…”

Pain Management in Patients with Multiple Myeloma: An Update

“…In 2012, tapentadol was the first opioid approved by the FDA for neuropathic pain associated with diabetic peripheral neuropathy, however, studies on PHN are not available yet. There is insufficient evidence to support or refute the use of other opioids, such as oxycodone, buprenorphine, and tramadol, which have been shown to provide clinically relevant pain relief in highly selected patients with neuropathic pain syndromes [94].…”

Repeated Administration of Clinical Doses of Tramadol and Tapentadol Causes Hepato- and Nephrotoxic Effects in Wistar Rats

“…Tramadol ((1 RS ,2 RS )-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)-cyclohexanol) and tapentadol (3-[(1 R ,2 R )-3-(dimethylamino)-1-ethyl-2-methylpropyl]phenol) are fully synthetic analgesic opioids that synergistically combine mu-opioid receptor (MOR) agonism with monoamine reuptake inhibition, justifying their classification as “atypical opioids” [ 1 , 2 , 11 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. Such dual mechanism of action optimizes analgesia and minimizes opioid-typical side effects, such as drowsiness, nausea, vomiting, constipation, motor incoordination and respiratory depression [ 1 , 2 , 11 , 19 , 27 ], explaining their indications for the treatment of post-surgical, musculoskeletal, inflammatory, cancer and neuropathic pain, as well as mixed pain states [ 1 , 19 , 27 , 28 , 29 , 30 , 31 , 32 ]. Also, owing to the synergistic combination of their mechanisms of action, these opioids allow the dose administered to be reduced without compromising analgesic efficacy, thus reducing the potential for abuse and addiction [ 11 , 33 ].…”