Tolerability of Opioid Analgesia for Chronic Pain: A Network Meta-Analysis

Abstract

Aim of this study was to study the tolerability of opioid analgesia by performing a network meta-analysis (NMA) of randomized-controlled trials (RCTs) which investigated effectiveness of opioids for the management of chronic pain. Research articles reporting outcomes of RCT/s comparing 2 or more opioid analgesics for the management of chronic pain were obtained by database search. Bayesian NMAs were performed to combine direct comparisons between treatments with that of indirect simulated evidence. Study endpoints were: incidence of adverse events, incidence of constipation, trial withdrawal rate, and patient satisfaction with treatment. Outcomes were also compared with conventional meta-analyses. Thirty-two studies investigating 10 opioid drugs fulfilled the eligibility criteria. Tapentadol treatment was top-ranking owing to lower incidence of overall adverse events, constipation, and least trial withdrawal rate. Tapentadol was followed by oxycodone-naloxone combination in providing better tolerability and less trial withdrawal rate. Patient satisfaction was found to be higher with oxycodone-naloxone followed by fentanyl and tapentadol. These results were in agreement with those achieved with conventional meta-analyses. Tapentadol and oxycodone-naloxone are found to exhibit better tolerability characteristics in comparison with other opioid drugs for the management of chronic pain and are associated with low trial withdrawal rate and better patient satisfaction.

Drugs for Treating Opioid-Induced Constipation: A Mixed Treatment Comparison Network Meta-analysis of Randomized Controlled Clinical Trials

“…9 A network meta-analysis comparing the adverse events between the opioids confirmed that tapentadol followed by oxycodone-naloxone combination was associated with least incidence of constipation. 10 Laxatives such as senna, lactulose, and co-danthramer were found to be useful in individual trials, but unfortunately small number of randomized controlled clinical trials with these agents precluded any firm conclusion in a Cochrane review. 11 Naloxone, alvimopan, naltrexone, naloxegol, and methyl naltrexone antagonize m receptor and form another group used for treating opioid-induced constipation.…”

Comparative pharmacology and toxicology of tramadol and tapentadol

“…However, other studies suggest that acute administration of tapentadol may not have significant advantages in gastrointestinal motor dysfunction, delaying gastric and small bowel transit, similarly to oxycodone (Jeong et al., ). In turn, a network meta‐analysis of randomized‐controlled trials showed tapentadol to have the best tolerability profile when compared to oxycodone‐naloxone, tramadol, oxycodone, fentanyl, morphine, hydromorphone, buprenorphine and oxymorphone, as it leads to the lowest rates of adverse events, constipation and trial withdrawal, ranking third for the ‘patient satisfaction’ criteria only (Meng et al., ). In a prospective open‐label study on tapentadol efficacy and tolerability in patients with moderate‐to‐severe cancer pain, pain intensity significantly decreased from baseline, with quality of life improvement and no changes in adverse effects; the tendency to increase the dose was low and independent of sex, age and pain mechanism (Mercadante et al., ).…”

Multiple effectiveness aspects of tapentadol for moderate–severe cancer-pain treatment: an observational prospective study

“…Probably, the moderate affinity on MOR combined with the opioid-sparing effect due to NRI is responsible for the well-tolerable profile of TP 10. In chronic cancer and noncancer pain patients, Meng et al’s meta-analysis showed that the use of TP was associated with a better tolerability profile – lower withdrawal rate and adverse events (AEs)/constipation — when compared with other opioids 11. In a prospective study on opioid-naïve cancer patients, Mercadante et al12 demonstrated that TP was effective and well tolerated for treating moderate–severe chronic pain.…”