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.

Chronic pain is defined as the pain lasting for more than 3 months and is characterized by a continuum with an inherently uncertain prognosis1, 2. Pain in its severe form significantly affects physical and mental health3, 4. Up to 70% of cancer patients suffer from etiological or iatrogenic pain5. In US alone, approximately 100 million individuals suffer from chronic pain6. At least 20% of adult population in western countries experience chronic pain at any stage of life7,8,9 and approximately 40% exhibit their dissatisfaction over adequate pain management3.

Opioid receptor agonists are widely used to treat chronic pain and are considered as the standard of care10, 11. Short-term use of opioids for chronic pain is associated with reduction in pain intensity, improved functional outcomes but with significant side effects and discontinuation rates12,13,14,15. Recently issued Center for Disease Control and Prevention (CDC) guidelines for prescribing opioids for chronic pain stress for risk assessment as a continuous process during opioid therapy16, 17.

Whereas, use of opioids receptor agonists (hereinafter opioids) for chronic cancer and non-cancer pain is reviewed18, 19, a head-to-head comparison of the risks in terms of tolerability and adherence associated with different types of opioid analgesics is not available in literature. We have carried out a systematic review of literature in order to identify RCTs which addressed this issue and performed network meta-analyses to evaluate the tolerability…