Abstract
Pain is very common in patients with terminal illness, which severely affects the quality of life and functional status. Even though opioids continue to form the foundation of treating patients with moderate-to-severe levels of cancer-related pain, the issue of adverse effects, tolerance, and opioid-related toxicity has led to a growing interest in multimodal and non-opioid approaches. This systematic review aimed to determine the effectiveness and safety of opioid-based interventions in comparison to non-opioid interventions or multi modal interventions in pain management in advanced or cancer-related patients. Eligible articles were paral lel-group or crossover randomized trials with validated results of pain intensity. The trials used were varied in terms of oncologic populations, such as head and neck cancer patients who were receiving chemoradiotherapy, those who were having metastatic disease, and those who were on strong opioids and on chronic or acute cancer-related pain. Combination opioid with non-opioid agents generally resulted in the control of pain equal to or substantially greater than that of opioid monotherapy. Although the uniformity of opioid- sparing effects was not always proved, adjunctive treatments tended to enhance the analgesic effect with minimal or no rise in serious toxicity. Direct comparisons between opioids and non-opioid monotherapy produced conflicting results, with opioids having better results in several environments, and non-opioid or integrative treatment had similar analgesia with better tolerability. Opioids are still a cornerstone of moderate-to-severe cancer-related pain management, but multimodal and chosen non-opioid approaches could be used to increase anal gesic efficacy and improve safety profiles.

Key words: Opioid, non-opioid, interventions, pain relief, terminal illness, systematic review