Introduction: The primary goal in treating acute pain is to provide effective analgesia while minimizing the risk of progression to chronic pain. Opioids have long been the mainstay for treating moderate to severe pain. However, their use is increasingly questioned due to challenges such as addiction, tolerance, and adverse effects, including respiratory depression. A multimodal approach (balanced analgesia, multimodal analgesia— MMA), which includes non-opioid analgesic agents (NOAAs), adjuvant medications, and opioids, is recommended. This review was designed to cover the current characteristics and use of typical NOAAs, specifically nefopam and flupirtine, in contemporary practice. Methods: A review search was conducted to abstract articles for analysis. All studies published in English from 1990 to 2025, mainly investigating NOAAs, specifically nefopam and flupirtine, were included. We used Google Scholar, PubMed, Scopus, Web of Science, EBSCO, and MEDLINE databases to extract articles. The findings of these articles were analyzed narratively to highlight mechanisms of action, indications, safety, and specific features. Results: NOAAs may represent a viable alternative in contemporary analgesic treatments. Unlike opioids, centrally acting NOAAs do not carry the same risk of dependence and abuse, making them suitable alternatives for patients with acute and/or chronic pain. Recent studies provide valuable insights into these agents’ evolving role in pain management. Typical NOAAs, such as nefopam and flupirtine, are associated with mild side effects, including nausea, dizziness, and anticholinergic symptoms, which may affect their acceptability in certain patient populations. Furthermore, their contraindications render them potentially dangerous for individuals with convulsive disorders or those taking specific medications, necessitating careful patient selection and clinical judgment. Conclusion: Although these agents are beneficial in reducing opioid consumption, their use should be tailored to each patient, with careful follow-up. Patients receiving NOAAs should be monitored for adverse effects, particularly during treatment initiation. Monitoring is also essential for elderly patients and those with cardiovascular or neurological conditions to ensure safe administration. In conclusion, the clinical use of NOAAs requires careful consideration of potential adverse effects, contraindications, and drug interactions. Further well-designed studies are needed to better define these agents’ characteristics, limitations, and comparisons with alternative pain management approaches.
Öztürk et al. (Wed,) studied this question.