Pro–con debate on perioperative gabapentinoids: a nuanced approach is the best one

In the age of the opioid epidemic and a widespread desire to reduce opioid prescriptions, both in outpatient practices and hospitals, we have welcomed non-opioid medications as one possible strategy to reduce the reliance on opioids for the treatment of pain. For anesthesiologists, surgeons, and other perioperative physicians, minimizing exposure to opioids in the perioperative period has been a focal point for several decades now and countless protocols have been described, adopted, and studied. Gabapentin and pregabalin, known collectively as gabapentinoids, have been included in many of these protocols and it is not difficult to see why. They have predictable pharmacokinetics, are one of the only medication classes to treat neuropathic pain, and have sizeable literature support for their ability to reduce pain and opioid consumption. Their use for acute perioperative pain remains off-label. As with many drugs, we have learned more over time and now have a fuller picture of the benefits and risks associated with gabapentinoids. In particular, the central nervous system adverse effects, including dizziness and sedation, are now well established and can be especially problematic in the elderly. Synergistic respiratory depression when combined with opioids and even possible cognitive deficits from prolonged use have been described, forcing some perioperative physicians to rethink their inclusion in enhanced recovery and other perioperative protocols. In this pro-con discussion, we debate the merits of perioperative gabapentinoids in 2025, relying on published evidence for our positions, and ultimately call for a nuanced approach that considers the individual patient before us.