For years, gabapentinoids have enjoyed VIP status in multimodal pain protocols.
They’ve been the “responsible adult” in the room — non-opioid, neuropathic pain–targeting, and generally well-tolerated.
But what if that trusted sidekick has been quietly stirring up trouble?
A recent retrospective propensity-matched analysis takes a hard look at this assumption — and the results may make you rethink your post-ACDF (anterior cervical discectomy and fusion) order sets.
The Setup: A Fair Fight
Using the TriNetX research network, the authors identified adult patients who underwent ACDF between 2003 and 2023. To keep things clean, chronic opioid users were excluded — no confounding from preexisting dependence.
After 1:1 propensity matching, two evenly matched heavyweights emerged: Gabapentinoid group and Acetaminophen-only group.
Each corner had an impressive 32,455 patients, making this less of a bar fight and more of a heavyweight title match.
The primary outcome? Opioid utilization over time. Secondary outcomes included complications like pneumonia and respiratory failure. Follow-up ranged from 30 days all the way out to a staggering 5 years.
More gabapentin, more opioids?
Here’s where things get interesting — and a little uncomfortable.
Contrary to expectations, gabapentinoid use was associated with higher opioid consumption at every single time point. Not just early postoperative use, but persistent differences extending out to 5 years.
At the 5-year mark: Gabapentinoid group: 2.29% opioid use. The Acetaminophen group: 0.51%. Risk Ratio: 4.61 (P < 0.001)
That’s not a subtle signal — that’s a neon sign.
Kaplan-Meier curves showed clear and sustained separation between groups, suggesting this isn’t just a short-term phenomenon or statistical noise. The divergence is real — and durable.
Complications Crash the Party
As if increased opioid use wasn’t enough, gabapentinoids also brought some unwanted guests: Higher rates of pneumonia and increased respiratory failure.
These differences appeared across multiple time points and, again, persisted over time. Now, before you blame gabapentin entirely, remember this is a retrospective study. But even with careful matching, the signal is hard to ignore.
So…what’s going on?
This is where things get speculative — but fun.
Are gabapentinoids markers of more painful patients, sedating patients into hypoventilation and complications and/or blunting pain in a way that paradoxically leads to more opioid reliance?
Or are you simply overestimating their benefit in this specific surgical population?
Whatever the mechanism, the long-term association with increased opioid use is particularly eyebrow-raising. The very drug we hoped would reduce opioid dependence may be doing the opposite.
Takeaway: Time to Rethink the Recipe?
This study challenges a deeply ingrained assumption in spine surgery: that gabapentinoids are a harmless (and helpful) addition to multimodal analgesia after ACDF.
Instead, the data suggest no opioid-sparing benefit, potential for increased complications and a surprising link to long-term opioid use.
While prospective trials are needed before you rewrite protocols entirely, this paper should at least prompt a pause. Perhaps the “safe” choice isn’t so safe after all.
Origin Study Title: Does Gabapentin Use Following ACDF Decrease Opioid Utilization? A Retrospective Propensity-Matched Analysis Conducted in Academic Medical Centers
Authors: Mark Miller, DO; Hunter Smith, DO; Omar Sbaih, B.S.; Matthew Meade, DO; Ruchir Nanavati, DO; Nithin Gupta, DO; William DiCiurcio, DO; Gregory Schroeder, M.D.; Christopher Kepler, M.D., M.B.A.; Barrett Woods, M.D.