Gabapentin and pregabalin, collectively called gabapentinoids, have quietly become some of the most prescribed drugs in the world. In the US alone, gabapentin is now the seventh most commonly prescribed medication. They’re handed out for nerve pain, anxiety, insomnia, restless legs, and a growing list of off-label uses. They were supposed to be the safer alternative to opioids. But a new study published in PLOS Medicine is raising some urgent questions about just how safe they really are.Researchers from University College London looked at data from nearly 17,000 people in the UK who were prescribed gabapentinoids and had experienced a drug poisoning event. What they found wasn’t subtle. The risk of drug poisoning was more than doubled in the 90 days before patients even started gabapentinoids and it remained elevated in the first 28 days of treatment, before dropping to a more modest but still-raised level throughout the rest of the treatment period. So the danger doesn’t just appear during treatment. People who are about to be prescribed these drugs are already in a vulnerable window.
The combination problem is where it gets serious
On their own, gabapentinoids carry risks. But add opioids or benzodiazepines to the mix — which happens far more often than it should — and that risk climbs sharply. Co-administration with opioids elevated the risk of drug poisoning by 30%, while benzodiazepines increased it two-fold. These aren’t rare combinations. People on gabapentinoids for chronic pain are often already on opioids. People prescribed pregabalin for anxiety may well be on a benzo. The drugs are routinely co-prescribed, and the evidence that doing so is dangerous has been building for years.In the UK, this has already played out in real-world tragedies. Earlier research cited in the study found that gabapentinoid-related poisoning fatalities increased substantially in recent years, with 79% of them also involving opioids. And in the US, gabapentin was found in nearly one in ten poisoning deaths between 2019 and 2020. These aren’t just statistics, they’re a pattern that keeps repeating.Gabapentinoids aren’t inherently villainous drugs. For the right patient, prescribed carefully, they help. But the casual assumption that they’re low-risk has never really been supported by the evidence.
