Cosmos Study

Pregabalin Plus Opioids Correlated with Greater Risk of Opioid Use Disorder Than Opioids Alone

July 20, 2023

Team A:Dave Little, MD, MSAlex Piff

Team B:Kersten Bartelt, RNJoe Deckert, PhDOwen Torczon

Key Findings

Patients prescribed pregabalin and opioids have a 42% greater risk of developing OUD or experiencing an opioid overdose than patients only prescribed opioids.
Patients prescribed pregabalin both before and after and only after their opioid prescription have an increased risk of OUD or opioid overdose compared to patients prescribed pregabalin only before their opioid prescription.

Gabapentin and pregabalin, anti-convulsant medications sometimes prescribed for pain, are both part of a class of medications called gabapentinoids.¹ We previously published that gabapentin, when prescribed with opioids, is correlated with an increased risk of opioid use disorder (OUD)² for patients when compared to opioid use alone, and we wanted to understand whether there might be similar risks for patients prescribed pregabalin and opioids.

We studied 612,246 patients, half with opioid prescriptions and half with both pregabalin and opioid prescriptions, to determine their risk of OUD. We matched the two populations based on age, sex, morphine equivalent daily dose, comorbidities, and length of time for follow-up. We found that patients prescribed both pregabalin and opioids were more than 40% more likely to be diagnosed with OUD or experience an opioid overdose.

Figure 1

Risk of Opioid Use Disorder or Overdose for Pregabalin and Opioids

Figure 1. Risk of OUD or opioid overdose by whether the patient is prescribed pregabalin and the timing of the pregabalin prescription.

Similar to what we observed with gabapentin, patients prescribed pregabalin both before and after and only after opioids have the greatest risk of developing OUD or experiencing an opioid overdose. These results suggest that, like other gabapentinoids, concomitant use of opioids and pregabalin is correlated with an increased risk of OUD or opioid overdose.

These data come from Cosmos, a HIPAA-defined Limited Data Set of more than 193 million patients from 208 Epic organizations including 1,197 hospitals and more than 25,400 clinics, serving patients in all 50 states and Lebanon. This study was completed by two teams that worked independently, each composed of a clinician and research scientists. The two teams came to similar conclusions.

References

Chincholkar M. Gabapentinoids: pharmacokinetics, pharmacodynamics and considerations for clinical practice. Br J Pain. 2020;14(2):104-114. doi:10.1177/2049463720912496
Little D, Stamp T, et al. Opioids plus gabapentin associated with increased risk of opioid use disorder over opioids alone. Epic Research. Opioids Plus Gabapentin Associated with Increased Risk of Opioid Use Disorder Over Opioids Alone (epicresearch.org). Published April 7, 2023. Accessed July 3, 2023.