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Cosmos Study

Opioids Plus Gabapentin Associated with Increased Risk of Opioid Use Disorder Over Opioids Alone

April 7, 2023
Dual-Team Study
Team A:Dave Little, MD, MSTed Stamp
Team B:Gretchen Vitek, RN, MSNEric Barkley

Key Findings

  • Patients prescribed gabapentin in combination with opioids are at a 47% greater risk of developing opioid use disorder (OUD) or experiencing opioid-related overdose than patients who are taking opioids without gabapentin. 
  • Patients with gabapentin prescriptions both before and after their opioid prescription have the greatest risk of OUD or opioid overdose. 

Gabapentin is a non-opioid medication used to treat chronic pain conditions, including shingles and diabetic neuropathy.1 It is also used for other medical conditions, including seizures, restless legs syndrome, and anxiety. Recently, gabapentin was recommended as part of surgical recovery protocols to reduce opioid use while maintaining satisfactory post-operative pain control.2 

A previous study found that use of gabapentin and opioids together may increase the risk of opioid-related overdose,3 while another study found an increased risk of mortality for patients prescribed both gabapentin and opioids compared to those only prescribed opioids.4 However, there is little known about the prevalence of OUD in patients who are prescribed both gabapentin and opioids. 

To better understand how use of gabapentin and opioids may influence a patient’s risk of developing opioid-related conditions, we matched 1.5 million patients with both gabapentin and opioid prescriptions to 2.1 million patients with only opioid prescriptions and evaluated their likelihood of being diagnosed with OUD or having an opioid-related overdose. Patients were matched by prescribed opioid amount, age, at least one shared comorbidity, and length of time in the observation period. 

We found that patients taking gabapentin in combination with opioids are 47% more likely to develop OUD or experience an opioid-related overdose than patients who are solely prescribed opioids, as shown in Figure 1. While we observed slight differences in risk based on which comorbidities a patient has, an increased risk is seen across all comorbid factors assessed. 

To further evaluate whether gabapentin and opioid prescribing timing influenced risk, we compared patients who had gabapentin prescriptions only before, only after, or both before and after their opioid prescription. We found that the greatest risk of OUD or opioid overdose is seen in patients who had gabapentin prescribed both before and after their opioid prescription. 

Figure 1
Risk of Opioid Use Disorder or Overdose for Gabapentin and Opioids
Risk of Opioid Use Disorder or Overdose for Gabapentin and Opioids
Figure 1. Percentage of patients with an OUD or opioid overdose diagnosis between January 2017 and January 2023 stratified by medications prescribed and timing of gabapentin and opioid prescriptions. Opioid-only risk is assessed for patients matched to the opioid plus gabapentin populations based on prescribed opioid amount, age, observation time, and at least one shared comorbidity.

These findings add to the previous literature on the increased risk of opioid-related conditions with concomitant use of gabapentin and opioids.2,3 While we did match patients on several characteristics, we did not study all potential factors that might contribute to the increased risk, such as level of pain control or social vulnerability index. 

Original Publication Date: April 4, 2023
Last Updated: April 7, 2023

These data come from Cosmos, a HIPAA-defined Limited Data Set of more than 183 million patients from 199 Epic organizations including 1,141 hospitals and more than 24,500 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

  1. AFHS Drug Information Essentials.  American Society of Health System Pharmacists, 2004-2022.  Accessed March 15, 2023. 
  2. Chou, R, Gordon, DB, de Leon-Casasola, OA, et al. Management of Postoperative Pain: a clinical practice guideline from the American pain society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists’ committee on regional anesthesia, executive committee, and administrative council. The Journal of Pain. 2016;17(2), 131-157. 
  3. Olopoenia A, Camelo-Castillo W, Qato DM, et al. Adverse outcomes associated with concurrent gabapentin, opioid, and benzodiazepine utilization: A nested case-control study. Lancet Reg Health Am. 2022;13:100302. Published 2022 Jun 23. doi:10.1016/j.lana.2022.100302 
  4. Waddy SP, Becerra AZ, Ward JB, et al. Concomitant Use of Gabapentinoids with Opioids Is Associated with Increased Mortality and Morbidity among Dialysis Patients. Am J Nephrol. 2020;51(6):424-432. doi:10.1159/000507725