Taking gabapentin with opioids for acute conditions increases the risk of opioid use disorder

When prescribed with an opioid, a nonopioid gabapentin (Horizant, GlaxoSmithKline, and XenoPort, Inc; Gralise, Almatica Pharma LLC; and Neurontin, Pfizer) increases the risk of opioid use disorder (OUD) and opioid-related overdose, according to Dave Little , MD, computer scientist at Epic, who discussed the risks associated with concomitant gabapentin and opioid prescriptions in an interview with Pharmacy Times. Little emphasizes that the patient is not to blame OUD is a complication of treatment for which the medical community must take responsibility.

Credit: Andy Dean – stock.adobe.com.

Traditionally, gabapentin and other non-opioid medications were used for long-term chronic pain conditions, including anxiety, seizures, shingles, and diabetic neuropathy, as opposed to opioids, which were prescribed for short-term pain relief. term in acute situations, such as post-op, according to Little.

However, some patients have acute conditions that become chronic. Although prescribers try to help the patient switch from 1 type of drug to another, patients may unwittingly take the 2 together, Little said. Gabapentin is now recommended for acute situations, including surgical recovery protocols to manage pain and reduce opioid use.

The idea of ​​using gabapentin in acute situations is a relatively new approach, Little said in the interview. Not all doctors are experienced with this type of treatment, and there are still gaps in research to support our understanding of this approach.

Previous research had linked patients taking gabapentin and opioids together with an increased risk of opioid overdose; however, data on the prevalence of OUD in such situations is limited. To further address this topic, Epic Research evaluated the likelihood of receiving a diagnosis of OUD or having an opioid-related overdose with concomitant gabapentin and opioid treatment.

After matching 1.5 million patients with gabapentin and opioid prescriptions to 2.1 million patients with opioid-only prescriptions, the team found that gabapentin with opioids increased the risk of OUD or drug-related overdose by 47 percent. opioids versus prescription opioids alone.

In a second analysis, Little and team found that gabapentin prescribed before and after prescribing opioids increased the risk of OUD/opioid-related overdose more than prescriptions only before and only after opioid treatment. Additionally, they found that the availability of opioids from non-prescribed sources may increase the risk of OUD/opioid-related overdose.

The combination of other non-opioid agents with opioids such as benzodiazepine, which is used to treat anxiety and insomnia, with opioids can have adverse outcomes and increase the risk of OUD. Additionally, adding gabapentin to benzodiazepines and opioids may further increase this risk, according to Little.

Little noticed there may be 2 biomechanical mechanisms that help explain why dual medication increases the risk of overdose and OUD:

  • Opioids and gabapentin are sedatives that synergistically increase respiratory depression.
  • Treatment with opioids may cause a decrease in gastric motility which increases the absorption of gabapentin. This increases the risk of the effects of respiratory depression.

Gabapentin with over-the-counter pain relievers, such as acetaminophen, reduced the risk of adverse outcomes. Also, gabapentin taken before an opioid and not concomitantly with an opioid did not pose an elevated risk of developing OUD; however, further clinical trials are needed.

In general, according to Little, healthcare professionals can significantly influence patients’ perceptions of opioids. Their influence can help improve drug-related outcomes.

I think patients as a whole are increasingly aware of the risks of opioids, and if they receive appropriate counseling and are involved in shared decision-making, perceptions can be shaped around the idea that effective pain management without opioids is the safest way to go, said Little.

Little further explained that there is one significant conclusion from this study that provides clarity on the topic for practicing physicians: When treating a condition with a high likelihood of developing in a chronic pain setting, initiate gabapentin treatments all ‘Start and try to bypass the opioids altogether,’ said Little.


Little D, Stamp T, Vitek G, Barkely E. Oppioids Plus Gabapentin Associated with Increased Risk of Opioid Use Disorder Compared with Opioids Alone. Epic quest. April 7, 2023. Accessed May 15, 2023. https://epicresearch.org/articles/opioids-plus-gabapentin-associated-with-increased-risk-of-opioid-use-disorder-over-opioids-alone

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