- Non-medical gabapentin use remains prevalent, data from two studies suggested.
- Most adverse event cases involving non-prescribed gabapentin included multiple substances, especially opioids.
- Clinicians should remain vigilant for misuse and polysubstance risks, researchers warned.
Two analyses suggested that non-medical (illicit) gabapentin use persisted in recent years as patterns in prescribing shifted.
The first analysis, led by Sara Karami, PhD, MPH, of the FDA's Center for Drug Evaluation and Research, reviewed U.S. poison center data from 2013 to 2023 and found 196,903 adverse event cases involving non-prescribed gabapentin.
Cases involving non-prescribed gabapentin increased between 2013 and 2017 but then declined through 2022, mirroring a rise and subsequent stabilization in gabapentin prescriptions over the same period, according to Karami and colleagues in Drug and Alcohol Dependence.
The second analysis focused on urine drug tests from substance use disorder (SUD) treatment centers between 2016 and 2023. During that period, the rate of gabapentin use without a prescription (11.3%) was nearly double that of prescribed use (5.9%).
Over time, non-prescribed gabapentin use among SUD patients fell from 15.2% in 2016 to 9.9% in 2023, while prescribed use rose from 3.9% to 7.6%, reported Matthew Ellis, MD, PhD, of Washington University in St. Louis, and colleagues in Drug and Alcohol Dependence.
Gabapentin prescriptions are increasing in substance use treatment settings, Ellis observed. "But the finding that strikes me most is the positivity rate for people not prescribed gabapentin," he told MedPage Today. "These patients are using gabapentin outside of prescriptions at about double the rate of those who were actually prescribed it."
The analysis also showed that non-prescribed gabapentin use was strongly related to opioid use disorder (OUD), Ellis said. Other reports have indicated that people with OUD may use gabapentin to potentiate the effects of buprenorphine and methadone, self-manage withdrawal, or self-treat mental and physical comorbidities, he noted.
Both studies echoed trends seen in other research, including a CDC analysis which found that gabapentin prescribing rates doubled between 2010 to 2016, but increased more slowly from 2016 to 2022.
Prescription rates started to fall after the FDA warned about potential central nervous system (CNS) side effects associated with gabapentinoids, Karami and colleagues observed.
In 2018 and 2019, the FDA cautioned about serious breathing problems for patients who used gabapentinoids with opioids or other drugs that depress the CNS, or those who had conditions like chronic obstructive pulmonary disease that reduce lung function.
Gabapentin is approved by the FDA for seizures and postherpetic neuralgia; gabapentin enacarbil is approved for restless legs syndrome. Despite limited indications, gabapentin and its cousin pregabalin are widely prescribed off-label for chronic pain or other conditions, including alcohol use disorder and OUD.
In their study, Karami and co-authors analyzed prescription drug dispensing in Symphony Health's Metys database and adverse events from the National Poison Data System for gabapentin and three comparator drugs: pregabalin, diazepam, and oxycodone.
Between 2013 and 2022, non-medical gabapentin case rates were similar to those for pregabalin, while diazepam and oxycodone had higher rates. Most adverse event cases involving non-prescribed gabapentin (68%) or comparator drugs (55% to 80%) included multiple substances, especially opioids.
"Because gabapentin is frequently prescribed as part of opioid-sparing protocols, it is important for clinicians and patients to be aware that gabapentin is also used non-therapeutically, and that acute harms may be more severe" when gabapentin and opioids are used together, Karami and colleagues noted.
In the second analysis, Ellis and colleagues reviewed 206,161 urine drug tests from SUD treatment practices using Millennium Health records from 2016 to 2023. Specimens were tested for gabapentin and other drugs, with prescribed medications documented separately.
SUD patients who used non-medical gabapentin were more likely to have sedative use disorder (adjusted OR 1.54) or OUD (adjusted OR 2.00) compared with other SUD patients.
"Although there is debate about the abuse/addictive potential of gabapentin, there are clear, positive associations between a history of substance use and likelihood of engaging in the non-medical use of gabapentin," Ellis and co-authors noted.
Patients with SUD should be carefully monitored for polysubstance use, and "harm reduction efforts should include information about gabapentin-associated risks to persons who use drugs," they added.
Both analyses were based on observational data and causal relationships could not be determined. Both also were subject to the limitations of the databases that the researchers used.
More work is needed "to understand drivers of gabapentin use outside of a prescription, such as the role of polysubstance use or gaps in care," Ellis and colleagues wrote.
Disclosures
Karami and colleagues had no disclosures.
The urine drug test analysis was supported by Millennium Health.
Ellis reported conducting this research in collaboration with Millennium Health through an unpaid consulting agreement; he is a member of the Scientific Advisory Group for the National Drug Early Warning System and receives support from Denver Health and Hospital Authority and the National Institute on Drug Abuse. Co-authors reported relationships with Millennium.
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