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Gabapentin, An Emerging Threat in Today’s Opioid Epidemic

by: Kelly Hack

Gabapentin prescribing increased 64 percent from 39 million prescriptions in 2012 to 64 million by 2016, becoming the 10th most commonly prescribed medication in the United States.1

A recent study from the American Journal of Psychiatry disclosed that the number of Appalachian drug users who reported using gabapentin to get “high” has increased nearly 30-fold from 2008-2014.2 These alarming statistics among other supporting data significantly contributes to the reality that gabapentin is now considered an emerging threat in today’s opioid epidemic.4

What is Gabapentin?

Gabapentin, a gamma-aminobutyric acid (GABA) analog was originally developed as an anticonvulsant and prescribed as an analgesic for neuropathic pain. It is currently sold under the brand names: Neurontin®, Gralise®, Horizant®. The medication is also prescribed as an off-label medication for the treatment of migraines, mental illness, and fibromyalgia. Gabapentin first approved in the United States in 1993 with minimal potential for misuse is now classified as a controlled substance and a current drug of abuse.2 Gabapentin’s effects on the central nervous system including drowsiness and low-level euphoria have been recognized within the addiction community to enhance the euphoric effects of heroin and when consumed exclusively in high doses, produces a marijuana-like high.2 A study from 2016 found that gabapentin misuse was only 1 percent among the general population, however for those that misuse opioids, gabapentin misuse significantly increased to 15-22 percent.3

Side Effects

  • Viral infection
  • Fever
  • Nausea and vomiting
  • Trouble speaking
  • Hostility
  • Jerky Movements4

Gabapentin Overdoses

In 2017, 70,237 drug overdose deaths occurred in the United States, and a vast majority of those fatalities were directly related to opioids.1 In efforts to significantly reduce opioid abuse, providers began to increase their prescribing of gabapentin, with the understanding that the medication was a safer alternative to opioids for the management of acute pain. However, during 2013-2017, 74,175 gabapentin exposures were reported to poison control centers (PCCs) and a clear correlation was documented that the increase of accessibility to gabapentin directly increased toxic exposures.

According to data from the Louisville coroner’s office in Kentucky, gabapentin was found in nearly one-fourth of all overdoses. Throughout the state, the drug is now showing up in about 1 in every 3 overdose deaths.3 Due to the alarming rates of reported overdoses associated with gabapentin, states including Tennessee and Michigan have reclassified the drug as a Schedule V Controlled Substance. Massachusetts, Minnesota, Nebraska, North Dakota, Ohio, Virginia, West Virginia, and Wyoming also require reporting of gabapentin prescriptions through the Prescription Drug Monitoring Program (PDMP) database.

Respiratory Depression and Withdrawal

Drug-induced respiratory depression has been well documented with gabapentin use. The Federal Drug Administration (FDA) now requires new warning labels on all gabapentinoids regarding potential respiratory depressant effects. There is an increased risk for serious breathing difficulties among patients who use gabapentanoids alone or with other drugs that depress the central nervous system (CNS). Patients with a preexisting respiratory impairment such as chronic obstructive pulmonary disease (COPD) also have an augmented risk for experiencing respiratory distress with gabapentanoid usage.6 Additional health complications affiliated with continued gabapentin use occur with abrupt discontinuation of the medication, which has been documented to often mirror symptoms of those withdrawing from alcohol and benzodiazepines.7

Withdrawal Symptoms

  • Anxiety
  • Irritability
  • Agitation
  • Confusion
  • Tachycardia
  • Catatonia7

Co-Prescribing

Since gabapentin and opioids have historically been prescribed for pain, co-prescription of these two medications is quite prevalent. In a population-based nest case-control study among opioid users who were residents of Ontario, Canada between August 1, 1997, and December 31, 2013, it was found that among patients receiving prescription opioids, gabapentin was concomitant with a substantial increase to opioid-related deaths.5 The primary analysis of the study conveyed that the likelihood of opioid-related death was 49 percent higher among individuals exposed to gabapentin and opioids in comparison to those exposed to opioids solely.5 Approximately 8 percent of patients from the study receiving opioids were co-prescribed gabapentin and that co-prescription was directly linked to a 50 percent increase in death probability. Overall, similar studies conducted within the United States and the United Kingdom have drawn parallel conclusions that between 15 and 22 percent of people with opioid use disorder (OUD) are also misusing gabapentin.5

“Misuse of gabapentin is just one more collateral effect of the opioid epidemic. When one drug becomes less available, drug users historically seek out alternatives,” said Caleb Alexander, an epidemiologist at Johns Hopkins University.

In Utero Exposure

Studies are finding a definitive correlation to gabapentin and opioid use among pregnant mothers, as increases in co-exposure, are documented. In a study of 19 infants born to mothers who used opioids and gabapentin during pregnancy, 10 percent of those babies developed Neonatal Abstinence Syndrome (NAS). The failure to control gabapentin withdrawal symptoms with methadone exclusively, lead to gabapentin and methadone being administered congruently. The response from this combined medication-assisted treatment (MAT) showed rapid improvement with newborn withdrawal, indicating that the combined usage of opioid and gabapentin during pregnancy is evident.8

It is imperative that testing for licit drugs such as gabapentin becomes part of a healthcare system’s newborn toxicology testing protocol. It is our goal to continually adapt our offerings to support the systems that are addressing these issues for their population health.

We offer gabapentin in umbilical cord tissue as part of our 17-Panel test. This specimen type captures substances in the newborn’s system up to approximately 20-weeks prior to birth. As a leader in newborn forensic toxicology, it is our mission to provide the most comprehensive testing panels to meet the needs of our clients and to proactively address the current trends in today’s substance abuse landscape.

References

  1. Reynolds, K., Kaufman, R., Korenoski, A., Fennimore, L., Shulman, J. and Lynch, M. (2019). Trends in gabapentin and baclofen exposures reported to U.S. poison centers. [online] Taylor & Francis. Available at: https://www.tandfonline.com/doi/full/10.1080/15563650.2019.1687902 [Accessed 14 Feb. 2020].
  2. Vestal, C. (2018). Abuse of Opioid Alternative Gabapentin Is on the Rise. [online] Pewtrusts.org. Available at: https://www.pewtrusts.org/en/research-and-analysis/blogs/stateline/2018/05/10/abuse-of-opioid-alternative-gabapentin-is-on-the-rise [Accessed 14 Feb. 2020].
  3. Mammoser, G. (2019). Opioid Overdoses and Gabapentin. [online] Healthline. Available at: https://www.healthline.com/health-news/gabapentin-latest-pain-medication-in-opioid-overdoses [Accessed 14 Feb. 2020].
  4. Healthline. (n.d.). Gabapentin: Side Effects, Dosage, Uses, and More. [online] Available at: https://www.healthline.com/health/gabapentin-oral-capsule [Accessed 14 Feb. 2020].
  5. Gomes, T., Juurlink, D., Antoniou, T., Mamdani, M., Paterson, M. and Brink, W. (2017). Gabapentin, opioids, and the risk if opioid-related death: A population-based nested case-control study. [online] Public Library of Science. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5626029/ [Accessed 14 Feb. 2020].
  6. U.S. Food and Drug Administration. (2019). FDA requires new respiratory depression risk gabapentinoids warnings. [online] Available at: https://www.fda.gov/news-events/fda-brief/fda-brief-fda-requires-new-warnings-gabapentinoids-about-risk-respiratory-depression [Accessed 15 Feb. 2020].
  7. Medscape. (2010). Withdrawal Symptoms After Gabapentin Discontinuation. [online] Available at: https://www.medscape.com/viewarticle/722526 [Accessed 15 Feb. 2020].
  8. Loudin, S., Murray, S., Prunty, L., Davies, T., Evans, J. and Werthammer, J. (2017). An Atypical Withdrawal Syndrome in Neonates Prenatally Exposed to Gabapentin and Opioids. [online] jpeds.com. Available at: https://www.jpeds.com/article/S0022-3476(16)31232-X/fulltext [Accessed 17 Feb. 2020].

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