Gabapentin Presents High Potential for Misuse

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Pharmacy Times Health Systems Edition, November 2022, Volume 11, Issue 6

Although the anticonvulsant is not considered a controlled substance, some state legislation focuses on monitoring the use of or reclassifying it.

The FDA approved gabapentin in 1993 as a non-controlled substance and it has remained a non-controlled substance at the federal level.

The drug was created as an anticonvulsant and used to treat seizure disorders. The medication has also been used to treat hot flashes, neuropathic pain, pain, postoperative nausea, substance abuse issues, and vomiting.1,2

It is estimated that approximately 1% of people in the United States misuse gabapentin.1 This fact has compelled certain states to generate legislative initiatives designed to monitor the use and/or reclassify gabapentin 3 In 2019, US pharmacies dispensed 69 million prescriptions for gabapentin.4,5

Although gabapentin is not considered a controlled substance by the federal government, it does have a potential for abuse. As of September 2022, gabapentin was classified as a controlled substance in Alabama, Kentucky, Michigan, North Dakota, Tennessee, Virginia, and West Virginia.6,7 Adding gabapentin to the list of controlled substances has required providers to have a Drug Enforcement Administrationregistration number to prescribe it, adding another layer of restriction for its prescription and allowing for additional medication monitoring.8

Gabapentin has known abuse potential and has been reported as an agent highly pursued for use in potentiating opioids. In an examination of opioid and gabapentin co-abuse, approximately 24% of patients with prescriptions for both gabapentin and opioids had at least 3 prescription claims surpassing specified dosage thresholds compared with the 3% and 8% of patients prescribed gabapentin or opioids alone, respectively.9 This co-abuse is of particular concern, as abuse of gabapentin in concert with opioids has been associated with a 4-fold raised risk of respiratory depression,9 which is the primary cause of death in opioid-related overdoses.10

It has been suggested that gabapentin at doses exceeding 900 mg may lead to as much as a 60% augmentation in the likelihood of opioid-related death, comparable to misuse of opioids alone.11

Gabapentin grew to 64 million prescriptions in the United States in 2016 from 39 million prescriptions in 2012,12 making it the 10th most prescribed medication that year.13 Gabapentin has been widely recognized as a drug related to opioid abuse in West Virginia.14 Studies have shown that gabapentin in toxicology reports constituted a considerable number of drug overdose deaths around the country, with West Virginia among the highest.14,15 The significant increase in gabapentin dispenses is thought to have been the result of efforts to reduce the abuse of Schedule II drugs, such as hydrocodone and oxycodone.

By 2017, West Virginia had taken notice of gabapentin misuse across the state. The Prescription Drug Monitoring Program (PDMP) is a database of controlled substance prescriptions maintained by each state that allows providers access to information on patient abuse behaviors for a quick and targeted response.16 West Virginia’s PDMP, called the West Virginia Controlled Substances Monitoring Program (WV CSMP), is supported by the West Virginia Board of Pharmacy and collects dispensing data for all Schedule II, III, IV, and V drugs. Although data regarding dispensing of gabapentin is not required to be maintained, the WV CSMP recognized the potential for this drug to be abused and started collecting data as of July 2017.17 The West Virginia Legislature also began reviewing issues with the significant increase in gabapentin prescriptions throughout the state and, by May 2018, took action to list it as a Schedule V drug.

Preliminary data from the WV CSMP showed a decline in the number of dispenses of gabapentin since these changes were implemented, with 73.8 million dispenses in 2021, down from 79 million in 2019.18 The decreases appeared across the state when examined by county, with some counties experiencing decreases of more than 30%. The reasons for this decrease are multifactorial and include a general increase in awareness of the addictive potential of gabapentin, limits on the length of time prescriptions are valid, and requirements to check the WV CSMP before prescribing. The most significant decrease in the dispensing of gabapentin occurred between 2018 and 2019, after the reclassification to Schedule V and the Opioid Reduction Act went into effect.

One study noted an increase in overdose deaths involving gabapentin as recorded in the State Unintentional Drug Overdose Reporting System, which tracks drug overdoses in 23 states, including West Virginia.4 The investigators did not, however, break down the data at the state level. Thus, while it is probable that there was an increase in overall gabapentin-related deaths, the trend in West Virginia alone appears to bemore positive.

Practical Implications

The effectiveness of different strategies, such as policies regarding opioid abuse that regulate access to controlled drugs or the education of patients and prescribers and patients on the addictiveness of gabapentin or restricting supply, is still in question in West Virginia. Further analysis is needed to determine what methods and strategies in West Virginia and across the United States successfully reduce the rate of gabapentin misuse.

References

1. Pauly N, Delcher C, Slavova S, Lindahl E, Talbert J, Freeman P. Trends in gabapentin prescribing in a commercially insured U.S. adult population, 2009-2016. J Manag Care Spec Pharm. 2020;26(3):246-252. doi:10.18553/jmcp.2020.26.3.246

2. Anton RF, Latham P, Voronin K, et al. Efficacy of gabapentin for the treatment of alcohol use disorder in patients with alcohol withdrawal symptoms: a randomized clinical rial. JAMA Int Med. 2020;180(5):728-736. doi:10.1001/jamainternmed.2020.0249

3. Peckham AM, Ananickal MJ, Sclar DA. Gabapentin use, abuse, and the US opioid epidemic: the case for reclassification as a controlled substance and the need for pharmacovigilance. Risk Manag Healthc Policy. 2018;11:109-116. doi:10.2147/rmhp.S168504

4. Mattson CL, Chowdhury F, Gilson TP. Notes from the field: trends in gabapentin detection and involvement in drug overdose deaths — 23 states and the District of Columbia, 2019–2020. MMWR Morb Mortal Wkly Rep. 2022;71(190):664-666. doi:10.15585/mmwr.mm7119a3

5. Smith RV, Havens JR, Walsh SL. Gabapentin misuse, abuse and diversion: a systematic review. Addiction. 2016;111(7):1160-1174. doi:10.1111/add.13324

6. Collins S. More states make gabapentin a Schedule V controlled substance. Pharmacy Today. 2021;27(10):1. doi:10.1016/j.ptdy.2021.09.016

7. Karavolis ZA, Su AB, Peckham AM. State-level response to gabapentin misuse in the United States: implications and future direction. Am J Health Syst Pharm. 2022;79(9):e143-e148. doi:10.1093/ajhp/zxab486

8. Snoderly J. New laws on opioids and gabapentin go into effect. The Exponent Telegram. June 7, 2018. Accessed October 19, 2022. https://www.wvnews.com/theet/news/new-laws-on-opioids-and-gabapentin-go-into-effect/article_b9013859-8871-50e9-a460-2b69f3c4b73a.html

9. Peckham AM, Fairman KA, Sclar DA. All-cause and drug-related medical events associated with overuse of gabapentin and/or opioid medications: a retrospective cohort analysis of a commercially insured US population. Drug Saf. 2018;41(2):213-228. doi:10.1007/s40264-017-0595-1

10. Opioid overdose. World Health Organization. Updated August 4, 2021. Accessed September 9, 2022. https://www.who.int/news-room/fact-sheets/detail/opioid-overdose

11. Gomes T Juurlink DN, Antoniou T, Mamdani MM, Paterson JM, van den Brink W. Gabapentin, opioids, and the risk of opioid-related death: a population-based nested case-control study. PLoS Med. 2017;14(10):e1002396. doi:10.1371/jounral.pmed.1002396

12. Kuehn BM. Gabapentin increasingly implicated in overdose deaths. JAMA. 2022;327(24):2387-2387. doi:10.1001/jama.2022.10100

13. Delcher C, Pauly N, Moyo P. Advances in prescription drug monitoring program research: a literature synthesis (June 2018 to December 2019). Curr Opin Psychiatry. 2020;33(4):326-333. doi:10.1097/yco.0000000000000608

14. Slavova S, Miller A, Bunn TL, et al. Prevalence of gabapentin in drug overdose postmortem toxicology testing results. Drug and Alcohol Depend. 2018;186:80-85. doi:10.1016/j.drugalcdep.2018.01.018

15. Reynolds K, Kaufman R, Korenoski A, Fennimore L, Shulman J, Lynch M. Trends in gabapentin and baclofen exposures reported to U.S. poison centers. Clin Toxic (Phila). 2020;58(7):763-772. doi:10.1080/15563650.2019.1687902

16. Watson CJ, Ganetsky M, Burke RC, Dizitzer Y, Leventhal EL, Boyle KL. Impact of a mandatory prescription drug monitoring program check on emergency department opioid prescribing rates. J Med Toxic. 2021;17(3):265-270. doi:10.1007/s13181-021-00837-4

17. 2017 Controlled Substances Monitoring Program Annual Report. West Virginia Board of Pharmacy. 2017. Accessed September 19, 2022. https://www.wvbop.com/about/annualreports.asp

18. West Virginia Controlled Substance Monitoring Program Data Dashboard 2014 to 2021. West Virginian Board of Pharmacy. 2022. Accessed September 19, 2022. https://www.arcgis.com/apps/dashboards/4b314711d252496d941048cd4867ab85