Background and Objectives
Gabapentin and pregabalin have been considered relatively safe opioid-sparing adjuncts for pain management. However, rising prescribing trends, presence of gabapentinoids in opioid-related overdoses, and the growing body of evidence regarding gabapentinoid misuse and abuse, have caused gabapentinoids to emerge as a drug class of public health concern. This study aimed to assess the prevalence of, and factors associated with gabapentinoid use and misuse.
This retrospective study of Texas Medicaid data from 1/1/2012 to 30/8/2016 included patients aged 18–63 years at index date, with ≥ 1 gabapentinoid prescription, and continuously enrolled 6 months pre-index and 12 months post-index. Gabapentinoid misuse was defined as ≥ 3 claims exceeding daily doses of 3600 mg for gabapentin and 600 mg for pregabalin. Age, gender, concurrent opioid use, neuropathic pain diagnoses and gabapentinoid type were independent variables. Descriptive and inferential statistics were used.
Of included subjects (N = 39,000), 0.2% (N = 81) met study criteria for gabapentinoid misuse. Overall, the majority (76.4%) of gabapentinoid users were aged 41–63 years with a mean ± SD age of 48.2 ± 10.7 years. Those patients meeting the study criteria for gabapentinoid misuse were significantly younger (45.1 ± 11.0 vs 48.2 ± 10.7, p = 0.0084). Majority of the study sample was female (68.1%). However, a significantly higher proportion of males met the study criteria for gabapentinoid misuse compared to females (0.3% vs 0.2%, p = 0.0079). Approximately one-half (51.9%) of the study sample had neuropathic pain, and gabapentinoid misuse was significantly higher in neuropathic pain patients compared to those without neuropathic pain (0.3% vs 0.1%, p = 0.0078). Over three-quarters (77.4%) of patients were using gabapentin; however, gabapentinoid misuse was significantly higher among pregabalin users (0.4% vs 0.2%, p = 0.0003). Approximately 20% (17.3%) of gabapentinoid users had ≥ 90 days of concurrent opioid use. However, there was no significant difference in gabapentinoid misuse among patients with concurrent opioid use compared to patients without (0.3% vs 0.2%, p = 0.1440). Factors significantly associated with misuse included: male sex (odds ratio [OR] 0.486; 95% confidence interval [CI] 0.313–0.756; p = 0.0013); neuropathic pain (OR 2.065; 95% CI 1.289–3.308; p = 0.0026); and pregabalin versus gabapentin use (OR 2.337, 95% CI 1.492–3.661; p = 0.0002). Concurrent opioid use was not significantly associated with gabapentinoid misuse (OR 1.542, 95% CI 0.920–2.586; p = 0.1006).
Prevalence of gabapentinoid misuse was low (0.2%) among Texas Medicaid recipients. Younger age, male gender, neuropathic pain diagnosis and pregabalin use were significantly associated with higher levels of gabapentinoid misuse.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Goodman CW, Brett AS. Gabapentin and pregabalin for pain—is increased prescribing a cause for concern? N Engl J Med. 2017;377(5):411–4. https://doi.org/10.1056/NEJMp1704633.
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;11:109–16. https://doi.org/10.2147/RMHP.S168504.
Jones MR, Viswanath O, Peck J, Kaye AD, Gill JS, Simopoulos TT. A brief history of the opioid epidemic and strategies for pain medicine. Pain Ther. 2018;7(1):13–21. https://doi.org/10.1007/s40122-018-0097-6.
National Institute on Drug Abuse (NIDA). The federal response to the opioid crisis. https://www.drugabuse.gov/about-nida/legislative-activities/testimony-to-congress/2017/federal-response-to-opioid-crisis Accessed 1 Nov 2020.
Drug Enforcement Administration. Prescription monitoring programs: creating a national network. https://www.deadiversion.usdoj.gov/mtgs/drug_chemical/2014/droz.pdf#search=State%20prescription%20drug%20monitoring%20programs. Accessed 1 Nov 2020.
Haffajee RL, Jena AB, Weiner SG. Mandatory use of prescription drug monitoring programs. JAMA. 2015;313(9):891–2. https://doi.org/10.1001/jama.2014.18514.
IQVIA. Medicine Use and Spending in the U.S. https://www.iqvia.com/-/media/iqvia/pdfs/institute-reports/medicine-use-and-spending-in-the-us---a-review-of-2018-outlook-to-2023.pdf?_=1563673044396 Accessed 20 Jul 2019.
Bockbrader HN, Wesche D, Miller R, Chapel S, Janiczek N, Burger P. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet. 2010;49(10):661–9. https://doi.org/10.2165/11536200-000000000-00000.
Calandre EP, Rico-Villademoros F, Slim M. Alpha 2 delta ligands, gabapentin, pregabalin and mirogabalin: a review of their clinical pharmacology and therapeutic use. Expert Rev Neurother. 2016;16(11):1263–77. https://doi.org/10.1080/14737175.2016.1202764.
Tharp AM, Hobron K, Wright T. Gabapentin-related deaths: patterns of abuse and postmortem levels. J Forensic Sci. 2019;64(4):1105–11. https://doi.org/10.1111/1556-4029.14021.
Chiappini S, Schifano F. A decade of gabapentinoid misuse: an analysis of the European medicines agency’s ‘suspected adverse drug reactions’ database. CNS Drugs. 2016;30(7):647–54. https://doi.org/10.1007/s40263-016-0359-y.
Evoy KE, Covvey JR, Peckham AM, Ochs L, Hultgren KE. Reports of gabapentin and pregabalin abuse, misuse, dependence, or overdose: an analysis of the food and drug administration adverse events reporting system (FAERS). Res Social Adm Pharm. 2018. https://doi.org/10.1016/j.sapharm.2018.06.018.
Peckham AM, Fairman KA, Sclar DA. Prevalence of gabapentin abuse: comparison with agents with known abuse potential in a commercially insured US population. Clin Drug Investig. 2017;37(8):763–73. https://doi.org/10.1007/s40261-017-0530-3.
Smith BH, Higgins C, Baldacchino A, Kidd B, Bannister J. Substance misuse of gabapentin. Br J Gen Pract. 2012;62(601):406–7. https://doi.org/10.3399/bjgp12X653516.
Hagg S, Jonsson AK, Ahlner J. Current evidence on abuse and misuse of gabapentinoids. Drug Saf. 2020. https://doi.org/10.1007/s40264-020-00985-6.
Slavova S, Miller A, Bunn TL, et al. Prevalence of gabapentin in drug overdose postmortem toxicology testing results. Drug Alcohol Depend. 2018;186:80–5. https://doi.org/10.1016/J.DRUGALCDEP.2018.01.018.
Bossard JB, Ponté C, Dupouy J, Lapeyre-Mestre M, Jouanjus E. Disproportionality analysis for the assessment of abuse and dependence potential of pregabalin in the French pharmacovigilance database. Clin Drug Investig. 2016;36(9):735–42. https://doi.org/10.1007/s40261-016-0421-z.
Gahr M, Freudenmann RW, Hiemke C, Kölle MA, Schönfeldt-Lecuona C. Pregabalin abuse and dependence in Germany: results from a database query. Eur J Clin Pharmacol. 2013;69(6):1335–42. https://doi.org/10.1007/s00228-012-1464-6.
Schwan S, Sundström A, Stjernberg E, Hallberg E, Hallberg P. A signal for an abuse liability for pregabalin—results from the Swedish spontaneous adverse drug reaction reporting system. Eur J Clin Pharmacol. 2010;66(9):947–53. https://doi.org/10.1007/s00228-010-0853-y.
Smith VR, Boland EM, Young AM, et al. A qualitative analysis of gabapentin misuse and diversion among people who use drugs in Appalachian Kentucky. Psychol Addict Behav. 2018;32(1):115–21. https://doi.org/10.1037/adb0000337.
Smith VR, Lofwall MR, Havens JR. Abuse and diversion of gabapentin among nonmedical prescription opioid users in Appalachian Kentucky. Am J Psychiatry. 2015;172(5):487–8. https://doi.org/10.1176/appi.ajp.2014.14101272.
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. https://doi.org/10.1371/journal.pmed.1002396.
Gomes T, Greaves S, Van Den Brink W, et al. Pregabalin and the risk for opioid-related death: a nested case-control study. Ann Intern Med. 2018;169(10):732–4. https://doi.org/10.7326/M18-1136.
Abrahamsson T, Berge J, Öjehagen A, Håkansson A. Benzodiazepine, z-drug and pregabalin prescriptions and mortality among patients in opioid maintenance treatment—a nation-wide register-based open cohort study. Drug Alcohol Depend. 2017;174:58–64. https://doi.org/10.1016/j.drugalcdep.2017.01.01325.
Driot D, Jouanjus E, Oustric S, Dupouy J, Lapeyre-Mestre M. Patterns of gabapentin and pregabalin use and misuse: results of a population-based cohort study in France. Br J Clin Pharmacol. 2019;85(6):1260–9. https://doi.org/10.1111/bcp.13892.
Hill R, Dewey WL, Kelly E, Henderson G. Oxycodone-induced tolerance to respiratory depression: reversal by ethanol, pregabalin and protein kinase C inhibition. Br J Pharmacol. 2018;175(12):2492–503. https://doi.org/10.1111/bph.14219.
Lyndon A, Audrey S, Wells C, et al. Risk to heroin users of poly-drug use of pregabalin or gabapentin HHS Public Access. Addiction. 2017;8(1):1580–9. https://doi.org/10.1111/add.13843.
Food and Drug Administration. FDA warns about serious breathing problems with seizure and nerve pain medicines gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR). https://www.fda.gov/drugs/fda-drug-safety-podcasts/fda-warns-about-serious-breathing-problems-seizure-and-nerve-pain-medicines-gabapentin-neurontin. Accessed 1 Nov 2020.
Food and Drug Administration. FDA In Brief: FDA requires new warnings for gabapentinoids about risk of respiratory depression. https://www.fda.gov/news-events/fda-brief/fda-brief-fda-requires-new-warnings-gabapentinoids-about-risk-respiratory-depression. Accessed 1 Nov 2020.
Warren B. Drug touted as a safe alternative to painkillers has been found in more Louisville deaths. Louisville Courier Journal. https://www.courier-journal.com/story/news/crime/2018/03/26/gabapentin-overdose-deaths-louisville-fatal-addiction/372489002/. Accessed 1 Nov 2020.
Drug Enforcement Administration. Prescriptions. https://www.deadiversion.usdoj.gov/faq/prescriptions.htm. Accessed 21 Mar 2019.
Wingblad A. State classifies Neurontin as schedule V controlled substance | Local News | theoaklandpress.com. https://www.theoaklandpress.com/news/local/state-classifies-neurontin-as-schedule-v-controlled-substance/article_63284076-1446-11e9-8c09-97d46afc31a4.html. Accessed 1 Nov 2020.
Virginia Board of Pharmacy. Scheduling of gabapentin. https://www.dhp.virginia.gov/pharmacy/docs/Gabapentin06172019.pdf. Accessed 1 Nov 2020.
West Virginia Board of Pharmacy. Current Topics—West Virginia Board of Pharmacy. https://www.wvbop.com/article.asp?id=23. Accessed 1 Nov 2020.
North Dakota State Board of Pharmacy. Gabapentin added as a schedule V substance in the North Dakota Controlled Substance Act.; 2019. https://nabp.pharmacy/wp-content/uploads/2016/06/North-Dakota-Newsletter-June-2019.pdf. Accessed 25 May 2020.
Medical Association of the State of Alabama. Effective Nov. 18: Gabapentin changed to schedule V. https://alabamamedicine.org/effective-nov-18-gabapentin-changed-to-schedule-v/. Accessed 25 May 2020.
Medicaid.gov. August 2020 Medicaid & CHIP enrollment data highlights. https://www.medicaid.gov/medicaid/program-information/medicaid-and-chip-enrollment-data/report-highlights/index.html. Accessed 7 Jan 2020.
Texas Medicaid Benefits.gov. https://www.benefits.gov/benefit/1640. Accessed 7 Jan 2021.
Texas Medicaid. Texas and the ACA’s Medicaid expansion: eligibility, enrollment and benefits. https://www.healthinsurance.org/texas-medicaid/#parent. Accessed 7 Jan 2021.
Food and Drug Administration. Consumer updates—combating misuse and abuse of prescription drugs: Q&A with Michael Klein, Ph.D. https://www.hemophiliafed.org/uploads/FDA_Combating-Misuse-and-Abuse-of-Prescription-Drugs.pdf. Accessed 1 Nov 2020.
Smith RV, Havens JR, Walsh SL. Gabapentin misuse, abuse and diversion: a systematic review. Addiction. 2016;111(7):1160–74. https://doi.org/10.1111/add.13324.
Peckham AM, Evoy KE, Covvey JR, Ochs L, Fairman KA, Sclar DA. Predictors of gabapentin overuse with or without concomitant opioids in a commercially insured U.S. population. Pharmacother. 2018;38(4):436–43. https://doi.org/10.1002/phar.2096.
Buttram ME, Kurtz SP. Descriptions of gabapentin misuse and associated behaviors among a sample of opioid (mis)users in South Florida. J Psychoactive Drugs. 2020. https://doi.org/10.1080/02791072.2020.1802087.
Piper BJ, Suarez MJ, Piserchio JP, et al. Illicit and prescription drug misuse as reported to the Maine Diversion Alert Program. Forensic Sci Int. 2018;285:65–71. https://doi.org/10.1016/j.forsciint.2018.01.025.
Chatterjee A, Lopez D, Ramkellawan S, et al. “That’s what we call the cocktail”: non-opioid medication and supplement misuse among opioid users. Subst Abus. 2019. https://doi.org/10.1080/08897077.2019.1671943.
Pauly NJ, Delcher C, Slavova S, Lindahl E, Talbert J, Freeman PR. Trends in gabapentin prescribing in a commercially insured US adult population, 2009–2016. JMCP. 2020;26(3):246–52. https://doi.org/10.18553/jmcp.2020.26.3.246.
Evoy KE, Sadrameli S, Contreras J, Covvey JR, Peckham AM, Morrison MD. Abuse and misuse of pregabalin and gabapentin: a systematic review update. Drugs. 2020. https://doi.org/10.1007/s40265-020-01432-7.
No funding was received.
Conflict of interest
There are no conflicts of interests to declare.
The datasets analyzed during the current study were obtained from the Texas Medicaid medical and prescription claims database.
This study was classified as exempt by the University of Texas at Austin Institutional Review Board.
Consent to participate
EAI is the principal author of this study. All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by EAI. The first draft of the manuscript was written by EAI and all authors commented on and critically revised the manuscript before preparation for publication.
Below is the link to the electronic supplementary material.
About this article
Cite this article
Ibiloye, E.A., Barner, J.C., Lawson, K.A. et al. Prevalence of and Factors Associated with Gabapentinoid Use and Misuse Among Texas Medicaid Recipients. Clin Drug Investig (2021). https://doi.org/10.1007/s40261-021-01009-6