Abuse and Misuse of Pregabalin and Gabapentin: A Systematic Review Update.

BACKGROUND: A 2017 systematic review (SR) identified 59 studies examining gabapentinoid (pregabalin and gabapentin) misuse/abuse. Evidence of gabapentinoid misuse/abuse has since grown substantially. OBJECTIVE: Update previous SR and describe new insights regarding gabapentinoid abuse. METHODS: A SR of PubMed was conducted to identify studies published from 7/29/2016-8/31/2020. Four searches were performed using the following terms: "gabapentin [MeSH] OR pregabalin [MeSH] OR gabapentinoid" AND one of the following substance misuse/abuse-related terms: "substance-related disorders [MeSH]", "overdose", "abuse", or "misuse". Clinicaltrials.gov and the Cochrane Library database were searched to identify ongoing studies or similar SRs. Reference lists of included studies were reviewed to identify additional literature. All studies with novel data related to pregabalin and/or gabapentin abuse, misuse, or overdose conducted during the study period were included. Articles not written in English, review articles, and animal studies were excluded. RESULTS: Fifty-five studies were included (29 [52.7%] from North America, 17 [30.9%] Europe, 6 [10.9%] Asia, and 3 [5.5%] Australia). Forty-six observational studies and 10 case reports/series were included (one manuscript included both). Twenty (36.4%) studied gabapentin only, 18 (32.7%) pregabalin only, and 17 (30.9%) both pregabalin/gabapentin. These studies corroborate findings from the previous SR that gabapentinoids are increasingly abused or misused to self-medicate, that gabapentinoids can produce desirable effects alone but are often used concomitantly with other drugs, and that opioid use disorder is the greatest risk factor for gabapentinoid abuse. While the original SR identified the largest studies having been published in Europe, this review identified several more generalisable US studies that have subsequently been conducted. The most concerning finding was increased evidence of associated patient harm, including increased hospital utilisation and opioid-related overdose mortality risk. CONCLUSION: Evidence suggests that gabapentinoid misuse/abuse represents a growing trend that is causing significant patient harm. Prescribers should exercise appropriate caution with use in high-risk populations and monitor for signs of misuse or abuse.

Abuse and Misuse of Pregabalin and Gabapentin.

BACKGROUND: Gabapentinoid (pregabalin and gabapentin) abuse is increasingly being reported. OBJECTIVE: To assess the extent of gabapentinoid abuse, characteristics of typical abusers, patterns of abuse, and potential harms in order to bring this trend to providers' attention. METHODS: A systematic review of MEDLINE, Cochrane Library, ClinicalTrials.gov, and US FDA data, indexed through 28 July 2016, utilizing the following searches: pregabalin OR gabapentin OR gabapentinoid AND one of the following: abuse, misuse, overdose, or substance-related disorders[MESH], was conducted. Additional studies were identified through review of references. English-language epidemiological studies, clinical studies, and case reports/series of gabapentinoid abuse/misuse/overdose were included. The authors reached consensus regarding study inclusion after full-text review. The body of literature was assessed for bias qualitatively. RESULTS: Fifty-nine studies were included in this systematic review (24 epidemiological, three clinical abuse liability, 16 abuse/misuse/dependence case reports/series, 17 acute overdose case reports/series-one included both an epidemiological study and case series and was included in both counts). Analysis of these studies indicates increasing numbers of patients are self-administering higher than recommended doses to achieve euphoric highs. In the general population, a 1.6% prevalence of gabapentinoid abuse was observed, whereas prevalence ranged from 3% to 68% among opioid abusers. An international adverse event database identified 11,940 reports of gabapentinoid abuse from 2004-2015, with >75% reported since 2012. Risk factors include a history of substance abuse, particularly opioids, and psychiatric co-morbidities. While effects of excessively high doses are generally non-lethal, gabapentinoids are increasingly being identified in post-mortem toxicology analyses. CONCLUSION: Evidence suggests gabapentinoids possess potential for abuse, particularly in individuals with a history of opioid abuse, and reports of such abuse are increasingly being documented. Prescribers should be aware of high-risk populations and monitor for signs of abuse.