Gabapentin is an oral anticonvulsant approved by the United States Food and Drug Administration (FDA) as an adjunctive treatment for partial seizures and postherpetic neuralgia.(Evoy et al., 2021a) Despite limited indications, prescriptions for gabapentin have significantly increased in recent years, doubling from 2004 to 2019.(Kuehn, 2022; Peet et al., 2023; United States Department of Jusice, 2023; Johansen and Maust, 2024) It is estimated that 83–95 % of gabapentin prescriptions are “off-label”, used to treat a myriad of conditions including a range of neuropathic and nonneuropathic pain syndromes, bipolar affective disorder, anxiety, chronic refractory cough, headaches, insomnia, hiccups, and the management of substance use disorders (SUD).(Mack, 2003; Arnold et al., 2007; Ryan et al., 2012; Steger et al., 2015; Chou et al., 2016; Smith et al., 2016; Peckham et al., 2018b; Reus et al., 2018; Goodman and Brett, 2019; Campbell et al., 2021; Hong et al., 2022; Peet et al., 2023)

In the context of SUD treatment settings, gabapentin is prescribed “off-label” to facilitate detoxification or mitigate withdrawal symptoms, as well as manage comorbid conditions that are highly prevalent in these populations such as anxiety, insomnia and chronic pain.(Verduin et al., 2007; Ahmed et al., 2019; Buttram et al., 2019; McAnally et al., 2020; Castillo et al., 2022; Martins et al., 2022; Martin and Gainer, 2022) Gabapentin has long been perceived to be a safe substitute for substances with known nonmedical use potential and health risks such as opioids and benzodiazepines.(Esechie et al., 2021; Evoy et al., 2021a; Mattle et al., 2022; Covvey et al., 2023)

The evidence base for gabapentin prescribing in SUD treatment settings is limited. Several systematic reviews and meta-analyses have found mixed or low strength of evidence for associations of gabapentin and alcohol use disorder (AUD) outcomes, although positive associations have been found for reductions in heavy drinking days and returning to heavy drinking, and managing alcohol withdrawal syndrome.(Ahmed et al., 2019; Kranzler et al., 2019; Cheng et al., 2020; Martins et al., 2022; Mattle et al., 2022; McPheeters et al., 2023; Qu et al., 2024) Data on the outcomes of gabapentin in the population with opioid use disorder (OUD) have also been mixed, although some studies have noted improvement in withdrawal symptoms and reductions in opioid consumption.(Sanders et al., 2013; Ahmed et al., 2019; Martin and Gainer, 2022) Limited randomized controlled trials have shown gabapentin to be associated with decreased cannabis use/withdrawal and negative affect, as well as improving sleep and executive functioning in those with cannabis use disorder (CUD).(Smith et al., 2016; Martins et al., 2022; Prisciandaro et al., 2022) Randomized controlled trials thus far have shown no benefit of gabapentin for cocaine or methamphetamine use disorder,(Karila et al., 2010, Brackins et al., 2011, Ahmed et al., 2019, Martin and Gainer, 2022) and to our knowledge no studies exist on its utility for managing sedative use disorder.

In tandem with rising prescriptions, numerous surveillance reports have documented a corresponding increase in gabapentin nonmedical use (NMU), particularly among those with a history of substance use.(Smith et al., 2016; Buttram et al., 2017; Reynolds et al., 2020; Evoy et al., 2021b; Riley et al., 2021; Kuehn, 2022; Mattson et al., 2022; Carter et al., 2024) While the rate of gabapentin NMU is estimated to be between 1.6 % and 6.6 % in the general population, it is estimated to be between 3 % and 68 % in those with SUDs.(Evoy et al., 2017; Evoy et al., 2021b) 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 NMU of gabapentin.(Bastiaens et al., 2016; Smith et al., 2016; Bonnet and Scherbaum, 2017; Peckham et al., 2018a; Hagg et al., 2020; Evoy et al., 2021b) Motivations for gabapentin NMU in SUD populations mirror many of its off-label uses. Therapeutic motivations include self-management of pain, sleep issues, anxiety, or to self-manage one’s substance use, craving or withdrawals.(Smith et al., 2016; Vickers Smith et al., 2018; Stein et al., 2020; Evoy et al., 2021b) Nontherapeutic motivations include euphoria-seeking, or potentiating the effects of other drugs.(Smith et al., 2016; Vickers Smith et al., 2018; Evoy et al., 2021b; Ellis et al., 2022; Ellis et al., 2023a) In addition to adverse events commonly associated with gabapentin such as drowsiness, dizziness, and difficulty with coordination/concentration, recent research has highlighted associations between gabapentin and respiratory depression alongside opioids, suicidal behaviors, dependence/withdrawal of the drug itself, and harms associated with poly-intoxication.(Gomes et al., 2017; Savelloni et al., 2017; Chincholkar, 2020; Evoy et al., 2021b; Evoy et al., 2021a; Goins et al., 2021; Alothman et al., 2023; Meaadi et al., 2023; Tambon et al., 2023; Bierly and Chan-Hosokawa, 2024; Porwal et al., 2024; Peckham et al., 2018c)

Despite reports of gabapentin’s increased use as an adjunctive medication in managing SUDs alongside increasing NMU, there currently exists no epidemiological assessment on the temporal trends or prevalence of gabapentin use with or without a prescription across various types of SUD treatment settings. While nonmedical use of gabapentin may also include the use of one’s prescription outside of directed dosing, gabapentin use without a prescription is used here as a proxy to nonmedical use. The objective of this study was to assess the prevalence and temporal trends in the use of gabapentin, with or without a prescription, among those in substance use treatment settings, along with associated demographics, comorbid conditions, and substance use patterns.