Trends in and Characteristics of Buprenorphine Misuse Among Adults in the US

Key Points Question With recent increases in buprenorphine treatment for opioid use disorder (OUD), is buprenorphine misuse increasing in the US? Findings In this survey study of 214 505 respondents to the National Survey on Drug Use and Health Data, nearly three-fourths of adults reporting buprenorphine use did not misuse their prescribed buprenorphine in 2019. Among adults with OUD, prevalence of buprenorphine misuse trended downward during the period from 2015 to 2019, and “because I am hooked” and “to relieve physical pain” were the most common motivations for the most recent buprenorphine misuse. Meaning These findings underscore the need to expand access to buprenorphine-based OUD treatment while monitoring and implementing strategies to reduce buprenorphine misuse.


Introduction
Buprenorphine hydrochloride is a critical medication for treating opioid use disorder (OUD) [1][2][3] and is prescribed to relieve severe pain for patients who need daily, continuous, long-term opioid treatment when other medications are inadequate. 4-6 To prescribe buprenorphine for treatment of OUD, clinicians must obtain a waiver and are limited in the number of patients they can treat at one time.
However, clinicians do not need a waiver to prescribe buprenorphine for pain management.
Multiple steps have been taken recently to expand access to buprenorphine-based OUD treatment (eg, expanding prescription authority to nonphysicians, raising the maximum patient limit to 275 for qualified clinicians, expanding insurance coverage). Although the number of clinicians receiving a waiver to prescribe buprenorphine for OUD has increased over time, [7][8][9] only a small fraction of clinicians eligible to obtain a waiver have requested one, and an even smaller fraction actually prescribe buprenorphine. Concerns include unease with treating patients who have OUD, lack of adequate reimbursement, and risks for diversion, misuse, and overdose. [10][11][12][13][14][15][16] On April 28, 2021, the US Department of Health and Human Services released practice guidelines for the administration of buprenorphine for treating OUD, aiming to increase OUD treatment, primarily by allowing a limited waiver for prescribing buprenorphine without the specialized training requirement. 17 The exemption, specifically addressing reported barriers of the training requirement, allows licensed clinicians to (1) treat as many as 30 patients with OUD using buprenorphine without having to make certain training-related certifications and (2) treat patients with buprenorphine without certifying their capacity to provide counseling and ancillary services. 17 Notably, buprenorphine treatment is complicated by concerns for misuse, defined as using buprenorphine without a prescription or without following a physician's instructions. 18 In particular, understanding the most frequently used and misused prescription opioids and the differences in the main motivations between buprenorphine misuse and other prescription opioid misuse can help address clinicians' and policy makers' concerns. Better understanding of buprenorphine use and misuse can inform policy and clinical practice development, education, training, and initiatives to expand access to this life-saving medication in a manner that is safe and minimizes harm.
To address these issues, we used nationally representative samples to examine the following: 1. Which prescription opioids are the most frequently misused by US adults? 2. Among US adults with buprenorphine use, has annual prevalence of buprenorphine misuse changed over time? 3. Among US adults who misuse prescription opioids, are there differences in the main motivations between the most recent buprenorphine misuse and nonbuprenorphine prescription opioid misuse? 4. Among US adults with buprenorphine use, what are sociodemographic characteristics, health conditions, and behavioral health factors associated with buprenorphine misuse? Clinical and policy implications differ for persons with or without OUD who misuse buprenorphine. Moreover, because the primary use of buprenorphine is to treat OUD, 19,20 because buprenorphine misuse and OUD are highly correlated, and because some people with OUD misuse nonprescribed buprenorphine to self-treat their OUD symptoms, 21-24 we examined buprenorphine misuse among those with and without OUD as distinct categories.

Survey Methods and Study Population
We examined data from 214 505 adult respondents participating in the 2015-2019 National Survey

Measures of Main Outcomes and Participant Characteristics
The 2015-2019 NSDUH asked about lifetime and past-year use and misuse of specific prescription opioids (eg, buprenorphine). 28 The NSDUH defined prescription opioid misuse (including buprenorphine misuse) as use "in any way that a doctor [physician] did not direct you to use them, including (1) use without a prescription of your own; (2) use in greater amounts, more often, or longer than you were told to take them; or (3) use in any other way a doctor did not direct you to use them." 18,25,26 Any respondent meeting 1 of these 3 criteria would be classified as having buprenorphine misuse. For respondents with past-year prescription opioid misuse, NSDUH asked about using any prescription opioids without having their own prescriptions, the name of the prescription opioid most recently misused, and the main motivation for their most recent misuse, including the following: "to relieve physical pain," "to relax or relieve tension," "to experiment," "to feel good or get high," "to help with my feelings or emotions," "to increase or decrease the effect(s) of other drugs," or "because I am hooked." The NSDUH also collected lifetime and past-year use of tobacco, alcohol, cannabis, cocaine, heroin, inhalants, and hallucinogens and use and misuse of prescription stimulants and sedatives/ Fourth, among adults with past-year buprenorphine use, we examined differences in sociodemographic characteristics, health conditions, and behavioral health status between those with and without past-year buprenorphine misuse by OUD status at the bivariable level. To assess past-year buprenorphine use with and without misuse or OUD (4 outcomes) simultaneously, multivariable multinomial logistic regression modeling was applied. Multicollinearity and potential interaction effects were tested and were not found in final multinomial logistic regression models. All analyses used SUDAAN software 35 to account for NSDUH's complex sample design and sample weights. For all analyses, P < .05 (2-tailed) was considered statistically significant.  (Figure 1). Among US adults in 2019, an estimated 2.4 (95% CI, 2.2-2.7) million used buprenorphine and an estimated 0.7 (95% CI, 0.5-0.9) million misused buprenorphine in the past 12 months, whereas an estimated 1.7 (95% CI, 1.5-1.9) million used buprenorphine without misuse.

Past-Year Prevalence of Using Any Prescription Opioid Without a Prescription
Among US adults with past-year prescription opioid misuse, prevalence of using any prescription opioid (including buprenorphine) without having their own prescriptions at any time during the past 12 months was higher among those with buprenorphine misuse than among those with nonbuprenorphine prescription opioid misuse regardless of OUD status (  Table 1 shows differences in the main motivation between the most recent buprenorphine misuse and nonbuprenorphine prescription opioid misuse among adults with past-year prescription opioid misuse. "Because I am hooked" (27.3% [95% CI, 21.6%-33.8%]) and "to relieve physical pain" (20.5%

Differences in Sociodemographic Characteristics, Health Conditions, and Behavioral Health Status by OUD and Buprenorphine Misuse
Among adults with past-year buprenorphine use and OUD (

Factors Associated With Buprenorphine Misuse and OUD
Multivariable multinomial logistic regression results (

Discussion
Despite recent increases in buprenorphine treatment for OUD in the US, 10  it, suggesting that almost three-fourths of adults reporting buprenorphine use in the past 12 months did not misuse their prescribed buprenorphine. Notably, among adults with past-year prescription opioid misuse, using prescription opioids without having their own prescriptions was more frequent among those who misused buprenorphine (71.8%-74.7%) than those who misused other prescription opioids (53.2%-60.0%), regardless of OUD status, suggesting that diversion from other persons is particularly common among adults with buprenorphine misuse. We also found that "because I am hooked" (27.3%) for self-treatment of craving and withdrawal symptoms and "to relieve physical pain" (20.5%) were the most common motivations for the most recent buprenorphine misuse among adults with OUD, whereas "to relieve physical pain" (29.3%) and "to Past-year use, lifetime misuse 5.8 (0. b Each estimate is significantly (P < .05) different from the estimate of the corresponding group with no buprenorphine misuse (within each major column and within each row).
c Determined according to NSDUH respondents' self-classification of racial and ethnic origin and identification based on the classifications developed by the US Census Bureau.
d Interpret with caution owing to low statistical precision.  Prescription sedative/tranquilizer

JAMA Network Open | Substance Use and Addiction
Past-year misuse and disorder 0.9 (0.5-1.7) 0.9 (0.6-1.5) Past increase in overdose death rates involving synthetic opioids, 36 but White individuals were more likely to receive buprenorphine treatment for OUD. 14,15,37,38 Furthermore, among adults using prescription opioids, Medicaid beneficiaries and uninsured adults are 2 to 3 times more likely to have OUD than those with private insurance 24 ; however, those with private insurance tend to receive buprenorphine treatment for OUD, 14 and low-income people also face additional financial barriers to buprenorphine treatment. 36,37 Even among Medicaid enrollees, non-Hispanic Black individuals had less use of medications for OUD than their White counterparts. 38 These findings, along with evidence that sociodemographic factors do not affect buprenorphine treatment engagement, 39 underscore the urgency to address economic, health insurance, and racial and ethnic disparities in buprenorphine treatment access.
Researchers have identified that the growth of waivers for clinicians to prescribe buprenorphine is markedly slower in small nonmetropolitan counties than urban counties 8 and that rural counties are associated with low buprenorphine dispensing. 9 We found that among adults with buprenorphine use and OUD, residing in nonmetropolitan areas was associated with buprenorphine misuse. Together, these results highlight the importance of strengthening buprenorphine treatment access and treatment quality in rural areas (eg, by expanding and improving access to broadband and other technologies for telehealth services).
The US opioid and suicide crises overlap, because researchers have found that suicide is a silent contributor to opioid overdose deaths 40,41 and that suicidal ideation before opioid overdose is  Table 2 but not in Table 3, were not significantly associated with the outcomes and were removed from this final multinomial logistic regression model. Age, sex, and race and ethnicity remained in the final model regardless of their statistical significance. All multinomial logistic regression results are provided in the eTable in the Supplement. common. 41,42 Similarly, we found that among adults with buprenorphine use, 8.2% to 12.3% of adults with OUD (with and without buprenorphine misuse, respectively) and 11.0% of adults with buprenorphine misuse but without OUD reported making a suicide plan in the past year; by contrast, 2.0% of adults with buprenorphine use but without buprenorphine misuse and without OUD planned suicide in the past year. Our multivariable results are consistent with these descriptive findings. Together, these results suggest that both OUD and buprenorphine misuse are associated with suicide risk. Having a suicide plan is considered a psychiatric emergency because it is associated with imminent lethal attempts. 43-45 Thus, for patients using buprenorphine, providing timely and tailored interventions to reduce suicide risk and prevent opioid overdose deaths due to suicidal intent is warranted.

JAMA Network Open | Substance Use and Addiction
Our multivariable results also suggest that other substance use and use disorders are quite common in adults who misuse buprenorphine, consistent with previous research on correlates of prescription opioid misuse. 24,46-50 Such co-occurrences are a reminder for clinicians that buprenorphine misuse often co-occurs with use and use disorders of multiple substances. 51 Because polysubstance use and use disorders are associated with increased risk of overdose and negatively associated with buprenorphine treatment engagement 40 and retention, 52,53 early screening and timely interventions for co-occurring substance use and use disorders are critical.
We found that among adults with buprenorphine use, regardless of their OUD status, those receiving treatment for drug use were less likely to misuse buprenorphine than those not receiving drug use treatment. Moreover, adults with OUD and buprenorphine misuse were more likely to report "because I am hooked" as a motivation for their most recent buprenorphine misuse compared with their counterparts with nonbuprenorphine prescription opioid misuse. Because only 43% of US adults with buprenorphine misuse and OUD received drug use treatment in the past year, and because our study and multiple other studies 21-23,54 found self-treatment of craving and withdrawal symptoms as the predominant motivation for using nonprescribed buprenorphine among people with OUD, our results highlight the need for adults with OUD to engage and be retained in goodquality buprenorphine treatment. These findings underscore the importance of future research to improve understanding of strategies that improve treatment access, engagement, and retention.
Importantly, the chronic nature of addiction, along with the time needed to stabilize a patient receiving buprenorphine, should preclude administrative discharge of patients from treatment based on detection of misuse. In addition, the prevalence of individuals with buprenorphine use but with neither buprenorphine misuse nor OUD remained stable from 2015 to 2019. This group could include people undergoing management of chronic pain, people receiving long-term treatment with buprenorphine and in recovery for their opioid use disorder for more than 12 months, or both. Future research is needed to continue monitoring related trends among this group while expanding access to buprenorphine-based OUD treatment and developing strategies to reduce buprenorphine misuse.

Limitations
Our study has several limitations. The NSDUH excludes people experiencing homelessness and not living in shelters or people residing in institutions (eg, incarcerated adults), which could lead to underestimates in drug use and use disorders and suicidality. Because of the cross-sectional nature of NSDUH data, we could not establish temporal or causal relationships. Future studies may examine the specific timing of measures of past-year behaviors (eg, misuse before or during opioid treatment) and related clinical implications. More research is needed to separately assess the misuse measure of buprenorphine, distinguishing use without a prescription (a sign of diversion) from use without following a physician's instructions to understand related clinical implications. The NSDUH neither assesses pain or pain management nor captures the details of treatment with buprenorphine. In addition, the NSDUH is a self-reported survey and is subject to recall bias. Additionally, future research should examine how changes to buprenorphine prescribing during the COVID-19 pandemic (eg, prescription via telehealth by clinicians who receive waivers 55 and increasing coverage through emergency Medicaid expansion 56 ) affect buprenorphine misuse.