More than 47,000 individuals died from an opioid overdose in 2017.1 According to preliminary data from 2018, more than half of opioid overdose deaths involved another substance like methamphetamine, cocaine, or benzodiazepines.2 Those who co-use opioids with other substances are at a higher risk of fatal and nonfatal overdose, psychiatric diagnoses, HIV, and hepatitis.3–5 Co-use of opioids and other substances has increased substantially in the last decade. For example, rates of opioid/methamphetamine co-use increased 15 percentage points from 2011 to 2017 among a sample of adults seeking treatment for opioid use disorder (OUD).6
Medications for opioid use disorder (MOUD), such as methadone and buprenorphine, decrease opioid cravings and substantially decrease overdose-related mortality.7 Opioid agonist treatments are first line therapy for treatment of OUD, and evidence suggests that they may also decrease use of other substances.8,9 Prior to 2017, the FDA advised caution when prescribing MOUD for individuals who co-used opioids with alcohol or benzodiazepines.10 However, new guidelines indicate that MOUD can safely be prescribed independent of co-use with stimulants,8 alcohol, or benzodiazepines.11,12 Nonetheless, many clinicians are reluctant to prescribe agonist medications for OUD for patients who are actively using other substances.13
Given that opioids are frequently used with other substances, it is essential to understand patterns of co-use and their associations with receipt of MOUD. We examined longitudinal trends in the co-use of opioids with other substances and analyzed associations between co-use patterns and likelihood of receiving MOUD among US adults seeking treatment for opioid use. We hypothesized that substances co-used with opioids would change over time and that those who co-used opioids with other substance would receive MOUD at lower rates.
Data Source and Sample
We used data from the Treatment Episodes Data Set-Admissions (TEDS-A) from the Substance Abuse and Mental Health Services Administration (SAMHSA).14 SAMHSA requests that treatment centers who receive public funding report all admissions and the primary, secondary, and tertiary substances leading to admission to treatment. We restricted our sample to those who had an OUD by only including admissions that listed heroin, nonprescription methadone, or other synthetic opioids as the primary reason for treatment. We included admissions of adults (18 and older) to treatment from 1992 to 2017, inclusive of all years of available data.
Our primary outcome variable was receipt of MOUD while in treatment. TEDS-A includes one MOUD variable that includes methadone, buprenorphine, and naltrexone. We restricted this analysis to the most recent 2 years of data (2016–2017) to reflect current clinical practice and prescribing guidelines.
We examined longitudinal trends in co-use of opioids with other substances for all available years. Treatment facilities reported up to three substances that led to the patient's admission. We examined trends in co-use of opioids with any alcohol, cocaine (including crack cocaine), methamphetamine (including other psychostimulants; 84% of reported psychostimulant use was related to methamphetamine), and benzodiazepines. Categories were not mutually exclusive.
We used STATA 15.1 for all analyses. We used logistic regression models to assess trends in use of opioids only and co-use of opioids with any alcohol, cocaine, methamphetamine, or benzodiazepines over time, adjusted for sociodemographic variables and treatment setting (see Table, Supplemental Digital Content 1, http://links.lww.com/JAM/A210). We also used a multiple logistic regression model to predict receipt of MOUD by co-use category in 2016 to 2017. We again adjusted for sociodemographic variables and treatment setting and included 4 binary co-use variables to examine independent relationships between each co-use category and MOUD. We used postestimation predictive margins with covariates held at observed sample values to generate the adjusted rate of MOUD for opioids only and each co-use category. We estimated the number of people who would have received MOUD if those who co-used opioids with other substances received MOUD at the same rate as those who used opioids alone by multiplying the number of people who co-used opioids with other substances in 2016/2017 by the difference in MOUD rates.
During the study period (1992–2017), 9,440,157 admissions had opioids as the primary substance leading to the treatment episode. There was a substantial increase in opioid-related admissions from 1992 (N = 182,276) to 2017 (N = 680,612). Approximately half of admissions were for opioids without other substances (N = 4,728,081, 50.1%). Opioid/cocaine co-use was the most common combination (N = 2,666,971, 28.3%), followed by opioid/alcohol co-use (N = 1,915,751; 20.3%), opioid/benzodiazepine co-use (N = 683,340; 7.2%), and opioid/methamphetamine co-use (N = 464,951; 4.9%).
Longitudinal Trends in Co-use
There were substantial changes in co-use trends across substances during the study period (Fig. 1). The percentage of admissions for co-use of opioids with other substances (vs. opioids alone) ranged from 44% to 55%. Opioid/cocaine co-use was the most common combination throughout the study period, but its prevalence decreased between 1992 and 2017 (Percentage Points [PP]: −17.2%, 95% confidence interval [CI]: −17.5, −17.0), as did opioid/alcohol co-use (PP: −12.5%, 95% CI: −12.7, −12.3). Opioid/benzodiazepine co-use increased during the study period (PP: 5.6%, 95% CI: 5.5, 5.7), as did opioid/methamphetamine co-use (PP: 10.1%, 95% CI: 10.0, 10.2). Over half of the increase in opioid/methamphetamine co-use occurred between 2012 and 2017 (PP: 6.3%, 95% CI: 6.2, 6.3).
Medications for Treating OUD
Across the 5 co-use patterns, admissions for opioids only were more likely to receive MOUD (38.5%, 95% CI: 38.4, 38.6) than those for co-use of opioids with other substances (Cocaine: 35.7%, 95% CI: 35.6, 35.9; Benzodiazepines: 34.6%, 95% CI: 34.3, 34.9; Methamphetamine: 23.9%, 95% CI: 23.7, 24.2; Alcohol: 25.0%, 95% CI: 24.8, 25.2) (Supplemental Digital Content 2: Table, http://links.lww.com/JAM/A211, Fig. 2). Adjusted differences between opioid use alone and each co-use category were statistically significant. If those who co-used opioids with other substances had received MOUD at the same rate as those who used opioids only, 47,400 additional admissions would have received MOUD across 2016 and 2017, a 27.5% relative increase.
From 1992 to 2017, trends in the substances co-used with opioids changed, despite the prevalence of co-use of opioids with any substance remaining stable. The prevalence of opioid/cocaine and opioid/alcohol co-use fell, while the prevalence of opioid/methamphetamine and opioid/benzodiazepine co-use increased. Admissions for co-use of opioids with other substances, particularly methamphetamine or alcohol, received MOUD at substantially lower rates. Because of disparities in MOUD between people who use opioids with and without other substances, 47,000 people who could have benefited from MOUD did not receive it in 2016 and 2017. Additional research is needed to identify key barriers and facilitators to providing MOUD to individuals who co-use opioids with other substances.
This study has important limitations. First, although many states report all admissions to facilities that accept public funding to SAMHSA, states are only obligated to report on admissions paid for with public funding. We do not have information on privately funded treatment facilities, which may provide MOUD at different rates, or whether barriers to MOUD were at the facility or provider level.15 Second, we are unable to draw causal conclusions about why those who co-use opioids with other substances receive MOUD at a lower rate than those who use opioids only. Third, MOUD is an aggregate variable and, therefore, we cannot differentiate between medications, nor do we know details of the MOUD administration, such as days of medication prescribed.
Improving access to MOUD has been a cornerstone of the nation's response to the opioid crisis, yet there are disparities in access. Patients who co-use opioids with other substances received MOUD at a lower rate, yet are at the highest risk of fatal and nonfatal overdose.4 As the crisis becomes more complex with the rise of methamphetamine and other substances, barriers to MOUD for individuals who co-use opioids with other substances should be identified and removed.
1. Wilson N, Kariisa M, Seth P, Iv HS, Davis NL. Drug and opioid-involved overdose deaths – United States, 2017–2018
2020; 69 (11):290–297.
2. Gladden RM, O’Donnell J, Mattson CL, Seth P. Changes in opioid-involved overdose deaths by opioid type and presence of benzodiazepines, cocaine, and methamphetamine — 25 states, July–December 2017 to January–June 2018. MMWR Morb Mortal Wkly Rep
2019; 68 (34):737–744.
3. Al-Tayyib A, Koester S, Langegger S, Raville L. Heroin and methamphetamine injection: an emerging drug use pattern. Subst Use Misuse
2017; 52 (8):1051–1058.
4. Riley ED, Evans JL, Hahn JA, et al. A longitudinal study of multiple drug use and overdose among young people who inject drugs. Am J Public Health
2016; 106 (5):915–917.
5. Hakansson A, Schlyter F, Berglund M. Associations between polysubstance use
and psychiatric problems in a criminal justice population in Sweden. Drug Alcohol Depend
2011; 118 (1):5–11.
6. Ellis MS, Kasper ZA, Cicero TJ. Twin epidemics: the surging rise of methamphetamine use in chronic opioid users. Drug Alcohol Depend
7. Gastberger S, Baumgartner MR, Soyka M, et al. Concomitant heroin and cocaine use among opioid-dependent patients during methadone, buprenorphine or morphine opioid agonist therapy. Eur Addict Res
2019; 25 (4):207–212.
8. Comer S, Cunningham C, Fishman MJ, et al. National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use. Published online 2015:66.
9. Ahmadi J, Razeghian Jahromi L. Comparing the effect of buprenorphine and methadone in the reduction of methamphetamine craving: a randomized clinical trial. Trials
2017; 18 (1):259.
10. Food and Drug Administration. FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. Published September 31, 2016. https://www.fda.gov/media/99761/download
. Accessed September 3, 2019.
11. Food and Drug Administration. FDA Drug Safety Communication: FDA urges caution about withholding opioid addiction medications from patients taking benzodiazepines or CNS depressants: careful medication management can reduce risks. Published September 20, 2017. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-urges-caution-about-withholding-opioid-addiction-medications
. Accessed September 3, 2019.
12. Substance Abuse and Mental Health Services Administration. Medications for Opioid Use Disorder for Healthcare and Addiction Professionals, Policymakers, Patients, and Families. Published 2018. https://store.samhsa.gov/system/files/tip63_fulldoc_052919_508.pdf
. Accessed September 3, 2019.
13. Knudsen HK, Lofwall MR, Walsh SL, Havens JR, Studts JL. Physicians’ decision-making when implementing buprenorphine with new patients: conjoint analyses of data from a cohort of current prescribers. J Addict Med
2017; 12 (1):31–39.
14. Substance Abuse and Mental Health Services Administration (SAMHSA). Treatment episode data set (TEDS) 1992-2017. https://www.datafiles.samhsa.gov/study-series/treatment-episode-data-set-admissions-teds-nid13518
. Accessed May 28, 2020.
15. Knudsen HK, Ducharme LJ, Roman PM. Early adoption of buprenorphine in substance abuse treatment centers: data from the private and public sectors. J Subst Abuse Treat
2006; 30 (4):363–373.