Search the Library

Abstract: This study was a secondary analysis of two CTN trials comparing buprenorphine (BUP-NX) and extended-release naltrexone (XR-NTX), CTN-0051, X:BOT and CTN-0067, CHOICES. The purpose was to estimate how ongoing stimulant use affects return to illicit opioid use after initiation onto medication for opioid use disorder (MOUD). A total of 528 participants who initiated MOUD as part of trial participation were included; participants were recruited from 13 opioid treatment programs and HIV clinics across 10 states in the U.S. from 2014-2019. Nearly half (49%) were between 30 and 49 years of age, 69% were male and 66% were non-Hispanic White. The primary outcome was first self-reported day of non-prescribed opioid use following MOUD initiation, and the exposure of interest was daily stimulant use (methamphetamine, amphetamines or cocaine). Both were defined using time-line follow-back. Among participants reporting at least 1 day of illicit opioid use, we also examined relapse to ongoing use, defined as (1) 7 days of continuous opioid use or (2) 4 consecutive weeks with self-reported opioid use, one or more positive urine drug screens (UDS) for opioids or one or more missing UDS. Forty-seven per cent of participants reported stimulant use following MOUD initiation, 58% returned to illicit opioid use and 66% of those relapsed to ongoing use. Stimulant use was strongly associated with increased risk of misusing opioids after MOUD initiation when measured daily [adjusted hazard ratio (aHR)=9.23, 95% confidence interval (CI)=6.80–12.50, P<0.001] and over a 7-day period (aHR=1.27 for each additional day, CI=1.18–1.37, P<0.001). Using stimulants weekly or more often was associated with increased likelihood of relapse to ongoing opioid use compared with less than weekly or no stimulant use (adjusted odds ratio=2.30, CI=1.05–5.39, P=0.044). Conclusions: People initiated on medication for opioid use disorder who subsequently use stimulants appear to be more likely to return to and continue using non-prescribed opioids compared with those without stimulant use. The association appears to be stronger among patients who initiate buprenorphine compared with those who initiate extended-release naltrexone. Related protocols: CTN-0051, CTN-0067

Abstract:

Patients in treatment with medications for opioid use disorder (MOUD) often report use of other substances in addition to opioids. Few studies exist that examine the relationship between use at treatment entry and early non-opioid use in opioid treatment outcome.

In this study, researchers combined and harmonized three randomized, controlled MOUD clinical trials from the National Institutes of Drug Abuse (NIDA) Clinical Trials Network (CTN) (N=2,197) and investigated the association of non-opioid substance use at treatment entry and during early treatment with a return to opioid use. The trials (CTN-0027 [START], CTN-0030 [POATS], and CTN-0051 [X:BOT]) compared MOUD treatment (buprenorphine, methadone, extended-release naltrexone) in populations with opioid use disorder (OUD). Non-opioid substances were identified through harmonizing self-reported use. The primary outcomes were markers of return to opioid use by 12 weeks.

When treatment cohorts were adjusted, no association between self-reported treatment entry use of non-opioid substances and week-12 opioid use was detected. During the first month of treatment, higher use of cocaine and amphetamine was found to be associated with higher likelihood of illicit opioid use by week 12. Exploratory analyses of potential treatment cohort-by-predictor interactions showed that those with heavier cocaine use had a lower rate of returning to opioid use in the extended-release naltrexone group than in the methadone group.

Conclusions: Substance use other than opioids at treatment entry is not associated with relapse. Use of cocaine or amphetamines during the first few weeks of MOUD treatment may signal a worse outcome, suggesting a need for additional interventions.

Related protocols: CTN-0027, CTN-0030, CTN-0051

Abstract:

Methamphetamine use is increasing among persons with opioid use disorder (OUD). The study aims were to describe methamphetamine/amphetamine (MA/A) use among patients treated for OUS with buprenorphine/naloxone (BUP-NX) or extended-release naltrexone (XR-NTX), and to explore associations between treatment arm and MA/A use.

The study used data from the CTN X:BOX trial (CTN-0059), a multi-site, open-label, randomized controlled trial of XR-NTX vs. BUP-NX for 24 weeks. The outcome variable was MA/A use defined by either positive urine drug toxicology or self-report. The main predictor was treatment assignment (BUP-NX vs. XR-NTX). Longitudinal mixed-effects logistic regression models were fit to model the odds of MA/A use during the study. Additional predictors included study visit and baseline MA/A use.

Among the sample of 570 participants with OUD, baseline use of MA/A was observed in 105 (18.4%). There was no significant treatment effect over the study period, though BUP-NX subjects, on average, had about half the odds of MA/A use compared to XR-NTX subjects. In the same model, baseline MA/A use and study visit were both significantly associated with MA/A use over time.

Conclusions: In this sample of treated OUD patients, nearly a fifth (18.4%) of participants had MA/A use at baseline and the frequency of use did not decline over time: in fact, the odds of use slightly increased for each later visit. These secondary analyses found no significant difference in MA/A use between BUP-NX and XR-NTX treatment arms, however, the observation of less MA/A in the buprenorphine arm merits further investigation.

Related protocols: CTN-0051

Abstract:

Concurrent use of amphetamine-type stimulants among individuals with opioid use disorder can exacerbate social and medical harms, including overdose risk. This study evaluated rates of amphetamine-type stimulant use among patients with untreated opioid use disorder presenting at emergency departments in Baltimore, MD; New York, NY; Cincinnati, OH; and Seattle, WA.

Emergency department (ED) patients with untreated opioid use disorder (N=396) and enrolled between February 2017 and January 2019 in a multisite hybrid type III implementation science study (CTN-0069, Opioid Use Disorder in the Emergency Department) were evaluated for concurrent amphetamine-type stimulant use. Individuals with urine tests positive for methamphetamine, amphetamine, or both were compared with amphetamine-type stimulant-negative patients.

Overall, 38% of patients (150/396) were amphetamine-type stimulant positive; none reported receiving prescribed amphetamine or methamphetamine medications. Amphetamine-type stimulant-positive versus -negative patients were younger: mean age was 36 years versus 40 years. Other differences: 69% versus 46% were white, 65% versus 54% were unemployed, 67% versus 49% had unstable housing, 47% versus 25% reported an incarceration during 1 year before study admissions, 60% versus 45% were hepatitis C positive, 79% versus 47% reported drug injection during 1 month before study admission, and 42% versus 29% presented to the ED for an injury. Lower proportions of amphetamine-type stimulant-positive patients had cocaine-positive urine test results (33% versus 52%) and reported seeking treatment for substance use problems as a reason for their ED visit (10% versus 19%). All comparisons were statistically significant.

Conclusions: Amphetamine-type stimulant use among ED patients with untreated opioid use disorder was associated with distinct sociodemographic, social, and health factors. Improved ED-based screening, intervention, and referral protocols for patients with opioid use disorder and amphetamine-type stimulant use are needed.

Related protocols: CTN-0069

Abstract:

This study, supported in part by a CTN Invest Fellowship awarded to the first author, aimed to assess the prevalence of non-opioid drug use among opioid-addicted buprenorphine injecting individuals in Georgia (former Soviet republic), during and after a 12-week course of buprenorphine-naloxone (Suboxone) or methadone. This randomized, controlled trial used daily observed Suboxone or methadone and weekly counseling, urine tests, and Timeline Followback (TLFB) in weeks 0-12, and 20, as well as the Addiction Severity Index (ASI) at weeks 0, 4, 8, 12, and 20. Of the 80 patients (40/group, 4 women), 68 (85%) completed the 12 weeks of study treatment and 66 (82.5%) completed the 20 week follow-up.

At baseline, injecting more than one drug in the last 30 days was reported by 68.4% of patients in the methadone and 72.5% in the Suboxone groups. Drug use was markedly reduced in both treatment conditions, but there were significant differences in the prevalence of specific drugs with more opioid (1.5 vs. 0.2%; p = 0.03), less amphetamine (0.2 vs. 2.8%; p < 0.001) and less marijuana (1.7 vs. 10.2%; p < 0.001) positive urine tests in the methadone vs. Suboxone groups. At the 20 week follow-up, TLFB results on the 34 that continued methadone or the 3 on Suboxone showed less opioid (5.6 vs. 27.6%; p < 0.001), illicit buprenorphine (2.7 vs. 13.8%; p = 0.005), benzodiazepine (13.5 vs. 34.5%; p < 0.001), and marijuana (2.8 vs. 20.7%; p < 0.001) use than the 29 who did not continue opioid substitution therapy.

Conclusions: Daily observed methadone or buprenorphine-naloxone therapy with weekly counseling was markedly effective in reducing not only opioid use, but use of other psychoactive substances in Georgia, though there was more non-opioid use in patients treated with Suboxone, and more opioid use in patients treated with methadone. As in other settings, stopping opioid substitution therapy was associated with relapse to non-prescribed and other drug use.

Abstract:

Research over the past 20 years has shown that methadone maintenance (MET) reduces opioid use and is an effective HIV risk reduction intervention. Like methadone, treatment with buprenorphine-naloxone (BUP) also appears to reduce HIV risk. To date, only one study has compared HIV risk in patients receiving MET versus BUP. This article reports on a similar comparison of a much larger samples in a secondary analysis of data from the National Drug Abuse Treatment Clinical Trials Network (CTN) protocol “Starting Treatment with Agonist Replacement Therapies (START).” START was a randomized, open-label phase 4 study in participants entering opioid agonist treatment programs throughout the country that aimed to compare the effect of BUP and MET on liver function. The Risk Behavior Survey (RBS) was administered to participants, measuring past 30-day HIV risk, at baseline and weeks 12 and 24.

Among the 529 patients randomized to MET, 391 (74%) were completers; among the 740 randomized to BUP, 340 (46%) were completers; 700 completed the RBS. There were significant reductions in injecting risk with no differences between groups in mean number of times reporting injecting heroin, speedball, other opiates, and number of injections. There were also no differences between groups in terms of percent who shared needles, did not clean shared needles with bleach, shared cookers, or engaged in front/back loading of syringes. The percent having multiple sex partners decreased equally in both groups. For males on BUP, the sex risk composite increased; for males on MET, the sex risk decreased, resulting in significant group differences over time. For females there was a significant reduction in sex risk with no group differences.

Conclusions: Among MET and BUP patients who remained in treatment, HIV injecting risk was equally and markedly reduced, however MET retained more patients. Sex risk was equally and significantly reduced among females in both treatment conditions, but increased for males on BUP and decreased for males on MET. Overall, these findings further support the important of expanding availability of evidence-based medical treatments for opioid addiction.

Related protocols: CTN-0027

Abstract:

A substantial number of substance abusers entering outpatient psychosocial counseling treatment are referred from the criminal justice (CJ) system. This secondary analysis of previously published findings from National Drug Abuse Treatment Clinical Trials Network (CTN) protocol CTN-0006 (Motivational Incentives for Enhanced Drug Abuse Recovery: Drug Free Clinics), a large, multi-site trial of a prize-based abstinence incentive intervention, examined the influence of CJ referral on usual care outcomes and response to the incentive procedure. CJ referrals (n=138) were more likely than those not CJ referred (n=277) to provide stimulant negative urine samples whether missing samples were counted as positive or as missing. A significant interaction term was found only for percentage of treatment completers (p=0.27). On that retention variable, and three additional drug use measures, significant incentive effects were confined to participants who entered treatment without referral from the criminal justice system. Nevertheless, there were trends toward better retention and less drug use in CJ referrals who received abstinence incentives as well.

Conclusions: This study suggests that abstinence incentives should be offered as a first priority to stimulant users entering treatment without criminal justice referral. However, incentives can also be considered for use with criminal justice-referred stimulant users, based on the observation that best outcomes were obtained in CJ referrals who also received the abstinence incentive program.

Related protocols: CTN-0006

Abstract:

Stimulant users who sought treatment in a psychosocial outpatient treatment program participated in a multi-site 12-week randomized controlled trial (n=415) of a prize-based abstinence incentive intervention. Primary study outcomes were published previously (Petry et al., 2005); the present analysis examined the influence of criminal justice referral on treatment retention and stimulant use. In this study, participants were categorized based on study condition (incentives vs. usual care) and whether they were referred to treatment by the criminal justice system. Analyses assessed the separate and interactive effects of these factors on retention and stimulant use. Participants referred from the criminal justice system were more likely to be retained in treatment and to provide stimulant negative urine samples than those not referred from criminal justice. There was a significant interaction of criminal justice referral and incentives on treatment retention. Among voluntary referrals, those receiving abstinence incentives submitted 11.2 negative urines on average vs. 7.8 submitted by those in usual care. Among criminal justice referrals, mean number of negative urines submitted was 12.5 in those who received abstinence incentives vs. 10.3 in usual care.

Conclusions: Abstinence incentives significantly improved outcomes in voluntary but not in criminal justice referred admissions to outpatient treatment, probably due to higher base rates of retention and abstinence in the CJ referrals. Nevertheless, an additive effect of external motivation sources was seen with best outcomes in those exposed to both positive (abstinence incentives) and negative (CJ monitoring and sanctions) motivators and worst outcomes in those with neither source of external motivation.

Abstract:

This article reports on an ancillary investigation of data from protocols CTN-0001 and CTN-0002 (Buprenorphine/Naloxone versus Clonidine for Inpatient/Outpatient Opiate Detoxification). The sample included 343 opioid-dependent adults enrolled in the protocols. Researchers examined associations between depressive symptoms, co-occurring substance use (i.e., the use of substances other than opioids), and HIV-related sexual and injection risk behaviors. Data were collected using the Addiction Severity Index and the HIV Risk Behavior Scale, and analyzed using linear regression. Depressive symptoms were associated with an increased level of injection risk behaviors but were not associated with risky sexual behaviors. The co-occurring use of amphetamines also increased the likelihood of risky sexual behaviors.

Conclusions: Treatment of depression can make a contribution to decreasing injection risk among opioid-dependent injection drug users, especially if combined with other risk reduction interventions. This study also revealed that noninjecting amphetamine use was independently associated with sexual risk behaviors among opioid-dependent individuals.

Supported by the Duke Clinical Research Institute (CTN DSC 1).

Related protocols: CTN-0001, CTN-0002

Abstract:

Selection of appropriate outcome measures is important for clinical studies of drug addiction treatment. Researchers use various methods for collecting drug use outcomes and must consider substances to be included in a urine drug screen (UDS), accuracy of self-report, use of various instruments and procedures for collecting self-reported drug use, and timing of outcome assessments. This study sought to define a set of candidate measures to (1) assess their intercorrelation and (2) identify any differences in results. To that end, data were combined from seven completed protocols in the National Drug Abuse Treatment Clinical Trials Network (CTN), with a total of 1897 participants. Nine outcome measures were defined, based on UDS, self-report, or a combination, then multivariable, multilevel generalized estimating equation models were used to assess subgroup differences in intervention success, controlling for baseline differences and accounting for clustering by CTN protocols. Results found high correlations among all candidate outcomes. All outcomes showed consistent overall results with no significant intervention impact on drug use during follow-up. However, with most UDS variables, but not with self-report or “corrected self-report,” a significant gender–ethnicity interaction with benefit shown in African American women, White women, and Hispanic men was observed.

Conclusions: Despite strong associations between candidate measures, important differences in results were found. This study demonstrates the potential utility and impact of combining UDS and self-report data for drug use assessment. The results suggest possible differences in intervention efficacy by gender and ethnicity, but highlight the need to cautiously interpret observed interactions. Additional studies like this one will help guide implementation of methodological recommendations to construct combined measures.

Abstract:

There is need to improve treatment effectiveness for stimulant misusers, and one means of doing so is by tailoring services to account for the common diagnostic comorbidities and psychosocial challenges this population can face. Using its publicly available datasets, this CTN-approved secondary analysis project examined prevalence of alcohol use disorders (AUDs) among primary stimulant misusing treatment-seekers as well as impact of AUD comorbidity on their pre-treatment psychosocial functioning. Upon identifying a primary stimulant misuser subsample (N = 1133) from among aggregated treatment-seekers across eight CTN trials, diagnostic data were used to document lifetime AUD rates. Paired comparisons, stratified by stimulant drug type (e.g., amphetamine, cocaine) then tested the influence of AUD comorbidity on psychosocial indices from the Addiction Severity Index–Lite. A high AUD rate (45%) was found in this client population. Among primary cocaine misusers, those with AUD were more likely to: (1) show elevated Addiction Severity Index composite scores, (2) perceive greater importance of drug treatment, and (3) endorse psychiatric symptoms and perceived need for their treatment. Among primary amphetamine misusers, those with AUD were more likely to endorse specific psychiatric symptoms.

Conclusions: Study findings document AUD comorbidity as a fairly common diagnostic feature of primary stimulant misusers, and suggest it is a pervasive influence on the pre-treatment psychosocial functioning of cocaine misusers. This study demonstrates the utility of CTN common assessment battery for secondary analysis projects, though challenges noted during its conduct highlight the value of consistent data collection and documentation within and across CTN trials.

Related protocols: CTN-0004, CTN-0006, CTN-0007, CTN-0009, CTN-0013, CTN-0017, CTN-0018, CTN-0019

Abstract:

In response to the rising rate of treatment admissions related to illicit use of amphetamines (e.g., methamphetamine), this ancillary investigation examined the prevalence of amphetamine use among treatment-seeking, opioid-dependent adults, explored whether amphetamine users were as likely as non-amphetamine users to enroll in opioid-dependence treatment trials, and determined whether amphetamine users manifested greater levels of medical and psychiatric comorbidity than nonusers. The sample included 1257 opioid-dependent adults screened for participation in three multisite studies of the National Drug Abuse Treatment Clinical Trials Network (protocols CTN-0001, -0002, and -0003), which studied the effectiveness of buprenorphine for opioid detoxification under varying treatment conditions. Five mutually exclusive groups were examined, i.e., nonusers, current amphetamine injectors, current amphetamine non-injectors, former amphetamine injectors, and former amphetamine non-injectors Of the sample, 22.3% had a history of regular amphetamine use; of those users, 30.3% reported injection as their primary route. Amphetamine users were as likely as nonusers to enroll in treatment trials. Bivariate analyses indicated elevated rates of psychiatric problems (depression, anxiety, etc.) and medical illnesses (dermatological, hepatic, etc.) among amphetamine users. After adjusting for demographic variables and lifetime use of other substances: current amphetamine users and former injectors showed an increased likelihood of having medical illnesses and hospitalizations; current injectors had elevated odds of suicidal thoughts or attempts; current non-injectors had exhibited elevated odds of anxiety, cognitive impairment, and violent behaviors; and former non-injectors had increased odds of depression.

Conclusions: Treatment-seeking, amphetamine-using, opioid-dependent adults manifest greater levels of medical and psychiatric morbidity than treatment-seeking, opioid-dependent adults who have not used amphetamines, indicating a greater need for intensive clinical management.

Supported by the Duke Clinical Research Institute (CTN DSC 1).

Abstract:

Accumulating evidence indicates important gender differences in substance use disorders. Little is known, however, about gender differences and opioid use disorders. This study aimed to compared demographic characteristics, substance use severity, and other associated areas of functioning (as measured by the Addiction Severity Index-Lite (ASI-Lite)) among opioid-dependent men and women participating in a multisite effectiveness trial. Participants were 892 adults screened for the National Drug Abuse Treatment Clinical Trials Network (CTN) investigation of the effectiveness of two buprenorphine tapering schedules (protocol CTN-0003). The majority of men and women tested positive for oxycodone (68% and 65%, respectively) and morphine (89% each). More women than men tested positive for amphetamines (4% vs. 1%, p < .01), methamphetamine (11% vs. 4%, p < .01), and phencyclidine (8% vs. 4%, p = .02). More men than women tested positive for methadone (11% vs. 6%, p = .05) and marijuana (22% vs. 15%, p = .03). Craving for opioids was significantly higher among women (p < .01). Men evidenced higher alcohol (p < .01) and legal (p = .04) ASI composite scores, whereas women had higher drug (p < .01), employment (p < .01), family (p < .01), medical (p < .01), and psychiatric (p < .01) ASI composite scores. Women endorsed significantly more current and past medical problems.

Conclusions: Important gender differences in the clinical profiles of opioid-dependent individuals were observed with regard to substance use severity, craving, medical conditions, and impairment in associated areas of functioning. The findings enhance understanding of the characteristics of treatment-seeking men and women with opioid dependence, and may be useful in improving identification, prevention, and treatment efforts for this challenging and growing population.

Related protocols: CTN-0003