Treatment outcomes in opioid dependent patients with different buprenorphine/naloxone induction dosing patterns and trajectories.

BACKGROUND AND OBJECTIVES: Induction is a crucial period of opioid addiction treatment. This study aimed to identify buprenorphine/naloxone (BUP) induction patterns and examine their association with outcomes (opioid use, retention, and related adverse events [AEs]). METHODS: The secondary analysis of a study of opioid-dependent adults seeking treatment in eight treatment settings included 740 participants inducted on BUP with flexible dosing. RESULTS: Latent class analysis models detected six distinctive induction trajectories: bup1-started and remained on low; bup2-started low, shifted slowly to moderate; bup3-started low, shifted quickly to moderate; bup4-started high, shifted to low; bup5-started and remained on moderate; bup6-started moderate, shifted to high dose (Fig. 1). Baseline characteristics, including Clinical Opioid Withdrawal Scale (COWS), were important predictors of retention. When controlled for the baseline characteristics, bup6 participants were three times less likely to drop out the first 7 days than bup1 participants (adjusted hazard ratio (aHR) = .28, p = .03). Opioid use and AEs were similar across trajectories. Participants on ≥16 mg BUP compared to those on <16 mg at Day 28 were less likely to drop out (aHR = .013, p = .001) and less likely to have AEs during the first 28 days (aOR = .57, p = .03). DISCUSSION AND CONCLUSIONS: BUP induction dosing was guided by an objective measure of opioid withdrawal. Participants with higher baseline COWS whose BUP doses were raised more quickly were less likely to drop out in the first 7 days than those whose doses were raised slower. SCIENTIFIC SIGNIFICANCE: This study supports the use of an objective measure of opioid withdrawal (COWS) during BUP induction to improve retention early in treatment.

The construct and measurement equivalence of cocaine and opioid dependences: a National Drug Abuse Treatment Clinical Trials Network (CTN) study.

INTRODUCTION: Although DSM-IV criteria are widely used in making diagnoses of substance use disorders, gaps exist regarding diagnosis classification, use of dependence criteria, and effects of measurement bias on diagnosis assessment. We examined the construct and measurement equivalence of diagnostic criteria for cocaine and opioid dependences, including whether each criterion maps onto the dependence construct, how well each criterion performs, how much information each contributes to a diagnosis, and whether symptom-endorsing is equivalent between demographic groups. METHODS: Item response theory (IRT) and multiple indicators-multiple causes (MIMIC) modeling were performed on a sample of stimulant-using methadone maintenance patients enrolled in a multisite study of the National Drug Abuse Treatment Clinical Trials Network (CTN) (N=383). Participants were recruited from six community-based methadone maintenance treatment programs associated with the CTN and major U.S. providers. Cocaine and opioid dependences were assessed by DSM-IV Checklist. RESULTS: IRT modeling showed that symptoms of cocaine and opioid dependences, respectively, were arrayed along a continuum of severity. All symptoms had moderate to high discrimination in distinguishing drug users between severity levels. "Withdrawal" identified the most severe symptom of the cocaine dependence continuum. MIMIC modeling revealed some support for measurement equivalence. CONCLUSIONS: Study results suggest that self-reported symptoms of cocaine and opioid dependences and their underlying constructs can be measured appropriately among treatment-seeking polysubstance users.

An item response theory modeling of alcohol and marijuana dependences: a National Drug Abuse Treatment Clinical Trials Network study.

OBJECTIVE: The aim of this study was to examine psychometric properties of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), diagnostics criteria for alcohol and marijuana dependences among 462 alcohol users and 311 marijuana users enrolled in two multisite trials of the National Drug Abuse Treatment Clinical Trials Network. METHOD: Diagnostic questions were assessed by the DSM-IV checklist. Data were analyzed by the item response theory and the multiple indicators-multiple causes method procedures. RESULTS: Criterion symptoms of alcohol and marijuana dependences exhibited a high level of internal consistency. All individual symptoms showed good discrimination in distinguishing alcohol or marijuana users between high and low severity levels of the continuum. In both groups, "withdrawal" appeared to measure the most severe symptom of the dependence continuum. There was little evidence of measurement nonequivalence in assessing symptoms of dependence by gender, age, race/ethnicity, and educational level. CONCLUSIONS: These findings highlight the clinical utility of the DSM-IV checklist in assessing alcohol- and marijuana dependence syndromes among treatment-seeking substance users.

Serious adverse events in randomized psychosocial treatment studies: safety or arbitrary edicts?

Human subjects protection policies developed for pharmaceutical trials are now being widely applied to psychosocial intervention studies. This study examined occurrences of serious adverse events (SAEs) reported in multicenter psychosocial trials of the National Institute on Drug Abuse Clinical Trials Network. Substance-abusing participants (N = 1,687) were randomized to standard care or standard care plus either contingency management or motivational enhancement. Twelve percent of participants experienced 1 or more SAEs during the 27,198 person-weeks of follow-up. Of the 260 SAEs recorded, none were judged by the data safety monitoring board to be study related, and there were no significant differences between experimental and control conditions in SAE incidence rates. These data underscore the need to reconsider the rationale behind, and appropriate methods for, monitoring safety during psychosocial therapy trials.

Extended vs short-term buprenorphine-naloxone for treatment of opioid-addicted youth: a randomized trial.

CONTEXT: The usual treatment for opioid-addicted youth is detoxification and counseling. Extended medication-assisted therapy may be more helpful. OBJECTIVE: To evaluate the efficacy of continuing buprenorphine-naloxone for 12 weeks vs detoxification for opioid-addicted youth. DESIGN, SETTING, AND PATIENTS: Clinical trial at 6 community programs from July 2003 to December 2006 including 152 patients aged 15 to 21 years who were randomized to 12 weeks of buprenorphine-naloxone or a 14-day taper (detox). INTERVENTIONS: Patients in the 12-week buprenorphine-naloxone group were prescribed up to 24 mg per day for 9 weeks and then tapered to week 12; patients in the detox group were prescribed up to 14 mg per day and then tapered to day 14. All were offered weekly individual and group counseling. MAIN OUTCOME MEASURE: Opioid-positive urine test result at weeks 4, 8, and 12. RESULTS: The number of patients younger than 18 years was too small to analyze separately, but overall, patients in the detox group had higher proportions of opioid-positive urine test results at weeks 4 and 8 but not at week 12 (chi(2)(2) = 4.93, P = .09). At week 4, 59 detox patients had positive results (61%; 95% confidence interval [CI] = 47%-75%) vs 58 12-week buprenorphine-naloxone patients (26%; 95% CI = 14%-38%). At week 8, 53 detox patients had positive results (54%; 95% CI = 38%-70%) vs 52 12-week buprenorphine-naloxone patients (23%; 95% CI = 11%-35%). At week 12, 53 detox patients had positive results (51%; 95% CI = 35%-67%) vs 49 12-week buprenorphine-naloxone patients (43%; 95% CI = 29%-57%). By week 12, 16 of 78 detox patients (20.5%) remained in treatment vs 52 of 74 12-week buprenorphine-naloxone patients (70%; chi(2)(1) = 32.90, P < .001). During weeks 1 through 12, patients in the 12-week buprenorphine-naloxone group reported less opioid use (chi(2)(1) = 18.45, P < .001), less injecting (chi(2)(1) = 6.00, P = .01), and less nonstudy addiction treatment (chi(2)(1) = 25.82, P < .001). High levels of opioid use occurred in both groups at follow-up. Four of 83 patients who tested negative for hepatitis C at baseline were positive for hepatitis C at week 12. CONCLUSIONS: Continuing treatment with buprenorphine-naloxone improved outcome compared with short-term detoxification. Further research is necessary to assess the efficacy and safety of longer-term treatment with buprenorphine for young individuals with opioid dependence. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00078130.

Infrequent illicit methadone use among stimulant-using patients in methadone maintenance treatment programs: a national drug abuse treatment clinical trials network study.

We sought to determine the prevalence, patterns, and correlates of past-month illicit methadone use and history of regular illicit use among stimulant-using methadone maintenance treatment patients. We obtained self-reported information on illicit methadone use from 383 participants recruited from six community-based methadone maintenance programs. Overall, 1.6% of participants reported illicit use in the past month, and 4.7% reported a history of regular use. Younger age and history of outpatient psychological treatment were associated with increased odds of past-month illicit use. Illicit methadone use among patients in maintenance programs is infrequent; however, a number of factors may increase risk of illicit use.

Abstinence-based incentives in methadone maintenance: interaction with intake stimulant test results.

Baseline drug use detected in urine toxicology has been shown to predict drug abuse treatment outcome, including response to contingency management interventions with drug abstinence as their target. This study examined the association between baseline urine test result and treatment outcome in stabilized methadone maintenance patients with ongoing stimulant use to determine whether abstinence incentives were differentially effective in those testing stimulant negative versus positive at study entry. Participants were 386 methadone-maintained patients who took part in a National Drug Abuse Treatment Clinical Trials Network multisite study aimed at reducing stimulant abuse during treatment (J. M. Peirce et al., 2006). At study intake, 24% of participants tested stimulant negative and 76% tested positive. Those testing negative at entry submitted 82% negative urines during the study versus 36% for those testing positive at entry (odds ratio [OR] = 8.67; confidence interval [CI] = 5.81-12.94). Compared with those receiving usual care, the addition of abstinence incentives resulted in a significant increase in stimulant-negative urine samples submitted during the study both for those testing negative at study entry (OR = 2.27; CI = 1.13- 4.75) and for those testing positive (OR = 1.84; CI = 1.25-2.71). These findings suggest that abstinence incentives have significant clinical benefits independent of initial drug use severity among methadone maintenance patients with ongoing stimulant drug use.

Contingency management for the treatment of methamphetamine use disorders.

OBJECTIVE: Theory and some preliminary evidence suggest that contingency management may be an effective treatment strategy or adjunct to psychosocial treatment for methamphetamine use disorders. An experimentally rigorous investigation on the topic was provided by a large multisite trial conducted under the auspices of the Clinical Trials Network of the National Institute on Drug Abuse. METHOD: The authors report data on 113 participants who were diagnosed with methamphetamine abuse or dependence. They were randomly assigned to receive 12 weeks of either treatment as usual or treatment as usual plus contingency management. Urine samples were tested for illicit drugs, and breath samples were tested for alcohol. The reinforcers for drug-negative samples were plastic chips, some of which could be exchanged for prizes. The number of plastic chips drawn increased with each week of negative samples but was reset to one after a missed or positive sample. RESULTS: The participants in both groups remained in treatment for equivalent times, but those receiving contingency management in addition to usual treatment submitted significantly more negative samples, and they were abstinent for a longer period of time (5 versus 3 weeks). CONCLUSIONS: These results suggest that contingency management has promise as a component in treatment strategies for methamphetamine use disorder.

Effects of lower-cost incentives on stimulant abstinence in methadone maintenance treatment: a National Drug Abuse Treatment Clinical Trials Network study.

BACKGROUND: Contingency management interventions that provide tangible incentives based on objective indicators of drug abstinence have improved treatment outcomes of substance abusers, but have not been widely implemented in community drug abuse treatment settings. OBJECTIVE: To compare outcomes achieved when a lower-cost prize-based contingency management treatment is added to usual care in community methadone hydrochloride maintenance treatment settings. DESIGN: Random assignment to usual care with (n = 198) or without (n = 190) abstinence incentives during a 12-week trial. SETTING: Six community-based methadone maintenance drug abuse treatment clinics in locations across the United States. PARTICIPANTS: Three hundred eighty-eight stimulant-abusing patients enrolled in methadone maintenance programs for at least 1 month and no more than 3 years. INTERVENTION: Participants submitting stimulant- and alcohol-negative samples earned draws for a chance to win prizes; the number of draws earned increased with continuous abstinence time. MAIN OUTCOME MEASURES: Total number of stimulant- and alcohol-negative samples provided, percentage of stimulant- and alcohol-negative samples provided, longest duration of abstinence, retention, and counseling attendance. RESULTS: Submission of stimulant- and alcohol-negative samples was twice as likely for incentive as for usual care group participants (odds ratio, 1.98; 95% confidence interval, 1.42-2.77). Achieving 4 or more, 8 or more, and 12 weeks of continuous abstinence was approximately 3, 9, and 11 times more likely, respectively, for incentive vs usual care participants. Groups did not differ on study retention or counseling attendance. The average cost of prizes was 120 dollars per participant. CONCLUSION: An abstinence incentive approach that paid 120 dollars in prizes per participant effectively increased stimulant abstinence in community-based methadone maintenance treatment clinics.

Effect of prize-based incentives on outcomes in stimulant abusers in outpatient psychosocial treatment programs: a national drug abuse treatment clinical trials network study.

CONTEXT: Contingency management interventions that provide tangible incentives based on objective indicators of drug abstinence are efficacious in improving outcomes in substance abusers, but these treatments have rarely been implemented in community-based settings. OBJECTIVE: To evaluate the efficacy of an abstinence-based contingency management intervention as an addition to usual care in community treatment settings. DESIGN: Random assignment to usual care or usual care plus abstinence-based incentives for 12 weeks. SETTING: Eight community-based outpatient psychosocial drug abuse treatment programs. PARTICIPANTS: A total of 415 cocaine or methamphetamine users beginning outpatient substance abuse treatment. INTERVENTION: All participants received standard care, and those assigned to the abstinence-based incentive condition also earned chances to win prizes for submitting substance-free urine samples; the chances of winning prizes increased with continuous time abstinent. MAIN OUTCOME MEASURES: Retention, counseling attendance, total number of substance-free samples provided, percentage of stimulant- and alcohol-free samples submitted, and longest duration of confirmed stimulant abstinence. RESULTS: Participants assigned to the abstinence-based incentive condition remained in treatment for a mean +/- SD of 8.0 +/- 4.2 weeks and attended a mean +/- SD of 19.2 +/- 16.8 counseling sessions compared with 6.9 +/- 4.4 weeks and 15.7 +/- 14.4 sessions for those assigned to the usual care condition (P<.02 for all). Participants in the abstinence-based incentive condition also submitted significantly more stimulant- and alcohol-free samples (P<.001). The abstinence-based incentive group was significantly more likely to achieve 4, 8, and 12 weeks of continuous abstinence than the control group, with odds ratios of 2.5, 2.7, and 4.5, respectively. However, the percentage of positive samples submitted was low overall and did not differ between conditions. CONCLUSION: The abstinence-based incentive procedure, which provided a mean of 203 dollars in prizes per participant, was efficacious in improving retention and associated abstinence outcomes.

The effect of 12-step self-help group attendance and participation on drug use outcomes among cocaine-dependent patients.

OBJECTIVE: Although cocaine-dependent patients are frequently referred to 12-step self-help groups, little research has examined the benefits of 12-step group attendance in this population. Moreover, the distinction between attending meetings and actively participating in 12-step activities has not typically been examined. METHOD: In the National Institute on Drug Abuse Collaborative Cocaine Treatment Study, 487 cocaine-dependent outpatients were recruited at five sites for a randomized controlled trial of 24-week behavioral treatments. Study data were examined to see whether self-help attendance or active participation were related to subsequent drug use. RESULTS: Twelve-step group attendance did not predict subsequent drug use. However, active 12-step participation in a given month predicted less cocaine use in the next month. Moreover, patients who increased their 12-step participation during the first 3 months of treatment had significantly less cocaine use and lower ASI Drug Use Composite scores in the subsequent 3 months. Finally, Individual Drug Counseling, based on a 12-step model, and increasing levels of 12-step participation each offered discrete benefits. CONCLUSIONS: Results suggest that active 12-step participation by cocaine-dependent patients is more important than meeting attendance, and that a combination of Individual Drug Counseling and active 12-step participation is effective for these patients.

Selection of a substance use disorder diagnostic instrument by the National Drug Abuse Treatment Clinical Trials Network.

Several instruments for diagnosing substance use disorders (SUD) have been developed, but to date none has emerged as the standard for community-based clinical studies. To select the most suitable SUD diagnostic instrument for its clinical trials, the National Drug Abuse Treatment Clinical Trials Network (CTN) implemented a procedure in which 36 university-based addiction researchers and 62 community-based addiction treatment providers evaluated and ranked five widely recognized diagnostic instruments: (1) the SUD section of the Structured Clinical Interview for DSM-IV (SCID); (2) the SUD section of the Composite International Diagnostic Interview, 2nd ed. (CIDI-2); (3) the SUD section of the Diagnostic Interview Schedule for DSM-IV Diagnosis (DIS-IV); (4) the Diagnostic Statistical Manual-IV Checklist (DSM-IV Checklist); and (5) the Substance Dependence Severity Scale (SDSS). To assist the evaluation and ranking process, key characteristics of each instrument were presented in tabular and narrative formats. Participants ranked each instrument from 1 (most preferred) to 5 (least preferred). The SCID received the best overall mean score (2.24) followed by the CIDI-2 (2.59), DIS (2.94), DSM Checklist (3.40) and the SDSS (3.83). After discussing the pragmatic and scientific advantages and disadvantages of each instrument, the CTN Steering Committee selected the CIDI-2. The selection of the CIDI-2 standardizes the collection of diagnostic data and provides a common diagnostic tool for practitioners and clinical researchers in the CTN. Implications for practice/research collaboration and initiatives are explored.

Rates and symptoms of PTSD among cocaine-dependent patients.

OBJECTIVE: This study evaluated lifetime traumatic events and current posttraumatic stress disorder (PTSD) symptoms in a substance abuse sample. METHOD: Participants in the study consisted of 558 (75.1% male) cocaine-dependent individuals who completed self-report measures of trauma and PTSD symptoms prior to entry into treatment. RESULTS: Results showed a high number of lifetime traumatic events, even among those without PTSD. General disaster was the most prevalent. Current PTSD was found in 10.9% of the participants, with a significantly higher rate among women (21.6%) than among men (7.2%). For those with PTSD, the most prominent PTSD symptom cluster was arousal, and the most common symptoms were restricted affect, detachment and irritability. Participants with PTSD endorsed a large number of symptoms, almost double that needed to meet diagnostic criteria; however, neither number of traumas nor type of trauma was associated with their level of PTSD symptoms. Even among those not meeting PTSD criteria, subthreshold symptoms were found, with avoidance the most prominent cluster. Sociodemographic and recent cocaine use variables did not differentiate the PTSD from non-PTSD groups. CONCLUSIONS: PTSD is present in a sizeable percentage of cocaine-dependent treatment-seeking patients, particularly women. Clinicians might address arousal symptoms in particular, which were the most prominent symptom cluster, and which may be exacerbated by cocaine use. Even among those without PTSD, lifetime trauma is substantial and subthreshold PTSD symptoms are common. Vulnerability to PTSD needs further study, as sociodemographic and cocaine use variables did not distinguish between PTSD and non-PTSD groups.

The relationship between cocaine craving, psychosocial treatment, and subsequent cocaine use.

OBJECTIVE: Regular measurement of craving during treatment for cocaine dependence can monitor patients' clinical status and potentially assess their risk for drug use in the near future. Effective treatment can reduce the correlation between craving and subsequent drug use by helping patients abstain despite high craving. This study examined the relationship between cocaine craving, psychosocial treatment, and cocaine use in the ensuing week. METHOD: In the National Institute on Drug Abuse Collaborative Cocaine Treatment Study, which compared four psychosocial treatments for cocaine dependence, a three-item craving questionnaire was administered weekly to 449 patients to see whether it predicted cocaine use in the ensuing week. Cocaine use was assessed with self-reports and urine screening. RESULTS: With control for the previous week's cocaine use, a higher composite score on the craving questionnaire was associated with greater likelihood of cocaine use in the subsequent week; each 1-point increase on the composite score of the craving questionnaire increased the likelihood of cocaine use in the ensuing week by 10%. However, among patients who received individual plus group drug counseling, the treatment condition with the best overall cocaine use outcome, increased craving scores were not associated with greater likelihood of cocaine use in the subsequent week. CONCLUSIONS: A three-item cocaine craving questionnaire predicted the relative likelihood of cocaine use during the subsequent week. Moreover, the relationship between craving and subsequent cocaine use varied by treatment condition, suggesting that the most effective treatment in the study might have weakened the link between craving and subsequent use.

HIV risk reduction in the National Institute on Drug Abuse Cocaine Collaborative Treatment Study.

HIV risk was evaluated among 487 cocaine-dependent patients recruited from five treatment programs in a trial that examined the efficacy of four outpatient-based psychosocial treatments. Treatments were offered two to three times per week for 6 months and consisted of group drug counseling (GDC) or group counseling plus individual drug counseling (IDC), cognitive therapy (CT), or supportive-expressive therapy (SE). The average patient had used cocaine for 7 years, with 10 days of use in the last month. Crack smoking was the main route in 79%, and HIV risk was mainly due to multiple partners and unprotected sex. Treatment was associated with a decrease in cocaine use from an average of 10 days per month at baseline to 1 day per month at 6 months. Reduction in cocaine use was associated with an average 40% decrease in HIV risk across all treatment, gender, and ethnic groups, mainly as a result of fewer sexual partners and less unprotected sex. The combination of IDC and GDC was associated with an equal or even greater reduction in HIV risk than the other treatment conditions and thus shows promise as an effective HIV prevention strategy, at least for some patients.

Who starts treatment: engagement in the NIDA collaborative cocaine treatment study.

This study addressed the role of demographic variables, severity of drug dependence, and drug-related problems infacilitating or impeding engagement into a research treatment. Patients were tracked through various stages of entry for the research treatment: phone screening, intake, and randomization to treatment. Results suggested that certain demographic factors put patients more at risk for dropping out at intake and randomization. African-American and unemployed patients were less likely to stay in treatment at both stages, with largest differences at intake. Younger patients were less likely to complete both phases, with bigger differences noted at randomiZation. Patients with more days of cocaine use andpatients referred from advertisements were less likely to keep their intake appointments.

Retention in psychosocial treatment of cocaine dependence: predictors and impact on outcome.

This report describes retention in treatment in the National Institute on Drug Abuse Collaborative Cocaine Treatment Study (CCTS), a multi-site trial of four psychosocial treatments for 487 cocaine dependent patients. Younger, African-American, and unemployed patients were retained in treatment for fewer days than their counterparts. African-American patients who lived with a partner were retained in treatment for less time than if they lived alone. Higher psychiatric severity kept men in treatment longer but put women at risk for dropping out sooner. Patients who completed the full treatment used drugs less often than patients who dropped out, but outcome did not differ at each month. Patients in the drug counseling condition stayed in treatment for fewer days than patients in psychotherapy, but they were more likely to be abstinent after dropout. Patients with higher psychiatric severity were more at risk for continuing to use drugs after dropout.