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.

Predicting in-treatment performance and post-treatment outcomes in methamphetamine users.

AIMS: This study examines the utility of individual drug use and treatment characteristics for predicting in-treatment performance and post-treatment outcomes over a 1-year period. DESIGN, SETTING AND PARTICIPANTS: Data were collected from 420 adults who participated in the Methamphetamine Treatment Project (MTP), a multi-site study of randomly assigned treatment for methamphetamine dependence. Interviews were conducted at baseline, during treatment and during three follow-up time-points: treatment discharge and at 6 and 12 months following admission. MEASUREMENTS: The Addiction Severity Index (ASI); the Craving, Frequency, Intensity and Duration Estimate (CFIDE); and laboratory urinalysis results were used in the current study. FINDINGS: Analyses addressed both in-treatment performance and post-treatment outcomes. The most consistent finding is that pre-treatment methamphetamine use predicts in-treatment performance and post-treatment outcomes. No one variable predicted all in-treatment performance measures; however, gender, route of administration and pre-treatment methamphetamine use were significant predictors. Similarly, post-treatment outcomes were predicted by a range of variables, although pre-treatment methamphetamine use was significantly associated with each post-treatment outcome. CONCLUSIONS: These findings provide useful empirical information about treatment outcomes for methamphetamine abusers, and highlight the utility of assessing individual and in-treatment characteristics in the development of appropriate treatment plans.

Utilizing a Two-stage Design to Investigate the Safety and Potential Efficacy of Monthly Naltrexone Plus Once-daily Bupropion as a Treatment for Methamphetamine Use Disorder.

OBJECTIVES: This 2-stage open-label pilot study evaluated the safety and potential efficacy of naltrexone + bupropion as a pharmacotherapy for methamphetamine (MA) use disorder. METHODS: The study was conducted in 2 stages of recruitment across 3 sites; 20 participants were enrolled in stage 1 and 29 participants were enrolled in stage 2. Eight weeks of open-label pharmacotherapy with a combination of extended-release injectable naltrexone (XR-NTX; Vivitrol) plus extended-release oral bupropion (BRP; Wellbutrin XL) were provided with a smartphone-assisted medication adherence platform. Participants met Diagnostic and Statistical Manual of Mental Disorders, 5th Edition criteria for severe MA use disorder, self-reported ≥20 days of MA use in the 30 days prior to consent, and submitted 3 MA-positive urine drug screens (UDS) out of 4 collected during screening. Participants attended clinic twice weekly for observed BRP dosing, UDS testing, assessments, and medical management; XR-NTX was administered at weeks 1 and 5. A BRP taper and follow-up visit occurred in week 9. RESULTS: Analyses evaluated effects of XR-NTX + BRP to determine the number of "responders" according to a statistically predefined response criterion (6 of 8 MA-negative UDS during the last 4 weeks of medication). The 2-stage design required that stage 1 yield ≥3 responders to continue to stage 2; 11 of the 49 participants met responder criteria across both stages (5 in stage 1, 6 in stage 2). CONCLUSIONS: Under the statistical analysis plan, study "success" required ≥9 responders. With 11 responders, the study demonstrated sufficient potential of naltrexone plus bupropion as a combination pharmacotherapy for MA use disorder to warrant further study.

Buprenorphine + naloxone plus naltrexone for the treatment of cocaine dependence: the Cocaine Use Reduction with Buprenorphine (CURB) study.

AIMS: To examine the safety and effectiveness of buprenorphine + naloxone sublingual tablets (BUP, as Suboxone(®) ) provided after administration of extended-release injectable naltrexone (XR-NTX, as Vivitrol(®) ) to reduce cocaine use in participants who met DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse. METHODS: This multi-centered, double-blind, placebo-controlled study, conducted under the auspices of the National Drug Abuse Treatment Clinical Trials Network, randomly assigned 302 participants at sites in California, Oregon, Washington, Colorado, Texas, Georgia, Ohio, New York and Washington DC, USA to one of three conditions provided with XR-NTX: 4 mg/day BUP (BUP4, n = 100), 16 mg/day BUP (BUP16, n = 100, or no buprenorphine (placebo; PLB, n = 102). Participants received pharmacotherapy for 8 weeks, with three clinic visits per week. Cognitive behavioral therapy was provided weekly. Follow-up assessments occurred at 1 and 3 months post-intervention. The planned primary outcome was urine drug screen (UDS)-corrected, self-reported cocaine use during the last 4 weeks of treatment. Planned secondary analyses assessed cocaine use by UDS, medication adherence, retention and adverse events. RESULTS: No group differences were found between groups for the primary outcome (BUP4 versus PLB, P = 0.262; BUP16 versus PLB, P = 0.185). Longitudinal analysis of UDS data during the evaluation period using generalized linear mixed equations found a statistically significant difference between BUP16 and PLB [P = 0.022, odds ratio (OR) = 1.71] but not for BUP4 (P = 0.105, OR = 1.05). No secondary outcome differences across groups were found for adherence, retention or adverse events. CONCLUSIONS: Buprenorphine + naloxone, used in combination with naltrexone, may be associated with reductions in cocaine use among people who meet DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse.

Replicating the Addicted-Self Model of recovery.

The purpose of this investigation is to replicate previous studies supporting a developing model of recovery from alcohol and drug addiction, the Addicted-Self Model [Fiorentine & Hillhouse, 2000c; Journal of Drug Issues 31 (2002a) 395; American Journal on Addictions (2002b) in press]. Data was utilized from the first phase of the Los Angeles Target Cities Treatment Enhancement Evaluation, a 2-year prospective study of 260 alcohol and drug treatment outpatients. The Addicted-Self Model is briefly outlined and four hypotheses are tested. Consistent with the assumptions of the model, low controlled use self-efficacy and a decline in controlled use self-efficacy over time predicts: (1) higher levels of the perceived certainty of negative consequences resulting from continued alcohol and drug use, (2) higher levels of abstinence acceptance, and (3) higher rates of abstinence from alcohol and drug use. Also consistent with the Addicted-Self Model, high controlled use self-efficacy does not predict lower levels of alcohol and drug use for those who relapse or continue to use these substances. These findings replicate previous findings supporting the developing Addicted-Self Model of recovery. Study limitations and directions for future research are discussed.

Why extensive participation in treatment and twelve-step programs is associated with the cessation of addictive behaviors: an application of the addicted-self model of recovery.

Applying the Addicted-Self Model of recovery to explain why extensive participation in recovery activities predicts abstinence, it was hypothesized that high levels of participation in treatment and Twelve-step programs promote abstinence because these activities reinforce the notion that controlled use is not possible for dependent alcohol and drug users. Findings from a prospective treatment outcomes study (n = 356) indicate general support for this hypothesis. Yet the cognitive transformation described by the Addicted-Self Model involving acknowledgement of loss of control over alcohol and other drugs is only a partial explanation of why extensive participation in recovery activities promotes recovery. Reiterating the conclusion that "more is better," frequent counseling participation, treatment completion, and weekly or more frequent participation in Twelve-Step programs promote absti- nence independently from their influence on controlled use self-efficacy. Theoretical and clinical implications, and directions for future research are discussed.

An intronic variant in OPRD1 predicts treatment outcome for opioid dependence in African-Americans.

Although buprenorphine and methadone are both effective treatments for opioid dependence, their efficacy can vary significantly among patients. Genetic differences may explain some of the variability in treatment outcome. Understanding the interactions between genetic background and pharmacotherapy may result in more informed treatment decisions. This study is a pharmacogenetic analysis of the effects of genetic variants in OPRD1, the gene encoding the δ-opioid receptor, on the prevalence of opioid-positive urine tests in African-Americans (n=77) or European-Americans (n=566) undergoing treatment for opioid dependence. Patients were randomly assigned to treatment with either methadone or buprenorphine/naloxone (Suboxone) over a 24-week open-label clinical trial, in which illicit opioid use was measured by weekly urinalysis. In African-Americans, the intronic SNP rs678849 predicted treatment outcome for both medications. Methadone patients with the CC genotype were less likely to have opioid-positive urine tests than those in the combined CT and TT genotypes group (relative risk (RR)=0.52, 95% confidence interval (CI)=0.44-0.60, p=0.001). In the buprenorphine treatment group, however, individuals with the CC genotype were more likely to have positive opioid drug screens than individuals in the combined CT and TT genotypes group (RR=2.17, 95% CI=1.95-2.68, p=0.008). These findings indicate that the genotype at rs678849 predicts African-American patient response to two common treatments for opioid dependence, suggesting that matching patients to treatment type based on the genotype at this locus may improve overall treatment efficacy. This observation requires confirmation in an independent population.

Buprenorphine/naloxone and methadone maintenance treatment outcomes for opioid analgesic, heroin, and combined users: findings from starting treatment with agonist replacement therapies (START).

OBJECTIVE: The objective of this secondary analysis was to explore differences in baseline clinical characteristics and opioid replacement therapy treatment outcomes by type (heroin, opioid analgesic [OA], or combined [heroin and OA]) and route (injector or non-injector) of opioid use. METHOD: A total of 1,269 participants (32.2% female) were randomized to receive one of two study medications (methadone or buprenorphine/naloxone [BUP]). Of these, 731 participants completed the 24-week active medication phase. Treatment outcomes were opioid use during the final 30 days of treatment (among treatment completers) and treatment attrition. RESULTS: Non-opioid substance dependence diagnoses and injecting differentiated heroin and combined users from OA users. Non-opioid substance dependence diagnoses and greater heroin use differentiated injectors from non-injectors. Further, injectors were more likely to be using at end of treatment compared with non-injectors. OA users were more likely to complete treatment compared with heroin users and combined users. Non-injectors were more likely than injectors to complete treatment. There were no interactions between type of opioid used or injection status and treatment assignment (methadone or BUP) on either opioid use or treatment attrition. CONCLUSIONS: Findings indicate that substance use severity differentiates heroin users from OA users and injectors from non-injectors. Irrespective of medication, heroin use and injecting are associated with treatment attrition and opioid misuse during treatment. These results have particular clinical interest, as there is no evidence of superiority of BUP over methadone for treating OA users versus heroin users.

Pain and continued opioid use in individuals receiving buprenorphine-naloxone for opioid detoxification: secondary analyses from the Clinical Trials Network.

Pain complaints are common among individuals with opioid dependence. However, few studies investigate pain during opioid detoxification or the impact this pain has on continued opioid use. This secondary analysis utilized data from two Clinical Trials Network randomized controlled trials of buprenorphine-naloxone for short-term opioid detoxification to examine the extent to which pain was associated with continued opioid use during and immediately following a 13-day detoxification protocol. At follow-up, more severe pain was associated with a greater number of self-reported days of opioid use during the prior 30 days (p < .05) but was not associated with urine toxicology results collected at follow-up. These results, although mixed, have potentially important clinical implications for assessing and addressing pain during opioid detoxification. Pain that is experienced during and immediately following medically monitored detoxification may be associated with continued opioid use. These findings lend further support for continued research on pain among patients with opioid dependence.

The Addicted-Self Model of addictive behavior cessation: does it predict recovery for gender, ethnic, age and drug preference populations?

Although previous research provided empirical support for the main assumptions of the Addicted-Self (A-S) Model of recovery, it is not known whether the model predicts recovery for various gender, ethnic, age, and drug preference populations. It may be that the model predicts recovery only for some groups of addicts and should not be viewed as a general theory of the recovery process. Addressing this concern using data from the Los Angeles Target Cities Drug Treatment Enhancement Project, it was determined that only trivial population differences exist in the primary variables associated with the A-S Model. The A-S Model predicts abstinence with about the same degree of accuracy and parsimony for all populations. The findings indicate that the A-S Model is a general theory of drug and alcohol addictive behavior cessation.

When low self-efficacy is efficacious: toward an addicted-self model of cessation of alcohol- and drug-dependent behavior.

The relationship between self-efficacy and the cessation of alcohol- and drug-dependent behavior was examined in this study. Evidence suggests that the Relapse Prevention Approach may incorrectly specify a relationship between self-efficacy and recovery. Instead of high situational coping self-efficacy, it may be that the acknowledgment of a loss of control over alcohol and drug use, or low controlled use self-efficacy, promotes recovery because the addict embraces the need for lifelong abstinence. Findings from a prospective study of 356 drug treatment outpatients indicate that low controlled use self-efficacy predicted higher levels of abstinence acceptance independent from the possible influences of alcohol and drug use histories and treatment history. A decrease in controlled use self-efficacy overtime was associated with an increase in abstinence acceptance, and high and increasing levels of abstinence acceptance predicted alcohol and drug abstinence. Contrary to the Relapse Prevention Approach, controlled use self-efficacy does not predict severity or level of use for those who relapse or continue to use alcohol and other drugs. These findings suggest a new social-cognitive theory of recovery--the Addicted-Self Model. This model asserts that the cessation of alcohol- and drug-dependent behavior is more likely to occur when the addict attributes the loss of control over drug and alcohol use to a stable, permanent property of the self and embraces the need for life-long abstinence.