Bupropion and Naltrexone in Methamphetamine Use Disorder.

BACKGROUND: The use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied. METHODS: We conducted this multisite, double-blind, two-stage, placebo-controlled trial with the use of a sequential parallel comparison design to evaluate the efficacy and safety of extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg per day) in adults with moderate or severe methamphetamine use disorder. In the first stage of the trial, participants were randomly assigned in a 0.26:0.74 ratio to receive naltrexone-bupropion or matching injectable and oral placebo for 6 weeks. Those in the placebo group who did not have a response in stage 1 underwent rerandomization in stage 2 and were assigned in a 1:1 ratio to receive naltrexone-bupropion or placebo for an additional 6 weeks. Urine samples were obtained from participants twice weekly. The primary outcome was a response, defined as at least three methamphetamine-negative urine samples out of four samples obtained at the end of stage 1 or stage 2, and the weighted average of the responses in the two stages is reported. The treatment effect was defined as the between-group difference in the overall weighted responses. RESULTS: A total of 403 participants were enrolled in stage 1, and 225 in stage 2. In the first stage, 18 of 109 participants (16.5%) in the naltrexone-bupropion group and 10 of 294 (3.4%) in the placebo group had a response. In the second stage, 13 of 114 (11.4%) in the naltrexone-bupropion group and 2 of 111 (1.8%) in the placebo group had a response. The weighted average response across the two stages was 13.6% with naltrexone-bupropion and 2.5% with placebo, for an overall treatment effect of 11.1 percentage points (Wald z-test statistic, 4.53; P<0.001). Adverse events with naltrexone-bupropion included gastrointestinal disorders, tremor, malaise, hyperhidrosis, and anorexia. Serious adverse events occurred in 8 of 223 participants (3.6%) who received naltrexone-bupropion during the trial. CONCLUSIONS: Among adults with methamphetamine use disorder, the response over a period of 12 weeks among participants who received extended-release injectable naltrexone plus oral extended-release bupropion was low but was higher than that among participants who received placebo. (Funded by the National Institute on Drug Abuse and others; ADAPT-2 ClinicalTrials.gov number, NCT03078075.).

Gender differences among treatment-seeking adults with cannabis use disorder: Clinical profiles of women and men enrolled in the achieving cannabis cessation-evaluating N-acetylcysteine treatment (ACCENT) study.

BACKGROUND AND OBJECTIVES: Recent evidence suggests that women may fare worse than men in cannabis trials with pharmacologic interventions. Identifying baseline clinical profiles of treatment-seeking cannabis-dependent adults could inform gender-specific treatment planning and development. METHODS: The current study compared baseline demographic, cannabis use, and psychiatric factors between women (n = 86) and men (n = 216) entering the Achieving Cannabis Cessation-Evaluating N-acetylcysteine Treatment (ACCENT) study, a multi-site, randomized controlled trial conducted within the National Drug Abuse Treatment Clinical Trials Network. RESULTS: Women reported greater withdrawal intensity (p = .001) and negative impact of withdrawal (p = .001), predominantly due to physiological and mood symptoms. Women were more likely to have lifetime panic disorder (p = .038) and current agoraphobia (p = .022), and reported more days of poor physical health (p = .006) and cannabis-related medical problems (p = .023). Women reporting chronic pain had greater mean pain scores than men with chronic pain (p = .006). Men and women did not differ on any measures of baseline cannabis use. DISCUSSION AND CONCLUSIONS: Cannabis-dependent women may present for treatment with more severe and impairing withdrawal symptoms and psychiatric conditions compared to cannabis-dependent men. This might help explain recent evidence suggesting that women fare worse than men in cannabis treatment trials of pharmacologic interventions. Baseline clinical profiles of treatment-seeking adults can inform gender-specific treatment planning and development. SCIENTIFIC SIGNIFICANCE: Cannabis-dependent women may benefit from integrated treatment focusing on co-occurring psychiatric disorders and targeted treatment of cannabis withdrawal syndrome.(Am J Addict 2017;26:136-144).

Smoking cessation treatment among patients in community-based substance abuse rehabilitation programs: exploring predictors of outcome as clues toward treatment improvement.

BACKGROUND: Predictors of smoking cessation (SC) treatment outcome were explored in a multisite clinical trial of SC treatment at community-based, outpatient, substance abuse rehabilitation programs affiliated with the National Drug Abuse Treatment Clinical Trials Network. OBJECTIVES: To explore baseline demographic and clinical predictors of abstinence during treatment. METHODS: Cigarette smokers from five methadone maintenance programs and two drug and alcohol dependence treatment programs were randomly assigned to SC treatment as an adjunct to substance abuse treatment as usual or to substance abuse treatment as usual. SC treatment consisted of group counseling (weeks 1-8) plus transdermal nicotine patch treatment (21 mg/day, weeks 1-6; 14 mg/day, weeks 7-8). Demographic and clinical predictors of smoking abstinence were evaluated among those patients assigned to the active SC condition (N = 153) using logistic regression. RESULTS: Abstinence during treatment was positively associated with younger age, Hispanic or Caucasian (as opposed to African American) ethnicity/race, employment or student status, fewer cigarettes per day at baseline, lower severity of the primary substance problem at baseline, and higher methadone doses (among the subsample in methadone treatment). CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: During future efforts to improve SC treatments among drug- and alcohol-dependent patients, consideration should be given to adequate treatment to reduce the severity of the primary drug or alcohol problem, tailoring treatments for patients with greater severity of smoking and of the primary substance problem, and culturally sensitive interventions. Analysis of predictors of outcome may be a useful tool for treatment development.

The relationship between depression and smoking cessation outcomes in treatment-seeking substance abusers.

The National Drug Abuse Treatment Clinical Trials Network (CTN) recently completed a randomized, open label trial comparing treatment as usual (TAU) combined with nicotine patches plus cognitive behavioral group counseling for smoking cessation (n = 153) to TAU alone (n = 72) for patients enrolled in treatment programs for drug or alcohol dependence, who were interested in quitting smoking. This report is a secondary analysis evaluating the effect of depressive symptomatology (n = 70) or history of depression (n = 110) on smoking cessation outcomes. A significant association was seen between measures of depression and difficulty quitting cigarettes. Specifically, there was a greater probability for smoking abstinence for those with lower baseline Beck Depression Inventory II (BDI-II) scores. These data suggest that evaluation and treatment of depressive symptoms may play an important role in improving smoking cessation outcomes. (Am J Addict 2010;00:1-8).

Overcoming non-compliance with clinical trial registration and results reporting: One Institution's approach.

ClinicalTrials.gov is a web-based resource which provides the general public, healthcare professionals, patients, and caregivers access to privately and publicly supported clinical trials and trial results. The web site is maintained by the National Library of Medicine (NLM) at the National Institutes of Health (NIH) (ClinicalTrials.gov Background, 2018). The penalties for non-compliance with the legal obligations under FDAAA 801 (Food and Drug Administration Amendments Act of 2007) and the NIH requirements for registering and reporting results on studies within certain timeframes can result in large monetary fines and the withholding of federal funds (ClinicalTrials.gov FDAAA 801 and the Final Rule, 2019). Years following, in 2016, the Final Rule expanded upon the requirement with additional data elements for both registration and result submission records in accordance of FDAAA 801 (ClinicalTrials.gov FDAAA 801 and the Final Rule, 2019). The Medical University of South Carolina (MUSC), along with the institution's Office of Clinical Research and Regulatory Knowledge & Support group, identified issues affecting their own compliance rate with FDAAA 801 and the NIH and implemented several processes to overcome these challenges. In short, these processes included hiring a designated full-time ClinicalTrials.gov coordinator, implementing a workflow that identifies trials early in the IRB approval process requiring registration (without effecting study start up timelines), assisting researchers when navigating the registration and results reporting process through one-on-one consultations, Lunch and Learns, and disseminating new training tools as they become available. Over the next 12 months the results of this approach demonstrated a marked increase to 98% overall compliance with these federal regulations which may provide valuable guidance for other institutions working toward improved compliance rates.

Depressive symptoms and cannabis use in a placebo-controlled trial of N-Acetylcysteine for adult cannabis use disorder.

RATIONALE: Depression is common among individuals with cannabis use disorder (CUD), particularly individuals who present to CUD treatment. Treatments that consider this comorbidity are essential. OBJECTIVES: The goal of this secondary analysis was to examine whether N-acetylcysteine (NAC) reduced depressive symptoms among adults (age 18-50) with CUD (N = 302) and whether the effect of NAC on cannabis cessation varied as a result of baseline levels of depression. Bidirectional associations between cannabis use amount and depression were also examined. METHODS: Data for this secondary analysis were from a National Drug Abuse Treatment Clinical Trials Network (NIDA CTN) multi-site clinical trial for CUD. Adults with CUD (N = 302) were randomized to receive 2400 mg of NAC daily or matched placebo for 12 weeks. All participants received abstinence-based contingency management. Cannabis quantity was measured by self-report, and weekly urinary cannabinoid levels (11-nor-9-carboxy-Δ9-tetrahydrocannabinol) confirmed abstinence. Depressive symptoms were measured by the Hospital Anxiety and Depression Scale. RESULTS: Depressive symptoms did not differ between the NAC and placebo groups during treatment. There was no significant interaction between treatment and baseline depression predicting cannabis abstinence during treatment. Higher baseline depression was associated with decreased abstinence throughout treatment and a significant gender interaction suggested that this may be particularly true for females. Cross-lagged panel models suggested that depressive symptoms preceded increased cannabis use amounts (in grams) during the subsequent month. The reverse pathway was not significant (i.e., greater cannabis use preceding depressive symptoms). CONCLUSIONS: Results from this study suggest that depression may be a risk factor for poor CUD treatment outcome and therefore should be addressed in the context of treatment. However, results do not support the use of NAC to concurrently treat co-occurring depressive symptoms and CUD in adults. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01675661.

Blunts versus joints: Cannabis use characteristics and consequences among treatment-seeking adults.

BACKGROUND: Despite the high prevalence of blunt smoking among cannabis users, very few studies examine the clinical profile of blunt smokers relative to those using more common methods of cannabis use, such as joints. METHODS: The current study uses baseline data from the ACCENT (Achieving Cannabis Cessation-Evaluating N-acetylcysteine Treatment) study, a multi-site randomized pharmacotherapy clinical trial within the National Drug Abuse Treatment Clinical Trials Network, to predict the association between blunt and joint use frequency and cannabis use characteristics (e.g., grams of cannabis used) and consequences (e.g., withdrawal) among past-month cannabis users (N = 377) who were screened for study participation. RESULTS: After controlling for race, age, gender, other forms of cannabis use (including joint use) and nicotine dependence, multivariable linear regression models indicated that the number of days of blunt use in the past month was a significant predictor of the average amount of cannabis per using day (t = 3.04, p < .01), the estimated average cost of cannabis (t = 2.28, p < .05) and Cannabis Withdrawal Scale scores (t = 1.94, p < .05). Frequency of joint use did not significantly predict any of the cannabis use characteristics or consequences. CONCLUSIONS: Blunt smokers may present to treatment with greater amounts of cannabis smoked and more intense withdrawal symptoms, which may adversely impact their likelihood of successful abstinence. Cannabis-dependent blunt smokers may be more likely to benefit from treatment that targets physiological and mood-related withdrawal symptoms.

Smoking cessation treatment in community-based substance abuse rehabilitation programs.

Nicotine dependence is highly prevalent among drug- and alcohol-dependent patients. A multisite clinical trial of smoking cessation (SC) treatment was performed at outpatient community-based substance abuse rehabilitation programs affiliated with the National Drug Abuse Treatment, Clinical Trials Network. Cigarette smokers (N=225) from five methadone maintenance programs and two drug and alcohol dependence treatment programs were randomly assigned in a 2:1 ratio to receive either (1) SC treatment as an adjunct to substance abuse treatment-as-usual (TAU) or (2) substance abuse TAU. Smoking cessation treatment consisted of 1 week of group counseling before the target quit date and 8 weeks of group counseling plus transdermal nicotine patch treatment (21 mg/day for Weeks 1-6 and 14 mg/day for Weeks 7 and 8) after the target quit date. Smoking abstinence rates in SC, 10%-11% during treatment and 5%-6% at the 13- and 26-week follow-up visits, were significantly better than those in TAU during treatment (p< .01). In addition, SC was associated with significantly greater reductions as compared with TAU in cigarettes smoked per day (75% reduction, p< .001), exhaled carbon monoxide levels (p< .001), cigarette craving (p< .05), and nicotine withdrawal (p< .05). Smoking cessation did not differ from TAU on rates of retention in substance abuse treatment, abstinence from primary substance of abuse, and craving for primary substance of abuse. Compliance with SC treatment, moderate at best, was positively associated with smoking abstinence rates. Smoking cessation treatment resulted in significant reductions in daily smoking and modest smoking abstinence rates without having an adverse impact on substance abuse rehabilitation when given concurrently with outpatient substance abuse treatment. Substance abuse treatment programs should not hesitate to implement SC for established patients.

Providing Restricted Access to an Electronic Medical Record for Research Monitoring.

As hospital systems and healthcare institutions adopt electronic medical records (EMRs), this creates a new challenge in the normal conduct of clinical research. When protected health information (PHI) is stored in an EMR, there is inherent risk that general access to these systems for source verification purposes could allow research monitors to also have access to the PHI of non-study participants.

Regulatory Support Improves Subsequent IRB Approval Rates in Studies Initially Deemed Not Ready for Review: A CTSA Institution's Experience.

We evaluated the impact of a regulatory support service (known as the Regulatory Knowledge and Support [RKS] program), part of the Medical University of South Carolina's Clinical and Translational Science Award, on the success of Institutional Review Board (IRB) applications that have previously been deemed by the IRB to be Not Ready for Review (NRR). At the time of this evaluation, 77 studies had been deemed NRR, 53 of which came from trainees and junior faculty. All the applications that received regulatory support either received IRB approval or were deemed to not be research, and therefore did not require IRB review. In all, 39.1% (n = 18) of the research teams who did not accept regulatory support successfully received IRB approval. Providing regulatory support, particularly to trainees and junior faculty, may be associated with better success in obtaining IRB approval as well as preventing the unnecessary submission of projects that are not research and would therefore not require IRB review or approval.

Tobacco use during cannabis cessation: Use patterns and impact on abstinence in a National Drug Abuse Treatment Clinical Trials Network study.

BACKGROUND: It is common for cannabis users to also use tobacco. While data suggest that tobacco users have more difficulty achieving cannabis cessation, secondary analyses of clinical trial data sets may provide insight into the moderating variables contributing to this relationship, as well as changes in tobacco use during cannabis treatment. Those were the aims of this secondary analysis. METHODS: The parent study was a multi-site trial of N-acetylcysteine for cannabis dependence conducted within the National Drug Abuse Treatment Clinical Trials Network. Participants were treatment-seeking adults (ages 18-50) who met criteria for cannabis dependence (N = 302). For cigarette smokers (n = 117), tobacco use was assessed via timeline follow-back and nicotine dependence was assessed via the Fagerström Test for Nicotine Dependence (FTND). Outcome measures included: 1) changes in tobacco use based on treatment assignment, nicotine dependence, and concurrent cannabis reduction/abstinence, and 2) independent associations between nicotine dependence and cannabis abstinence. RESULTS: Cigarette smokers accounted for 39% of the sample (117/302), with a median FTND score of 3.0 (10-point scale). Among those with lower baseline nicotine dependence scores, cigarette smoking was reduced in the active treatment group compared to placebo. Those with moderate/high levels of nicotine dependence showed slight increases in smoking following active treatment. Nicotine dependence did not affect cannabis cessation. CONCLUSIONS: Cigarette smoking during cannabis treatment was affected, but depended on baseline nicotine dependence severity, though dependence levels did not impact cannabis abstinence. Interventions that address both tobacco and cannabis are needed, especially due to an increasing prevalence of cannabis use.

Incremental validity of estimated cannabis grams as a predictor of problems and cannabinoid biomarkers: Evidence from a clinical trial.

BACKGROUND: Quantifying cannabis use is complex due to a lack of a standardized packaging system that contains specified amounts of constituents. A laboratory procedure has been developed for estimating physical quantity of cannabis use by utilizing a surrogate substance to represent cannabis, and weighing the amount of the surrogate to determine typical use in grams. METHOD: This secondary analysis utilized data from a multi-site, randomized, controlled pharmacological trial for adult cannabis use disorder (N=300), sponsored by the National Drug Abuse Treatment Clinical Trials Network, to test the incremental validity of this procedure. In conjunction with the Timeline Followback, this physical scale-based procedure was used to determine whether average grams per cannabis administration predicted urine cannabinoid levels (11-nor-9-carboxy-Δ9-tetrahydrocannabinol) and problems due to use, after accounting for self-reported number of days used (in the past 30 days) and number of administrations per day in a 12-week clinical trial for cannabis use disorder. RESULTS: Likelihood ratio tests suggest that model fit was significantly improved when grams per administration and relevant interactions were included in the model predicting urine cannabinoid level (X2=98.3; p<0.05) and in the model predicting problems due to cannabis use (X2=6.4; p<0.05), relative to a model that contained only simpler measures of quantity and frequency. CONCLUSIONS: This study provides support for the use of a scale-based method for quantifying cannabis use in grams. This methodology may be useful when precise quantification is necessary (e.g., measuring reduction in use in a clinical trial).

Comparing adult cannabis treatment-seekers enrolled in a clinical trial with national samples of cannabis users in the United States.

BACKGROUND: Cannabis use rates are increasing among adults in the United States (US) while the perception of harm is declining. This may result in an increased prevalence of cannabis use disorder and the need for more clinical trials to evaluate efficacious treatment strategies. Clinical trials are the gold standard for evaluating treatment, yet study samples are rarely representative of the target population. This finding has not yet been established for cannabis treatment trials. This study compared demographic and cannabis use characteristics of a cannabis cessation clinical trial sample (run through National Drug Abuse Treatment Clinical Trials Network) with three nationally representative datasets from the US; 1) National Survey on Drug Use and Health, 2) National Epidemiologic Survey on Alcohol and Related Conditions-III, and 3) Treatment: Episodes Data Set - Admissions. METHODS: Comparisons were made between the clinical trial sample and appropriate cannabis using sub-samples from the national datasets, and propensity scores were calculated to determine the degree of similarity between samples. RESULTS: showed that the clinical trial sample was significantly different from all three national datasets, with the clinical trial sample having greater representation among older adults, African Americans, Hispanic/Latinos, adults with more education, non-tobacco users, and daily and almost daily cannabis users. CONCLUSIONS: These results are consistent with previous studies of other substance use disorder populations and extend sample representation issues to a cannabis use disorder population. This illustrates the need to ensure representative samples within cannabis treatment clinical trials to improve the generalizability of promising findings.

A randomized placebo-controlled trial of N-acetylcysteine for cannabis use disorder in adults.

BACKGROUND: Cannabis use disorder (CUD) is a prevalent and impairing condition, and established psychosocial treatments convey limited efficacy. In light of recent findings supporting the efficacy of N-acetylcysteine (NAC) for CUD in adolescents, the objective of this trial was to evaluate its efficacy in adults. METHODS: In a 12-week double-blind randomized placebo-controlled trial, treatment-seeking adults ages 18-50 with CUD (N=302), enrolled across six National Drug Abuse Treatment Clinical Trials Network-affiliated clinical sites, were randomized in a 1:1 ratio to a 12-week course of NAC 1200mg (n=153) or placebo (n=149) twice daily. All participants received contingency management (CM) and medical management. The primary efficacy measure was the odds of negative urine cannabinoid tests during treatment, compared between NAC and placebo participants. RESULTS: There was not statistically significant evidence that the NAC and placebo groups differed in cannabis abstinence (odds ratio=1.00, 95% confidence interval 0.63-1.59, p=0.984). Overall, 22.3% of urine cannabinoid tests in the NAC group were negative, compared with 22.4% in the placebo group. Many participants were medication non-adherent; exploratory analysis within medication-adherent subgroups revealed no significant differential abstinence outcomes by treatment group. CONCLUSIONS: In contrast with prior findings in adolescents, there is no evidence that NAC 1200mg twice daily plus CM is differentially efficacious for CUD in adults when compared to placebo plus CM. This discrepant finding between adolescents and adults with CUD may have been influenced by differences in development, cannabis use profiles, responses to embedded behavioral treatment, medication adherence, and other factors.

Gender Differences in Internalizing Symptoms and Suicide Risk Among Men and Women Seeking Treatment for Cannabis Use Disorder from Late Adolescence to Middle Adulthood.

Cannabis continues to rise in popularity as the perception of its harmfulness decreases and evidence of its deleterious developmental effect increases. While internalizing distress and suicide risk have been linked with cannabis use problems [DSM-5 cannabis use disorder (CUD); DSM-IV cannabis abuse and dependence] it remains unclear how this association varies over the course of development in treatment-seeking men and women. The current study utilized the National Drug Abuse Treatment Clinical Trials Network (NIDA CTN) to conduct a cross-sectional comparison of internalizing distress and suicide risk among men (n=437) and women (n=163) spanning ages 18-50 who met DSM-5 criteria for CUD. Interactions between gender and developmental stage (i.e., late adolescence, early adulthood, and middle adulthood) were observed for suicide risk and anxiety but not depression problems. Specifically, women seeking CUD treatment in late adolescence and middle adulthood exhibited significantly higher rates of anxiety and suicide risk compared to men seeking treatment during the same developmental stages. Internalizing distress and suicide risk did not differ between treatment-seeking men and women in the early adult stage. Overall, results suggest that the structure of risk for CUD may differ in men and women across the lifespan and that women presenting for CUD treatment during late adolescence and middle adulthood may uniquely benefit from intervention designed to address these elevations in anxiety and suicide risk.

Practical considerations for estimating clinical trial accrual periods: application to a multi-center effectiveness study.

BACKGROUND: Adequate participant recruitment is vital to the conduct of a clinical trial. Projected recruitment rates are often over-estimated, and the time to recruit the target population (accrual period) is often under-estimated. METHODS: This report illustrates three approaches to estimating the accrual period and applies the methods to a multi-center, randomized, placebo controlled trial undergoing development. RESULTS: Incorporating known sources of accrual variation can yield a more justified estimate of the accrual period. Simulation studies can be incorporated into a clinical trial's planning phase to provide estimates for key accrual summaries including the mean and standard deviation of the accrual period. CONCLUSION: The accrual period of a clinical trial should be carefully considered, and the allocation of sufficient time for participant recruitment is a fundamental aspect of planning a clinical trial.

Alcohol dependence and posttraumatic stress disorder: differences in clinical presentation and response to cognitive-behavioral therapy by order of onset.

Alcohol dependence (AD) and posttraumatic stress disorder (PTSD) frequently co-occur. However, little systematic study has examined the importance of their temporal order of onset. In this study, differences in clinical presentation and response to cognitive-behavioral substance-use therapy by order of onset were examined among 94 (51 men and 43 women) individuals with AD and PTSD. The findings revealed that women with primary AD and men with primary PTSD presented as more distressed and/or depressed than their counterparts at treatment entry. A relationship between increased alcohol intake and higher PTSD symptom levels was observed during treatment. In general, the primary PTSD group derived greater overall benefit (e.g., in physical health, alcohol use, social functioning) as compared with the primary AD group. Finally, women with primary AD appeared particularly vulnerable to continued psychiatric distress and depression at the end of treatment. These findings increase awareness of the importance of considering the order of onset and may ultimately lead to treatment improvements for this population.

Concordance of Direct and Indirect Measures of Medication Adherence in A Treatment Trial for Cannabis Dependence.

The current study compared adherence rates as measured by two indirect measurement methods (pill count and daily medication diary) to two direct measurement methods (urine riboflavin and serum 6-OH-buspirone level measurement) among participants (n = 109) in a medication treatment trial for cannabis dependence. Pill count and diary data showed high levels of percent agreement and strong kappa coefficients throughout the study. Riboflavin levels indicated lower level of percent in adherence during the study as compared to both pill count and self-report. In the subset of participants with 6-OH-buspirone levels (n = 58), the kappa coefficient also showed low to moderate agreement between the pill count and medication diaries with 6-OH-buspirone levels. In contrast to pill count and medication diaries, adherence as measured by riboflavin and 6-OH-buspirone significantly decreased over time. The findings from this study support previous work demonstrating that pill count and patient self-report of medication taking likely overestimate rates of medication adherence, and may become less reliable as the duration of a clinical trial increases.

Carbamazepine in the treatment of cocaine dependence: subtyping by affective disorder.

Studies investigating carbamazepine (CBZ) in the treatment of cocaine dependence have been inconsistent. In this study, cocaine-dependent individuals with (n = 57) and without (n = 82) affective disorder were compared in a 12-week, double-blind, placebo-controlled trial. Urine drug screens (UDS) and self-report of drug use were collected weekly. Affective symptoms were measured monthly. Subjects receiving CBZ attended more medication sessions (p = .03). The CBZ-treated affective group had a trend toward fewer cocaine-positive UDS (p = .08) and a significantly longer time to first cocaine use (p = .06). CBZ treatment did not have any impact on cocaine use in individuals without affective disorders.

A randomized trial of concurrent smoking-cessation and substance use disorder treatment in stimulant-dependent smokers.

OBJECTIVE: To evaluate the impact of concurrent treatments for substance use disorder and nicotine-dependence for stimulant-dependent patients. METHOD: A randomized, 10-week trial with follow-up at 3 and 6 months after smoking quit date conducted at 12 substance use disorder treatment programs between February 2010 and July 2012. Adults meeting DSM-IV-TR criteria for cocaine and/or methamphetamine dependence and interested in quitting smoking were randomized to treatment as usual (n = 271) or treatment as usual with smoking-cessation treatment (n = 267). All participants received treatment as usual for substance use disorder treatment. Participants assigned to treatment as usual with concurrent smoking-cessation treatment received weekly individual smoking cessation counseling and extended-release bupropion (300 mg/d) during weeks 1-10. During post-quit treatment (weeks 4-10), participants assigned to treatment as usual with smoking-cessation treatment received a nicotine inhaler and contingency management for smoking abstinence. Weekly proportion of stimulant-abstinent participants during the treatment phase, as assessed by urine drug screens and self-report, was the primary outcome. Secondary measures included other substance/nicotine use outcomes and treatment attendance. RESULTS: There were no significant treatment effects on stimulant-use outcomes, as measured by the primary outcome and stimulant-free days, on drug-abstinence, or on attendance. Participants assigned to treatment as usual with smoking-cessation treatment, relative to those assigned to treatment as usual, had significantly better outcomes for drug-free days at 6-month follow-up (χ(2)(1) = 4.09, P <.05), with a decrease in drug-free days from baseline of -1.3% in treatment as usual with smoking-cessation treatment and of -7.6% in treatment as usual. Participants receiving treatment as usual with smoking-cessation treatment, relative to those receiving treatment as usual, had significantly better outcomes on smoking point-prevalence abstinence (25.5% vs 2.2%; χ(2)(1) = 44.69, P < .001; OR =18.2). CONCLUSIONS: These results suggest that providing smoking-cessation treatment to illicit stimulant-dependent patients in outpatient substance use disorder treatment will not worsen, and may enhance, abstinence from nonnicotine substance use. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01077024.