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Abstract: In a multisite, randomized study (CTN-0029), a 3-month course of osmotic-release oral system mehtylphenidate (OROS-MPH) improved smoking cessation in a group of patients with higher baseline severity in Attention Deficit/Hyperactivity Disorder (ADHD). This treatment, however, worsened smoking cessation outcome in the group with lower baseline ADHD severity. This studied aimed to examine whether this differential treatment effect persisted after OROS-MPH was discontinued. A secondary analysis of the 1-month follow-up data from CTN-0029 after discontinuation of OROS-MPH was conducted (N=134). Nicotine patch was tapered during this month. Researchers tested whether OROS-MPH had an effect on self-reported 7-day abstinence by week, as well as possible treatment by baseline ADHD severity interactions. Abstinence diminished overall in time after the end of the treatment. In the high baseline severity group, patients who received OROS-MPH had an advantage in 7-day abstinence at week 15 (40% for OROS-MPH vs. 32% for placebo). In the lower severity group (n=121), no difference was detected (29% for OROS-MPH vs. 32% for placebo) between the two treatment groups. There was also a significant treatment by baseline ADHD severity interaction. Conclusions: OROS-MPH promotes abstinence beyond the course of treatment for patients with more severe ADHD, while the paradoxical effects in the lower baseline severity group is not persistent after medication discontinuation. Targeting ADHD in smoking cessation as a comorbidity therefore can have broader impact with more precise patient selection. Related protocols: CTN-0029

Abstract:

Smoking prevalence is high among substance abusers, making it important to understand when nicotine abstinence will aid, impair, or not affect abstinence from other substances. This study tested novel hypotheses about the coupling of nicotine and stimulant craving over time during stimulant dependence treatment. Adults (N=538) with cocaine and/or methamphetamine dependence completed a 10-week randomized controlled trial of substance use treatment with or without smoking cessation treatment (NIDA Clinical Trials protocol CTN-0046, Smoking Cessation and Stimulant Treatment, S-CAST). Participants reported nicotine and stimulant craving weekly and use twice per week. Latent change score modeling tested the association between weekly increases in nicotine craving and subsequent weekly changes in stimulant craving. Interestingly, results revealed a “substitution” effect: increases in nicotine craving predicted subsequent decreases in stimulant craving. Additionally, increases in nicotine craving predicted subsequent increases in nicotine use, and decreases in stimulant use. As expected, the substitution effect between nicotine and stimulant craving was stronger when stimulants were administered through the same route as nicotine (i.e., smoking), versus other routes. Finally, smoking cessation treatment eliminated the coupling between nicotine craving and stimulant craving.

Conclusions: Contrary to concerns about nicotine abstinence during substance dependence treatment, increases in nicotine craving may be associated with later reductions in stimulant craving and use, and unrelated when smoking cessation treatment is introduced. Weekly changes in nicotine craving convey information that can help clinicians to predict and understand shifts in stimulant craving and use during substance use disorder treatment. This research improves the understanding of how the ebb and flow of craving relates across substances and holds promise for treatments that harness these interrelationships to improve abstinence from co-occurring substance use problems.

Related protocols: CTN-0046

Abstract:

This is the primary outcomes article for CTN-0046.

The purpose of this study, National Drug Abuse Treatment Clinical Trials Network protocol CTN-0046, was to evaluate the impact of concurrent treatments for substance use disorder and nicotine-dependence for stimulant-dependent patients. It was 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 (TAU) (n=271) or TAU with smoking-cessation treatment (n=267). All participants received TAU for substance use disorder treatment. Participants assigned to TAU with concurrent smoking-cessation treatment received weekly individual smoking cessation counseling and extended-release bupropion (300mg/d) during weeks 1-10. During post-quit treatment (weeks 4-10), participants assigned to TAU with smoking-cessation treatment received a nicotine inhaler and contingency management for smoking abstinence. The primary outcome was weekly proportion of stimulant-abstinent participants during the treatment phase, as assessed by urine drug screens and self-report. Secondary measures included other substance/nicotine use outcomes and treatment attendance.

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. Overall, participants assigned to treatment as usual with smoking-cessation treatment averaged 77.2% stimulant-abstinent weeks compared to 78.1% stimulant-abstinent weeks for participants assigned to treatment as usual. There was a similar lack of significant treatment effect on stimulant abstinence at 3-month and 6-month follow-ups. Participants receiving TAU with smoking cessation treatment, relative to those receiving TAU alone, however, had significantly better outcomes on smoking point-prevalence abstinence. Additionally, participants receiving TAU with smoking cessation treatment, relative to those receiving TAU alone, had significantly better outcomes for drug-free days (abstinence from all illicit substances, not just stimulants) at 6-month follow-up.

Conclusions: Providing smoking-cessation treatment to cocaine- and/or methamphetamine-dependent patients in outpatient substance use disorder treatment had no effect on stimulant-use outcomes or treatment attendance, but significantly improved smoking-abstinence outcomes and outcomes for drug-free days at 6-month follow-up. Concurrent smoking-cessation and substance use disorder treatment can significantly improve smoking-abstinence outcomes and do not negatively impact non-nicotine outcomes.

Related protocols: CTN-0046

Abstract:

Past research suggests that a significant relationship exists between cigarette smoking and illicit-stimulant abuse. The present study, a secondary analysis of the National Drug Abuse Treatment Clinical Trials Network protocol CTN-0046 (Smoking Cessation and Stimulant Treatment (S-CAST)), evaluated the association between achieving smoking abstinence in response to smoking-cessation treatment (SCT) and illicit-stimulant abstinence in cocaine- and/or methamphetamine-dependent participants.

Two hundred and sixty-seven adults meeting DSM-IV-TR criteria for cocaine- and/or methamphetamine-dependence and interested in quitting smoking were randomized to SUD treatment-as-usual plus SCT consisting of weekly individual smoking cessation counseling, extended-release (XL) bupropion (300 mg/day), nicotine inhaler, and contingency management for smoking abstinence. Smoking abstinence was assessed via self-report and carbon monoxide levels. The analysis found a significant effect for the cocaine-dependent subsample (n=147) in which participants who stopped smoking were abstinent for illicit stimulants an average of 78.2% of the post-smoking-quit weeks (weeks 4-10) relative to 63.6% in participants who continued smoking. No significant effects were found for the sample as a whole (n=249) or for the methamphetamine-dependent subsample (n=102).

Conclusions: The present results suggest that cocaine-dependent patients achieving smoking abstinence in response to smoking-cessation treatment might evidence not only improved smoking outcomes but improved cocaine use outcomes as well. Because the prevalence of smoking in cocaine-dependent patients is 75-80%, and cigarette smoking itself is deadly, using smoking-cessation treatment to intervene with both cocaine use and cigarette smoking would impact two important public health issues. Future research to replicate this finding appears warranted.

Related protocols: CTN-0046

Abstract:

The majority of individuals seeking treatment for substance use disorders are cigarette smokers, yet smoking cessation is rarely addressed during treatment. Conducting a detailed smoking-related characterization of substance abuse treatment patients across treatment modalities may facilitate the development of tailored treatment strategies. This CTN platform study, funded in part by the Mid-Atlantic Node, administered a battery of self-report instruments to compare tobacco use, quit attempts, smoking knowledge and attitudes, program services, and interest in quitting among smoking patients enrolled in opioid replacement therapy (ORT) versus non-opioid replacement (non-ORT). ORT compared with non-ORT participants smoked more heavily, had greater tobacco dependence, and endorsed greater exposure to smoking cessation services at their treatment programs. Favorable attitudes towards cessation during treatment were found within both groups. These data identify several potential clinical targets, most notably including confidence in abstaining and attitudes toward cessation pharmacotherapies that may be addressed by substance abuse treatment clinics. Tailored program interventions across treatment modalities may include increased access to cessation products for ORT, while non-ORT services may need to focus on motivation and educational information to promote interest and sampling of cessation products.

Abstract:

This secondary analysis of data from National Drug Abuse Treatment Clinical Trials Network protocol CTN-0029 (NIDA-CTN-0029 A Pilot Study of Osmotic-Release Methylphenidate in Initiating and Maintaining Abstinence in Smokers with ADHD) aimed to determine whether treatment of attention deficit/hyperactivity disorder (ADHD) with osmotic-release oral system (OROS) methylphenidate promotes abstinence from smoking among smokers with ADHD who have greater severity of ADHD symptoms at baseline or greater improvement in ADHD during treatment. CTN-0029 was a randomized, double-blind, 11-week trial conducted between December 2005 and January 2008 at 6 clinical sites. Adult cigarette smokers (aged 18-55 years) who met DSM-IV criteria for ADHD were randomly assigned to OROS methylphenidate (72 mg/d) (n=127) or matching placebo (n=128). All participants received nicotine patches (21 mg/d) and weekly individual smoking cessation counseling. Logistic regression was used to model prolonged abstinence from smoking (ascertained by self-report and breath carbon monoxide testing) as a function of treatment, baseline ADHD Rating Scale-IV (ADHD-RS) score, change in ADHD-RS score during treatment, and their interactions.

Results found that treatment interacted with both ADHD-RS score at baseline and change in ADHD-RS score during treatment. Among patients with higher ADHD-RS scores (>36) at baseline and the most improvement in ADHD during treatment (change score > 24), 70% of those who took OROS methylphenidate achieved abstinence from smoking compared to 36.8% of those who took placebo. In contrast, among patients with the lowest ADHD-RS baseline scores (< 30), 30.3% of those who took OROS methylphenidate achieved abstinence from smoking compared to 60.7% of those who took placebo.

Conclusions: OROS methylphenidate, in combination with nicotine patch, may be an effective treatment for nicotine dependence among smokers with more severe ADHD and more robust response of ADHD symptoms to medication. OROS methylphenidate may be counterproductive among smokers with lower severity of ADHD. The identification and aggressive treatment of ADHD and other comorbidities hold out the promise of a treatment strategy complementary to existing medication and behavioral approaches.

Related protocols: CTN-0029

Abstract:

This one-day conference was designed to benefit front-line clinical staff delivering addiction treatments in Texas. Speakers presented sessions in the morning on Motivational Interviewing (MI) with a focus on shifting talk to action, an introduction to Acceptance and Commitment Therapy (ACT) and review of its effectiveness, and a review of pharmacological treatments for addictive disorders. Afternoon breakout sessions for MI and ACT expanded upon information discussed in the morning sessions and attendees engaged in experiential learning and practice.

View conference agenda.

Presentations:

Advanced Motivational Interviewing: Shifting from Talk to Action, Scott Walters, PhD

An Introduction to Acceptance and Commitment Therapy (ACT) with a Focus on Opioid Dependent Patients (morning session | afternoon session), Angela Stotts, PhD.

Pharmacotherapy for Addictive Disorders, Sidarth Wakhlu, MD

Abstract:

Few studies have evaluated predictors of smoking cessation outcomes in smokers with attention-deficit/hyperactivity disorder (ADHD), which could help to improve suboptimal treatment outcomes in this population. The purpose of this study was to examine pretreatment thoughts about smoking abstinence (i.e., desire to quit, perceived difficulty quitting, and expected success in quitting) as predictors of smoking cessation outcomes in smokers with ADHD and to determine the extent to which treatment adherence mediates these relationships.

Participants in this CTN ancillary investigation were adult smokers with ADHD (n=255) who were enrolled in National Drug Abuse Treatment Clinical Trials Network protocol CTN-0029 (“A Pilot Study of Osmotic-Release Methylphenidate in Initiating and Maintaining Abstinence in Smokers with ADHD”) and received either osmotic-release oral system methylphenidate (OROS-MPH) or placebo in combination with transdermal nicotine replacement and brief cessation counseling. Bootstrapped logistic regression models were generated to test main effects of thoughts about abstinence on smoking cessation outcomes and to examine treatment adherence as a mediator of these relationships. Desire to quit and expected success in quitting, but not perceived difficulty of quitting, predicted smoking cessation outcomes, as did all of the treatment adherence variables (i.e., percent sessions attended, counselor ratings of counseling adherence, and percent patch adherence). Counseling adherence partially mediated the relationship between smoking cessation outcomes and both pretreatment desire to quit and expected success.

Conclusions: Smokers with ADHD who have higher self-efficacy (i.e., expected success) and motivation (i.e., desire) to quit are more adherent to smoking cessation counseling and have better smoking cessation outcomes. Additional research is needed to determine whether treatment-seeking smokers with ADHD would benefit from an intervention designed to increase self-efficacy and motivation to quit. Interventions such as contingency management, for example, have been shown to increase motivation and self-efficacy for quitting in non-treatment-seeking adult smokers and might effectively promote long-term abstinence in smokers with ADHD as well.

Related protocols: CTN-0029

Abstract:

Adults with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for both cigarette smoking and being overweight or obese. Although smoking cessation tends to result in weight increase, potentially initiating or exacerbating weight problems, adults with ADHD who are treated with osmotic release system methylphenidate (OROS-MPH) tend to lose weight. It is unclear how the use of OROS-MPH during a smoking-cessation attempt might affect the typical weight gain that accompanies cessation. This study focused on changes in weight and hunger during a smoking cessation attempt in 215 adults with ADHD who completed National Drug Abuse Treatment Clinical Trials Network trial CTN-0029 (“A Pilot Study of Osmotic-Release Methylphenidate in Initiating and Maintaining Abstinence in Smokers with ADHD”). Patients in this study were randomized to either OROS-MPH (n=107) or placebo (n=108), with both groups also receiving open-label transdermal nicotine replacement and counseling. Participants who received OROS-MPH lost an average of 1.6% of their body weight during the 11-week study, whereas those who received placebo gained an average of 1.3% of their weight (p<.001). Hunger ratings were lower in the OROS-MPH group than in the placebo group.

Conclusions: The use of OROS-MPH during a smoking-cessation attempt prevents weight gain in adults with ADHD who substantially reduce or quit smoking. Although its effects on hunger and weight did not translate into better overall efficacy for smoking cessation in this study (see Winhusen et al., 2010), when coupled with OROS-MPH’s previously established safety in smokers with ADHD and its efficacy in reducing ADHD symptoms, this clear indication of its effects on postcessation weight gain suggests that future research on the potential benefit of OROS-MPH among particular subgroups of smokers with ADHD — such as those who are deterred from making a quit attempt due to weight concerns or who are prone to relapse as a result of weight gain — may be in order.

Related protocols: CTN-0029

Abstract:

Cigarette smoking is prevalent in cocaine/methamphetamine-dependent patients and associated with significant morbidity and mortality, yet the provision of smoking cessation treatment in conjunction with substance use disorder (SUD) treatment is not standard practice. This is due, in part, to clinician concern that combining smoking cessation treatment with SUD treatment could lead to poorer SUD outcomes. The National Drug Abuse Treatment Clinical Trials Network is conducting a 10-week, two-group, randomized trial to evaluate the impact of providing smoking cessation treatment (SCT) with SUD treatment as usual (TAU), compared to TAU alone, in smokers who are in outpatient treatment for cocaine or methamphetamine dependence (protocol CTN-0046, S-CAST). Approximately 528 participants recruited from 12 community treatment programs will be randomized into the trial. This paper describes key design decisions make during protocol development. The trial is designed to evaluate the relationship between cigarette smoking and stimulant use, which prior research suggests is linked, and should contribute to our understanding of how best to address the co-occurring problems of nicotine dependence and cocaine/methamphetamine-dependence.

Unique aspects of the trial include the primary question of interest, which concerns the impact of providing SCT on SUD outcomes rather than on smoking outcomes, and the intensity of the SCT chosen, which includes bupropion, nicotine replacement, and two psychosocial interventions. S-CAST is designed to answer questions of interest to clinicians as well as more basic researchers and should contribute significantly to our understanding of how best to address the co-occurring problems of nicotine and cocaine/methamphetamine dependence.

Related protocols: CTN-0046

Abstract:

Little is known about the relationship between attention-deficit/hyperactivity disorder (ADHD) subtypes and substance-use disorder (SUD). As there is literature suggesting different subtype phenotypes, there may be subtype differences in regard to the risk for developing SUD and substance treatment response. The purpose of this study was to characterize the sample in a National Drug Abuse Treatment Clinical Trials Network (CTN) study (protocol CTN-0029, “A Pilot Study of Osmotic-Release Methylphenidate in Initiating and Maintaining Abstinence in Smokers with ADHD”), according to ADHD subtypes and baseline psychosocial and substance-use characteristics and to compare subtypes on response to treatment. Secondary analyses were performed on data collected from adolescents diagnosed with ADHD and SUD (non-nicotine) and treated with stimulant medication or placebo and cognitive behavioral therapy for substance abuse. Participants were characterized as inattentive or combined ADHD subtype and compared on baseline characteristics and treatment outcome. Results found that the combined subtype presented with more severe SUDs and higher rates of conduct disorder. There were a greater proportion of boys with inattentive subtype, and the inattentive subtype also appeared less ready for treatment with poorer coping skills at baseline. However, the two subtypes responded equally to treatment even after controlled for baseline differences.

Conclusions: Findings from this large community sample indicate that there were no subtype differences in treatment response, although there were differences in terms of substance use, antisocial behavior, readiness for treatment, and gender prior to treatment. This study is the first to report on subtype differences for treatment response for non-nicotine substance use disorder in a comorbid ADHD-SUD population. Despite some baseline differences, the fact both subtypes responded equally to treatment suggests that subtype designation may not be relevant when assessing treatment needs for an adolescent with comorbid ADHD-SUD.

Related protocols: CTN-0028

Abstract:

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 (protocol CTN-0009). 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 found that 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: During future efforts to improve smoking cessation 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.

Related protocols: CTN-0009

Abstract:

Multisite trials, the gold standard for conducting studies in community-based settings, can mask variability across sites resulting in misrepresentation of effects in specific sites. In a placebo-controlled trial of osmotic-release oral system methylphenidate (OROS-MPH) as augmentation treatment for smokers with attention deficit hyperactivity/impulsivity disorder (ADHD) (protocol CTN-0029), three types of sites were selected according to their clinical research specialty (ADHD, smoking cessation, and general mental health). Analysis was conducted to determine if clinical outcomes, that is, reduction in ADHD symptoms and smoking cessation rates, and the effect of treatment on these outcomes would differ by type of site. A total of 255 adult smokers diagnosed with ADHD were enrolled in three clinic types: 72 in ADHD, 79 in tobacco dependence, and 104 in the mental health clinics. The three site-types were similar in demographic characteristics, smoking history, baseline level of ADHD symptoms, and history of psychiatric illness. Site-type but not site-type-by-treatment-interaction predicted prolonged smoking abstinence. A significant three-way interaction of site-type, treatment, and time predicted improvement in ADHD symptoms. Moderate to strong effects of OROS-MPH relative to placebo were observed in the mental health and the ADHD clinics, while only a weak effect was observed in the tobacco dependence clinics. Accordingly, had the study only been conducted in tobacco dependence clinics, an erroneous null or, at best, weak effect of OROS-MPH on ADHD symptoms might have emerged.

Conclusions: OROS-MPH benefit varied by site for reducing ADHD symptoms but not for improving smoking abstinence. The uneven presence of site-type effects, observed in this analysis, affirms the need for a priori consideration and measurement of potentially influential site-related factors in the design and analysis of multisite trials. Scientific assessment of site-type effects can indicate the generalizability of findings from multisite trials and should be routinely incorporated in the design of multisite trials.

Related protocols: CTN-0029

Abstract:

The focus of this presentation is on the outcomes of medication studies in the CTN and how those outcomes can be applied to treatment in community-based settings. Medication studies in the CTN have included four studies on opioid dependence (buprenorphine vs. clonidine, buprenorphine taper, buprenorphine for adolescents, and the Prescription Opioid Addiction Treatment Study) and two studies on methylphenidate (methylphenidate for smokers with ADHD and methylphenidate for adolescents with ADHD and substance use disorder). Outcomes from each trial are presented, along with implications for community-based treatment providers. Overall, these protocols have demonstrated that medication studies — both straight-forward studies and highly complex ones — can be conducted safely and effectively in community drug abuse treatment programs. Staff members in these programs can be highly enthusiastic about the new therapies, something that aids in implementation, and evidence supports the fact that successful medication trials can lead to increased use of empirically validated pharmacotherapies.

The presentation ends with a look at ongoing and future medication research in the CTN, including buprenorphine for cocaine dependence, long-acting injectable naltrexone for opioid dependence, bupropion for smokers with stimulant dependence, buspirone for cocaine dependence, and treatments for cannabis dependence.

Related protocols: CTN-0001, CTN-0002, CTN-0003, CTN-0009, CTN-0010, CTN-0028, CTN-0030

Abstract:

Attention deficit hyperactivity disorder (ADHD) is a neuropsychiatric condition subclassified in the DSM-IV according to its core symptom domains as (a) predominantly inattentive (ADHD-IN), (b) predominantly hyperactive/impulsive (ADHD-H), and (c) combined inattentive and hyperactive/impulsive (ADHD-C). Whether these subtypes represent distinct clinical entities or points on a severity continuum is controversial. Divergence in treatment response is a potential indicator of qualitative heterogeneity. This study, an ancillary investigation of data from protocol CTN-0029 (“A Pilot Study of Osmotic-Release Methylphenidate in Initiating and Maintaining Abstinence in Smokers with ADHD”), examined smoking cessation response by ADHD subtype to osmotic-release oral system methylphenidate (OROS-MPH). The analysis found that the subtypes were similar in baseline demographic, smoking, and psychiatric history, but differed in smoking cessation response to OROS-MPH or placebo as a function of nicotine dependence level. Among highly dependent smokers, the prolonged abstinence rates were greater with OROS-MPH than with placebo in the ADHD-C group, but higher with placebo than with OROS-MPH in the ADHD-IN group. Abstinence rates did not differ by subtype or treatment among smokers who were less nicotine dependent. Contrasting treatment response and divergence in the impact of nicotine dependence level support the hypothesis of ADHD subtypes as distinct clinical entities and may indicate the need and directions for personalized targeted treatments of smokers with ADHD.

Related protocols: CTN-0029