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Abstract: Researchers often want to examine two comorbid conditions simultaneously. One strategy to do so is through the use of parallel latent growth curve modeling (LGCM). This statistical technique allows for the simultaneous evaluation of two disorders to determine the explanations and predictors of change over time. Additionally, a piecewise model can help identify whether there are more than two growth processes within each disorder (e.g., during a clinical trial). A parallel piecewise LGCM was applied to self-reported attention-deficit/hyperactivity disorder (ADHD) and self-reported substance use symptoms in 303 adolescents enrolled in cognitive-behavioral therapy treatment for a substance use disorder and receiving either oral-methylphenidate or placebo for ADHD across 16 weeks (protocol CTN-0028). Assessing these two disorders concurrently allowed us to determine whether elevated levels of one disorder predicted elevated levels or increased risk of the other disorder. First, a piecewise growth model measured ADHD and substance use separately. Next, a parallel piecewise LGCM was used to estimate the regressions across disorders to determine whether higher scores at baseline of the disorders (i.e., ADHD or substance use disorder) predicted rates of change in the related disorder. Finally, treatment was added to the model to predict change. Conclusions: While the analyses revealed no significant relationships across disorders, this study explains and applies a parallel piecewise growth model to examine the developmental processes of comorbid conditions over the course of a clinical trial. Strengths of piecewise and parallel LGCMs for other addictions researchers interested in examining dual processes over time are discussed. Related protocols: CTN-0028

Abstract:

The purpose of this study was to examine sensitivity to missing data procedures on treatment effects in a randomized controlled trial (RCT) of osmotic-release methylphenidate (OROS) for adolescents with co-occurring attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUD). Data came from a National Drug Abuse Treatment Clinical Trials Network study (CTN-0028, N=303), which evaluated the safety/efficacy of a 16-week RCT of OROS vs. placebo in adolescents aged 13-18 with ADHD who were also receiving cognitive-behavioral therapy for their SUD. The two primary outcomes were clinician-reported ADHD symptoms and self-reported past 28 days of substance use (SU). A parallel grow model was used to assess the effect sizes assuming missing at random (MAR) compared to two missing not at random (MNAR) models: Diggle-Kenward (DK) selection model and Wu-Carroll (WC) selection model.

The MAR model found no significant treatment effect on ADHD or SU, and the effect sizes were small for both ADHD and SU. The MNAR DK model also produced non-significant treatment effects with similar effect sizes of ADHD and SU. The MNAR WC model evidenced a significant effect of OROS relative to placebo on SU, and the effect sizes for both ADHD and SU were larger than reported in the other models.

Conclusions: While the MAR model and one MNAR model found similarly sized effects as the original RCT, the second MNAR model produced different results for both of the outcomes. This sensitivity analysis highlights an important need for future RCTs of co-morbid mental illness and SUDs to carefully evaluate the missing data assumptions made when assessing treatment effects.

Related protocols: CTN-0028

Abstract:

Attention-Deficit/Hyperactivity Disorder (ADHD) frequently co-occurs with substance use disorder (SUD) and is associated with poor substance-use treatment outcomes. A National Drug Abuse Treatment Clinical Trials Network study (CTN-0028) evaluating osmotic-release oral system methylphenidate (OROS-MPH) for adolescents with ADHD and SUD, concurrently receiving behavioral therapy, revealed inconsistent medication effects on ADHD or SUD. Clinical care for this population would be advanced by knowledge of treatment outcome predictors. Data from the randomized placebo-controlled trial (n=299) were analyzed. Significant treatment predictors included: 1) Substance use severity, associated with poorer ADHD and SUC outcomes, 2) ADHD severity, associated with better ADHD and SUD outcomes, 3) comorbid conduct disorder, associated with poorer ADHD outcomes, and 4) court-mandated status, associated with better SUD outcomes by poorer treatment completion. An interaction effect showed that OROS-MPH improved SUD outcomes in adolescents with comorbid conduct disorder compared to placebo.

Conclusions: Individuals with ADHD and SUD who are also diagnosed with conduct disorder could benefit from concurrent treatment with OROS-MPH in addition to treatment for SUD. The study also found that individuals with more severe ADHD but less severe SUD showed better treatment outcomes. With regards to mandating treatment, better SUD outcomes were found in adolescents court-mandated to receive treatment, but there were also lower treatment completion rates in the court-mandated group. Thus, particular focus on treatment retention efforts might be important for this group in order to achieve better SUD outcomes.

Related protocols: CTN-0028

Abstract:

Major depressive disorder (MDD) frequently co-occurs in adolescents with substance use disorders (SUDs) and attention deficit hyperactivity disorder (ADHD), but the impact of MDD on substance treatment and ADHD outcomes and implications for clinical practice are unclear. To examine this impact, adolescents aged 13-18 meeting DSM-IV criteria for ADHD and SUD were randomized to osmotic release methylphenidate (OROS-MPH) or placebo and 16 weeks of cognitive behavioral therapy, as part of protocol CTN-0028 (“Osmotic-Release Methylphenidate for ADHD in Adolescents with Substance Use Disorders”). Adolescents with (n=38) and without (n=265) MDD were compared on baseline demographic and clinical characteristics as well as non-nicotine substance use and ADHD treatment outcomes. Results found that adolescents with MDD reported more non-nicotine substance use days at baseline and continued using more throughout treatment compared to those without MDD. There was no difference between adolescents with and without MDD in retention or CBT sessions attended. ADHD symptom severity (based on DSM-IV ADHD rating scale) followed a slightly different course of improvement although with no difference between groups in baseline or 16-week symptom severity or 16-week symptom reduction. There was no difference in days of substance use or ADHD symptom outcomes over time in adolescents with MDD or those without MDD treated with OROS-MPH or placebo. Depressed adolescents were more often female, older, and not court ordered.

Conclusions: These preliminary findings suggest that compared to non-depressed adolescents with ADHD and SUD, those with co-occurring MDD have more severe substance use at baseline and throughout treatment. Such youth may require interventions targeting depression. Adequately powered trials evaluating treatments focused on MDD in the context of SUD and other frequently present, co-occurring psychiatric disorders are needed. In the interim, mechanisms for assessing and treating these disorders are essential in SUD treatment settings since their presence appears to interfere with maximizing SUD outcomes.

Related protocols: CTN-0028

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:

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:

Psychostimulants are effective treatments for attention-deficit/hyperactivity disorder (ADHD) but may be associated with euphoric effects, misuse/diversion, and adverse effects. These risks are perceived by some clinicians to be greater in substance-abusing adolescents relative to non–substance-abusing adults. The present study evaluates the subjective effects, misuse/diversion, and adverse effects associated with the use of osmotic-release oral system methylphenidate (OROS-MPH), relative to placebo, for treating ADHD in adolescents with a substance use disorder (SUD) as a function of substance use severity and compared these risks with those associated with the treatment of ADHD in adults without a non-nicotine SUD. Datasets from two randomized placebo-controlled trials of OROS-MPH for treating ADHD, one conducted with 303 adolescents (CTN-0028) with at least one non-nicotine SUD and one with 255 adult smokers (CTN-0029), were analyzed. Outcome measures included the Massachusetts General Hospital Liking Scale, self-reported medication compliance, pill counts, and adverse events (AEs). Euphoric effects and misuse/diversion of OROS-MPH were not significantly affected by substance use severity. The euphoric effects of OROS-MPH did not significantly differ between the adolescent and adult samples. Adults rated OROS-MPH as more effective in treating ADHD, whereas adolescents reported feeling more depressed when taking OROS-MPH. The adolescents lost more pills relative to the adults regardless of treatment condition, which suggests the importance of careful medication monitoring. Higher baseline use of alcohol and cannabis was associated with an increased risk of experiencing a treatment-related AE in OROS-MPH, but baseline use did not increase the risk of serious AEs or of any particular category of AE and the adolescents did not experience more treatment-related AEs relative to the adults.

Conclusions: With good monitoring, and in the context of substance abuse treatment, OROS-MPH can be safely used in adolescents with an SUD despite non-abstinence.

Related protocols: CTN-0028, CTN-0029

Abstract:

The National Drug Abuse Treatment Clinical Trials Network (CTN) has faced many challenges over its first eleven years. This review explores some of these challenges and the paths the CTN took to meet these challenges, including: designing clinical trials that reflect the CTN’s mission and changing public health needs, finding the synergies in the varied expertise of clinical treatment providers and academic researchers, promoting evidence-based practices, and expanding the Network into mainstream medical practices to reach a broader patient population. Included in this exploration are specific examples from CTN clinical trials.

CTN studies have shown that quality clinical trials can be successfully implemented into practice settings unfamiliar with research logistics by taking clinicians’ practical needs and research knowledge level into account. The challenges yet to be faced in the CTN’s efforts to expand opportunities to offer existing treatments to the segment of the drug-abusing population that utilizes mainstream health care seem large, but not as large as the potential for improvements in public health.

Related protocols: CTN-0001, CTN-0002, CTN-0003, CTN-0004, CTN-0005, CTN-0006, CTN-0007, CTN-0009, CTN-0010, CTN-0011, CTN-0013, CTN-0014, CTN-0015, CTN-0017, CTN-0018, CTN-0019, CTN-0020, CTN-0021, CTN-0027, CTN-0028, CTN-0029, CTN-0030, CTN-0031, CTN-0032, CTN-0037, CTCN-0044, CTN-0047, CTN-0048, CTN-0049

Abstract:

This presentation provides an overview of the design and main findings of protocol CTN-0028, which evaluated the efficacy of osmotic-release methylphenidate (OROS-MPH, sold under the brand name Concerta), relative to placebo, in treating co-occurring attention deficit hyperactivity disorder (ADHD) and substance use in adolescents. Both groups experienced clinically and statistically significant reductions in ADHD symptoms and (past-28-days) drug use, but there was no significant difference between the two groups. OROS-MPH appears to be safe and well-tolerated, but the similar reduction in ADHD symptoms between the OROS-MPH and placebo groups suggests that cognitive behavioral therapy (CBT), which was given to both groups, may have been the primary contributing factor. The presentation continues by examining emerging research on the use of CBT to treat ADHD, and then presents secondary objectives of the protocol, including an examination of depression, marijuana, and cigarette smoking in the study population.

Related protocols: CTN-0028

Abstract:

American Society of Addiction Medicine (ASAM) criteria are widely used to determine level of care/treatment intensity. However, there is a lack of research on the validity of ASAM placement criteria in adolescents with co-occurring psychiatric and substance use disorders (SUD), who generally meet ASAM criteria for more intensive treatment. No studies have been done evaluating whether integrated treatment approaches for co-occurring disorders might produce similar outcomes to more intensive (and costly) levels of care. This study examined the charts of 32 adolescents who participated in protocol CTN-0028 (OROS-MPH for ADHD in Adolescents with Substance Use Disorders) to determine ASAM placement criteria.

Despite the fact 82% of the sample would have been assigned to more intensive treatment based on retrospective determination of ASAM placement criteria, treatment outcomes were comparable across all study groups. If replicated, results would suggest that less intensive integrated treatment approaches may produce comparable outcomes to more intensive (e.g., residential) for adolescents with co-occurring psychiatric and substance use disorders.

Related protocols: CTN-0028

Abstract:

This presentation provides an overview of protocol CTN-0028, which had three study aims: 1) to evaluate the efficacy of osmotic-release methylphenidate (OROS-MPH) vs. placebo in adolescents with ADHD, 2) to evaluate the impact of OROS-MPH plus cognitive behavioral therapy (CBT) vs. placebo plus CBT on substance abuse outcomes in this population, and 3) to evaluate the overall safety, tolerability, and abuse potential of OROS-MPH. The main study findings are presented, in terms of both ADHD outcomes and substance abuse outcomes, which found the OROS-MPH was safe and well-tolerated, ADHD outcomes were as good or better for the study group than they were for adolescents without substance use disorder, and that the contribution of CBT to both SUD and ADHD outcomes was beneficial for adolescents.

The presentation ends with a discussion of the implications of both the design and outcomes of this study on future research. For example, the results suggest that ADHD clinical response may be important to substance abuse outcomes, and that in the context of CBT (for substance use disorders), significant reduction in ADHD symptoms may occur with or without pharmacotherapy. The study also demonstrated the feasibility of recruitment and enrollment, as well as high compliance, with the difficult-to-recruit population of adolescents with co-occurring disorders.

Related protocols: CTN-0028

Abstract:

This presentation provides an overview of protocol CTN-0028, which had three study aims: 1) to evaluate the efficacy of osmotic-release methylphenidate (OROS-MPH) vs. placebo in adolescents with ADHD, 2) to evaluate the impact of OROS-MPH plus cognitive behavioral therapy (CBT) vs. placebo plus CBT on substance abuse outcomes in this population, and 3) to evaluate the overall safety, tolerability, and abuse potential of OROS-MPH. The main study findings are presented, in terms of both ADHD outcomes and substance abuse outcomes, which found the OROS-MPH was safe and well-tolerated, ADHD outcomes were as good or better for the study group than they were for adolescents without substance use disorder, and that the contribution of CBT to both SUD and ADHD outcomes was beneficial for adolescents. Results of CTN-0028 were inconsistent with most controlled trials of psychostimulants vs. placebo (alone) for ADHD, but consistent with three controlled psychostimulant trials in adults concurrently receiving weekly individual CBT for substance use disorders. This suggests that in the context of individual CBT (for substance use disorder), significant reductions in ADHD symptoms may occur with or without pharmacotherapy, and that reductions in co-occurring ADHD symptoms may be important in helping adolescents achieve greater abstinence during substance treatment.

Related protocols: CTN-0028

Abstract:

Adolescents with substance use disorders (SUDs) have a higher prevalence of ADHD (30%-50%) compared to adolescents in the general population (5%-10%), but little is known about the safety and efficacy of pharmacotherapy for ADHD in adolescents with co-occurring disorders. Clinicians are reluctant to prescribe medications for ADHD in substance-involved adolescents due to their exclusion from pharmacotherapy trials, commonly first referring them for substance treatment. A number of studies have shown that such youths have poorer treatment outcomes. The researchers could find no previous controlled trials evaluating the impact of psychostimulant treatment on both ADHD and substance treatment outcomes in comorbid adolescents concurrently enrolled in substance treatment.

This study, protocol CTN-0028, was a randomized controlled multisite trial of OROS-MPH + CBT vs placebo + CBT. It found that, overall, OROS-MPH was well-tolerated, had low abuse liability, and had a good safety profile despite non-abstinence. There was no difference between OROS-MPH and placebo on primary ADHD and substance outcome measures. However, secondary measures suggested some added benefit of OROS-methylphenidate (OROS-MPH) compared to placebo based on lower parent-rated DSM-IV ADHD-RS scores at 8 and 16 weeks. Greater than expected reduction in ADHD symptoms in both groups suggests that CBT may have contributed to ADHD response consistent with findings from adult studies. However, if ADHD does not respond to CBT early in treatment, OROS-MPH may be considered, even in youths who have not yet achieved abstinence.

Related protocols: CTN-0028

Abstract:

This presentation provides an overview of the CTN protocols that examined various pharmacotherapies for opiate dependence (buprenorphine/naloxone, e.g.), smoking cessation, and adolescents.

Each protocol is described, along with its aims and conclusions, and the presentation ends with a “to-do list” for future CTN pharmacotherapy research, in the hopes that protocols about cocaine, methamphetamine, marijuana, pharmacogenetics, combination therapies (medication plus behavioral treatments), and comorbidity will be explored down the line.

Related protocols: CTN-0001, CTN-0002, CTN-0003, CTN-0009, CTN-0010, CTN-0027, CTN-0028, CTN-0029, CTN-0030

Abstract:

A lack of research on effective methods of recruiting dually-diagnosed adolescents to clinical trials has been a barrier to addressing research gaps in this important clinical population. This poster reports on the use of respondent-driven sampling to enhance recruiment efforts at one of eleven community-based substance treatment programs participating in protocol CTN-0028 (“Osmotic-Release Methylphenidate for ADHD in Adolescents with Substance Use Disorders”). Site recruitment efforts initially focused on evaluating adolescents meeting pre-screening criteria who were referred to the treatment program Lexington-Richland Alcohol and Drug Abuse Council (LRADAC) through existing referral services (e.g. juvenile justice, social services, schools). Slower than expected recruitment prompted study staff to request IRB approval to compensate study participants who referred potential study participants from among their acquaintances who successfully completed the informed consent process. Nineteen of the 32 adolescents enrolled in the study were recruited from existing treatment program referral sources. Recruitment efforts were significantly enhanced by RDS after IRB approval at approximately study mid-point. Thirteen of the 32 participants enrolled at the LRADAC site were recruited from referrals by other study participants (RDS). In conclusion, researchers found that respondent driven sampling may be an effective method to enhance recruiment of dually-diagnosed adolescents for clinical trial participation.

Related protocols: CTN-0028