Predictors of treatment response in adolescents with comorbid substance use disorder and attention-deficit/hyperactivity disorder.

Attention-Deficit/Hyperactivity Disorder (ADHD) frequently co-occurs with substance use disorder (SUD) and is associated with poor substance-use treatment outcomes. A trial 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 SUD 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 but poorer treatment completion. An interaction effect showed that OROS-MPH improved SUD outcomes in adolescents with comorbid conduct disorder compared to placebo. While severe SUD may require more intensive psychosocial treatment, OROS-MPH may improve substance treatment outcomes in adolescents with co-morbid attention and conduct problems.

Major depression and treatment response in adolescents with ADHD and substance use disorder.

BACKGROUND: 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. METHODS: Adolescents (n=303; ages 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 (CBT). 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: Adolescents with MDD reported more non-nicotine substance use days at baseline and continued using more throughout treatment compared to those without MDD (p<0.0001 based on timeline followback; p<0.001 based on urine drug screens). 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.

Randomized controlled trial of osmotic-release methylphenidate with cognitive-behavioral therapy in adolescents with attention-deficit/hyperactivity disorder and substance use disorders.

OBJECTIVE: To evaluate the efficacy and safety of osmotic-release methylphenidate (OROS-MPH) compared with placebo for attention-deficit/hyperactivity disorder (ADHD), and the impact on substance treatment outcomes in adolescents concurrently receiving cognitive-behavioral therapy (CBT) for substance use disorders (SUD). METHOD: This was a 16-week, randomized, controlled, multi-site trial of OROS-MPH + CBT versus placebo + CBT in 303 adolescents (aged 13 through 18 years) meeting DSM-IV diagnostic criteria for ADHD and SUD. Primary outcome measures included the following: for ADHD, clinician-administered ADHD Rating Scale (ADHD-RS), adolescent informant; for substance use, adolescent-reported days of use in the past 28 days. Secondary outcome measures included parent ADHD-RS and weekly urine drug screens (UDS). RESULTS: There were no group differences on reduction in ADHD-RS scores (OROS-MPH: -19.2, 95% confidence interval [CI], -17.1 to -21.2; placebo, -21.2, 95% CI, -19.1 to -23.2) or reduction in days of substance use (OROS-MPH: -5.7 days, 95% CI, 4.0-7.4; placebo: -5.2 days, 95% CI, 3.5-7.0). Some secondary outcomes favored OROS-MPH, including lower parent ADHD-RS scores at 8 (mean difference = 4.4, 95% CI, 0.8-7.9) and 16 weeks (mean difference =6.9; 95% CI, 2.9-10.9) and more negative UDS in OROS-MPH (mean = 3.8) compared with placebo (mean = 2.8; p = .04). CONCLUSIONS: OROS-MPH did not show greater efficacy than placebo for ADHD or on reduction in substance use in adolescents concurrently receiving individual CBT for co-occurring SUD. However, OROS-MPH was relatively well tolerated and was associated with modestly greater clinical improvement on some secondary ADHD and substance outcome measures. Clinical Trial Registration Information-Attention Deficit Hyperactivity Disorder (ADHD) in Adolescents with Substance Use Disorders (SUD); http://www.clinicaltrials.gov; NCT00264797.