Elizabeth A. Whitmore

Influences on adolescent substance dependence: conduct disorder, depression, attention deficit hyperactivity disorder, and gender

OBJECTIVE In adolescents, conduct disorder (CD), attention deficit hyperactivity disorder (ADHD), and depression are frequently comorbid with substance dependence (SD). We hypothesized that the prevalence and severity of CD, major depressive disorder (MDD), and ADHD would differ by gender, and that these conditions would associate differentially with severity of SD in males and females. METHODS We examined these issues, using standardized diagnostic interviews, in 285 male and 82 female adolescents referred for comorbid CD and SD. RESULTS Males and females did not differ significantly in severity of substance involvement, MDD, or ADHD, but males had more severe CD. MDD severity was the only variable significantly associated with SD severity for females, while for males, severity of CD combined with MDD and ADHD was significantly associated with SD severity. CONCLUSIONS Among referred adolescents, CD, MDD, and ADHD may all be important concomitants of SD in males, while in females, depression may be the primary variable related to SD.

Relationship of ADHD, depression, and non-tobacco substance use disorders to nicotine dependence in substance-dependent delinquents

This study used standardized interviews to examine the relationship of attention deficit hyperactivity disorder (ADHD), major depression (MDD), and other illicit substance use disorders (SUD) to onset and severity of nicotine dependence in 82 female and 285 male adolescents with conduct disorder (CD) and SUD. Results indicate that both ADHD and MDD significantly contribute to severity of nicotine dependence in delinquents with SUD. ADHD is further associated with earlier onset of regular smoking in males. Severity of non-tobacco SUD also was related directly to nicotine dependence severity in both males and females, and to earlier onset of smoking in males. Our findings illuminate the contribution of comorbidity to nicotine dependence and its relationship to other SUD severity among adolescents with CD and SUD and highlight the need for coordinated assessment and treatment of smoking cessation along with concurrent treatment of other drug use and psychiatric comorbidity such as ADHD and MDD in such youths.

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.

One-year outcome of adolescent females referred for conduct disorder and substance abuse/dependence.

We investigated whether substance abuse/dependence, conduct disorder, and other psychiatric disorders improved in adolescent females who were referred to outpatient treatment and which variables were related to 1-year outcome. Forty-six out of 60 conduct-disordered (CD) adolescent females with substance abuse or dependence were re-evaluated approximately 1 year after discharge. Treatment length averaged 16 weeks. Significant improvements were seen in three areas: (1) criminality and CD; (2) attention deficit hyperactivity disorder (ADHD); and (3) educational and vocational status. However, neither substance involvement nor depression improved, regardless of length of stay in treatment, and these females demonstrated significant risky sexual behaviors. In contrast to our previous work with adolescent males (Crowley, T.J., Mikulich, S.K., Macdonald, M., Young, S.E., Zerbe, G.O., 1998. Substance-dependent, conduct-disordered adolescent males: severity of diagnosis predicts 2-year outcome. Drug Alcohol Depend. 49, 225-237), we were not able to identify pre-intake variables, other than performance IQ, that were related to substance use and conduct outcomes. Only two post-treatment factors (peer problems and number of ADHD symptoms at follow-up) were found to be related to CD and substance use disorders outcomes. The overall lack of pre- and post-treatment predictors presents interesting challenges for future research on adolescent females with these disorders.

Measuring impulsivity in adolescents with serious substance and conduct problems.

Adolescents with substance use and conduct disorders have high rates of aggression and attention deficit hyperactivity disorder (ADHD), all of which have been characterized in part by impulsivity. Developing measures that capture impulsivity behaviorally and correlate with self-reported impulsivity has been difficult. One promising behavioral measure, however, is a variant of the continuous performance test, the Immediate Memory Test/Delayed Memory Test (IMT/DMT). The authors showed significant group differences between adolescents in treatment for serious substance and conduct problems and community controls on impulsivity measures, both behavioral and self-report, as well as on aggression and problem behavior measures. Furthermore, the IMT/DMT correlated significantly with selfreported impulsivity. In summary, the IMT/DMT may be an effective behavioral measure of impulsivity in adolescents.

An Open Trial of Pemoline in Drug-Dependent Delinquents with Attention-Deficit Hyperactivity Disorder

OBJECTIVE Adolescents with conduct disorder and substance use disorders have high rates of comorbid attention-deficit hyperactivity disorder (ADHD); ADHD may contribute to the severity and persistence of substance use disorders and antisocial behaviors. Treatment of ADHD may help patients utilize substance and other behaviorally focused treatment. Yet little is known about the response of ADHD symptoms to psychopharmacological intervention in substance-dependent delinquents. METHOD Pilot data are presented for 13 male adolescents with conduct disorder, substance use disorders, and ADHD, in a residential substance use treatment program. Patients were treated with pemoline. Scores from the Conners Hyperactivity Index and continuous performance tasks were obtained at baseline and after about 1 month of treatment with pemoline. Physical activity measurements were also assessed at baseline and 1 month. Postmedication assessments were obtained after at least 1 week at maximal dosage (1.2 to 3.3 mg/kg). RESULTS Mean Conners Hyperactivity Index scores declined 13.9% (p < or = .002) and mean motility declined 7% (p < or = .04) with pemoline treatment. Continuous performance task scores did not change. CONCLUSIONS Preliminary data indicate that pemoline may be a useful treatment for ADHD in substance-dependent delinquents; the authors propose a controlled trial of pemoline in such youths.

Concordance between DSM-III-R and DSM-IV diagnoses of substance use disorders in adolescents

Except for cannabis and alcohol, concordance between DSM-III-R and DSM-IV substance use disorder diagnoses has not been reported in adolescents. We assessed a clinical sample of 102 adolescents using CIDI-SAM. Prevalence of either an abuse or dependence diagnosis was lower with DSM-IV than DSM-III-R except for cannabis and alcohol, and concordance rates were better for dependence than for abuse. For most substances, rates of DSM-IV withdrawal were lower than in DSM-III-R, but rates of DSM-IV physiological dependence remained high. Changes in DSM-IV criteria appear to have impacted diagnoses in these adolescents, particularly for the substances they use most--i.e. alcohol, tobacco, and cannabis.

Stress, Cortisol, and Externalizing Behavior in Adolescent Males: An Examination in the Context of Multisystemic Therapy

Stress and hypothalamic–pituitary–adrenal (HPA) axis dysregulation have been associated with externalizing behavior in adolescence, but few studies have examined these factors in a treatment context. This study investigated the relationship between stress, cortisol, and externalizing behavior among 120 adolescent males (mean age = 15) receiving Multisystemic Therapy (MST). To examine the differential relationship of cortisol with various types of stressors, self-report measures assessed lifetime stress, current episodic stress, and daily hassles. Morning and afternoon cortisol samples were collected to examine whether the relationship between stress and treatment outcome depended on the youth’s biological stress levels. Regression analyses indicated that awakening cortisol levels moderated the relationship between daily hassles and externalizing behaviors at post-treatment. More specifically, higher levels of daily hassles predicted worse outcomes only among adolescents with high levels of morning cortisol. In addition, lifetime stressors and afternoon measures of cortisol interacted to predict changes in caretaker reports of externalizing problems and youth arrests following treatment; lifetime stressors were positively associated with externalizing behavior when adolescents had low levels of afternoon cortisol. Implications for theory and future directions for evidence-based treatment are discussed.

Predicting early positive change in multisystemic therapy with youth exhibiting antisocial behaviors

This study examined individual and family characteristics that predicted early positive change in the context of Multisystemic Therapy (MST). Families (n = 185; 65% male; average youth age 15 years) receiving MST in community settings completed assessments at the outset of treatment and 6-12 weeks into treatment. Early positive changes in youth antisocial behavior were assessed using the caregiver report on the Child Behavior Checklist Externalizing Behaviors subscale and youth report on the Self-Report Delinquency Scale. Overall, families showed significant positive changes by 6-12 weeks into treatment; these early changes were maintained into midtreatment 6-12 weeks later. Families who exhibited clinically significant gains early in treatment were more likely to terminate treatment successfully compared with those who did not show these gains. Low youth internalizing behaviors and absence of youth drug use predicted early positive changes in MST. High levels of parental monitoring and low levels of affiliation with deviant peers (mechanisms known to be associated with MST success) were also associated with early positive change.

Biosocial Processes Predicting Multisystemic Therapy Treatment Response

This study examined biological (testosterone) and social (deviant peer affiliation) factors early in treatment as predictors of treatment outcome among adolescent boys receiving Multisystemic Therapy (MST) in community settings. Outcome variables included changes in youth aggression and delinquency as reported by the primary caregiver. Testosterone and deviant peer affiliation were assessed at treatment onset; and outcome variables (aggression and delinquency) were assessed at treatment onset, mid-treatment and end-of-treatment. Participants were 112 adolescent boys (M age=15.42, SD=1.31) and their caregivers. Growth curve analyses revealed that the combination of high testosterone and high deviant peer affiliation early in treatment were significantly associated with less of a decline in aggression and delinquency over the course of treatment. Results provide novel evidence for the role of testosterone in the prediction of future externalizing behaviors. Clinical and theoretical implications are discussed.