Validity of structured clinical evaluations in adolescents with conduct and substance problems.

OBJECTIVE: To determine discriminative and convergent validity for certain structured diagnostic assessments among adolescents with conduct and substance problems. METHOD: Patients were 87 adolescents (both genders) in treatment for conduct and substance problems. Most controls (n = 85; both genders) came from patients' neighborhoods. Assessments included Diagnostic Interview Schedule for Children, Composite International Diagnostic Instrument-Substance Abuse Module, Child Behavior Checklist, and others. Patients' data guided clinical care. RESULTS: Youths' self-reports significantly discriminated patients from controls in DSM-IVconduct and substance use disorders (CD, SUD) and in numerous associated measures. CD and SUD symptoms correlated strongly. However, some patients apparently minimized symptoms. Youths' self-reports did not discriminate patients from controls in attention-deficit/hyperactivity disorder (ADHD) or major depression (MDD). Parent information raised prevalence rates of ADHD and MDD, which then discriminated patients from controls. However, patients and parents usually disagreed on MDD and ADHD diagnoses. CONCLUSIONS: Despite some dissimulation, patients' self-reports of CD and SUD correlated highly and had superb discriminative validity, making them useful for treatment and research. Self-reports of ADHD and MDD, apparently lacking discriminative validity, are less useful. Parent reports improve these discriminations but present additional problems.

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.

Thrice-weekly supervised dosing with the combination buprenorphine-naloxone tablet is preferred to daily supervised dosing by opioid-dependent humans.

A sublingual tablet formulation of buprenorphine combining 8 mg of buprenorphine with 2 mg of naloxone is being targeted for use in settings where less than daily dosing strategies and/or prescription-based dispensing will likely be employed. This study determined patient preferences for, and clinical outcomes during, daily and 3-day per week supervised dosing schedules using the combination tablet. Twenty-four opioid-dependent subjects completing a 16-day baseline entered an outpatient triple crossover trial. Twenty-one days of daily dosing were compared to two different 21-day periods of 3-day per week supervised dosing: a 3-day per week clinic schedule and a 3-day per week take-home schedule in which tablets were provided to subjects to take at home on days between clinic visits. Thirteen patients completed the study. Significantly more doses were ingested under the 3-day per week schedules. Illicit drug use did not differ across conditions and 45% of urine samples tested positive for illicit opioids. Subjects 'liked' both 3-day per week schedules more than the daily schedule, and ratings of feeling 'good' were higher for the 3-day take-home as opposed to 3-day clinic condition. Almost all subjects (91%) rated 3-day take-home as the most preferred schedule. Overall, reducing clinic attendance improved medication compliance and increased client satisfaction without impacting illicit drug use.

Heroin use among adolescents in treatment for substance use disorders.

OBJECTIVE: To clarify prevalence rates and describe patterns of adolescent heroin users who are in treatment for substance use disorders. METHOD: The Treatment Episode Data Set (TEDS) was examined for trends in the number of adolescents admitted to substance abuse treatment centers and for changes in the routes of heroin administration. Thirteen adolescents who used heroin from one treatment program were compared with 536 adolescents who did not. RESULTS: Between 1992 and 1996, heroin-using youths represented 2.0% of youths in treatment and in 1997 they represented 2.6%. Heroin-using youths represented 56% of those using injection drugs. Heroin-using youths from one treatment program had significantly more polysubstance dependence in comparison with adolescents who did not use heroin. CONCLUSIONS: Nationally, there has been an increasing number, but not percentage, of heroin-using youths in treatment between 1992 and 1996. In 1997 there was an increase in both the number and percentage of heroin-using youths in treatment. Heroin-using adolescents have the highest rate of injection drug use when compared with youths using other substances. Because of their greater risk of contracting human immunodeficiency virus through injection drug use, treatment trials for these adolescents are needed.

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.

Efficacy of daily and alternate-day dosing regimens with the combination buprenorphine-naloxone tablet.

This study evaluated the efficacy of a combination tablet formulation of buprenorphine containing 8 mg of buprenorphine and 2 mg of naloxone for every other day treatment and whether increasing the daily maintenance dose was essential for maintaining an efficacious alternate-day treatment. Twenty-six opioid-dependent outpatients completing a 16-day baseline entered a double-blind, placebo-controlled, triple crossover trial. Twenty-one days of daily combination tablet administration were compared to two different 21-day periods of alternate-day buprenorphine administration where subjects received either 8 or 16 mg of the combination tablet every other day with placebo on the interposed day. Fifty-four percent (14/26) of subjects completed the study, but only two subjects dropped out during the 16-mg alternate-day condition. Rates of medication compliance, illicit opioid use and subject- and observer-rated measures of opioid effects did not distinguish daily from alternate-day treatments in subjects completing the study. However, pupillary diameter was significantly increased during 8-mg alternate-day compared to the 8-mg daily or 16-mg alternate-day treatment. These data replicate earlier findings describing the acceptability of alternate-day buprenorphine treatment using multiples of the daily maintenance dose and extend these findings by establishing the clinical efficacy of daily and alternate-day dosing regimens with the combination buprenorphine naloxone tablet. This study also suggests slightly improved outcomes during alternate-day treatment using multiples of the daily dose.

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.

Relating the classical covariance adjustment techniques of multivariate growth curve models to modern univariate mixed effects models.

The relationship between the modern univariate mixed model for analyzing longitudinal data, popularized by Laird and Ware (1982, Biometrics 38, 963-974), and its predecessor, the classical multivariate growth curve model, summarized by Grizzle and Allen (1969, Biometrics 25, 357-381), has never been clearly established. Here, the link between the two methodologies is derived, and balanced polynomial and cosinor examples cited in the literature are analyzed with both approaches. Relating the two models demonstrates that classical covariance adjustment for higher-order terms is analogous to including them as random effects in the mixed model. The polynomial example clearly illustrates the relationship between the methodologies and shows their equivalence when all matrices are properly defined. The cosinor example demonstrates how results from each method may differ when the total variance-covariance matrix is positive definite, but that the between-subjects component of that matrix is not so constrained by the growth curve approach. Additionally, advocates of each approach tend to consider different covariance structures. Modern mixed model analysts consider only those terms in a model's expectation (or linear combinations), and preferably the most parsimonious subset, as candidates for random effects. Classical growth curve analysts automatically consider all terms in a model's expectation as random effects and then investigate whether "covariance adjusting" for higher-order terms improves the model. We apply mixed model techniques to cosinor analyses of a large, unbalanced data set to demonstrate the relevance of classical covariance structures that were previously conceived for use only with completely balanced data.

An open trial of bupropion for ADHD in adolescents with substance use disorders and conduct disorder.

OBJECTIVE: Adolescents with conduct disorder (CD) and substance use disorders (SUD) have higher rates of comorbid attention-deficit/hyperactivity disorder (ADHD) than those without CD and SUD. Comorbid ADHD may contribute to more severe SUD. Treatment of ADHD may enhance effective treatment of substance abuse and behavior problems, yet there are few data regarding pharmacological treatment of ADHD in such youths. METHOD: Pilot data are presented from a 5-week, open-label bupropian trial in 13 nondepressed adolescent boys in a residential treatment program focusing on substance and behavioral treatments. All had diagnoses of ADHD, CD, and SUD. Patients' doses were titrated to a maximum fixed daily dose of 300 mg of bupropion. The Conners Hyperactivity Index and Daydream Attention scores, along with Clinical Global Impressions Severity of Illness (CGI-S) ratings, were obtained at baseline and at the fifth week of treatment. RESULTS: Subjects' mean Conners Hyperactivity Index score declined from 75.5 to 65.4 (p < .01, Wilcoxon signed rank test) (13% decline). The mean Daydream Attention score declined from 59.5 to 53.6 (p < .02, Wilcoxon signed rank test) (10% decline). Mean CGI-S declined from 4.9 to 3.0 (p < .002, Wilcoxon signed rank test) (39% decline). CONCLUSIONS: These preliminary data suggest that bupropion may be a useful treatment for ADHD in adolescents with CD and SUD; they suggest the need for a controlled trial of bupropion in such youths.

Cannabis dependence, withdrawal, and reinforcing effects among adolescents with conduct symptoms and substance use disorders.

The prevalence of cannabis use is rising among adolescents, many of whom perceive little risk from cannabis. However, clinicians who treat adolescent substance users hear frequent reports of serious cannabis-use disorders and problems. This study asked whether cannabis produced dependence and withdrawal among such patients, and whether patients' reports supported previous laboratory findings of reinforcing effects from cannabis. This was a screening and diagnostic study of serial treatment admissions. The diagnostic standard was the DSM-III-R dependence criteria, and the setting was a university-based adolescent substance treatment program with male residential and female outpatient services. The patients were 165 males and 64 females from consecutive samples of 255 male and 85 female 13-19-year-olds referred for substance and conduct problems (usually from social service or criminal justice agencies). Eighty-seven patients were not evaluated, usually due to early elopement. Twenty-four others did not meet study admission criteria: > or = one dependence diagnoses and > or = three lifetime conduct-disorder symptoms. The main measures were items from diagnostic interview instruments for substance dependence, psychiatric disorders, and patterns of substance use. Diagnoses were substance dependence, 100%; current conduct disorder, 82.1%; major depression, 17.5%; attention-deficit/hyperactivity disorder, 14.8%. The results show that most patients claimed serious problems from cannabis, and 78.6% met standard adult criteria for cannabis dependence. Two-thirds of cannabis-dependent patients reported withdrawal. Progression from first to regular cannabis use was as rapid as tobacco progression, and more rapid than that of alcohol, suggesting that cannabis is a reinforcer. The data indicate that for adolescents with conduct problems cannabis use is not benign, and that the drug potently reinforces cannabis-taking, producing both dependence and withdrawal. However, findings from this severely affected clinical population should not be generalized broadly to all other adolescents.

Substance-dependent, conduct-disordered adolescent males: severity of diagnosis predicts 2-year outcome.

Most delinquent youths have conduct disorder (CD), often with comorbid substance use disorder (SUD), attention-deficit/hyperactivity disorder (ADHD) and depression. Some youths' conduct problems later abate, while those of others persist into adult antisocial personality disorder. Earlier CD onset and ADHD reportedly predict persisting antisocial problems, but predictors of persisting SUD are poorly understood. Males aged 13-19 years (n = 89), most referred by criminal justice and social service agencies, received residential treatment for comorbid CD and SUD. They had diagnostic assessments for SUD at intake and for CD, ADHD, and depression (as well as drug-use assessments) at intake and 6, 12 and 24 months later. At intake nearly all had DSM-III-R substance dependence (usually on alcohol and marijuana) and CD with considerable violence and criminality. The 2-year follow-ups revealed improvements in criminality, CD, depression and ADHD, but substance use remained largely unchanged. Various aspects of conduct, crime and substance outcomes at 2 years were predicted by intake measures of intensity of substance involvement, and by CD severity and onset age, but not by severity of either ADHD or depression, nor by treatment duration. Earlier CD onset, more severe CD and more drug dependence predicted worse outcomes, supporting the validity of these diagnoses in adolescents.

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.

Fluoxetine in drug-dependent delinquents with major depression: an open trial.

Although fluoxetine might be more effective than placebo for treating adolescent depression without major comorbidity, little is known about the response of depressive symptoms to antidepressants in adolescents with comorbid conduct disorder (CD) and substance use disorders (SUD). Male adolescents, who remained or became depressed after > or = 1 month of abstinence from abused substances during residential treatment for SUD, were treated in an open trial for > or = 7 weeks with a fixed dose of 20 mg of fluoxetine. The eight adolescents (ages 14-18 years) with CD, SUD, and major depression were not in drug withdrawal or receiving other pharmacotherapy. A > or = 50% improvement was observed in mean scores on Ten Point Depression Scale rated by clinician (p < 0.01) and patients (p < 0.01), Carroll Self-Ratings for depression (p < 0.02), and Severity of Illness scores on the Clinical Global Impression (p < 0.01). Of the eight adolescents, seven showed marked improvement and wished to continue fluoxetine after the trial. Side effects were mild and transient. No subject required dosage reduction or discontinuation of medication because of side effects. Fluoxetine appeared useful in treating substance-dependent delinquents whose major depressions persisted or emerged after 4 weeks of abstinence. These preliminary findings justify a controlled trial in such youths.

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.

Contribution of ADHD symptoms to substance problems and delinquency in conduct-disordered adolescents.

We examined adolescents with conduct disorder (CD) and substance problems to determine if those with attention deficit hyperactivity disorder (ADHD) symptomatology had more severe delinquency and substance involvement. ADHD symptomatology was assessed in two ways: (1) by self-reports using the Diagnostic Interview Schedule for Children (DISC) and (2) by use of DISC plus reports of others (parents, program staff, and program teacher). We divided boys into three ADHD groups based on DISC: those who met criteria, those who reported at least eight current symptoms, and those who reported fewer than eight symptoms. We also divided the same boys into two groups: those with reports of ADHD by two or more sources and those without this multisource ADHD. Examining these definitions of ADHD revealed that boys with either self- or multisource ADHD had more CD symptoms, earlier age of CD onset, more substance dependence diagnoses, and more comorbid depression and anxiety.

Depression in substance-dependent delinquents.

OBJECTIVE: Depression often is comorbid with conduct disorder. The purpose of this study is to assess whether, among youths with conduct disorder, those with depression differ in other ways from those without depression. METHOD: Ninety-nine delinquent boys (aged 13 through 19 years) were evaluated with the Diagnostic Interview Schedule for Children and other instruments. All boys had conduct disorder and substance use disorders. RESULTS: Staff-rated and self-rated depression scores correlated significantly. Twenty-one boys had major depression and/or dysthymia. Depressed boys had more substance dependence diagnoses and were more likely to have attention-deficit hyperactivity disorder, posttraumatic stress disorder, and anxiety disorders, compared with the nondepressed boys. Depressed boys tended to develop conduct symptoms earlier than did the nondepressed boys. Depression scores did not change after at least 4 weeks of abstinence, for either depressed or nondepressed boys. CONCLUSIONS: Depressed delinquents have more substance dependence diagnoses, tend to initiate behavioral problems at an earlier age, have increased anxiety and attentional problems, and more trauma effects, than nondepressed delinquents. Depression does not appear to be related to substance intoxication, since it is not alleviated after 4 weeks of abstinence. Such boys may require combined psychiatric and substance treatment.

Treated delinquent boys' substance use: onset, pattern, relationship to conduct and mood disorders.

We describe relationships between substance use, conduct disorder (CD), depression, and history of self-injury or suicide attempts, in referred, delinquent, substance involved, adolescent males. Sixty youths (mean age 16.3 years) completed standardized assessments for substance use and other psychiatric disorders, aggressiveness, and social class. All boys met modified criteria for CD. Most had high aggression ratings. Twenty percent had depressive diagnoses. By age 13, 78% had begun regular substance use. Marijuana was the first substance for 42%. The boys had substance dependence on a mean of 3.2 different drugs (usually including alcohol and marijuana), with abuse of an average of one additional drug. CD symptoms began 3.6 years (mean) before regular use. CD symptom count correlated with number of dependence diagnoses, and both of those (but not depression) related significantly to suicide attempt and self-injury histories. Improved understanding of substance involvement in youths with CD may generate more rational prevention and treatment.

Buprenorphine and cocaine effects on social behavior of monkeys.

We administered for 2 weeks intramuscular buprenorphine 0.3 mg/kg per day (and in a separate series, its vehicle) to each of 7 male, group-living Macaca fuscata (Japanese Snow Monkeys). Animals received one injection of cocaine 0.75 mg/kg and one of saline (about Days 9 and 14) in each series; after each of these doses ethologic observers recorded for 3 h the frequency of occurrence of 64 separate social, self-care, position and other behaviors. Cocaine alone changed the frequency of many behaviors. Buprenorphine alone only reduced the frequency of eating, yawning and ejaculation. The drugs had no interactive effects on behavior. In a dose reported to suppress monkeys' heroin and cocaine self-administration, buprenorphine showed remarkably few disruptions of normal group behavior. But it neither reversed nor enhanced cocaine's behavioral effects.

Cocaine, social behavior, and alcohol-solution drinking in monkeys.

Eight group-living male monkeys received cocaine (0 to 3.0 mg/kg) individually or as a group. Cocaine suppressed social affiliative behaviors, eating, and drinking (of both alcohol and control solutions). It induced bizarre stereotypies, hypervigilance, panic-like fleeing, enhancement and then suppression of locomotion, and a seizure. Cocaine had little effect on aggressiveness or sexual behavior. Proportion of time spent lying or sitting changed significantly. Cocaine produced severe behavioral abnormality in this social setting.