Susan K. Mikulich

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.

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.

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.

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.

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.

A genome-wide search for quantitative trait loci influencing substance dependence vulnerability in adolescence

This study describes results from a genome-wide search for quantitative trait loci (QTL) influencing substance dependence vulnerability in adolescence. We utilized regression-based multipoint (and single-point) QTL mapping procedures designed for selected sibpair samples. Selected sibling pairs included 250 proband-sibling pairs from 192 families. Clinical probands (13-19 years of age) were drawn from consecutive admissions to substance abuse treatment facilities in the Denver metropolitan area; siblings of probands ranged in age from 12 to 25 years. In addition to the selected sample, a community-based sample of 3676 adolescents and young adults were utilized to define a clinically-significant, heritable, age- and sex-normed index of substance dependence vulnerability-a priori and independent of our linkage results. Siblings and their parents were genotyped for 374 STR micro-satellite markers distributed across the 22 autosomes (average inter-marker distance=9.2 cM). Non-parametric single-point linkage results indicated 17 markers on 11 chromosomes with nominally significant tests of linkage; six markers with LOD scores greater than 1.0 and one marker (D3S1614) with a LOD score of 2.2. Multipoint mapping corroborated two locations and provided preliminary evidence for linkage to regions on chromosome 3q24-25 (near markers D3S1279 and D3S1614) and chromosome 9q34 (near markers D9S1826 and D9S1838).

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.

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.

Improving entry to methadone maintenance among out-of-treatment injection drug users

This study of 577 out-of-treatment drug injectors was designed to assess predictors of methadone maintenance treatment entry, including offering free treatment coupons. Using targeted sampling methods, participants were recruited through street outreach; randomly, they were either assigned a coupon for 90 days of free treatment or required to pay for their treatment. Regardless of assignment, all subjects who desired treatment were provided transportation, rapid intake, and a waiver of the treatment entry fee. Overall, 33% entered treatment, including 66% of those who received a free coupon. Other factors associated with treatment entry included desire for treatment, heroin use, prior treatment experience, associating with fewer drug-using friends, and injecting with a previously used unsterile needle/syringe. Injecting cocaine and smoking crack reduced the probability of treatment entry. Findings lend support to street outreach efforts designed to increase rates of treatment entry among chronic out-of-treatment drug injectors. Additional treatment options are required for those abusing cocaine.

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.