Daniel F. Connor

Psychopharmacology and aggression. I: A meta-analysis of stimulant effects on overt/covert aggression-related behaviors in ADHD.

OBJECTIVE To determine by meta-analysis the effect size for stimulants on overt and covert aggression-related behaviors in children with attention-deficit/hyperactivity disorder (ADHD), separately from stimulant effects on the core symptoms of ADHD. METHOD A review of the literature from 1970 to 2001 revealed 28 studies meeting inclusion/exclusion criteria for meta-analysis. These studies yielded 28 independent effects of overt aggression and 7 independent effects of covert aggression. RESULTS The overall weighted mean effect size was 0.84 for overt and 0.69 for covert aggression related behaviors in ADHD. Comorbid conduct disorder is associated with diminishing stimulant effect size for overt aggression. CONCLUSION Stimulant effects for aggression-related behaviors in ADHD have effect sizes similar to those for the core symptoms of ADHD.

A pilot study of methylphenidate, clonidine, or the combination in ADHD comorbid with aggressive oppositional defiant or conduct disorder.

A pilot comparison of the safety and efficacy of methylphenidate (MPH) combined with clonidine, clonidine monotherapy, or MPH monotherapy in 6to 16-year-old children diagnosed with attention deficit hyperactivity disorder (ADHD) and comorbid aggressive oppositional defiant disorder or conduct disorder was completed. Study design was a 3-month, randomized, blinded, group comparison with eight subjects per group. No placebo comparison was used. All three treatment groups showed significant improvements in attention deficits, impulsivity, oppositional, and conduct disordered symptoms as assessed by parent and teacher rating scales and laboratory measures. Significant differences among treatment groups were found only on a few measures. Only the clonidine monotherapy group showed significantly decreased fine motor speed. These results suggest the safety and efficacy of clonidine alone or in combination with MPH for the treatment of ADHD and aggressive oppositional and conduct disorders.

Characteristics of Children and Adolescents Admitted to a Residential Treatment Center

Studies of youths in residential treatment that utilize systematic assessments and validated measures are rare. We examined psychopathology, family characteristics, occurrence of physical or sexual abuse, types of aggressive behavior, hyperactive/impulsive behavior, medical and neurological problems, and self-reported drug and alcohol use in 397 youth who were assessed using reliable measures and consecutively treated in a residential treatment center. Results indicate high rates of internalizing and externalizing psychopathology, aggressive behavior, and consistent gender differences, with girls having higher levels of internalizing and externalizing psychopathology and aggressive behavior. The sample was characterized by high rates of medical problems including asthma, seizures, and obesity, as well as evidence of extensive family dysfunction, including high rates of parental alcohol use, violence, and physical or sexual abuse. Residential treatment needs to progress beyond the one size fits all approach and develop more specific and empirically proven treatments for the specific needs of this population.

Preschool attention deficit hyperactivity disorder: A review of prevalence, diagnosis, neurobiology, and stimulant treatment

ABSTRACT. The clinical use of stimulant medications for 3- to 6-year-old preschool children who meet diagnostic criteria for attention deficit hyperactivity disorder (ADHD) is becoming more common. A systematic computerized literature search extending back to 1970 identified nine controlled studies of stimulant treatment and two controlled trials of stimulant side effects in preschool ADHD children. Treatment benefits are reported for eight of nine (89%) controlled stimulant trials involving a total of 206 preschool subjects. In comparison with school-aged ADHD youth, there may be a greater variability of stimulant response in ADHD preschoolers. Domains assessing cognition, interpersonal interactions, and hyperactive-impulsive behavior are noted to improve on drugs relative to placebos. Side effects in this age range are generally reported as mild. ADHD preschool children may experience slightly more and different types of stimulant-induced side effects compared with older children. High rates of behavior reported as stimulant side effects are found for children receiving a placebo, necessitating a baseline evaluation for medication side effects before stimulants are initiated. Despite the lack of research assessing stimulant effects on the very young and developing brain and the need for more controlled medication trials in this age range, this review of the extant literature finds stimulants to meet evidence based criteria as beneficial and safe for carefully diagnosed ADHD preschool children aged 3 years and older.

Correlates of comorbid psychopathology in children with ADHD

OBJECTIVE To investigate correlates of internalizing and externalizing psychopathology in a clinical sample of children with attention-deficit/hyperactivity disorder (ADHD). METHOD Parent and teacher Child Behavior Checklists were administered to 300 children with ADHD to ascertain comorbid symptoms. Based on previous research, a seven-step hierarchical regression analysis was developed. Six hierarchical regression analyses were conducted with either parent or teacher Child Behavior Checklist aggression, delinquency, or anxious/depressive comorbid symptoms as dependent measures. RESULTS Controlling for (1) variables known to increase risk for ADHD child psychopathology and (2) estimated duration of ADHD, our results suggest that the presence of comorbid symptoms is influenced by age of onset. An early age of onset of ADHD was correlated with a greater rate of parent-reported child aggressive symptoms, and a later age of onset was correlated with a greater rate of parent-reported child anxious/depressive symptoms. Elevated levels of comorbid externalizing and internalizing symptoms are associated with greater ADHD symptom severity. CONCLUSIONS Comorbid externalizing and internalizing symptoms are correlated with age of ADHD onset and are related to the severity of clinical presentation in a referred sample of children with ADHD.

Bupropion XL in adults with attention-deficit/hyperactivity disorder : A randomized, placebo-controlled study

BACKGROUND Data remain limited on treatment strategies for adults with attention-deficit/hyperactivity disorder (ADHD). This study evaluated the efficacy and safety of an extended-release, once-daily formulation of bupropion (XL) in the treatment of adults with ADHD. METHODS This multisite, placebo-controlled, 8-week prospective trial evaluated 162 adult patients diagnosed with ADHD (combined and inattentive types). Subjects were treated with up to 450 mg/day of bupropion XL. The primary efficacy endpoint was the proportion of ADHD responders (defined as at least a 30% reduction in the investigator-rated ADHD Rating Scale score) at week 8 (last observation carried forward [LOCF]). RESULTS Bupropion XL responders (53%) exceeded placebo responders (31%) (p =.004 at week 8) with a significantly greater proportion of bupropion XL responders as early as week 2 (p = .01). Treatment effect size calculated for the ADHD Rating Scale total score was .6. Bupropion XL appeared to provide sustained benefit throughout the day compared with placebo (morning p =.033, afternoon p =.004, evening p = .024). Bupropion XL was safe and well tolerated, with no serious or unexpected adverse events and a low rate of drug-related study discontinuation (5%). CONCLUSIONS The results from this multisite study indicate that bupropion XL is an effective and well-tolerated nonstimulant treatment for adult ADHD.

Gender Differences in Reactive and Proactive Aggression

The purpose of our investigation was to study gender differences in proactive and reactive aggression in a sample of 323 clinically referred children and adolescents (68 females and 255 males). Proactive aggression and reactive aggression were assessed using the Proactive/Reactive Aggression Scale. Demographic, historical, family, diagnostic, and treatment variables were entered into stepwise regression analyses to determine correlates of proactive and reactive aggression in males and females. Results reveal high rates of aggression in both males and females in the sample. Self reported drug use, expressed hostility, and experiences of maladaptive parenting were correlated with proactive aggression for both genders. Hyperactive/impulsive behaviors were correlated with male reactive aggression. An early age of traumatic stress and a low verbal IQ were correlated with female proactive aggression. Gender differences in correlates of proactive and reactive aggression may provide possible targets for research, prevention, and treatment efforts focused on reducing maladaptive aggression in clinically referred youth.

COMPLEX TRAUMA AND AGGRESSION IN SECURE JUVENILE JUSTICE SETTINGS

Youth in secure juvenile justice settings (e.g., detention, incarceration) often have histories of complex trauma: exposure to traumatic stressors including polyvictimization, life-threatening accidents or disasters, and interpersonal losses. Complex trauma adversely affects early childhood biopsychosocial development and attachment bonding, placing the youth at risk for a range of serious problems (e.g., depression, anxiety, oppositional defiance, risk taking, substance abuse) that may lead to reactive aggression. Complex trauma is associated with an extremely problematic combination of persistently diminished adaptive arousal reactions, episodic maladaptive hyperarousal, impaired information processing and impulse control, self-critical and aggression-endorsing cognitive schemas, and peer relationships that model and reinforce disinhibited reactions, maladaptive ways of thinking, and aggressive, antisocial, and delinquent behaviors. This constellation of problems poses significant challenges for management, rehabilitation, and treatment of youth in secure justice settings. Epidemiological and clinical evidence of the prevalence, impact on development and functioning, comorbidity, and adverse outcomes in adolescence of exposure to complex trauma are reviewed. Implications for milieu management, screening, assessment, and treatment of youth who have complex trauma histories and problems with aggression in secure juvenile justice settings are discussed, with directions for future research and program development.

A review of attention-deficit/hyperactivity disorder complicated by symptoms of oppositional defiant disorder or conduct disorder.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent disorder with significant functional impairment. ADHD is frequently complicated by oppositional symptoms, which are difficult to separate from comorbidity with oppositional defiant disorder, conduct disorder, and aggressive symptoms. This review addresses the impact of oppositional symptoms on ADHD, disease course, functional impairment, clinical management, and treatment response. Review of clinical evidence: Oppositional defiant disorder or conduct disorder may be comorbid in more than half of ADHD cases and are more common with the combined than with the inattentive ADHD subtype. Comorbid symptoms of oppositional defiant disorder and conduct disorder in patients with ADHD can have a significant impact on the course and prognosis for these patients and may lead to differential treatment response to both behavioral and pharmacologic treatments. Impact on clinical management: Assessment of oppositional symptoms is an essential part of ADHD screening and diagnosis and should include parental, as well as educator, input. Although clinical evidence remains limited, some stimulant and nonstimulant medications have shown effectiveness in treating both core ADHD symptoms and oppositional symptoms. Conclusions: Oppositional symptoms are a key consideration in ADHD management, although the optimum approach to treating ADHD complicated by such symptoms remains unclear. Future research should focus on the efficacy and safety of various behavioral and medication regimens, as well as longitudinal studies to further clarify the relationships between ADHD, oppositional defiant disorder, and conduct disorder.

Proactive and Reactive Aggression in Referred Children and Adolescents

Investigating different types of aggression is important to facilitate a better understanding of excessive maladaptive aggression in referred youth. Using regression analysis, the authors investigated demographic, historical, diagnostic, and treatment correlates of proactive aggression and reactive aggression in a heterogeneous population (N = 323) of psychiatrically referred youths. Ratings of proactive and reactive aggression significantly correlated with more established measures of aggression. Results suggest the importance of hyperactive/impulsive behavior, disruptive behavior disorders, and self-reported hostility in youths with both reactive and proactive aggression. Substance use disorders, a family history of substance abuse, and family violence were specifically associated with proactive aggression. Younger age and a history of abuse were correlated with reactive aggression. Implications for clinical interventions and future research are discussed.