Pharmacotherapy of the Preschool ADHD Treatment Study (PATS) Children Growing Up.

OBJECTIVE: To describe the long-term psychopharmacological treatment of children first diagnosed with attention-deficit/hyperactivity disorder (ADHD) as preschoolers. METHOD: In a systematic, prospective, naturalistic follow-up, 206 (68.0%) of the 303 children who participated in the Preschool ADHD Treatment Study (PATS) were reassessed 3 years (mean age 7.4 years) and 179 (59.1%) were reassessed 6 years (mean age 10.4 years) after completion of the controlled study. Pharmacotherapy and clinical data were obtained from the parents. Pharmacotherapy was defined as use of a specific class of medication for at least 50% of the days in the previous 6 months. RESULTS: At year 3, a total of 34.0% of the participants were on no pharmacotherapy, 41.3% were on stimulant monotherapy, 9.2% were on atomoxetine alone or with a stimulant, 8.3% were on an antipsychotic usually together with a stimulant, and the remaining 7.2% were on other pharmacotherapy; overall, 65.0% were on an indicated ADHD medication. At year 6, a total of 26.8% of the participants were on no pharmacotherapy, 40.2% were on stimulant monotherapy, 4.5% were on atomoxetine alone or with a stimulant, 13.4% were on an antipsychotic, and 15.1% were on other pharmacotherapy; overall, 70.9% were on an indicated ADHD medication. Antipsychotic treatment was associated with more comorbidity, in particular disruptive behavior disorders and pervasive development disorders, and a lower level of functioning. CONCLUSION: In this study, the long-term pharmacotherapy of preschoolers with ADHD was heterogeneous. Although stimulant medication continued to be used by most children, about 1 child in 4 was off medication, and about 1 in 10 was on an antipsychotic.

The Preschool Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS) 6-year follow-up.

OBJECTIVE: To describe the clinical course of attention-deficit/hyperactivity disorder (ADHD) symptom severity and diagnosis from ages 3 to 5 up to 9 to 12 years during a 6-year follow-up after the original Preschool ADHD Treatment Study (PATS). METHOD: A total of 207 participants (75% male) from the original PATS, assessed at baseline (mean age, 4.4 years, when all met criteria for ADHD) and 3 months later (before medication treatment), were re-evaluated in three follow-up assessment visits (year 3, mean age 7.4 years; year 4, 8.3 years; and year 6, 10.4 years). Parents and teachers rated symptom severity, and clinicians established psychiatric diagnoses. Analyses examined longitudinal changes in symptom severity and ADHD diagnosis. RESULTS: Parent- and teacher-rated symptom severity decreased from baseline to year 3 but remained relatively stable and in the moderate-to-severe clinical range through year 6. Girls showed generally steeper decreases in symptom T-scores. At year 6, 89% (160/180) of remaining participants met ADHD symptom and impairment diagnostic criteria. Comorbidity of oppositional defiant disorder and/or conduct disorder was associated with a 30% higher risk of having an ADHD diagnosis at year 6 in the multiple logistic model. Medication status during follow-up, on versus off, did not predict symptom severity change from year 3 to year 6 after adjustment for other variables. CONCLUSIONS: ADHD in preschoolers is a relatively stable diagnosis over a 6-year period. The course is generally chronic, with high symptom severity and impairment, in very young children with moderate-to-severe ADHD, despite treatment with medication. Development of more effective ADHD intervention strategies is needed for this age group.

The open-label treatment of attention-deficit/hyperactivity disorder in 4- and 5-year-old children with beaded methylphenidate.

OBJECTIVE: The aim of this study was to assess the effectiveness and tolerability of a long-acting methylphenidate (MPH) formulation, beaded MPH (B-MPH), for treatment of attention-deficit/hyperactivity disorder (ADHD) in 4- and 5-year-old children. METHOD: Eleven children (9 boys and 2 girls) with ADHD received 4 weeks of B-MPH treatment in a single-site, open-label pilot study. Medication dosing was flexible, with titration to a maximum of 30 mg/day. A brief education session on behavior management was offered to parents at each treatment visit. RESULTS: Subjects experienced a mean decrease of 1.09 (standard deviation [SD]=0.73, p<0.01) on the Swanson, Nolan, and Pelham Questionnaire (SNAP-IV) ADHD composite score to an end point of 1.18 (SD=0.64). Subjects demonstrated mean decreases in scores of inattention of 1.01 (SD=0.85, p<0.01) and in hyperactivity/impulsivity of 1.17 (SD=0.74, p<0.01), with end point scores of 1.10 (SD=0.61) and 1.26 (SD=0.77), respectively. The Clinical Global Impressions-Severity (CGI-S) scale showed a statistically significant improvement from a baseline mean of 5 to the final visit mean of 3.36 (p<0.01). At the final visit, the mean daily B-MPH dose was 17.73 mg. Subjects did not experience any statistically significant changes in weight, blood pressure, or pulse during the study. The most common adverse event was decreased appetite. CONCLUSION: B-MPH was safe and effective for the treatment of ADHD in the 4- and 5-year-olds participating in this study.

A clinical review of outcomes of the multimodal treatment study of children with attention-deficit/hyperactivity disorder (MTA).

Over the past decade, the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder has provided a bewildering wealth of data (more than 70 peer-reviewed articles) addressing treatment-related questions for children with attention-deficit/hyperactivity disorder. However, the take-home messages for clinicians may not always be clear. Therefore, this article reviews key findings, including relative benefits of medication and behavioral treatments, long-term effects at 2 and 3 years, treatment mediators and moderators, preliminary delinquency and substance use outcomes, and growth suppression related to stimulant use. Appropriate interpretations of the findings and their limitations are discussed, and recommendations for clinical practice are derived.

A pilot study of atomoxetine in young children with attention-deficit/hyperactivity disorder.

OBJECTIVE: The purpose of this study was to assess the effectiveness and tolerability of atomoxetine during acute treatment of attention-deficit/hyperactivity disorder (ADHD) in 5 and 6 year olds. METHOD: Twenty two children (male n = 19, 86%) with ADHD were treated with atomoxetine for 8 weeks in a three-site, open-label pilot study. Dosing was flexible, with titration to a maximum of 1.8 mg/kg per day. Parent education on behavior management was provided as part of each pharmacotherapy visit. RESULTS: Subjects demonstrated a mean decrease of 20.68 points (SD = 12.80, p < 0.001)) on the ADHD Rating Scale-IV (ADHD-IV-RS) total score, 10.18 (SD = 7.48, p < 0.001) on the inattentive subscale and 10.50 (SD = 7.04, p < 0.001) on the hyperactive/impulsive subscale. Clinical Global Impression-Severity (CGI-S) was improved in 82% of the children (95% CI, 66-98%) and Children's Global Assessment (CGAS) scores improved 18.91 points on average (SD = 12.20, p < 0.001). The mean final dose of atomoxetine was 1.25 mg/kg per day (SD = 0.35 mg/kg per day). Mood lability was the most commonly reported adverse event (n = 12, 54.5%). Eleven subjects (50%) reported decreased appetite and a mean weight loss of 1.04 kg (SD = 0.80 kg) (p < 0.001) was observed for the group. Vital sign changes were mild and not clinically significant. There were no discontinuations due to adverse events or lack of efficacy. CONCLUSION: Atomoxetine was generally effective for reducing core ADHD symptoms in the 5 and 6 year olds in this open-label study.

Adverse life events in elderly patients with major depression or dysthymic disorder and in healthy-control subjects.

The authors compared elderly outpatients (> or =60 years) with major depression or dysthymic disorder and healthy-control subjects on the type and subjective impact of adverse life events. The Geriatric Adverse Life Events Scale (GALES) was developed for this purpose. Fifty patients with major depression, 79 patients with dysthymic disorder, and 40 healthy controls completed the GALES. Adverse life events during two time periods were assessed: the year before the evaluation, and the year before onset of the index episode (patients only). During the year before evaluation, patients with major depression reported more life events with greater negative impact, particularly for interpersonal conflicts, and dysthymic patients scored intermediate between patients and controls. Sum scores for perceived stress and negative impact on mood differed significantly among the groups: highest for major depression, intermediate for dysthymic disorder, and lowest for controls. During the year before onset, patients with major depression reported significantly higher sum scores for negative impact on mood than patients with dysthymic disorder. On several measures, patients with major depression perceived greater negative impact of life events than patients with dysthymic disorder and healthy controls, particularly for interpersonal conflicts. The subjective impact of adverse life events may play an important role in the expression of depressive illness in elderly patients, particularly in major depression, and it needs to be considered in clinical management.