American Academy

Atomoxetine Feasible in Young Children with Attention-Deficit/Hyperactivity Disorder

Speaker: Christopher J. Kratochvil, MD, Associate Professor, Department of Psychiatry, University of Nebraska; Member, Graduate Faculty of Psychiatry, University of Nebraska Medical Center; and Assistant Director, Psychopharmacol-ogy Research Consortium, University of Nebraska, Omaha, Nebraska

(Eli Lilly), a novel agent that strengthens the chemical signals between brain cells and increases neurotransmitters to improve concentration, was effective and well tolerated for the treatment of attention-deficit/hyper-activity disorder (ADHD) in children five to six years of age. The findings supported the feasibility of a multicenter, double-blind, placebo-controlled study of atomoxetine in this age group.

Twenty-two young children with ADHD were enrolled in an eight-week, open-label pilot study in which they received ato-moxetine daily. The pharmacotherapist presented psycho-educational modules for behavioral management with each pharmacotherapy visit.

Overall, the children demonstrated a significant mean decrease in ADHD-IV Rating Scale total scores of 20.68; on the Inattentive subscale, 10.18 (out of a total of 24); and on the Hyperactivity/Impulsive subscale, 10.50 (out of a total of 27) (P < .001).

The most frequently reported adverse event was decreased appetite, in 11 participants, with a mean decrease of 1.04 kg (P < .001). None of the children discontinued therapy because of adverse events or a lack of efficacy, but two children dropped out because of their inability to swallow capsules.

OROS Methylphenidate for Attention-Deficit/ Hyperactivity Disorder plus Epilepsy

Speaker: Joseph Gonzalez-Heydrich, MD, Chief of Psycho-pharmacology, Department of Psychiatry, Children’s Hospital; and Assistant Professor of Psychiatry, Harvard Medical School, Boston, Massachusetts

Osmotic Release Oral System methylphenidate (OROS MPH) (Concerta, McNeil-PPC, Inc.) was observed to be safe and well tolerated for the treatment of ADHD in patients with epilepsy. The stimulant produced no serious adverse events or increases in seizures. Compared with placebo, this agent resulted in a significant reduction in ADHD Rating Scale scores.
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Although package inserts for all MPH products contain warnings not to use MPH preparations in patients with epilepsy, few studies have evaluated the risks and benefits of MPH in children with ADHD and comorbid epilepsy, and none have evaluated OROS MPH in this population. A study was therefore performed to assess the safety and efficacy of OROS MPH in patients with ADHD and epilepsy.

Twenty-seven children, 10.7 years ±3.1 years of age (or 7.6 to 13.8 years of age), were randomly assigned to receive OROS MPH at target doses of 18, 36, or 54 mg/day or placebo. The children were then crossed over to the other group in a double-blind design. They underwent an initial one-day trial of intermediate-release (IR) MPH 5 mg twice daily, followed by weekly increases up to the maximum dose for each OROS MPH dose group.

Each patient continued with the maximum dose of OROS MPH for up to one week before endpoint measures were taken for that arm. The patients were then crossed over to the other arm of the study or referred to clinical care outside the study. If two patients had significant worsening of epilepsy during treatment at any dose level, the dose level just below that was fixed as the maximum dose to be used for the rest of the study.

Assessments at each study visit included scores from the Clinical Global Impressions (CGI) Scale and the ADHD Rating Scale, adverse events, and seizures. Responders were defined as having a CGI-Improvement (CGI-I) score of 1 (“much improved”) or 2 (“very much improved”).

Changes in total scores on the ADHD Rating Scale and the Hyperactivity and Inattentive Scale reflect a week of treatment; the longer the duration of treatment, the more changes were observed.

Improvement from baseline was greater during the study agent phase at all dose levels. Of the 27 patients given 18 mg, 11 responded to active treatment with OROS MPH and two responded to placebo. Of the 24 patients receiving OROS MPH 36 mg, 13 responded to active treatment and three responded to placebo. Of the 12 patients in the 54 mg OROS MPH group, nine responded; of the 16 patients given placebo, one responded.

The study medication and higher dosages predicted greater decreases in CGI-Severity (CGI-S) scores (P< .001).

There were no serious adverse effects. Seizures occurred with both OROS MPH treatment and with placebo in two patients. One other patient experienced a seizure while taking placebo but was seizure-free while taking OROS MPH. The weekly seizure rate with placebo treatment was higher (0.111 seizures per week) than with OROS MPH (0.074 seizures per week).