Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism

Autism is a developmental disorder that can cause severe and pervasive impairment in
thinking, feeling, language, and the ability to relate to others. It is usually first
diagnosed in early childhood. Children with autism demonstrate repetitive behaviors or
interests and deficits in social interaction, verbal communication, and nonverbal
communication. In addition, they often have unusual responses to sensory experiences, such
as certain sounds or the way objects look. Some symptoms of attention deficit hyperactivity
disorder (ADHD), such as inattention, hyperactivity, and impulsivity, are also associated
with autism. Atomoxetine is a selective norepinephrine reuptake inhibitor that is used to
treat ADHD. It works differently, however, than stimulant drugs and may help to reduce ADHD
symptoms in children with autism. This study will evaluate the effectiveness of atomoxetine
in treating children with ADHD symptoms associated with autism.

Potential participants will first attend a screening visit, which will include a psychiatric
diagnostic interview, a practice session for swallowing pill capsules, a physical exam, an
electrocardiogram (ECG), a blood test, and an assessment of pubertal stage. Females of
childbearing age will also undergo a urine pregnancy test. In an initial double-blind study
phase, eligible participants will be randomly assigned to receive either atomoxetine or
placebo for 8 weeks. A baseline visit will include several rating scales, observations, and
an interview to assess adaptive functioning. These measures and procedures will be used to
keep track of symptoms, side effects, and behavior that could change during the study.
Children who are assigned to placebo and do not notice an improvement in their ADHD symptoms
will be given the opportunity to receive atomoxetine at the end of 8 weeks. Study visits
will occur once a week for 4 weeks, and then every other week for the remainder of the 8
weeks. During these visits, many of the baseline questionnaires and interviews will be
repeated. At the Week 8 visit, the physical exam, ECG, blood tests, and some baseline
questionnaires will also be repeated. All children who respond well to atomoxetine may
continue taking the drug for an additional 10 months. During this time, participants will
report to the clinic once a month for the first 4 months, then once at the end of 7 months,
and finally once at the end of 10 months. The same measures and procedures that were done
during the 8-week phase will be done during the 10-month phase of this study.

Inclusion Criteria:

- Diagnosis of an autism spectrum disorder (autistic disorder, Asperger's syndrome, and
pervasive developmental disorder, not otherwise specified).

- Significant hyperactivity, inattention, or impulsivity as determined by a score on an
investigator-administered ADHD Rating Scale (ADHDRS)-Home Version that is at least
1.5 standard deviations above the mean for age and sex

- Parent/caregiver's primary complaint about the child is inattention, hyperactivity,
and/or impulsivity ("ADHD" symptoms)

- Symptoms present for 6 months prior to study entry

- Psychotropic drug-free for at least 2 weeks prior to starting study medication. This
drug-free period will be 5 weeks for fluoxetine (Prozac).

Exclusion Criteria:

- Weighs less than 15 kg (about 33 pounds)

- Any another psychiatric disorder that may require a different treatment, including
psychotic disorders, major affective disorders, obsessive-compulsive disorder, panic
disorder, or substance-related disorders

- Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)
diagnosis of Rett's disorder or childhood disintegrative disorder

- Presence of extreme aggression or self-injury

- Currently taking an effective psychotropic drug

- Currently using other medications that may be unsafe to take with atomoxetine (e.g.,
potent CYP 2D6 inhibitors, intravenous albuterol, monoamine oxidase inhibitors[MAO])

- Inability to swallow study medication

- Presence of a medical condition that would make treatment with atomoxetine unsafe
(e.g., unstable hypertension or cardiac disease, asthma requiring frequent treatment
with albuterol, narrow angle glaucoma, pregnancy, etc.)

- Mental age of less than 18 months

- Previous adequate trial of atomoxetine

- Previous evidence of hypersensitivity or an allergic reaction to atomoxetine

- Clinically significant abnormalities in laboratory measures indicating an undiagnosed
medical condition as determined by the study physician in discussion with the
participant's primary care physician

- Clinically significant abnormalities on ECG as determined by a pediatric cardiologist

- Pregnant

- Initiation of a new psychosocial intervention within 90 days prior to starting study
medication. Participants who have recently had a significant change in their
psychosocial interventions will not be eligible until this intervention has been
stable for 90 days in order to avoid confounding results of the study. Stable
interventions (e.g., speech and occupational therapy) will be allowed to continue
during the course of the study. Minor changes in ongoing treatment (e.g., missed
therapy sessions due to holiday/vacation planned break in therapy due to school
holidays) will not be considered significant.