Clinical trial NCT00918567: Impact of Strattera and Behavior Therapy on the Home and School Functioning of Children With ADHD
Official title: Effects of Strattera and Behavior Therapy on the School and Home Functioning of Elementary School Children With Attention-Deficit/Hyperactivity Disorder (ADHD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Attention Deficit Hyperactivity Disorder
Keywords: ADHD
Atomoxetine
Behavior Therapy
Lead sponsor: State University of New York at Buffalo
Sponsor class: OTHER
Collaborators: name: Eli Lilly and Company
First posted: 2009-06-11
Enrollment: 56
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Background: Multiple studies have found Atomoxetine (Strattera) to be efficacious but there is only one published study specifically designed to evaluate its efficacy in school settings. In this 7 week placebo-controlled study, Atomoxetine (ATX) at mean dose of 1.3 mg/kg, significantly reduced teacher rated ADHD symptoms (Weiss et al., 2005). However, children are typically referred for treatment because of "real life" problems in functioning, not symptoms (Pelham, Fabiano, \& Massetti, 2005). While ATX has been found to produce functional improvements at home, the Weiss study found limited results in this area at school.

Furthermore, almost no research has examined the effects of combining ATX and behavior therapy (BT). In the MTA, adding BT to stimulants improved teacher ratings of hyperactivity/impulsivity and increased the number of subjects reaching optimal response (Swanson et al., 2001). Therefore, it is possible that the addition of BT to ATX may improve functional performance in the classroom. The effects of combined therapy may be even larger for ATX as monotherapy with nonstimulants produces smaller effect sizes than with stimulants.

Objective: The primary objective was to evaluate the effects of ATX alone and in combination with BT on the school functioning of 56 children ages 6-12 with ADHD. Outcomes were assessed using traditional symptoms measures as well as functional measures of academic and behavioral improvements in the classroom.

Detailed description: The objectives were evaluated in an 8 week open label trial of where half of the participants were randomly assigned to receive (ATX+BT) while the rest received only ATX. An open label design was employed as the efficacy of ATX for ADHD symptoms has been established and to ensure that all patients received at least one active treatment. Parents in the ATX+BT group attended an eight week parenting course using the Community Oriented Parent Education (COPE) program (Cunningham, Bremner, \& Secord, 1998) while the child participated in an eight week social skills course. Teachers implemented a Daily Report Card (DRC) to track classroom behaviors. In the BT group, the child's DRC performance was communicated daily to parents and tied to consequences at home and school. In the ATX group, parents were not provided with the DRCs. The ATX dosing protocol was as follows: .5mg/kg per day on days 1-3, .8mg/kg/day days 4-7, 1.2mg/kg days 8+. After 3 weeks, subjects were eligible to increase to 1.8mg/kg/day. ATX was dosed once in the morning but could be dosed BID to address tolerability. The mean final dose was 1.4mg/kg/day.

To be enrolled, children must have had an IQ \> 75, not failed a trial of ATX, met DSM criteria for ADHD but not other psychiatric comorbidities except ODD/CD and be in good physical health. Children already taking ADHD medication were enrolled only if the average symptom score on the ADHD subscale of the Disruptive Behaviors Disorders (DBD) scale was \>2 (moderate impairment). ADHD was confirmed by parent report on the DISC and the DBD, which rates all DSM 3R and IV symptoms of ODD, CD and ODD on a 0-3 likert scale. Subjects were also required to evidence ADHD symptoms in the classroom as rated on the IOWA Conners. Psychiatric comorbidities were assessed using the DISC.

Measures of treatment response included:

1. Parents and teacher ratings on the IOWA Conners: 10 item Likert ratings to measure children's inattention-overactive-impulsive and oppositional-defiant behavior (Milich, Loney, \& Landau, 1982)
2. Parent and teacher ratings on the Impairment Rating Scale (IRS): 8 items using visual-analogue scales to measure children's functional impairment in peer relationships, adult-child relationships, academic performance, classroom behavior, and self esteem (Fabiano et al., 2006).
3. Parent and teacher side effect ratings using a structured list of common side effects seen with ATX modeled after the Pittsburgh Side Effects Rating Scale (Pelham, 1993).
4. Direct observations of subjects to measure rule violations and on/off task behavior using a modified version of the COCADD system (Atkins, Pelham \& Licht, 1988) in which trained observers watched children in their classroom for 30 minutes, recording each rule violation and off-task behavior.
5. Parent and teacher rating on the Social Skills Rating Scale (SSRS): a measure of teachers' and parents perceptions of children's social and academic skills and of their overall problem behaviors (Gresham \& Elliott, 1990).

Eligibility criteria: Inclusion Criteria:

1. meet DSM-IV diagnostic criteria for ADHD-combined type;
2. estimated IQ of 75 or higher;
3. agree to comply with the randomly assigned treatment condition;
4. enrolled in full time school at first grade level or higher; AND
5. have a primary teacher available to complete ratings for the entire study duration.

Exclusion Criteria:

1. current or past history of seizures (not including benign febrile seizures) or other neurological disorders;
2. physical conditions that preclude administration of Strattera or other medical illness that might confound study results or increase the safety risk to subjects exposed to study treatments (i.e. marked cardiac conduction delay, etc.);
3. prior failed trial of Strattera defined as 3 weeks or more on a daily dose of Strattera of at least .8mg/kg or a documented inability to tolerate at least .8mg/kg/day;
4. serious forms of psychopathology other than ADHD, such autism, bipolar disorder, schizophrenia or any other psychopathology requiring urgent treatment with psychotropic medication; OR
5. children for whom discontinuation of their current psychotropic medication would represent a serious risk to themselves or others.

The presence of Oppositional Defiant Disorder (ODD), Conduct Disorder (CD) or learning disabilities will not result in exclusion from the study as they are commonly occurring comorbidities that have not been found to moderate response to ADHD treatments (Jensen et al., 2001). Enrollment in special education services will also not be an exclusionary criteria as work by this research group has found that such services do not affect response to ADHD treatments (Niemic, Fabiano, Pelham, \& Fuller, 2002).

Primary outcomes:
measure: Rule Violations During Direct Classroom Observation at Endpoint (Week 8)
timeFrame: Endpoint (Week 8)
Secondary outcomes:
measure: Impairment Rating Scale (Parent Completed) at Endpoint
timeFrame: Endpoint (Week 8)
measure: Impairment Rating Scale (Teachers) at Endpoint
timeFrame: Endpoint (Week 8)
measure: Pittsburgh Side Effects Rating Scale (PSERS)(Parent Completed) at Endpoint:
timeFrame: Endpoint (Week 8)
measure: Pittsburgh Side Effects Rating Scale (PSERS)(Teacher Rated):
timeFrame: at weeks 8 (Endpoint)
measure: Disruptive Behavior Disorders Rating Scale ODD Subscale (DBD- Parent Completed) at Endpoint
timeFrame: Endpoint (Week 8)
measure: Disruptive Behavior Disorder Rating Scale ODD Subscale(DBD- Teacher Completed) at Endpoint
timeFrame: Endpoint (Week 8)
measure: Social Skills Rating Scale Problem Behavior Subscale(SSRS Parent) at Endpoint
timeFrame: Endpoint (Week 8)
measure: Social Skills Rating Scale Problem Behavior Subscale(SSRS Teachers) at Endpoint
timeFrame: Endpoint (Week 8)
measure: ADHD Subscale of the DBD (Parent Completed) at Endpoint
timeFrame: Endpoint (Week 8)
measure: ADHD Subscale of the DBD (Teacher Completed) at Endpoint
timeFrame: Endpoint (Week 8)
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Cennter for Children and Families
state: New York
Study officials:
affiliation: SUNY Buffalo
name: James G Waxmonsky
role: PRINCIPAL_INVESTIGATOR
affiliation: SUNY Buffalo
name: Daniel A Waschbusch
role: PRINCIPAL_INVESTIGATOR
References:
citation: Waxmonsky JG, Waschbusch DA, Pelham WE, Draganac-Cardona L, Rotella B, Ryan L. Effects of atomoxetine with and without behavior therapy on the school and home functioning of children with attention-deficit/hyperactivity disorder. J Clin Psychiatry. 2010 Nov;71(11):1535-51. doi: 10.4088/JCP.09m05496pur. Epub 2010 Jun 29.