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| Name | Class |
|---|---|
| Eli Lilly and Company | INDUSTRY |
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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.
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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Combined therapy | Experimental | atomoxetine plus behavior therapy |
|
| Drug therapy | Active Comparator | atomoxetine alone |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| atomoxetine | Drug | open label treatment dosed up to 1.8mg/kg/day |
|
| Measure | Description | Time Frame |
|---|---|---|
| Rule Violations During Direct Classroom Observation at Endpoint (Week 8) | Observations were conducted using the Student Behavior Teacher Response Observation Code. After learning the classroom rules, observers watched children in their classrooms for 30 minutes during an academic activity and recorded each time the subject violated a classroom rule. Total classroom rule violations were used as the primary outcome measures for the study. | Endpoint (Week 8) |
| Measure | Description | Time Frame |
|---|---|---|
| Impairment Rating Scale (Parent Completed) at Endpoint | The IRS is a 8 item measure that uses visual-analogue scales to evaluate the child's problem level and need for treatment in developmentally important areas, such as peer relationships, adult-child relationships, academic performance, and classroom behavior 51. The scale is scored from 0 (no problem) to 6 (extreme problem). The scale has excellent test-retest and inter-rater reliability and well supported validity 51, 52. |
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Inclusion Criteria:
Exclusion Criteria:
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).
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| Name | Affiliation | Role |
|---|---|---|
| James G Waxmonsky | SUNY Buffalo | Principal Investigator |
| Daniel A Waschbusch | SUNY Buffalo | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cennter for Children and Families | Buffalo | New York | 14214 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20673557 | Derived | 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. |
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uneven number because set of twins randomized as one unit at parental request
Subjects were recruited from schools, pediatric offices and the local community through radio and print advertisement. Subjects were recruited between Jan of 2007 and the spring of 2008.
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| ID | Title | Description |
|---|---|---|
| FG000 | Combined Therapy | atomoxetine plus behavior therapy |
| FG001 | Drug Therapy | atomoxetine alone |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Combined Therapy | atomoxetine plus behavior therapy |
| BG001 | Drug Therapy | atomoxetine alone |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Rule Violations During Direct Classroom Observation at Endpoint (Week 8) | Observations were conducted using the Student Behavior Teacher Response Observation Code. After learning the classroom rules, observers watched children in their classrooms for 30 minutes during an academic activity and recorded each time the subject violated a classroom rule. Total classroom rule violations were used as the primary outcome measures for the study. | all subjects analyzed using ITT | Posted | Mean | Standard Error | number occurences per 30 mins | Endpoint (Week 8) |
|
The Pittsburgh Side Effect Rating Scale (PSERS) measures adverse events commonly associated with ADHD medication rated from 0 ("none") to 3 ("severe"). Both teachers and parents completed it at weeks 1, 3 and 8.
Because of concerns over adverse emotional reactions with three specific items were examined separate from the total score: (1) suicidal statements (e.g., "I wish I was dead"); (2) crabby/irritable; and (3) tearful, sad, depressed. In addition, weight, height and resting blood pressure were monitored at each office visit (weeks 0, 3 and 8).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Combined Therapy | atomoxetine plus behavior therapy |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Trouble Sleeping | Psychiatric disorders | Systematic Assessment | computed from combined PSESR ratings from parents and teachers at weeks 1, 3 and 8 |
The primary limitation of this study was the lack of a control condition, thereby limiting our ability to detect the causality of observed improvements. Study may not have had sufficient subjects to detect group differences on secondary measures.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| James Waxmonsky M.D. | SUNY Buffalo | 305 348 3258 | jwaxmons@fiu.edu |
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| ID | Term |
|---|---|
| D001289 | Attention Deficit Disorder with Hyperactivity |
| ID | Term |
|---|---|
| D019958 | Attention Deficit and Disruptive Behavior Disorders |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D000069445 | Atomoxetine Hydrochloride |
| D004358 | Drug Therapy |
| D001521 | Behavior Therapy |
| ID | Term |
|---|---|
| D011437 | Propylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D013812 | Therapeutics |
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| Behavior Modification Therapy | Behavioral | 8 week behavioral modification course with school consultation, parenting groups using COPE and child social skills group |
|
|
| Endpoint (Week 8) |
| Impairment Rating Scale (Teachers) at Endpoint | The IRS is a 6 item measure that uses visual-analogue scales to evaluate the child's problem level and need for treatment in developmentally important areas, such as peer relationships, adult-child relationships, academic performance, and classroom behavior. The scale is scored from 0 (no problem) to 6 (extreme problem). The scale has excellent test-retest and inter-rater reliability and well supported validity. | Endpoint (Week 8) |
| Pittsburgh Side Effects Rating Scale (PSERS)(Parent Completed) at Endpoint: | The PSERS measures adverse events commonly associated with stimulant medication and has been used in multiple studies of ADHD. For this study, the PSERS was modified to also assess adverse emotional events potentially associated with ATX, including suicidal statements. The resulting scale consisted of 14 items (an additional sleep item for parents) rated from 0 ("none") to 3 ("severe"). An overall side effects score was computed by averaging across all ratings and used in analyses. | Endpoint (Week 8) |
| Pittsburgh Side Effects Rating Scale (PSERS)(Teacher Rated): | The PSERS measures adverse events commonly associated with stimulant medication and has been used in multiple studies of ADHD. For this study, the PSERS was modified to also assess adverse emotional events potentially associated with ATX, including suicidal statements. The resulting scale consisted of 13 items (for teachers) rated from 0 ("none") to 3 ("severe"). An overall side effects score was computed by averaging across all ratings and used in analyses. | at weeks 8 (Endpoint) |
| Disruptive Behavior Disorders Rating Scale ODD Subscale (DBD- Parent Completed) at Endpoint | The DBD consists of 8 items that are the DSM-IV symptoms of Oppositional Defiant Disorder (ODD). Items on the DBD were rated by parents and teachers using Likert scales that ranged from 0 ("not at all") to 3 ("very much"). The factor structure, reliability and validity of the DBD have been supported in multiple studies. | Endpoint (Week 8) |
| Disruptive Behavior Disorder Rating Scale ODD Subscale(DBD- Teacher Completed) at Endpoint | The DBD consists of 8 items that are the DSM-IV symptoms of Oppositional Defiant Disorder (ODD). Items on the DBD were rated by parents and teachers using Likert scales that ranged from 0 ("not at all") to 3 ("very much"). The factor structure, reliability and validity of the DBD have been supported in multiple studies. | Endpoint (Week 8) |
| Social Skills Rating Scale Problem Behavior Subscale(SSRS Parent) at Endpoint | completed by parents to measure children's problem behaviors (PB). Items are rated from 0 ("not at all") to 2 ("very often"). The scale has 55 items. The score reported below is the sum total of the items on the scale and then averaged for the whole group. Therefore, the range can be between 0 and 110. A higher score indicates a better outcome. | Endpoint (Week 8) |
| Social Skills Rating Scale Problem Behavior Subscale(SSRS Teachers) at Endpoint | The SSRS was completed by teachers to measure children's problem behaviors (PB). Items are rated from 0 ("not at all") to 2 ("very often"). The scale has 55 items. The score reported below is the sum total of the items on the scale and then averaged for the whole group. Therefore, the range can be between 0 and 110. A higher score indicates a better outcome. | Endpoint (Week 8) |
| ADHD Subscale of the DBD (Parent Completed) at Endpoint | The DBD consists of 18 items that are the DSM-IV symptoms of ADHD. Items on the DBD were rated by parents and teachers using Likert scales that ranged from 0 ("not at all") to 3 ("very much"). The factor structure, reliability and validity of the DBD have been supported in multiple studies. | Endpoint (Week 8) |
| ADHD Subscale of the DBD (Teacher Completed) at Endpoint | The ADHD subscale of the DBD consists of 18 items that are the DSM-IV symptoms of ADHD. Items on the DBD were rated by parents and teachers using Likert scales that ranged from 0 ("not at all") to 3 ("very much"). The factor structure, reliability and validity of the DBD have been supported in multiple studies. | Endpoint (Week 8) |
| Adverse Event |
|
| BG002 |
| Total |
Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
atomoxetine alone
|
|
|
| Secondary | Impairment Rating Scale (Parent Completed) at Endpoint | The IRS is a 8 item measure that uses visual-analogue scales to evaluate the child's problem level and need for treatment in developmentally important areas, such as peer relationships, adult-child relationships, academic performance, and classroom behavior 51. The scale is scored from 0 (no problem) to 6 (extreme problem). The scale has excellent test-retest and inter-rater reliability and well supported validity 51, 52. | Intent to treat | Posted | Mean | Standard Error | units on a scale | Endpoint (Week 8) |
|
|
|
|
| Secondary | Impairment Rating Scale (Teachers) at Endpoint | The IRS is a 6 item measure that uses visual-analogue scales to evaluate the child's problem level and need for treatment in developmentally important areas, such as peer relationships, adult-child relationships, academic performance, and classroom behavior. The scale is scored from 0 (no problem) to 6 (extreme problem). The scale has excellent test-retest and inter-rater reliability and well supported validity. | ITT was used | Posted | Mean | Standard Error | units on a scale | Endpoint (Week 8) |
|
|
|
|
| Secondary | Pittsburgh Side Effects Rating Scale (PSERS)(Parent Completed) at Endpoint: | The PSERS measures adverse events commonly associated with stimulant medication and has been used in multiple studies of ADHD. For this study, the PSERS was modified to also assess adverse emotional events potentially associated with ATX, including suicidal statements. The resulting scale consisted of 14 items (an additional sleep item for parents) rated from 0 ("none") to 3 ("severe"). An overall side effects score was computed by averaging across all ratings and used in analyses. | ITT was used | Posted | Mean | Standard Error | units on a scale | Endpoint (Week 8) |
|
|
|
|
| Secondary | Pittsburgh Side Effects Rating Scale (PSERS)(Teacher Rated): | The PSERS measures adverse events commonly associated with stimulant medication and has been used in multiple studies of ADHD. For this study, the PSERS was modified to also assess adverse emotional events potentially associated with ATX, including suicidal statements. The resulting scale consisted of 13 items (for teachers) rated from 0 ("none") to 3 ("severe"). An overall side effects score was computed by averaging across all ratings and used in analyses. | ITT was used | Posted | Mean | Standard Error | units on a scale | at weeks 8 (Endpoint) |
|
|
|
|
| Secondary | Disruptive Behavior Disorders Rating Scale ODD Subscale (DBD- Parent Completed) at Endpoint | The DBD consists of 8 items that are the DSM-IV symptoms of Oppositional Defiant Disorder (ODD). Items on the DBD were rated by parents and teachers using Likert scales that ranged from 0 ("not at all") to 3 ("very much"). The factor structure, reliability and validity of the DBD have been supported in multiple studies. | ITT was used | Posted | Mean | Standard Error | units on a scale | Endpoint (Week 8) |
|
|
|
|
| Secondary | Disruptive Behavior Disorder Rating Scale ODD Subscale(DBD- Teacher Completed) at Endpoint | The DBD consists of 8 items that are the DSM-IV symptoms of Oppositional Defiant Disorder (ODD). Items on the DBD were rated by parents and teachers using Likert scales that ranged from 0 ("not at all") to 3 ("very much"). The factor structure, reliability and validity of the DBD have been supported in multiple studies. | ITT was used | Posted | Mean | Standard Error | units on a scale | Endpoint (Week 8) |
|
|
|
|
| Secondary | Social Skills Rating Scale Problem Behavior Subscale(SSRS Parent) at Endpoint | completed by parents to measure children's problem behaviors (PB). Items are rated from 0 ("not at all") to 2 ("very often"). The scale has 55 items. The score reported below is the sum total of the items on the scale and then averaged for the whole group. Therefore, the range can be between 0 and 110. A higher score indicates a better outcome. | ITT was used | Posted | Mean | Standard Error | units on a scale | Endpoint (Week 8) |
|
|
|
|
| Secondary | Social Skills Rating Scale Problem Behavior Subscale(SSRS Teachers) at Endpoint | The SSRS was completed by teachers to measure children's problem behaviors (PB). Items are rated from 0 ("not at all") to 2 ("very often"). The scale has 55 items. The score reported below is the sum total of the items on the scale and then averaged for the whole group. Therefore, the range can be between 0 and 110. A higher score indicates a better outcome. | ITT was used | Posted | Mean | Standard Error | units on a scale | Endpoint (Week 8) |
|
|
|
|
| Secondary | ADHD Subscale of the DBD (Parent Completed) at Endpoint | The DBD consists of 18 items that are the DSM-IV symptoms of ADHD. Items on the DBD were rated by parents and teachers using Likert scales that ranged from 0 ("not at all") to 3 ("very much"). The factor structure, reliability and validity of the DBD have been supported in multiple studies. | Intent to treat | Posted | Mean | Standard Deviation | units on a scale | Endpoint (Week 8) |
|
|
|
|
| Secondary | ADHD Subscale of the DBD (Teacher Completed) at Endpoint | The ADHD subscale of the DBD consists of 18 items that are the DSM-IV symptoms of ADHD. Items on the DBD were rated by parents and teachers using Likert scales that ranged from 0 ("not at all") to 3 ("very much"). The factor structure, reliability and validity of the DBD have been supported in multiple studies. | ITT used | Posted | Mean | Standard Error | units on a scale | Endpoint (Week 8) |
|
|
|
|
| 0 |
| 29 |
| 25 |
| 29 |
| EG001 | Drug Therapy | atomoxetine alone | 0 | 27 | 24 | 27 |
|
| stomachaches | Gastrointestinal disorders | Systematic Assessment | computed from combined PSESR ratings from parents and teachers at weeks 1, 3 and 8 |
|
| appetite loss | Metabolism and nutrition disorders | Systematic Assessment | computed from combined PSESR ratings from parents and teachers at weeks 1, 3 and 8 |
|
| headaches | Nervous system disorders | Systematic Assessment | computed from combined PSESR ratings from parents and teachers at weeks 1, 3 and 8 |
|
| motor tics | Nervous system disorders | Systematic Assessment | computed from combined PSESR ratings from parents and teachers at weeks 1, 3 and 8 |
|
| picking at skin | Psychiatric disorders | Systematic Assessment | computed from combined PSESR ratings from parents and teachers at weeks 1, 3 and 8 |
|
| anxiety | Psychiatric disorders | Systematic Assessment | computed from combined PSESR ratings from parents and teachers at weeks 1, 3 and 8 |
|
| dulled/tired looking | Psychiatric disorders | Systematic Assessment | computed from combined PSESR ratings from parents and teachers at weeks 1, 3 and 8 |
|
| crabby/irritable | Psychiatric disorders | Systematic Assessment | computed from combined PSESR ratings from parents and teachers at weeks 1, 3 and 8 |
|
| depressed mood/crying episodes | Psychiatric disorders | Systematic Assessment | computed from PSERS ratings from parents & teachers at weeks 1,3+8; there were 2 cases (1 per group)of expressed suicidal ideation; these 2 subjects were assessed by study doctors; neither were found to have a genuine desire to commit suicide. |
|
| withdrawn from others | Psychiatric disorders | Systematic Assessment | computed from combined PSESR ratings from parents and teachers at weeks 1, 3 and 8 |
|
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| D011613 |
| Psychotherapy |
| D004191 | Behavioral Disciplines and Activities |