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Stimulant Versus Nonstimulant Medication for Attention Deficit Hyperactivity Disorder in Children

Phase 4
Completed
Conditions
Attention Deficit Disorder With Hyperactivity
Interventions
Registration Number
NCT00183391
Lead Sponsor
Icahn School of Medicine at Mount Sinai
Brief Summary

This study will determine the effectiveness of stimulant and nonstimulant medication in treating the symptoms of attention deficit hyperactivity disorder (ADHD) in children and adolescents.

Detailed Description

ADHD is one of the most frequently occurring disorders of children and adolescents and is a significant public health problem. The most common treatment for the condition is stimulant medication. However, there are an increasing number of children who are experiencing negative side effects from stimulants, such as dizziness, loss of appetite, and headaches; these side effects have made the need for alternative treatments all the more important. This study will compare the stimulant methylphenidate to the nonstimulant atomoxetine to determine which is more effective in treating ADHD symptoms in children and adolescents. The two medications differ in the neurotransmitters they influence. Stimulants such as methylphenidate act upon the neurotransmitter dopamine, while atomoxetine works on norepinephrine. It has been proposed that the difference in neurotransmitter stimulation may result in differences in an ADHD patient's response to treatment.

Participants will be randomly assigned to receive either methylphenidate or atomoxetine for between 4 to 6 weeks, depending on how soon they respond to the treatment. After the 4 to 6 week period, participants will be crossed-over to receive whichever medication they did not receive in the first part of the study.

Participants will have up to 14 weekly study visits. Over the first two visits, participants will undergo psychological and intelligence tests, a medical history, an electrocardiogram, blood and urine collection, and a physical exam. The remaining visits will occur weekly. During these visits, participants will receive their assigned medication and, along with their parents, will complete questionnaires about their response to treatment and any side effects they may be experiencing. The teachers of all participants will be asked to complete a questionnaire about their student's behavior at 4 different times during the study. Participant, parent, and teacher questionnaires will be used to assess the ADHD symptoms of participants, as well as self-report clinical scales completed by the participants.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
232
Inclusion Criteria
  • Meets DSM-IV-TR criteria for ADHD
  • Scores at least 1.5 standard deviation higher than age and gender mean on ADHD-RS keyed to ADHD subtype
  • CGI Severity ADHD Rating greater than or equal to 4
  • Currently attends school with at least 3 months left in high school
  • Currently lives at home with parent(s) or legal guardian(s), now and for the past year before study entry, and is expected to remain there
  • Normal physical exam, laboratory tests, and electrocardiogram
  • Pulse and blood pressure within 95% of age and gender mean
  • Full Scale IQ is greater than or equal to 75 OR if the results of testing indicate that Full Scale IQ is not a good indicator of intellectual ability, a General Ability Index greater than or equal to 75
  • Weight is between 20 and 85 kilograms
  • Able to swallow pills
  • Parent or guardian willing to provide informed consent
Exclusion Criteria
  • History of atomoxetine or methylphenidate intolerance
  • Any existing medical condition for which study medications are contraindicated
  • If the child is in psychotherapy, no changes in therapy expected during the study trial
  • Presence of any of the following: autism, mental retardation, schizophrenia, a psychotic disorder, bipolar disorder, severe depression, or conduct disorder
  • Presence of a comorbid disorder that should be the primary focus of treatment
  • Presence of a medical or neurological disorder precluding study medications or assessing ADHD
  • Allergic reactions to multiple medications
  • History of alcohol or drug abuse in the 3 months before study entry, or positive urine toxic screen that is not explained by a time limited medical circumstance
  • Involved in a medication treatment study in the 30 days before study entry
  • Female who is sexually active and is unwilling to use birth control
  • Evidence of child abuse or neglect

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
AtomoxetineAtomoxetineParticipants will receive treatment for ADHD with the non-stimulant atomoxetine
AtomoxetineMethylphenidateParticipants will receive treatment for ADHD with the non-stimulant atomoxetine
MethylphenidateMethylphenidateParticipants will receive treatment for ADHD with the stimulant methylphenidate
MethylphenidateAtomoxetineParticipants will receive treatment for ADHD with the stimulant methylphenidate
Primary Outcome Measures
NameTimeMethod
ADHD-RS Total Scoreup to 14 weeks

ADHD-RS Total Score Attention Deficit Hyperactivity Disorder Rating Scale. Each item on the 18-item measure is scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms), yielding a possible total score of 0-54. Higher score indicates higher probability of diagnosis.

Secondary Outcome Measures
NameTimeMethod
Treatment Preference SurveyMeasured at ends of treatments one and two
Clinical Global Impressions (CGI)- Severityup to 14 weeks

The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.

Social Skills Rating Scale (SSRS)- Parent Versionup to 14 weeks

Measure of social skills, higher score is better. This scale is based on t-scores and does not have psychometrics available.

Child Conflict Index (CCI)up to 14 weeks

Measure of conflict within the home over the past 24 hours. The CCI is a validated measure of family conflicts in the home and is completed by parents. It consists of 42 items (for boys) or 36 items (for girls) reflecting attention-seeking and conflictual behavior, as well as negativity and withdrawal. Items are scored as yes (1 point) or no (0 points). Mean score between 0 and 1 reported, with higher score indicating greater conflict.

Continuous Performance Test (CPT)up to 14 weeks

CPT Commissions, impulsive responses, higher score is worse. This scale is based on t-scores and does not have psychometrics available.

Children's Sleep Questionnaireup to 14 weeks

Children's Sleep Problems Severity, sum of scores, higher is worse.The scale assessed contains 16 items, each scored 0 to 3, with 0 representing no problems and 3 representing daily problems. total range from 0 to 48. This score does not have psychometrics available.

Assessment of Affective Range (AAR)up to 14 weeks

Affective problems. This scale consists of 8 items, scored 0-3, with 0 representing no problems and 3 representing extreme problems. This analysis presents sum of scores, higher is worse. Full range from 0 to 24. This score does not have psychometrics available.

Conners Teacher Rating Scale- Shortup to 14 weeks

Standardized measure of ADHD symptoms and severity, norm referenced T scores, higher = worse

Social Skills Rating Scale (SSRS)- Teacher Versionup to 14 weeks

Measure of social skills, higher score is better. This scale is based on t-scores and does not have psychometrics available.

ADHD - H/Iup to 14 weeks

Attention deficit/hyperactivity disorder - hyperactivity/impulsivity (ADHD- H/I). Each item on the 18-item measure is scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms), yielding a possible total score of 0-27. Higher score indicates higher probability of diagnosis.

ADHD-RS Inattentionup to 14 weeks

Each item on the 18-item measure is scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms), yielding a possible total score of 0-27. Higher score indicates higher probability of diagnosis.

SES (Hollingshead)up to 14 weeks

Measure of socioeconomic status, score calculated from averaging likert responses, lower = worse

Conners-Wells Adolescent Self Reportup to 14 weeks

Standardized measure of ADHD symptoms and severity, norm referenced T scores, higher = worse

Tics: Total Motorup to 14 weeks

Modified Yale Global Tic Severity Scale, sum, higher is worse. This score does not have psychometrics available. The Yale Global Tic Severity Scale (YGTSS) is a semistructured clinician-rated instrument that assesses the severity and frequency of motor and phonic tics over the previous week. Five index scores are obtained during the assessment, where higher scores indicate greater frequency or severity. These indices are: Total Motor Tic Score (0-25), Total Phonic Tic Score (0-25), Total Tic Score (0-50) Overall Impairment Rating (0-50).

Vital Signs - Systolic Blood Pressureup to 14 weeks

Systolic blood pressure - the amount of pressure in arteries during contraction of the heart muscle Normal range varies by age, sex, height and weight and can range from 80mm Hg to 130mmHg

Child Behavior Checklist (CBCL)Measured at screening

CBCL Total Score, measure of psychosocial problems, higher is worse.

Tics: Total Phonicup to 14 weeks

Modified Yale Global Tic Severity Scale, sum, higher is worse. This score does not have psychometrics available. The Yale Global Tic Severity Scale (YGTSS) is a semistructured clinician-rated instrument that assesses the severity and frequency of motor and phonic tics over the previous week. Five index scores are obtained during the assessment, where higher scores indicate greater frequency or severity. These indices are: Total Motor Tic Score (0-25), Total Phonic Tic Score (0-25), Total Tic Score (0-50) Overall Impairment Rating (0-50).

Tics: Total Impairmentup to 14 weeks

Modified Yale Global Tic Severity Scale, sum, higher is worse. This score does not have psychometrics available. The Yale Global Tic Severity Scale (YGTSS) is a semistructured clinician-rated instrument that assesses the severity and frequency of motor and phonic tics over the previous week. Five index scores are obtained during the assessment, where higher scores indicate greater frequency or severity. These indices are: Total Motor Tic Score (0-25), Total Phonic Tic Score (0-25), Total Tic Score (0-50) Overall Impairment Rating (0-50).

Vital Signs - Diastolic Blood Pressureup to 14 weeks

Diastole blood pressure - blood pressure when the heart muscle is between beats. normal range varies by age, sex, height and weight and can range from 34mm Hg to 90mmHg

Vital Signs - Pulseup to 14 weeks

Heartbeats per minute. Range varies from 50-205 depending on age and level of activity.

Permanent Mathematics Product Test (PERMP)up to 14 weeks

Measure of fluency in performance of simple mathematics, sum, lower = worse

ActigraphyMeasured daily throughout the study

Measure of physical activity

Sleep LogsMeasured daily throughout the study

Questionnaire, qualitative

Hyperactivity, Attention, and Learning Problems (HALP) Medical and Developmental History QuestionnaireMeasured at screening

Questionnaire, qualitative designed to collect family history, prenatal environmental influences, and developmental history.

HALP Rebound Effects Questionnaireup to 14 weeks

Questionnaire, qualitative assesses symptoms of rebound (moodiness, irritability, aggression, and ADHD symptoms) when the medication wears off at night.

Trial Locations

Locations (2)

University of Illinois, Chicago - Institute for Juvenile Research

🇺🇸

Chicago, Illinois, United States

Icahn School of Medicine at Mount Sinai

🇺🇸

New York, New York, United States

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