Attention Deficit Disorder With Hyperactivity
Conditions
Keywords
Subthreshold Manic States in Children, ADHD
Brief summary
This study will evaluate the effectiveness of an integrative group psychosocial therapy combined with stimulant medication in treating children with attention deficit hyperactivity disorder plus impairments in mood.
Detailed description
There has been increasing recognition that many children with attention deficit hyperactivity disorder (ADHD) exhibit depressive and manic-like symptoms suggestive of major depressive disorder (MDD) and bipolar disorder (BP). Many children with ADHD plus impairments in mood display symptoms of irritability, affective instability, and reactive aggression, but they typically lack the hallmark symptoms, such as extreme mood cycles and sustained depressed mood, that lead to a BD or MDD diagnosis. Significant debate exists as to whether these children have a true comorbid mood disorder, making treatment of mood symptoms in ADHD children controversial. ADHD is traditionally treated with stimulant medications and/or behavior modification therapy. However, little is known about the safety of stimulants in ADHD children with manic symptoms. Also, no treatments exist that are designed to simultaneously improve both ADHD and mood problems in children. Psychosocial treatments hold particular promise for ADHD children with impairments in mood because they are well-studied pediatric treatments with little risk of worsening mood symptoms. This study will develop an integrative psychosocial treatment that includes aspects of cognitive behavioral therapy (CBT) and psychoeducational techniques for pediatric and adult mood disorders. The study will then evaluate the effectiveness of the integrative psychosocial treatment, called group behavior therapy, combined with stimulant medication in improving moods and enhancing treatment responses in children with ADHD and impairments in mood. Participation in the study will last between 5 and 6 months. All eligible participants will begin treatment with stimulant medications for 2 to 6 weeks, or until an optimal medication dosage has been determined. During this medication dosing phase, study staff will collect weekly ratings of the child participant's behavior at home and school, and participants will be seen weekly by study doctors to monitor medication dosage. Upon achieving an optimal dose, child participants will answer questions about their mood and behavior. Participants who are still exhibiting mood problems will then be assigned randomly to receive 12 weeks of either group behavior therapy or community-based psychosocial treatment, while still continuing on their prescribed medications. Group behavior therapy sessions for child participants will focus on improving mood and ability to maintain friendships, practicing ways to better control emotions, and learning effective problem solving skills. Child participants will also be given weekly homework assignments to practice learned therapy skills. Group behavior therapy sessions for parent participants will teach parents ways to identify and address their child's mood problems, communicate better with their child, and work with school staff to address academic and behavioral problems. Participants assigned to community-based psychosocial treatment will not receive any counseling services as part of the study, but they will be referred to community services. Every 6 weeks during the therapy phase, all participants will answer repeat questions about their mood and behavior. Six weeks after completing the therapy phase, participants will return for a final follow-up visit, which will include repeat questions, rating of the child participant's mood and symptoms, and meeting with a study doctor to check medications.
Interventions
BEHAVIORALGroup-based behavior therapy
Group-based behavior therapy with a parenting class will include 12 weeks of sessions that focus on reducing oppositional and aggressive behaviors. Children will participate in 12 weeks of social skills training integrated with a cognitive behavioral therapy (CBT) component to target mood symptoms. Parents will learn ways to identify and address their child's mood problems, communicate better with their child, and work with school staff to address academic and behavioral problems.
DRUGStimulant medication therapy
All participants will be stabilized on an FDA-approved stimulant medication for 2 to 6 weeks prior to therapy assignment.
BEHAVIORALCommunity-based psychosocial treatment
Participants will receive referrals to community-based psychosocial treatments that will focus on ADHD symptoms and management of aggression.
Sponsors
National Institute of Mental Health (NIMH)
Florida International University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
7 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* ADHD combined subtype with evidence of depressive or manic-like symptoms, as assessed by CDRS, YMRS, and Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia, that persist after stimulant treatment
Exclusion criteria
* Full Scale IQ less than 80 * Current seizure disorder or history of seizures requiring treatment or other significant neurological problems * History of other medical problems for which stimulant treatment may involve considerable risk, including cardiac arrhythmias, hypertension, Tourette's disorder, or history of severe tic exacerbations caused by stimulant exposure (Note: child with uncomplicated tic disorders or a family history of tic disorders will not be excluded as stimulants are well tolerated in a majority of such cases) * Meets full criteria for Type I or II bipolar disorder or any child manifesting mood symptoms (manic or depressive), such as significant suicidal ideation or psychotic symptoms that require emergent pharmacological treatment or hospitalization * History or concurrent diagnosis of any of the following disorders: pervasive developmental disorder, schizophrenia or other psychotic disorders, post-traumatic stress disorder, sexual disorders, organic mental disorder, or eating disorder * No longer manifests impairing manic/depressive symptoms after stimulant therapy based on CDRS-R greater than 27 or YMRS greater than 11 with Clinical Global Impressions-Severity 3 or greater
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mood Severity Index Measures Severity of Mood Symptoms (MSI).Range of 0-116; Clinicians Give to Parents and Child to Get Composite Score; Higher Scores=Greater Severity; 0-10=no Symptoms, 11-20=Mild Symptoms, 21to 35 =Moderate Symptoms and >35 is Severe | measured at week 12 (endpoint) | averaged Composite of endpoint ratings from the Children's Depression Rating Scale (CDRS used to measure depressive symptoms) and Young mania rating scale (MRS used to measure manic like symptoms) that has been used before as primary outcome in treatment studies of children with a mixture of affective symptoms (Fristad, et al., 2009). Prior to commencement of data collection, we elected to use it as the primary mood measure for the therapy phase of the trial over the initially selected YMRS as subjects either had to have elevations on the YMRS or CDRS but not necessarily both to be eligible. Hence, some subjects had very low YMRS scores at baseline which is why we chose the MSI over the YMRS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Young Mania Rating Scale (YMRS) Score | Measured at weeks 12 (endpoint) | rates manic like symptoms in children; 7 items ranging from 0-4 and 4 items on a 0-8 scale; higher scores indicate more severe symptom severity (min total score=0, max=60). There are no subscales. Symptom severity information is obtained from direct interview of parent and child. It was initially selected as the primary outcome but prior to commencement of data collection the Mood Severity Index (MSI) was chosen instead based on recently published work in a related study (see above). |
| Disruptive Behavior Disorder Scale Score for ADHD Symptoms | Measured at Week12 (endpoint) | sum of severity rating for all 18 DSM (Diagnostic and Statistics Manual for Mental Disorders) IV ADHD symptoms and two from DSM 3R on a 0 to 3 scale obtained from parent rating; range is from 0 to 60 with higher numbers indicating more severe symptoms |
| Children's Depression Rating Scale-Revised (CDRS-R) Total Score | Measured at Week 12 (endpoint) | rates 17 items of depression on a severity scale using information obtained from parent and child. Higher numbers indicate more severity symptoms and range is from 17 to 113. |
| Disruptive Behavior Disorder Scale Score for ODD Symptoms | week 12 (endpoint) | parents rating all DSM symptoms of Oppositional Defiant Disorder on a 0-3 severity scale with higher scores indicating more severe symptoms and range is from 0-27 (8 DSM IV items and I item from DSM 3R) |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited as two cohorts- 50% in each wave. Wave one was recruited in Buffalo NY in the summer of 2009, from referrals from local pediatricians and therapists and mailings to families. The study was then moved to Florida International University where the second cohort was recruited from 9/10 to 12/10 using similar procedures.
Pre-assignment details
Subjects were assessed at intake on the current ADHD medication regimen to make sure that they needed additional treatment beyond what they were currently receiving. There was no washout prior to enrollment.
Participants by arm
| Arm | Count |
|---|---|
| Medication and Community Treatment Group Participants will receive stimulant medication therapy and referrals to community-based psychosocial treatments.
Stimulant medication therapy : All participants will be stabilized on an FDA-approved stimulant medication for 4 to 8 weeks prior to therapy assignment.
Community-based psychosocial treatment : Participants will receive referrals to community-based psychosocial treatments that will focus on ADHD symptoms and management of aggression. | 33 |
| Medication and Novel Therapy Group Participants will receive stimulant medication therapy and group-based behavior therapy.
Stimulant medication therapy : All participants will be stabilized on an FDA-approved stimulant medication for 4 to 8 weeks prior to therapy assignment.
Group-based behavior therapy : Group-based behavior therapy with a parenting class will include 12 weeks of sessions that focus on reducing oppositional and aggressive behaviors. Children will participate in 12 weeks of social skills training integrated with a cognitive behavioral therapy (CBT) component to target mood symptoms. Parents will learn ways to identify and address their child's mood problems, communicate better with their child, and work with school staff to address academic and behavioral problems. | 35 |
| Total | 68 |
Baseline characteristics
| Characteristic | Medication and Novel Therapy Group | Medication and Community Treatment Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 35 Participants | 33 Participants | 68 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age Continuous | 9.3 years STANDARD_DEVIATION 1.6 | 9.4 years STANDARD_DEVIATION 1.5 | 9.3 years STANDARD_DEVIATION 1.5 |
| Region of Enrollment United States | 35 participants | 33 participants | 68 participants |
| Sex: Female, Male Female | 11 Participants | 7 Participants | 18 Participants |
| Sex: Female, Male Male | 24 Participants | 26 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 30 | 20 / 35 |
| serious Total, serious adverse events | 1 / 30 | 4 / 35 |
Outcome results
Primary
Mood Severity Index Measures Severity of Mood Symptoms (MSI).Range of 0-116; Clinicians Give to Parents and Child to Get Composite Score; Higher Scores=Greater Severity; 0-10=no Symptoms, 11-20=Mild Symptoms, 21to 35 =Moderate Symptoms and >35 is Severe
averaged Composite of endpoint ratings from the Children's Depression Rating Scale (CDRS used to measure depressive symptoms) and Young mania rating scale (MRS used to measure manic like symptoms) that has been used before as primary outcome in treatment studies of children with a mixture of affective symptoms (Fristad, et al., 2009). Prior to commencement of data collection, we elected to use it as the primary mood measure for the therapy phase of the trial over the initially selected YMRS as subjects either had to have elevations on the YMRS or CDRS but not necessarily both to be eligible. Hence, some subjects had very low YMRS scores at baseline which is why we chose the MSI over the YMRS.
Time frame: measured at week 12 (endpoint)
Population: all subjects who were successfully stabilized on stimulant medication and then entered therapy phase; subjects not able to tolerate stimulant med for ADHD or whose mood symptoms resolved with optimization of their stimulant dose were not included in the therapy phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Medication and Community Treatment Group | Mood Severity Index Measures Severity of Mood Symptoms (MSI).Range of 0-116; Clinicians Give to Parents and Child to Get Composite Score; Higher Scores=Greater Severity; 0-10=no Symptoms, 11-20=Mild Symptoms, 21to 35 =Moderate Symptoms and >35 is Severe | 17.33 units on a scale | Standard Deviation 7.29 |
| Medication and Novel Therapy Group | Mood Severity Index Measures Severity of Mood Symptoms (MSI).Range of 0-116; Clinicians Give to Parents and Child to Get Composite Score; Higher Scores=Greater Severity; 0-10=no Symptoms, 11-20=Mild Symptoms, 21to 35 =Moderate Symptoms and >35 is Severe | 13.82 units on a scale | Standard Deviation 6.03 |
Comparison: A 2 x 2 repeated measures analysis (with time as within-subject factor and group as between-subject factor) was performed to compare the two groups on this measure at two time points (i.e., baseline which was week 0 and endpoint at week 12) and infer treatment success accordingly. The null hypothesis signified that there would be no difference between the groups over time, thus, there would be no difference in treatments. Statistical power was calculated as Cohen's d.p-value: 0.015ANOVA
Secondary
Children's Depression Rating Scale-Revised (CDRS-R) Total Score
rates 17 items of depression on a severity scale using information obtained from parent and child. Higher numbers indicate more severity symptoms and range is from 17 to 113.
Time frame: Measured at Week 12 (endpoint)
Population: all subjects who were successfully stabilized on stimulant medication and then entered therapy phase; subjects not able to tolerate stimulant med for ADHD or whose mood symptoms resolved with optimization of their stimulant dose were not included in the therapy phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Medication and Community Treatment Group | Children's Depression Rating Scale-Revised (CDRS-R) Total Score | 28.20 units on a scale | Standard Deviation 6.46 |
| Medication and Novel Therapy Group | Children's Depression Rating Scale-Revised (CDRS-R) Total Score | 25.10 units on a scale | Standard Deviation 3.96 |
Comparison: A 2 x 2 repeated measures analysis (with time as within-subject factor and group as between-subject factor) was performed to compare the two groups on this measure at two time points (i.e., baseline at week 0 and endpoint at week 12) and infer treatment success accordingly. The null hypothesis signified that there would be no difference between the groups over time, thus, there would be no difference in treatments. Statistical power was calculated as Cohen's d.p-value: 0.016ANOVA
Secondary
Disruptive Behavior Disorder Scale Score for ADHD Symptoms
sum of severity rating for all 18 DSM (Diagnostic and Statistics Manual for Mental Disorders) IV ADHD symptoms and two from DSM 3R on a 0 to 3 scale obtained from parent rating; range is from 0 to 60 with higher numbers indicating more severe symptoms
Time frame: Measured at Week12 (endpoint)
Population: all subjects who were successfully stabilized on stimulant medication and then entered therapy phase; subjects not able to tolerate stimulant med for ADHD or whose mood symptoms resolved with optimization of their stimulant dose were not included in the therapy phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Medication and Community Treatment Group | Disruptive Behavior Disorder Scale Score for ADHD Symptoms | 25.5 units on a scale | Standard Deviation 10.94 |
| Medication and Novel Therapy Group | Disruptive Behavior Disorder Scale Score for ADHD Symptoms | 25.10 units on a scale | Standard Deviation 9.12 |
Comparison: A 2 x 2 repeated measures analysis (with time as within-subject factor and group as between-subject factor) was conducted to compare the two groups on this measure at two time points (i.e., baseline at week 0 and endpoint at week 12) and infer treatment success accordingly. The null hypothesis signified that there would be no difference between the groups over time, thus, there would be no difference in treatments. Statistical power was calculated as Cohen's d.p-value: 0.38ANOVA
Secondary
Disruptive Behavior Disorder Scale Score for ODD Symptoms
parents rating all DSM symptoms of Oppositional Defiant Disorder on a 0-3 severity scale with higher scores indicating more severe symptoms and range is from 0-27 (8 DSM IV items and I item from DSM 3R)
Time frame: week 12 (endpoint)
Population: all subjects who were successfully stabilized on stimulant medication and then entered therapy phase; subjects not able to tolerate stimulant med for ADHD or whose mood symptoms resolved with optimization of their stimulant dose were not included in the therapy phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Medication and Community Treatment Group | Disruptive Behavior Disorder Scale Score for ODD Symptoms | 11.13 units on a scale | Standard Deviation 6.22 |
| Medication and Novel Therapy Group | Disruptive Behavior Disorder Scale Score for ODD Symptoms | 10.31 units on a scale | Standard Deviation 4.73 |
Comparison: A 2 x 2 repeated measures analysis (with time as within-subject factor and group as between-subject factor) was performed to compare the two groups on this measure at two time points (i.e., baseline at week 0 and endpoint at week 12) and infer treatment success accordingly. The null hypothesis signified that there would be no difference between the groups over time, thus, there would be no difference in treatments. Statistical power was calculated as Cohen's d.p-value: 0.095ANOVA
Secondary
Young Mania Rating Scale (YMRS) Score
rates manic like symptoms in children; 7 items ranging from 0-4 and 4 items on a 0-8 scale; higher scores indicate more severe symptom severity (min total score=0, max=60). There are no subscales. Symptom severity information is obtained from direct interview of parent and child. It was initially selected as the primary outcome but prior to commencement of data collection the Mood Severity Index (MSI) was chosen instead based on recently published work in a related study (see above).
Time frame: Measured at weeks 12 (endpoint)
Population: all subjects who were successfully stabilized on stimulant medication and then entered therapy phase; subjects not able to tolerate stimulant med for ADHD or whose mood symptoms resolved with optimization of their stimulant dose were not included in the therapy phase.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Medication and Community Treatment Group | Young Mania Rating Scale (YMRS) Score | 10.08 units on a scale | Standard Deviation 4.65 |
| Medication and Novel Therapy Group | Young Mania Rating Scale (YMRS) Score | 8.58 units on a scale | Standard Deviation 5.05 |
Comparison: A 2 x 2 repeated measures analysis (with time as within-subject factor and group as between-subject factor) was performed to compare the two groups on this measure at two time points (i.e., baseline at week 0 and endpoint at week 12) and infer treatment success accordingly. The null hypothesis signified that there would be no difference between the groups over time, thus, there would be no difference in treatments. Statistical power was calculated as Cohen's d.p-value: 0.106ANOVA