Background:

Irritability is defined as proneness to anger that may impair a person s ability to function. It is a common reason for why some children need mental health care. Yet no therapies have been developed just to target irritability. Researchers want to compare different types of therapy for irritability.

Objective:

To test different types of therapy for children and teens with severe irritability.

Eligibility:

People aged 8 to 16.5 years with severe irritability. Their parents are also needed.

Design:

Participants will have 28 study visits in 18 months.

They will have a baseline visit. They will answer questions about their mood, behavior, and daily life.

All parents and children will have 12 therapy sessions. Sessions will be once a week; they will last 30 to 60 minutes. Some of the child sessions may be done by telehealth.

Each parent and child will have 1 of 3 therapy types:

Exposure therapy (child). Participants will face things that make them angry. A therapist will help them practice managing their anger.

Management therapy (parent). Therapists will coach parents on ways to manage their child s behaviors.

Psychoeducation/supportive psychotherapy (child and/or parent). Participants will talk with therapists about their or their child s feelings and behaviors. They will list their problems and goals; build coping skills; learn to relax; improve communication; and work on managing stress.

Sessions may be videotaped. Participants may opt out of being recorded.

Participants will have phone calls every 2 weeks during therapy. They will answer questions about how they are doing. Follow-up calls will continue for 1 year after therapy.

Study Description:

This study will be a randomized psychotherapy study comparing the efficacy of learning-based active treatment teaching children/parent specific skills (either exposure therapy for irritability plus parental psychoeducation supportive psychotherapy or parent management therapy plus child psychoeducation supportive psychotherapy) vs. non active control treatment match on time with a therapist without skill advancement (child- and parent- psychoeducation supportive psychotherapy, typical current standard of care). A prior IRB protocol (15-M-0182) demonstrated efficacy of exposure therapy for irritability with parent management training. Here, we compare the learning-based active treatment (exposure with child or parent management training with parent) to non-active psychoeducation supportive psychotherapy sessions matched on time with a therapist.

Objectives:

Primary Objectives:

1. Compare the efficacy of learning based active treatment (arm 1, exposure therapy for irritability plus parental psychoeducation supportive psychotherapy or parent management therapy plus child psychoeducation supportive psychotherapy) vs. non-active support matched on time with a therapist (arm 2, child psychoeducation supportive psychotherapy plus parent psychoeducation supportive psychotherapy).

2. In each of two arms (arm 1, exposure plus parental support and parent training plus child support vs. arm 2, child and parent support), examine the degree of therapeutic adherence to exposure and parent management training, as well as support experienced by the child and parent.

Secondary Objective:

1. Examine if adherence to learning principles skills (i.e., exposure or parent management training) and/or support (i.e., alliance) are associated with symptom improvement in anxiety, depression, and attention deficit hyperactivity symptoms. In the exposure plus parental psychoeducation supportive psychotherapy condition, determine if the degree of exposure (e.g., number of exposures) is associated with level of clinical improvement.
2. Explore if the degree of implementation of concrete learning-based skills (e.g., exposure, active ignore, praise, parental consistency) is associated with the level of clinical response.
3. In all conditions, examine therapeutic support (measured by child/parent and clinician working alliance inventory measure).
4. Upon completion of the 12 sessions, conduct follow-up clinical assessments within 14 days and 3, 6, and 12 months later to determine stability of clinical improvement.

Exploratory Objective:

1. Use natural language processing to derive features/themes of sessions and determine:

1a. Similarities and differences between two treatment conditions.

1b. If specific learning related themes at specific times in treatment are associated with improvement.

2. Determine if there are specific clinical features of the child (e.g., co-occurring attention deficit hyperactivity disorder, anxiety, demographic characteristics) or the parent that are associated with improvement differentially across two active treatment conditions.

Endpoints:

Primary Endpoint:

1. Clinical response measured by parent, child, and clinical irritability metrics (affective reactivity index and clinical severity/improvement metrics) in each treatment condition (Primary Objective 1).
2. Association between adherence to manualized procedures (i.e., learning based skills) and alliance (i.e., degree of therapeutic support) with each treatment condition (Primary Objective 2)

Secondary Endpoints:

1. Association between adherence to manualized procedures (i.e., learning based skills) and alliance (i.e., degree of therapeutic support) with end of treatment anxiety, depression and attention deficit hyperactivity clinical response (Secondary Objective 1)
2. Determine if degree of exposure in exposure plus parental psychoeducation supportive psychotherapy condition is associated with level of clinical improvement (Secondary Objective 2).
3. Determine if degree of therapeutic support (measured by child/parent and clinician working alliance inventory measure) is associated with clinical response (Secondary Objective 3).
4. Determine stability of clinical assessments 3, 6, and 12 months later (Secondary Objective 4).

Exploratory Endpoint:

1. Using natural language processing to derive features/themes of sessions (Exploratory Endpoint 1).

1a. Examine similarities and differences between two treatment conditions

1b. Determine if specific learning related themes at specific times in treatment are associated with improvement.

2. In the pursuit of precision medicine, examine the clinical features of the child (e.g., co-occurring attention deficit hyperactivity disorder, anxiety, demographic characteristics) and the parent to assess if there is differential improvement across the two active treatment conditions associated with baseline factors (Exploratory Endpoint 2).

• INCLUSION CRITERIA FOR YOUTH

  1. Age 8-16.5 years
  2. Caregiver and/or child reports irritability as a primary clinical concern. Specifically, compared to his/her peers, the child exhibits markedly increased reactivity to negative emotional stimuli that manifests verbally or behaviorally. For example, the child responds to frustration with extended temper tantrums (inappropriate for age and/or precipitating event), verbal rages, and/or aggression toward people or property.

  2a. Such events occur, on average, at least three times a week.

  2b. This irritability is impairing in at least two of three domains (home, school, peers)

  3. Patients must be fluent in English

  3a. Participants must be able to speak and read English. This study evaluates English language, manualized psychotherapies. The intervention materials, therapist and rater training and supervision procedures, fidelity ratings, and primary outcome measure are

currently available and validated only in English. Because psychotherapy relies on nuanced verbal exchange, use of translation or interpreters could alter treatment content, affect therapeutic alliance, compromise fidelity, and limit accurate clinical risk assessment. Examining fidelity and alliance/support are our primary and secondary objective in this study. Therefore, enrolling non-English speakers can introduce a confound to these research questions. Restricting enrollment to English-speaking participants is therefore necessary to ensure participant safety and scientific validity in this trial. Critically, this eligibility criterion is based solely on the language requirements of the intervention and study procedures and is not intended to exclude participants on the basis of race or ethnicity or any other factors.

4. On the basis of record review and interviews with child and parent, the research team agrees that the child s response to his/her current treatment is no more than minimal (i.e. CGI-S of 3 or more).

5. Must have no planned changes in outpatient psychiatric treatment regimen, which can include psychotropic medications and/or psychotherapeutic interventions, two weeks prior to enrollment.

INCLUSION CRITERIA FOR PARENT

1. Parent of a child eligible for this protocol that can attend 12 parent sessions
2. Fluent in English

EXCLUSION CRITERIA

Participants will be screened to exclude participants who would not be able to engage in psychotherapy.

1. Active major depressive disorder or history of psychosis, bipolar I disorder, Level 2 or 3 autism spectrum disorder, active severe substance use disorders (within the last month), conduct disorder, have active suicidal intent or plan as detected on screening instruments.
2. IQ < 70
3. Past or present medical or neurological condition, disease, disorder, genetic finding, or injury that, in the opinion of the Investigator, may significantly increase the potential risks of study participation, reduce or compromise a subject s ability to fully comply with all study requirements for the duration of the study or may compromise the integrity of the data.

EXCLUSION CRITERIA FOR PARENTS

1. IQ < 70
2. Have any serious medical, mental health, or any condition that interferes with participation, such as active psychosis.
3. Current alcohol or substance use or dependence (excluding nicotine) within the past 3 months of sufficient magnitude to require independent, concurrent treatment intervention (e.g. Antabuse or opiate treatment but not including self-help groups).

This study is for children ages 8-16.5 with irritability as a primary concern, including frequent verbal outbursts, or aggression in response to frustration or negative emotions. Symptoms must occur at least three times weekly and impair functioning in at least two settings, such as home, school, or with peers. A parent must be able to attend 12 parent sessions. Both children and parent must be able to speak and read English. Children are excluded for active major depression, psychosis, bipolar I disorder, level 2 or 3 autism spectrum disorder, recent severe substance use, conduct disorder, active suicidal intent or plan, IQ below 70, or significant medical or neurological conditions. Parents are excluded for IQ below 70, active psychosis, or recent substance/alcohol problems needing separate treatment.

In compliance with current NIH data-sharing policies, de-identified data from participants who have consented to data sharing will be made available in a public repository.

De-identified data from participants who have consented to data sharing will be made available in a public repository at time of publication without an end date.

De-identified data from participants who have consented to data sharing will be made available in a public repository that can be accessed by anyone.