IrritabilityNCT02531893
Psychological Treatments for Youth With Severe Irritability.
An observational study of Irritability, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
Background: When children have severe irritability and temper outbursts, they can be so cranky or angry that it leads to problems at home, in school, and with friends. This is called Disruptive Mood Dysregulation Disorder (DMDD) and there have been no psychological treatments developed specifically for children with… Read more about this study
- Who is it for?
- Ages 8 to 17 years
- Conditions the study is for
- Irritability
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Nov 2015to 8 May 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 17 years
- All sexes
- No healthy volunteers
- Child
Study population: All outpatients, ages 8-17, enrolled in NIMH-DIRP Protocol 02-M-0021, and who are on stable, community treatment will be invited to participate in this study.
Who may be able to join
- Inclusion criteria for both Interpretation Bias Training and Cognitive Behavioral Therapy Studies:
- Age 8-17 years
- Must be enrolled into NIMH DIRP protocol 02-M-0021, Characterization and Pathophysiology of Severe Mood and Behavioral Dysregulation in children and youth.
- Must meet DSM 5 diagnostic criteria for DMDD which are (for CBT, must meet lifetime history of either DMDD or one of two core DMDD criteria [b or c]):
- Must meet all of the following:
- Diagnosis must first be made between ages 6-18 years
Show all 16Show fewer
- Abnormal mood (specifically, anger and/or irritability), present at least half of the day most days, and of sufficient severity to be noticeable by people in the child s environment (e.g. parents, teachers, peers).
- Compared to his/her peers, the child exhibits markedly increased reactivity to negative emotional stimuli that is manifest 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. Such events occur, on average, at least three times a week.
- The symptoms in b and c above are currently present and have been present for at least 12 months without any symptom-free periods exceeding two months.
- The onset of symptoms must be prior to age 10 years.
- The symptoms are severe in at least one setting (e.g. violent outbursts, assaultiveness at home, school, or with peers). In addition, there are at least mild symptoms (verbal aggression) in a second setting.
- Patients must be fluent in English
- All instruments have not been validated in other languages.
- Psychotherapy will be designed and conducted in English.
- 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).
- Must have no planned changes in outpatient psychiatric treatment regimen, which can include psychotropic medications and/or psychotherapeutic interventions, two weeks prior to enrollment and throughout the three weeks of training and post-training assessment.
Who cannot join
- Exclusion criteria both Interpretation Bias Training and Cognitive Behavioral Therapy Studies:
- The individual exhibits any of these cardinal bipolar symptoms:
- Elevated or expansive mood.
- Grandiosity or inflated self-esteem.
- Decreased need for sleep.
- Increase in goal-directed activity (this can result in the excessive involvement in pleasurable activities that have a high potential for painful consequences).
Show all 12Show fewer
- A history of hypomanic or manic symptoms that occurred in distinct episodes lasting more than 1 day.
- Meets DSM 5 criteria for schizophrenia, schizophreniform disorder, schizoaffective illness, Autism Spectrum Disorder, or posttraumatic stress disorder.
- IQ<70
- The symptoms are due to the direct physiologic effects of a drug of abuse, or to a general medical or neurological condition.
- Meets criteria for alcohol or substance abuse three months prior to enrollment.
- Meets DSM 5 criteria for current major depressive disorder. The rationale for the exclusion of youth with MDD is because the two novel interventions being tested are contraindicated for those with major depressive disorder. However, there is no contraindication to participation for those with treated/resolved or remitted major depressive disorder; only those with a current diagnosis need to be excluded.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
Official title: Psychological Treatments for Youth With Severe Irritability
Background:
When children have severe irritability and temper outbursts, they can be so cranky or angry that it leads to problems at home, in school, and with friends. This is called Disruptive Mood Dysregulation Disorder (DMDD) and there have been no psychological treatments developed specifically for children with this problem. Researchers think two forms of therapy, Cognitive Behavioral Therapy (CBT) and Interpretation Bias Training (IBT), might help children with DMDD.
Read more
Objective:
To test two whether IBT and CBT can decrease severe irritability in children and youth.
Eligibility:
Children 8-17 years old with DMDD. Their symptoms must have started before age 10.
Design:
Participants will be screened with a review of their symptoms. Parents and participants will answer questions.
Participants can do only one or both of these treatments if they wish. Those who wish to do both will start with IBT.
Participants who do CBT will have 12-16 weekly meetings of research talk therapy. A parent will participate in part of the sessions.
Participants will talk about what makes them irritable and how it affects them. They may be put in situations that might make them annoyed or irritable.
Participants will rate how intense their irritability is. Parents and participants will complete rating scales, questionnaires, and interviews.
Participants will do practice activities at home.
Participants doing IBT will have up to 14 sessions over 10 weeks.
Participants will view 15 faces, one at a time, on a computer. They will choose if the face looks happy or angry on a computer. Sometimes the computer gives feedback. Participants will complete some sessions at the NIH and some at home.
Participants and parents answer questions about their progress.
...
Read the detailed description
OBJECTIVE:
This purpose of this protocol is to further the development of two potential non-pharmacologic treatments for youths with chronic, severe and impairing irritability. The first potential treatment is Interpretation Bias Training (IBT), a computer-based training designed to shift emotional judgments of ambiguous faces away from angry, and toward happy, judgments. The first component of this protocol includes a randomized, controlled trial of active IBT in youth with severe irritability. The second potential treatment is a cognitive behavioral therapy (CBT) targeting severe irritability. The goal of this protocol is to conduct a preliminary study using a randomized within-subjects multiple-baseline design to test the efficacy of a new manualized exposure-based CBT with parenting training in the treatment of severe irritability.
Objective 1: Assess the efficacy of Interpretation Bias Training (IBT) in youths with severe irritability, operationalized as those meeting criteria for DSM-5 Disruptive Mood Dysregulation Disorder (DMDD). To accomplish this objective, we will conduct a randomized, controlled trial (RCT) of active IBT in 40 youths with DMDD. Subjects will be randomized to receive four IBT training sessions (active vs. placebo, in a double-blind design) over four days followed by weekly mood ratings for two weeks. Primary outcome measures in this trial will assess changes in irritability using the Affective Reactivity Index (ARI: clinician-rated, parent-rated, and child-rated) and Clinical Global Impressions-Improvement (CGI-I). After completing the RCT, all participants will be offered four open, active IBT sessions, delivered on the same schedule as in the RCT and using the same primary outcome measures.
Objective 2: Test the efficacy of a new manualized CBT for severe, impairing irritability in youth and adapt the in-person manual to being a hybrid intervention. To accomplish this objective, we will utilize a within-subjects multiple baseline design. The children will be randomized to their start times. Clinical ratings, as well as parent- and child- report ratings will be obtained every two weeks (plus or minus seven days) during both the baseline and active periods. This is not an RCT. All children will receive active CBT following variable (randomized) start times. Consistent with the manual we will continue to meet with children and their parents utilizing newly manualized exposure-based CBT procedures, such as eliciting hierarchies of irritability inducing events, exposure exercises (e.g., in-vivo, role-play, imaginal) and parent training. We will conduct the CBT on N=40 youth with severe, impairing irritability. Primary outcome measures for CBT will assess changes in irritability using the ARI (clinician-rated, parent-rated, and child-rated) and CGI-I.
Secondary Objective 1a and 1b: Assess the effect of IBT on clinical measures of depression, anxiety, and functional impairment.
Secondary Objective 2: Assess the effect of the CBT for irritability on clinical measures of depression, anxiety, and functional impairment.
Subjects can participate in one or both of these potential treatments. If they opt to do both, there will be a four-week wash-out period between treatments.
STUDY POPULATION:
The study is taking place at the National Institutes of Health (NIH). All outpatients, ages 8-17, enrolled in NIMH-DIRP Protocol 02-M-0021, who are in stable treatment in the community will be invited to participate in this study.
DESIGN:
The first part of the protocol will involve conducting a randomized controlled trial of IBT in 40 youths who meet criteria for DMDD. The goal of this novel, potential treatment is to decrease the severity of the child s irritability.
The second part of the protocol will involve conducting a randomized within-subjects multiple-baseline trial of CBT targeting severe irritability including N=40 youth.
Subjects can elect to participate in the IBT randomized controlled trial only, CBT treatment or both. If subjects elect to participate in both IBT and CBT, there will be a one-month wash-out period in between.
OUTCOME MEASURES:
The main outcome measures will assess changes in irritability using the ARI (clinician-rated, parent-rated, and child-rated, original and revised versions for IBT and CBT, respectively) and CGI-I. Secondary measures include parent and self-report measures of irritability, depression, anxiety, anger, social status, and aggression, as well as clinician ratings of depression, anxiety, and impairment. Data for ecological momentary assessments (EMA) will be collected using secure technology, with procedures approved by the NIMH ISSO; subjects and their caregivers will be asked a set of questions relating to recent experiences and emotions
- Conditions
- Irritability
- Keywords
- Interpretation Bias Training, Cognitive Behavioral Therapy, Children, Natural History
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Irritable youth | Participants meet full DMDD criteria for IBT and either full DMDD or one of two core DMDD criteria for CBT. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Global Impression--Improvement score
Clinician administered measure to assess clinical symptoms
Measured: Every two weeks
Affective Reactivity Index (ARI)
Clinician administered measure to assess clinical symptoms
Measured: Every two weeks
Secondary outcomes (1)
parent and self-report measures of irritability, depression, anxiety, anger, social status, and aggression, as well as clinician ratings of depression, anxiety, and impairment
Self- and parent-report measures to assess clinical symptoms
Measured: Weekly
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2015 (estimated)
- Study start17 Nov 2015
- Primary completion8 May 2028 (estimated)
- Study completion8 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for IrritabilityStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Melissa A Brotman, Ph.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02531893
- Sponsor's protocol ID
- 150182
- Other IDs
- 15-M-0182
- Status last verified
- 4 Nov 2026
- First submitted
- 22 Aug 2015
- Last updated
- 6 Nov 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No individual participant data (IPD) will be shared.
Publications
Leibenluft E. Severe mood dysregulation, irritability, and the diagnostic boundaries of bipolar disorder in youths. Am J Psychiatry. 2011 Feb;168(2):129-42. doi: 10.1176/appi.ajp.2010.10050766. Epub 2010 Dec 1.
PubMed 21123313Leibenluft E, Stoddard J. The developmental psychopathology of irritability. Dev Psychopathol. 2013 Nov;25(4 Pt 2):1473-87. doi: 10.1017/S0954579413000722.
PubMed 24342851Brotman MA, Kircanski K, Stringaris A, Pine DS, Leibenluft E. Irritability in Youths: A Translational Model. Am J Psychiatry. 2017 Jun 1;174(6):520-532. doi: 10.1176/appi.ajp.2016.16070839. Epub 2017 Jan 20.
PubMed 28103715Linke JO, Naim R, Haller SP, Khosravi P, Scheinberg B, Byrne ME, Harrewijn A, Leibenluft E, Brotman MA, Winkler AM, Pine DS. Reduced Threat-Related Neural Efficiency: A Possible Biomarker for Pediatric Anxiety Disorders. Am J Psychiatry. 2026 Jan 1;183(1):48-57. doi: 10.1176/appi.ajp.20241043. Epub 2025 Oct 8.
PubMed 41058235Naim R, German RE, White J, Pandya U, Dombek K, Clayton M, Perlstein S, Henry LM, Kircanski K, Lorenzo-Luaces L, Brotman MA. Treatment adherence, therapeutic alliance, and clinical outcomes during an exposure-based cognitive-behavioral therapy for pediatric irritability. BMC Psychiatry. 2025 Feb 26;25(1):181. doi: 10.1186/s12888-025-06601-0.
PubMed 40012036McKay CC, Scheinberg B, Xu EP, Kircanski K, Pine DS, Brotman MA, Leibenluft E, Linke JO. Modeling Shared and Specific Variances of Irritability, Inattention, and Hyperactivity Yields Novel Insights Into White Matter Perturbations. J Am Acad Child Adolesc Psychiatry. 2024 Dec;63(12):1239-1250. doi: 10.1016/j.jaac.2024.02.010. Epub 2024 Mar 5.
PubMed 38452811Grasser LR, Erjo T, Goodwin MS, Naim R, German RE, White J, Cullins L, Tseng WL, Stoddard J, Brotman MA. Can peripheral psychophysiological markers predict response to exposure-based cognitive behavioral therapy in youth with severely impairing irritability? A study protocol. BMC Psychiatry. 2023 Dec 11;23(1):926. doi: 10.1186/s12888-023-05421-4.
PubMed 38082431Linke JO, Haller SP, Xu EP, Nguyen LT, Chue AE, Botz-Zapp C, Revzina O, Perlstein S, Ross AJ, Tseng WL, Shaw P, Brotman MA, Pine DS, Gotts SJ, Leibenluft E, Kircanski K. Persistent Frustration-Induced Reconfigurations of Brain Networks Predict Individual Differences in Irritability. J Am Acad Child Adolesc Psychiatry. 2023 Jun;62(6):684-695. doi: 10.1016/j.jaac.2022.11.009. Epub 2022 Dec 21.
PubMed 36563874Haller SP, Archer C, Jeong A, Jaffe A, Jones EL, Harrewijn A, Naim R, Linke JO, Stoddard J, Brotman MA. Changes in Internalizing Symptoms During the COVID-19 Pandemic in a Transdiagnostic Sample of Youth: Exploring Mediators and Predictors. Child Psychiatry Hum Dev. 2024 Feb;55(1):206-218. doi: 10.1007/s10578-022-01382-z. Epub 2022 Jul 6.
PubMed 35794298Haller SP, Stoddard J, Botz-Zapp C, Clayton M, MacGillivray C, Perhamus G, Stiles K, Kircanski K, Penton-Voak IS, Bar-Haim Y, Munafo M, Towbin KE, Brotman MA. A Randomized Controlled Trial of Computerized Interpretation Bias Training for Disruptive Mood Dysregulation Disorder: A Fast-Fail Study. J Am Acad Child Adolesc Psychiatry. 2022 Jan;61(1):37-45. doi: 10.1016/j.jaac.2021.05.022. Epub 2021 Jun 17.
PubMed 34147585Naim R, Kircanski K, Gold A, German RE, Davis M, Perlstein S, Clayton M, Revzina O, Brotman MA. Across-subjects multiple baseline trial of exposure-based cognitive-behavioral therapy for severe irritability: a study protocol. BMJ Open. 2021 Mar 10;11(3):e039169. doi: 10.1136/bmjopen-2020-039169.
PubMed 33692176Linke JO, Abend R, Kircanski K, Clayton M, Stavish C, Benson BE, Brotman MA, Renaud O, Smith SM, Nichols TE, Leibenluft E, Winkler AM, Pine DS. Shared and Anxiety-Specific Pediatric Psychopathology Dimensions Manifest Distributed Neural Correlates. Biol Psychiatry. 2021 Mar 15;89(6):579-587. doi: 10.1016/j.biopsych.2020.10.018. Epub 2020 Nov 9.
PubMed 33386133Linke J, Kircanski K, Brooks J, Perhamus G, Gold AL, Brotman MA. Exposure-Based Cognitive-Behavioral Therapy for Disruptive Mood Dysregulation Disorder: An Evidence-Based Case Study. Behav Ther. 2020 Mar;51(2):320-333. doi: 10.1016/j.beth.2019.05.007. Epub 2019 May 21.
PubMed 32138941Haller SP, Kircanski K, Stringaris A, Clayton M, Bui H, Agorsor C, Cardenas SI, Towbin KE, Pine DS, Leibenluft E, Brotman MA. The Clinician Affective Reactivity Index: Validity and Reliability of a Clinician-Rated Assessment of Irritability. Behav Ther. 2020 Mar;51(2):283-293. doi: 10.1016/j.beth.2019.10.005. Epub 2019 Nov 27.
PubMed 32138938Cardinale EM, Kircanski K, Brooks J, Gold AL, Towbin KE, Pine DS, Leibenluft E, Brotman MA. Parsing neurodevelopmental features of irritability and anxiety: Replication and validation of a latent variable approach. Dev Psychopathol. 2019 Aug;31(3):917-929. doi: 10.1017/S095457941900035X. Epub 2019 May 8.
PubMed 31064595
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Psychological Treatments for Youth With Severe Irritability
- ClinicalTrials.gov ID
- NCT02531893
- Acronym / sponsor ID
- 150182
- Conditions
- Irritability
- Keywords
- Interpretation Bias Training, Cognitive Behavioral Therapy, Children, Natural History
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 17 Nov 2015 (actual)
- Primary completion
- 8 May 2028 (estimated)
- Study completion
- 8 May 2028 (estimated)
- First posted
- 25 Aug 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
When children have severe irritability and temper outbursts, they can be so cranky or angry that it leads to problems at home, in school, and with friends. This is called Disruptive Mood Dysregulation Disorder (DMDD) and there have been no psychological treatments developed specifically for children with this problem. Researchers think two forms of therapy, Cognitive Behavioral Therapy (CBT) and Interpretation Bias Training (IBT), might help children with DMDD.
Objective:
To test two whether IBT and CBT can decrease severe irritability in children and youth.
Eligibility:
Children 8-17 years old with DMDD. Their symptoms must have started before age 10.
Design:
Participants will be screened with a review of their symptoms. Parents and participants will answer questions.
Participants can do only one or both of these treatments if they wish. Those who wish to do both will start with IBT.
Participants who do CBT will have 12-16 weekly meetings of research talk therapy. A parent will participate in part of the sessions.
Participants will talk about what makes them irritable and how it affects them. They may be put in situations that might make them annoyed or irritable.
Participants will rate how intense their irritability is. Parents and participants will complete rating scales, questionnaires, and interviews.
Participants will do practice activities at home.
Participants doing IBT will have up to 14 sessions over 10 weeks.
Participants will view 15 faces, one at a time, on a computer. They will choose if the face looks happy or angry on a computer. Sometimes the computer gives feedback. Participants will complete some sessions at the NIH and some at home.
Participants and parents answer questions about their progress.
...
Detailed description
OBJECTIVE:
This purpose of this protocol is to further the development of two potential non-pharmacologic treatments for youths with chronic, severe and impairing irritability. The first potential treatment is Interpretation Bias Training (IBT), a computer-based training designed to shift emotional judgments of ambiguous faces away from angry, and toward happy, judgments. The first component of this protocol includes a randomized, controlled trial of active IBT in youth with severe irritability. The second potential treatment is a cognitive behavioral therapy (CBT) targeting severe irritability. The goal of this protocol is to conduct a preliminary study using a randomized within-subjects multiple-baseline design to test the efficacy of a new manualized exposure-based CBT with parenting training in the treatment of severe irritability.
Objective 1: Assess the efficacy of Interpretation Bias Training (IBT) in youths with severe irritability, operationalized as those meeting criteria for DSM-5 Disruptive Mood Dysregulation Disorder (DMDD). To accomplish this objective, we will conduct a randomized, controlled trial (RCT) of active IBT in 40 youths with DMDD. Subjects will be randomized to receive four IBT training sessions (active vs. placebo, in a double-blind design) over four days followed by weekly mood ratings for two weeks. Primary outcome measures in this trial will assess changes in irritability using the Affective Reactivity Index (ARI: clinician-rated, parent-rated, and child-rated) and Clinical Global Impressions-Improvement (CGI-I). After completing the RCT, all participants will be offered four open, active IBT sessions, delivered on the same schedule as in the RCT and using the same primary outcome measures.
Objective 2: Test the efficacy of a new manualized CBT for severe, impairing irritability in youth and adapt the in-person manual to being a hybrid intervention. To accomplish this objective, we will utilize a within-subjects multiple baseline design. The children will be randomized to their start times. Clinical ratings, as well as parent- and child- report ratings will be obtained every two weeks (plus or minus seven days) during both the baseline and active periods. This is not an RCT. All children will receive active CBT following variable (randomized) start times. Consistent with the manual we will continue to meet with children and their parents utilizing newly manualized exposure-based CBT procedures, such as eliciting hierarchies of irritability inducing events, exposure exercises (e.g., in-vivo, role-play, imaginal) and parent training. We will conduct the CBT on N=40 youth with severe, impairing irritability. Primary outcome measures for CBT will assess changes in irritability using the ARI (clinician-rated, parent-rated, and child-rated) and CGI-I.
Secondary Objective 1a and 1b: Assess the effect of IBT on clinical measures of depression, anxiety, and functional impairment.
Secondary Objective 2: Assess the effect of the CBT for irritability on clinical measures of depression, anxiety, and functional impairment.
Subjects can participate in one or both of these potential treatments. If they opt to do both, there will be a four-week wash-out period between treatments.
STUDY POPULATION:
The study is taking place at the National Institutes of Health (NIH). All outpatients, ages 8-17, enrolled in NIMH-DIRP Protocol 02-M-0021, who are in stable treatment in the community will be invited to participate in this study.
DESIGN:
The first part of the protocol will involve conducting a randomized controlled trial of IBT in 40 youths who meet criteria for DMDD. The goal of this novel, potential treatment is to decrease the severity of the child s irritability.
The second part of the protocol will involve conducting a randomized within-subjects multiple-baseline trial of CBT targeting severe irritability including N=40 youth.
Subjects can elect to participate in the IBT randomized controlled trial only, CBT treatment or both. If subjects elect to participate in both IBT and CBT, there will be a one-month wash-out period in between.
OUTCOME MEASURES:
The main outcome measures will assess changes in irritability using the ARI (clinician-rated, parent-rated, and child-rated, original and revised versions for IBT and CBT, respectively) and CGI-I. Secondary measures include parent and self-report measures of irritability, depression, anxiety, anger, social status, and aggression, as well as clinician ratings of depression, anxiety, and impairment. Data for ecological momentary assessments (EMA) will be collected using secure technology, with procedures approved by the NIMH ISSO; subjects and their caregivers will be asked a set of questions relating to recent experiences and emotions
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Irritable youth | – | –Participants meet full DMDD criteria for IBT and either full DMDD or one of two core DMDD criteria for CBT. |
Who may qualify
- Ages
- 8 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- All outpatients, ages 8-17, enrolled in NIMH-DIRP Protocol 02-M-0021, and who are on stable, community treatment will be invited to participate in this study.
Key inclusion criteria (16 listed)
- Inclusion criteria for both Interpretation Bias Training and Cognitive Behavioral Therapy Studies:
- Age 8-17 years
- Must be enrolled into NIMH DIRP protocol 02-M-0021, Characterization and Pathophysiology of Severe Mood and Behavioral Dysregulation in children and youth.
- Must meet DSM 5 diagnostic criteria for DMDD which are (for CBT, must meet lifetime history of either DMDD or one of two core DMDD criteria [b or c]):
- Patients must be fluent in English
Key exclusion criteria (12 listed)
- Exclusion criteria both Interpretation Bias Training and Cognitive Behavioral Therapy Studies:
- The individual exhibits any of these cardinal bipolar symptoms:
- Meets DSM 5 criteria for schizophrenia, schizophreniform disorder, schizoaffective illness, Autism Spectrum Disorder, or posttraumatic stress disorder.
- IQ<70
- The symptoms are due to the direct physiologic effects of a drug of abuse, or to a general medical or neurological condition.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Clinical Global Impression--Improvement score
Time frame: Every two weeks
Clinician administered measure to assess clinical symptoms
Affective Reactivity Index (ARI)
Time frame: Every two weeks
Clinician administered measure to assess clinical symptoms
1 secondary outcome
parent and self-report measures of irritability, depression, anxiety, anger, social status, and aggression, as well as clinician ratings of depression, anxiety, and impairment
Time frame: Weekly
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2026.
- Background: PubMed 21123313Leibenluft E. Severe mood dysregulation, irritability, and the diagnostic boundaries of bipolar disorder in youths. Am J Psychiatry. 2011 Feb;168(2):129-42. doi: 10.1176/appi.ajp.2010.10050766. Epub 2010 Dec 1.
- Background: PubMed 24342851Leibenluft E, Stoddard J. The developmental psychopathology of irritability. Dev Psychopathol. 2013 Nov;25(4 Pt 2):1473-87. doi: 10.1017/S0954579413000722.
- Background: PubMed 28103715Brotman MA, Kircanski K, Stringaris A, Pine DS, Leibenluft E. Irritability in Youths: A Translational Model. Am J Psychiatry. 2017 Jun 1;174(6):520-532. doi: 10.1176/appi.ajp.2016.16070839. Epub 2017 Jan 20.
- Derived from this study: PubMed 41058235Linke JO, Naim R, Haller SP, Khosravi P, Scheinberg B, Byrne ME, Harrewijn A, Leibenluft E, Brotman MA, Winkler AM, Pine DS. Reduced Threat-Related Neural Efficiency: A Possible Biomarker for Pediatric Anxiety Disorders. Am J Psychiatry. 2026 Jan 1;183(1):48-57. doi: 10.1176/appi.ajp.20241043. Epub 2025 Oct 8.
- Derived from this study: PubMed 40012036Naim R, German RE, White J, Pandya U, Dombek K, Clayton M, Perlstein S, Henry LM, Kircanski K, Lorenzo-Luaces L, Brotman MA. Treatment adherence, therapeutic alliance, and clinical outcomes during an exposure-based cognitive-behavioral therapy for pediatric irritability. BMC Psychiatry. 2025 Feb 26;25(1):181. doi: 10.1186/s12888-025-06601-0.
- Derived from this study: PubMed 38452811McKay CC, Scheinberg B, Xu EP, Kircanski K, Pine DS, Brotman MA, Leibenluft E, Linke JO. Modeling Shared and Specific Variances of Irritability, Inattention, and Hyperactivity Yields Novel Insights Into White Matter Perturbations. J Am Acad Child Adolesc Psychiatry. 2024 Dec;63(12):1239-1250. doi: 10.1016/j.jaac.2024.02.010. Epub 2024 Mar 5.
- Derived from this study: PubMed 38082431Grasser LR, Erjo T, Goodwin MS, Naim R, German RE, White J, Cullins L, Tseng WL, Stoddard J, Brotman MA. Can peripheral psychophysiological markers predict response to exposure-based cognitive behavioral therapy in youth with severely impairing irritability? A study protocol. BMC Psychiatry. 2023 Dec 11;23(1):926. doi: 10.1186/s12888-023-05421-4.
- Derived from this study: PubMed 36563874Linke JO, Haller SP, Xu EP, Nguyen LT, Chue AE, Botz-Zapp C, Revzina O, Perlstein S, Ross AJ, Tseng WL, Shaw P, Brotman MA, Pine DS, Gotts SJ, Leibenluft E, Kircanski K. Persistent Frustration-Induced Reconfigurations of Brain Networks Predict Individual Differences in Irritability. J Am Acad Child Adolesc Psychiatry. 2023 Jun;62(6):684-695. doi: 10.1016/j.jaac.2022.11.009. Epub 2022 Dec 21.
- Derived from this study: PubMed 35794298Haller SP, Archer C, Jeong A, Jaffe A, Jones EL, Harrewijn A, Naim R, Linke JO, Stoddard J, Brotman MA. Changes in Internalizing Symptoms During the COVID-19 Pandemic in a Transdiagnostic Sample of Youth: Exploring Mediators and Predictors. Child Psychiatry Hum Dev. 2024 Feb;55(1):206-218. doi: 10.1007/s10578-022-01382-z. Epub 2022 Jul 6.
- Derived from this study: PubMed 34147585Haller SP, Stoddard J, Botz-Zapp C, Clayton M, MacGillivray C, Perhamus G, Stiles K, Kircanski K, Penton-Voak IS, Bar-Haim Y, Munafo M, Towbin KE, Brotman MA. A Randomized Controlled Trial of Computerized Interpretation Bias Training for Disruptive Mood Dysregulation Disorder: A Fast-Fail Study. J Am Acad Child Adolesc Psychiatry. 2022 Jan;61(1):37-45. doi: 10.1016/j.jaac.2021.05.022. Epub 2021 Jun 17.
- Derived from this study: PubMed 33692176Naim R, Kircanski K, Gold A, German RE, Davis M, Perlstein S, Clayton M, Revzina O, Brotman MA. Across-subjects multiple baseline trial of exposure-based cognitive-behavioral therapy for severe irritability: a study protocol. BMJ Open. 2021 Mar 10;11(3):e039169. doi: 10.1136/bmjopen-2020-039169.
- Derived from this study: PubMed 33386133Linke JO, Abend R, Kircanski K, Clayton M, Stavish C, Benson BE, Brotman MA, Renaud O, Smith SM, Nichols TE, Leibenluft E, Winkler AM, Pine DS. Shared and Anxiety-Specific Pediatric Psychopathology Dimensions Manifest Distributed Neural Correlates. Biol Psychiatry. 2021 Mar 15;89(6):579-587. doi: 10.1016/j.biopsych.2020.10.018. Epub 2020 Nov 9.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No. No individual participant data (IPD) will be shared.
Related trials for Irritability
RecruitingObservational study
Augmenting Parent Management Training for Child Temper Outbursts Using a Digital Tool
Disruptive Behavior Disorders, Conduct Disorder
RecruitingPhase 3
A Study to Evaluate the Long-term Safety and Tolerability of Xanomeline and Trospium Chloride for the Treatment of Psychiatric Disorders in Children and Adolescents
Schizophrenia, Autism-Related Irritability
RecruitingObservational study
Psychotherapy for Irritability in Youth: Comparing Active Treatment to Nonactive Psychoeducation Supportive Psychotherapy
Irritability, Disruptive Mood Dysregulation Disorder
RecruitingObservational study
Abdominal Symptoms and Rosacea: An Observational Study on the Association Between Irritable Bowel Syndrome (IBS) and the Gut-Skin Axis
IBS (Irritable Bowel Syndrome), Rosacea
Recruiting
Stress Reduction and Lifestyle Modification in Irritable Bowel Syndrome Patients
Irritable Bowel Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Melissa A Brotman, Ph.D. principal investigator
National Institute of Mental Health (NIMH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Irritability, run by National Institute of Mental Health (NIMH) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Melissa A Brotman, Ph.D. ((301) 435-6645, melissa.brotman@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Global Impression--Improvement score (time frame: Every two weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02531893, which also lists 18 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2026.