Assessment and Management of Severe Irritability from Preschool to High School
Jeffrey Hunt, MD
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Learning Objectives
Describe the historical conceptualization of irritability as a symptom in psychiatric disorders Highlight the differences between episodic vs chronic irritability Define the criteria for DMDD Discuss severe irritability in the context of preschool age children Briefly discuss neuroscience and genetic research trends related to irritability Describe evidenced-based approaches in managing irritability
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Case history: Jed
Jed is a 9 year old male referred for evaluation of 2 year history of nearly daily temper tantrums. He is very easily frustrated and becomes rageful, most often toward mother, when his needs are not met. He has difficulty making friends and prefers to spend time on video games. Since COVID-19 quarantine began his moodiness has increased. The parents report substantial stress from parenting him. Mom reports “constant walking on egg shells”
PPH: he has a therapist but “hates going.” no medication
SH: only child – mom is teacher; father is engineer – recent treatment for glioblastoma
FH: post partum depression in mom; pat grandmother “I think she had bipolar disorder”
PMH: Healthy
Picture courtesy of www.dbsalliance.org
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Objectives
Describe the historical conceptualization of irritability as a symptom in psychiatric disorders Highlight the differences between episodic vs chronic irritability Define the criteria for DMDD Discuss severe irritability in the context of preschool age children Briefly discuss neuroscience research trends Describe evidenced-based approaches in managing irritability
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Pediatric Bipolar Disorder and Irritability: Primary Controversy
The frequent diagnosis of bipolar disorder in children with chronically irritable mood redefined bipolar disorder in early life as a non- episodic syndrome This diagnostic approach contributed to the dramatic rise in the rate of pediatric visits for bipolar disorder in the United States
Rise in polypharmacy Rise in use of atypical antipsychotics Led to introduction of DMDD
Roy, Lopes & Klein 2014, Carlson 2011; Francis 2012
3 • Of the 43 children who met criteria for mania • 77% (n=33) – persistent irritability • 14% (n=6) – elation • 9% (n = 4) - full of energy or many thoughts. – Only 16% (n=7) were episodic (> 1 episodes of mania) remainder were chronic – This study was very influential - irritability and chronicity as hallmark of BP
JAACAP 34(7), 1995
Bipolar Disorder: Over diagnosed?
1994-19952002-2003: Ped BD 40-fold increase! <19yo 25/100,0001003/100,000 DSM-IV >20yo 905/100,0001679/100,000 Published
National Ambulatory Medical Care Survey (NAMCS) annually by National Center for Health Statistics.
Moreno et al. Arch Gen Psych 2007
Irritability is Not Specific
Bipolar disorders Major depressive episode Gen. anxiety disorder PTSD Oppositional defiant disorder ADHD Conduct disorder Intermit. explosive disorder Autism spectrum disorders
4 Irritability: Terminology
Frustration: Irritability: Emotional state increased proneness Anger: Consciously induced by block to anger relative to perceived Rage: goal attainment; similarly developed emotion/feeling Intense anger Frustrative non- peers with irritability reward resulting in increased aggression
13 Stringaris A. J Child Psychol Psych 59;7 2018 721-739
Kraepelin Description of irritable mania
“.…On the other hand there often exists a great emotional irritability. The patient is dissatisfied, intolerant, fault-finding… he becomes pretentious, positive, regardless, impertinent and even rough, when he comes up against opposition to his wishes and inclinations; trifling external occasions may bring about violent outbursts of rage.”
Kraepelin, 1921
Irritability: Long recognized as a problem
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5 Irritability: Terminology
Chronic irritability: Worse than peers but not different than child’s baseline (DSM >12 months) Episodic Irritability: Change from child’s baseline and worse than peers; Found in MDD and BD Tonic Irritability: Persistent irritable mood in between outbursts (part of DMDD) Phasic Irritability: Temper outbursts on top of Tonic Irritability
Stringaris A. J Child Psychol Psych 59;7 2018 721-739 16
Irritability common in BP and ADHD
Geller et al., 2002
Irritablity as symptom of Bipolar Disorder across studies
Rates of irritability and elation vary significantly across study samples.
100
50 elation irritability 0 Findling Wozniak Geller Axelson
Adapted from Kowatch, et al., 2005
6 Hunt et al., JAACAP 2009 10%
15% both
75% ela on irritability Hunt et al, JAACAP, 2009
Identifying Irritability only subgroup in the COBY Sample
Secondary analysis using KSAD-MRS Category A symptoms to define three groups 361 subjects had both most serious past and current MRS ratings Looking for between group differences at baseline and longitudinally
Hunt et al., JAACAP 2009
K-SADS MRS: Irritability
• Mild: Often feels definitely more angry, irritable Subjective feeling of irritability, anger, than called for by the situation. relatively crankiness, bad temper, short tempered, frequent but never very intense resentment, or annoyance, externally directed, whether expressed overtly or not. • Moderate: Most days irritable/angry or over 50% of awake time.
Rate the intensity and duration of such • Severe: At least most of the time child is aware feelings. of feeling very irritable or quite angry or has frequent homicidal thoughts (no plan) or thoughts of hurting others. Or throws and Do not rate here if irritability is due to breaks things around the house. depression or disruptive disorders. • Extreme: Most of the time feels extremely angry or irritable, to the point s/he "can't stand it." Or frequent uncontrollable tantrums.
7 COBY: Episodic irritable mania exists
At baseline Irritable only, elated only, and both elation and irritable groups are phenomenologically similar At 48 months: Episodic Irritable BP patients remain similar to subjects with elation with regard to most longitudinal outcomes Most subjects went on to have both irrit and elation Irritable only BP patients more frequently subsyndromal and syndromal for depression Hunt et al., 2009; 2013
Episodicity vs. chronicity
longitudinal studies of irritability
1141 households in semirural NY. time 1 - mean age 13 time 2 - mean age 16 time 3 - mean age 22
Different associations with age: episodic=linear; chronic=curvilinear
Episodic irritability predicts mania
Chronic irritability predicts depression Leibenluft J Child Adolesc Psychopharm 2006
8 631 subjects followed from age 13.8 to 33.2 years: MDD, Dysthymia, and GAD significantly increased at 20 years Bipolar diagnosis not increased at 20 year follow-up
84 youths with SMD and 93 with BP-I followed a median of 28.4 months.
Stringaris et al., JAACAP 2011
Clinical Phenotypes of Pediatric Mania
Narrow: Broad: . full-duration episodes Severe mood dysregulation . hallmark symptoms (elevated expansive . chronic irritability mood) . no hallmark symptoms. Irritable Intermediate (Hypo)mania- (Hypo)mania: full NOS: hallmark symptoms duration episodes; but short episodes. NO hallmark symptoms
Leibenluft E Am J Psychiatry 2003
9 SMD: Precursor to DMDD
Severe Mood Dysregulation DMDD • Abnormal mood: anger or sadness • Irritable mood • No symptom-free period exceeding 2 • No symptom-free period exceeding 3 months months • Aged 7 – 17, with symptom onset before • Aged 6 – 17, with symptom onset before age 12 age 10 • Symptoms severe in at least 1 setting and • Symptoms must be present in at least 2 of mild symptoms in a second setting 3 settings • Hyperarousal
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Disruptive mood dysregulation disorder 296.99
Addresses concerns about potential for over diagnosis of bipolar disorder in children
Placed in Depressive Disorders chapter reflecting longitudinal research that children with this symptom pattern typically develop unipolar depression or anxiety and not bipolar disorder
DMDD criteria
Severe recurrent temper outbursts Verbally or behaviorally Grossly out of proportion in intensity and duration to situation Inconsistent with developmental level Occur three or more times per week Mood between temper outbursts is persistently irritable or angry Observable by others (parents, teachers, peers) Present for 12 + months No period longer than 3 months without all symptoms Present in at least two of three settings
10 DMDD criteria
Not made before age 6 or after 18
Age of onset (by history or observation) before age 10
Never a distinct period lasting one full day during which full criteria (except duration) for manic symptoms are met
Do not occur exclusively during MDD episode Also not better explained by ASD, PTSD, SAD, persistent depressive disorder
DMDD criteria
DMDD cannot coexist with ODD Intermittent Explosive Disorder Bipolar Disorder
Can coexist with MDD ADHD CD SUD
DMDD trumps ODD
DMDD ODD Duration: 12+ months Duration: 6+ months Age: 6 to 18 y.o. Age: < 18 y.o. Frequency: temper outbursts ≥ 3 x wk Frequency: < 5 y.o.: most days Mood: persistently angry most of the day nearly every day > 5 y.o.: 1 x week Spiteful or vindictive at least twice in last 6 Verbal and behavioral temper outbursts mos. Mood: often angry and resentful Verbal outbursts
If meet criteria for both, DMDD is the diagnosis
11 DMDD vs BP BP Symptoms are episodic and are above and beyond childs other psychiatric disorders
For example: Bipolar symptoms
DMDD, ADHD or ODD
DMDD: Field Trials
• Variable Kappa found between sites • More reliable in inpatient settings for more severe patients
35 Am J Psychiatry 2013; 170:59–70
DMDD: Trial Run
• Used existing data from 3 large epidemiological samples • Covered a broad age range: • Preschool (ages 2 – 5 years) • School-age through adolescence (ages 9 – 17 years)
36 Am J Psychiatry 170:2, February 2013
12 DMDD: Trial Run
• Nearly ½ of school-age youths were reported to have severe • 3.3% of preschoolers had DMDD temper outbursts during the 3 • Prevalence highly dependent months prior to assessment: upon applying criteria: • Applying the duration criteria • Frequency dropped the prevalence to 1.5% – • Intensity 2.8% • Persistence • Applying all the DMDD criteria resulted in a prevalence of about • Retrospective recall problematic 1%
37 Copeland et al., Am J Psychiatry 170:2, February 2013;
DMDD: Summary of Prevalence
3.3 % 1.1 % 0.8 %
38 Copeland et al., Am J Psychiatry 170:2, February 2013;
DMDD: Adult Outcomes
The long-term prognosis of children with DMDD is one of pervasive impaired functioning that in many cases is worse than that of other childhood psychiatric disorders
39 Copeland et al., Am J Psychiatry 2014
13 Objectives
Describe the historical conceptualization of irritability as a symptom in psychiatric disorders Highlight the differences between episodic vs chronic irritability Define the criteria for DMDD Discuss severe irritability in the context of preschool age children Briefly discuss neuroscience research trends Describe evidenced-based approaches in managing irritability
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Can DMDD be identified in early childhood?
• Core DMDD symptoms (e.g. recurrent temper loss and persistent irritability) are common presenting concerns for some preschoolers
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• Examined DMDD symptoms in preschool-aged children (4 – 5 years) • Frequency • Behavioral impairment • Comorbidity • Family functioning
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14 PPHP: Irritability in Young Children
• Participants: 139 children • Ages 4-0 to 5-11 years • 75% male • Median yearly income = $40,000
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PPHP: Irritability in Young Children
• Diagnostic Infant and Preschool • Child Behavior Functioning Assessment (DIPA): • Child Behavior Checklist (CBCL 1 ½ - 5) • Modified diagnostic criteria for DMDD • Peabody Picture Vocabulary Test • Frequent temper loss (e.g. tantrums, • Family Functioning and Psychiatric History screaming, hitting / throwing things) → ODD module • Parenting Stress Index • Temper outbursts at least 3x weekly • Family History Screening • Persistently irritable / angry mood at • Center for Epidemiological Studies least 5x weekly → MDD module Depression Scale • Duration of irritability of at least 12 months → MDD module
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PPHP: Frequency of DMDD symptoms
Criteria N (%)
(A &B) 128 (92%) Severe temper – inconsistent w developmental level
(C) 118 (85%) Temper 3+ times per week
(D) 94 (68%) Persistent irritability – 5+ days/week
(E) 77 (55%) Duration at least 12 months
(A-E) 63 (45%) 45 Meets all criteria
15 PPHP: DMDD symptoms in preschoolers
100% Comorbidity in DMDD+ preschoolers: 7 90% 4 • 63 children met criteria for DMDD 80% • 52 (82.5%) also met criteria for 70% 14 ODD 60% 50% • 38 (60.3%) of these children 40% also met criteria for ADHD 30% 38 20% • 7 (11.1%) met criteria for DMDD 10% alone 0%
DMDD + ODD + ADHD DMDD + ODD (No ADHD) DMDD + ADHD (No ODD) DMDD Only 46
DMDD symptoms are associated with:
High levels of child aggression and reactivity Decreased receptive language skills Increased parental stress High rates of co-occurrence with ODD and ADHD
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Irritability in Young Children
Next steps? • Affective Reactivity Index (ARI) • Parent report • Milieu staff report • Piloting ARI self-report interviews in preschool-age children
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16 Objectives
Describe the historical conceptualization of irritability as a symptom in psychiatric disorders Highlight the differences between episodic vs chronic irritability Define the criteria for DMDD Discuss severe irritability in the context of preschool age children Briefly discuss neuroscience and genetics research trends Describe evidenced-based approaches in managing irritability
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Irritability: Mechanisms
Threat Frustrative Non-Reward • Situation or object signals harm: • Normal emotional state but when unable to achieve a goal: • Fight or flight • Increased aggression and activity • Increased vigilance to threatening stimuli: • Decreased striatal activity • Angry faces • Decreased frontal cortex activation in • Misinterprets neutral faces irritable youths • Difficulty modulating amygdala
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Research: Neurocircuitry
Leibenluft, Trends in Cognitive Sciences, April 2017, 51
17 Research: Frustrative non-reward
Youth with SMD showed decreased amygdala activity when receiving frustrating, negative feedback
Leibenluft, Trends in Cognitive Sciences, April 2017 52
Research: Aberrant response to threat
Associations between aberrant responses to threat and irritability Irritability in youth is associated with aberrant amygdala-prefrontal cortex connectivity when viewing threatening faces
Leibenluft, Trends in Cognitive Sciences, April 2017, 53
• Examined whether there were multiple forms of irritability: • ”Neurodevelopmental / ADHD-like” subtype → childhood onset • “Depression / mood” type → onset in adolescence
Riglin et al., Am J Psychiatry 2019; 176:635–642 54
18 Irritability: Novel Types
• Avon Longitudinal Study of Parents Polygenic risk scores (PRSs) for and Children (ALSPAC) ADHD and MDD risk alleles • 7,924 participants were identified from Psychiatric • Irritability assessed using the ODD Genomics Consortium analysis section of the Development and Well-Being Assessment of case-control GWAS.
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Irritability: Novel Types
• Identified 5 irritability trajectory classes: • Low • Decreasing • Increasing • Late-childhood limited • High-persistent
Riglin et al., 2019 56
Irritability: associated with genetic liability
• The developmental context of irritability may be important in its conceptualization: early-onset persistent irritability may be more neurodevelopmental/ADHD-like and later-onset irritability more depression/mood-like.
• These findings may have implications for treatment as well as nosology.
Riglin et al., 2019 57
19 Objectives
Describe the historical conceptualization of irritability as a symptom in psychiatric disorders Highlight the differences between episodic vs chronic irritability Define the criteria for DMDD Discuss severe irritability in the context of preschool age children Briefly discuss neuroscience research trends Describe evidenced-based approaches in managing irritability
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Assessement of Irritability:
DMDD K-SADS • Semi-structured interview • Clinician-rated measures: Development and Wellbeing • Clinician Global Impression (CGI) Assessment • Clinician Affective Reactivity • DMDD module Index • Structured interview • Online
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Irritability: Questionnaires
Affective Reactivity Index (ARI) • Brief 7-item measure • Assesses: • Feelings and behaviors centered around irritability (items 1-6) • Associated functional impairment
60 Stringaris, Goodman, et al., 2012
20 Irritability: Questionnaires
Multidimensional Assessment of Preschool Disruptive Behavior (MAP-DB) Questionnaire • Valid instrument to assess irritability in preschool children • 20-item measure • Assess features of tantrums and anger regulation • Covers a broad range of behaviors
Wakschlag et al., 2010 61
Irritability: Management
• Treat comorbid conditions first! • Can add psychological treatment: • Cognitive behavioral therapy (CBT) • Parent management training (PMT) • Pharmacological treatment should be a last resort
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Irritability: Management
Depression
Anxiety ADHD
ODD / CD
•DMDD co-occurs with another disorder in 63 65% – 90% of cases
21 Stringaris et al. 2018 Mechanisms of Irritability
Assessment: Parental negativity /warmth
Treatment: Parenting intervention
Treating Irritability in Children: Therapy
• Parent management training (Barkley 1997, 2000) • Standardized daily routines and social rhythms (Frank 1997) • Collaborative problem solving used for ODD (Greene 2003, 2004). • Family therapy (Fristad 2003, Miklowitz 2003, Pavuluri 2004, Keitner 1995) • DBT for adolescents with mood disorders (Goldstein et al.,2007) • Interpretation Bias Training (Stoddard et al., 2016)
Treating Irritability in Children: Parent Management Therapy
Parent management training (Barkley 1997, 2000)
22 Treating Irritability in Children: Parent Management Therapy
Parent management training (Barkley 1997, 2000 http://www.continuingedcourses.net/active/courses/course079.php
Treating Irritability in Children: Interpersonal Social Rhythm Therapy
Standardized daily routines and social rhythms (Frank 1997) Treatment for adults with bipolar disorder modified for youth
•Principles: – Regular sleep, exercise, socialization keeps people’s mood and behavior regular – Converse: irregularities in sleep, exercise, socialization may be an early warning sign of problems/non-euthymic mood or behavior
Treating Irritability in Children: Family therapies
• Multi-family psychoeducational psychotherapy (Fristad 2009) – Psychoeducation; build skills in mood sx management, affect regulation, problem solving, communication • Family-focused therapy (FFT)=CBT+psychoed+famtx -effective in adults and adolescents (Miklowtiz 2000, Pavuluri 2004) – Psychoed about BD/tx; Communication & problem solving to reduce conflict/improve positive interactions – For example “RAINBOW” (Pavuluri 2004)
23 Treating Irritability in Children: Collaborative Problem Solving
Collaborative Problem Solving (Greene 2003, 2004) •2 principles: 1) Social/emotional/behavioral issues for children should be understood from lagging cognitive skills—rather than attention-seeking, manipulative, limit- testing, poor motivation 2) Resolve these problems collaboratively—rather than reward/punishment •3 steps: 1) Empathy Step: What is child’s concern about problem (chores, siblings, screen time)? 2) Define the Problem Step: Adult concerns 3) Brainstorm solution to address both
Dialectical Behavior Therapy (DBT) for Adolescents
Main target of which is emotion dysregulation, including high sensitivity to emotional stimuli and extreme emotional intensity This adapted intervention is delivered over the course of one year, and is comprised of two modalities: family skills training individual psychotherapy with the adolescent patient.
Goldstein T, Axelson D, Birmaher B, et al. J Am Acad Child Adolesc Psychiatry 2007; 46(7): 820-830. 71
Interpretation Bias Training
Targets hostile interpretation bias Participants are presented with stream of faces depicting emotions Training consists of 180 trials with goal of moving rating of ambiguous faces from angry to happy Open study of DMDD subjects demonstrated significant reduction on parent rated irritability
Stoddard et al, 2016 JCAP 26 (1) 49-57
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24 Irritability: Pharmacologic Management
Lithium = placebo
SSRIs = small impact alone - more in comb with stimulants
Stimulants = medium to large effect sizes
Atypical Antipsychotics = FDA approval in ASD
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Case study : Max
A 10-year-old boy presents to the outpatient clinic with a two year history of frequent temper tantrums in the context of frustration especially at home. He is described as “constantly cranky.” His teachers also report that he is prone to get into fights during recess when he feels slighted. There is no trauma or social adversity that explains his presentation. He has no evidence of psychosis. Family history includes anxiety and depression in some relatives. How would you proceed?
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AACAP Presidential Initiative:
“It would be a shame if we jumped from the frying pan of mislabeling children as “bipolar” because we had no accurate diagnosis to categorize their explosivity—to the fire of conflating the mood & behavioral components of irritability”
Carlson G, J Child Psychol Psych 58;7 2018 740-43
25 Acknowledgements
Ashley Martinez, BA John Boekamp, PhD Sarah Martin PhD Heather Hunter, PhD Maria Teresa Coutinho The COBY Team and all the subjects
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THANK YOU!
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