Irritability and DSM-5 Disruptive Mood Dysregulation Disorder (DMDD): Correlates, predictors, and outcome in children

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1 Irritability and DSM-5 Disruptive Mood Dysregulation Disorder (DMDD): Correlates, predictors, and outcome in children Ellen Leibenluft, M.D. Chief, Section on Bipolar Spectrum Disorders National Institute of Mental Health, USA Clinical Associate Professor Georgetown University School of Medicine

2 No disclosures Travel paid by conference. Research supported by NIMH

3 Talk Outline A historical perspective on DMDD: irritability and pediatric bipolar disorder Longitudinal course and familial correlates of irritability DSM-5 Disruptive mood dysregulation disorder (DMDD) criteria Treatment

4 1. How happy are you to be here? 1. Ecstatic, what could be better? 2. Quite contented. 3. Pretty neutral. 4. Would prefer not to be. 5. Last place on Earth I want to be.

5

6 2. How common is the diagnosis of bipolar disorder in children? All are true except: 1. Vanishingly small in American clinics in /1000 visits in American clinics in % in US and non-us community samples % in US and non-us community samples /100,000 in US hospital discharges from /100,000 in UK hospital discharges from

7

8 Increase in diagnosis of BD in youth in US clinics Moreno et al, 2007

9 US-UK pediatric bipolar disorder hospital discharge rates, James et al, 2014

10 3. What are pathognomonic symptoms of pediatric bipolar disorder? 1. Very severe temper outbursts 2. Distinct change in mood from baseline 3. Particularly marked ADHD 4. Change in sleep, cognition, activity from baseline

11

12 DSM-5 Criteria for Manic Episode A. Distinct period of elevated, expansive, or irritable mood. present most of the day, nearly every day 1 week B. Symptoms (3, or 4 if irritable) occur at the same time as A and represent a noticeable change from previous behavior: (1) grandiosity (2) decreased need for sleep (3) pressured speech (4) flight of ideas, racing thoughts (5) distractibility (6) increased goal-directed activity, psychomotor agitation (7) excessive pleasurable activities

13 DSM-5 Criteria for Manic Epısode: Overlap with ADHD A. Distinct period of elevated, expansive, or irritable mood. present most of the day, nearly every day 1 week B. Symptoms (3, or 4 if irritable) occur at the same time as A and represent a noticeable change from previous behavior: (1) grandiosity (2) decreased need for sleep (3) pressured speech (4) flight of ideas, racing thoughts (5) distractibility (6) increased goal-directed activity, psychomotor agitation (7) excessive pleasurable activities

14 Should children with severe irritability and ADHD be considered to have a pediatric form of BD?

15 4. To answer the question Should children with severe irritability and ADHD be considered to have a pediatric form of BD? the most important thing to know is whether: 1. children with BD tend to also have symptoms of ADHD. 2. children with BD tend to have a family history of ADHD. 3. children with severe irritability develop manic episodes as they grow up. 4. children with severe irritability tend to have a family history of BD. 5. brain function differs between severely irritable children and those with BD.

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17 5. When irritable children grow up, they are at risk for: 1. Mania or hypomania 2. Anxiety disorders 3. Unipolar depression 4. Psychopathy 5. Decreased education and income

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19 Do irritable children develop manic episodes when they grow up? Community-based studies: Irritability in youth predicts anxiety, unipolar depression in adulthood Duration of follow-up: 3 to 20 years ODD has irritable and headstrong dimensions irritable predicts to depression (Stringaris and Goodman 2009, Rowe et al 2010, Burke et al, 2010) headstrong predicts to conduct disorder, antisocial personality Irritability in youth does not predict bipolar disorder in adulthood

20 Chronic irritability in youth predicts MDD, dysthymia, anxiety at f/u Children in the Community N Age at baseline Age at f/u ( ) MDD GAD Dysthymia 1.72 ( ) 1.81 ( ) Chronic irritability did not predict mania or Axis II Disorders. It was associated with decreased education and income. Stringaris et al, 2009

21 6. Which of the following is true about the heritability of irritability? 1. Irritability is about as heritable as bipolar disorder. 2. Irritable children tend to have strong family histories of bipolar disorder. 3. Irritability is about as heritable as anxiety disorders. 4. The longitudinal association between irritability and depression has a significant genetic component.

22

23 Do irritable children tend to have a family history of BD? LAMS (Longitudinal Assessment of Mania Study) Screened 2622 youth presenting for assessment 25% (N=235) met proxy criteria for DMDD Compared DMDD vs. non-dmdd in rates of BD in 1 st and 2 nd degree relatives Degree of familial loading for mania No analysis reached significance, even before correcting for multiple comparisons D Axelson, RL Findling, EA Youngstrom, et al (unpublished)

24 Genetics of irritability Twin studies show: Irritability is moderately heritable (~ ) Longitudinal association between irritability and depression/anxiety has a significant genetic component (41-74% of variance) Stringaris et al, 2012; Roberson-Nay et al, 2015a Gender differences in genetic influences Swedish twin sample (TCHAD) N=2490 Assessment waves: 8, 13, 16, 19y (Roberson-Nay et al, 2015b)

25 Irritability in Fragile Families and Child Well- Being Study N= 4898 families from 20 US cities, recruited at birth Irritability measure from CBCL Wiggins et al, 2013

26 Association between child irritability and maternal depression if mother depressed > 2x Auto-regressive cross-lag models show bidirectional relationship between maternal depression and child irritability. Wiggins et al, 2013

27 7. Which of the following children should receive the diagnosis of BD? 1. An extremely irritable child with ADHD. 2. An extremely irritable child without ADHD. 3. An extremely irritable child with a parent who has BD. 4. A child who experienced a distinct episode of mania.

28

29 Diagnosis given for the first time > age 6, < age 18 no preschoolers, no adult data DSM-5 DMDD Criteria Chronic, severe irritability Severe, recurrent temper outbursts > 3x week, on average Verbal and/or behavioral Developmentally inappropriate Mood between outbursts persistently irritable or angry most days, most of the day Irritability impairing in > 2 settings (home, school, peers) not at home only Present > 12 months chronic presentation 2 components of severe irritability Syndrome must onset before age 10 not adolescence

30 DSM-5 DMDD Overlap Criteria If child meets criteria for DMDD and ODD, diagnose only DMDD If child meets criteria for DMDD and ADHD, diagnose both Exclusions: Distinct (hypo)manic episode > 1 day Only present during episode of MDD not better explained by ASD, PTSD, separation anxiety

31 Common pitfalls in diagnosing DMDD Severe recurrent temper outbursts manifested verbally (e.g., verbal rages) and/or behaviorally (e.g., physical aggression toward people or property) that are grossly out of proportion in intensity or duration to the situation of provocation. Verbal outbursts MUCH more common than physical aggression The mood between outbursts is persistently irritably or angry most of the day, nearly every day, and is observable by others (e.g., parents, teachers, peers) Modelled on criterion for depression Is the child generally grumpy? Cranky? Do you feel like you have to walk on eggshells? Accommodations

32 8. Which of the following were reasons for the creation of DMDD? 1. Severely irritable children may have been diagnosed with BD because there was no good home for them in DSM-IV. 2. The phenotype is very common. 3. These children are very ill and need more services than justified by the ADHD/ODD diagnoses. 4. Disruptive behavior disorders diagnoses don t do justice to their mood/anxiety symptoms. 5. Doctors diagnose these children as BD, won t prescribe stimulants or SRI s, and prescribe atypical antipsychotics instead. 6. Without a diagnosis, there aren t treatment trials.

33

34 Clinical Characteristics of Severe Mood Clinical Characteristics Dysregulation Age Age of onset Gender (% male) 65.2 % ADHD 86.1 % ODD 83.6 % Anxiety Disorders 66.7 Number medications Severe Mood Dysregulation (N=201) Children s Global Assessment Scale

35 9. For which of the following is there evidence suggesting possibly efficacy in chronic irritability? 1. Stimulants 2. SRI s 3. Atypical antipsychotics 4. Lithium 5. Psychotherapy

36

37 Few controlled clinical trials for irritability Medications Cuts across DSM diagnoses FDA indication: risperidone, aripiprazole for irritability in autism Psychotherapeutic interventions Treatments for other, related behaviors, syndromes Aggression Proactive vs. reactive aggression More specific treatments being developed

38 Irritability Treatment Algorithm

39 Meta-analysis of efficacy of stimulant Rx on overt and covert aggression Included 28 studies, total N=638 Effect size (Cohen s d) d= 0.84 for overt aggression (included rage attacks, irritability) d= 0.69 for covert aggression Connor et al, 2002

40 Irritability Treatment Algorithm

41 Rationale for prescribing SRI s in irritability Co-occurrence with anxiety and depression Some evidence in adults: anger attacks, PMDD Longitudinal and genetic associations with anxiety, depression More benign side-effect profile than atypical antipsychotics

42 SMD Lithium RCT: CGI-I Dickstein et al, 2009

43 Conclusions The diagnosis of BD should be reserved for children with history of distinct (hypo)manic episodes. Irritable children are at risk to develop anxiety and unipolar depressive disorders in adulthood. These longitudinal associations have a genetic component. DMDD should be used to diagnose severely irritable youth. Psychotherapy is likely to be important in the treatment of DMDD. Stimulants have a role in the treatment of youth with DMDD and ADHD. SRI s and atypical antipsychotic medications may also have a role in treating DMDD.

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