THINKING ABOUT SEVERE IRRITABILITY IN YOUTH

Transcription

1 1 THINKING ABOUT SEVERE IRRITABILITY IN YOUTH Kenneth E. Towbin, M.D. Chief, Clinical Child & Adolescent Psychiatry Emotion & Development Branch NIMH, NIH, DHHS

2 Talk Outline 2 Why study irritability? Pediatric Bipolar Disorder The Controversy over PBD Severe Mood Dysregulation & DMDD Treatment Implications Assessment Tips and Guidelines

3 Irritability 3 No official definition yet irritability runs all through the DSM Continuum from ordinary to pathological Developmental consideration Common in those with disorders In ADULTS estimated to be about 10% of population having impairing irritability at some point in lifetime (NCS Study) Of these 92% have other DSM-IV disorders: mood (45.8%) anxiety (62.3%), impulse control (68.2%) substance use (47.2%) In CHILDREN about 40% of those entering treatment have elevated symptoms of emotional lability (LAMS Study)

4 Irritability in DSM Diagnoses 4 Major depressive episode Manic episode Dysthymic disorder Post-traumatic stress disorder Oppositional defiant disorder Generalized anxiety disorder Intermittent Explosive Disorder PDD-spectrum disorders* ADHD* Conduct disorder* (* Only indicated in the text, not criteria)

5 How Irritability Shows 5 In the background A consistent state of grumpy, annoyed, negative mood, easily triggered to anger Outbursts Flashes of anger or explosiveness, verbal and/or physical, that are excessive responses to requests or events

6 Thinking about In-the-Background 6 Mood between outbursts Mood (sad, angry) Intensity (mild quite severe) Problems it creates for the person/those around him Descriptors Annoyed, grumpy, cranky easily angered often loses temper is often angry and resentful is often touchy or easily annoyed by others

7 Thinking about Outbursts 7 What are Measureable Features of Outbursts? Frequency Duration Intensity Settings Precipitating factors Perpetuating factors

8 What to Know About Irritability 8 There are many disorders that display irritability Irritability doesn t mean just one thing Severe irritability is not the same as bipolar disorder (or a manic episode) Irritability is: Common Hard to describe and measure Poorly understood but now getting studied

10 DSM-IV Criteria for Mania 10 A. A distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting at least 1 week (or any duration if hospitalization is necessary) B. During the period of mood disturbance, three (or more) of the following symptoms have persisted (4 if the mood is only irritable) and have been present to a significant degree: (1) inflated self-esteem, 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 with potential for painful consequences

11 Ambiguity in DSM-IV-TR 11 A-Criteria confusion lasting 1 week: is it always present for that week? If not, how long (or short) can it be? How short is a distinct period? [Could it last for an hour?] B-Criteria confusion Symptoms have persisted : could they precede mood symptoms? Or how long can they persist beyond it? What is a significant degree? Some interpreted that the condition of frequent angry outbursts fit into the definition

12 DSM5 Criteria for Manic Episode 12 A. Distinct period of elevated, expansive, or irritable mood and increased goal-directed activity or energy, lasting at least 1 wk and present most of the day nearly every day B. 3 of the following Sx [or 4, if only irritable] present to a significant degree and represent a noticeable change from usual behavior (1) inflated self-esteem, 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 with potential for painful consequences

13 Clinical Picture of Bipolar Disorder 13 Unmedicated teenage boy has one week with decreased need for sleep, revelations that he is writing 3 novels at once, writes to colleges saying he should be admitted to teach them his advanced math, has auditory hallucinations in which he hears rumors of the past. Unmedicated teenage girl has 4-days when she had 3 hrs sleep/night, awake painting and drawing, feeling so happy it was scary, like being high, was talking so fast her mother couldn t understand her, highly restless, reported having too many thoughts at once.

15 Increasing Rate of Office Visits Related to 15 Bipolar Disorder (Moreno et al, 2007)

16 Number of U.S. Acute-Care Inpatient Discharges per 10,000 Children, Adolescents and Adults with a Principal Diagnosis of a Psychiatric Disorder, Blader & Carlson, Biol Psych, Children: 438.6% increase Adolescents: 296.4% increase 16

17 Controversy of Pediatric BD 17 In s practitioners were encouraged to modify how criteria were applied to children The premise was that one cannot (or need not) identify episodes in children with bipolar disorder; the label would be given to conditions with chronic (i.e. nonepisodic) Sx We now know that making this modification is NOT correct but change comes about slowly DSM5 now makes it clear: bipolar disorder is characterized by episodes

18 Remove Episode Criterion & Double-Count Symptoms: Examples 18 ADHD Sx Bipolar Sx Often fidgets or squirms Often gets up from seat Often runs about or climbs Is "on the go" or acts as if "driven by a motor" Psychomotor agitation Inattention to details; makes careless mistakes Has trouble keeping attention on tasks Excessive pleasurable activities with potential for painful consequences

19 Remove Episode Criterion & then Double-Count Symptoms: Examples 19 ADHD Sx Has trouble organizing activities Lose things needed for tasks/ activities Is easily distracted Is forgetful in daily activities. Bipolar Sx Distractibility

20 From: Sleep Problems in Children With Attention-Deficit/Hyperactivity Disorder: Prevalence and the Effect on the Child and Family Arch Pediatr Adolesc Med. 2008;162(4): doi: /archpedi Sleep problems affected 73.3% (n = 175) of all participants The prevalence of: Mild problems 28.5% moderate or severe problems 44.8%. Date of download: 5/14/2015 Copyright 2015 American Medical Association. All rights reserved.

21 DSM-IV Criteria for Mania: Overlap with ADHD 21 A. Distinct period of elevated, expansive, or irritable mood 1 week B. Symptoms (1) inflated self-esteem, grandiosity (2) decreased need for sleep (3) pressured speech (4) flight of ideas, racing thoughts (5) distractibility Irritability Symptoms like ADHD (6) increased goal-directed activity, psychomotor agitation (7) excessive, pleasurable activities with potential for painful consequences

23 Using Data to Resolve the Question 23 Classic: > 1 full-duration episode (hypo)mania, with elation Intermediate: Episodes too short Irritability, no euphoria Severe mood dysregulation (SMD) Chronic Irritability ADHD-like sx s Impairing Leibenluft et al, 2003

24 Is SMD the same as Bipolar Disorder? 24 Data relevant to the question: Longitudinal course (epidemiological studies) Family history Pathophysiological studies Criteria created to answer this specific question Some similarities might be expected: Sharing some biological features w SMD (or be more dimensional ) than just present/absent

25 Four Goals in Designing the Criteria for Severe Mood Dysregulation (SMD) 25 Presentation must be non-episodic. Operationalize irritability clearly Ensure that the irritability is impairing: Appears in 2 settings SMD children should be as impaired as BD Children should have ADHD symptoms that overlap with B mania criteria

26 Dx Criteria for SMD 26 Anger, sadness, irritability that is Present most of the day, most days Evident to those around the child (in more that one setting) Hyperarousal symptoms ( 3 of 6) Insomnia, agitation, distractibility, racing thoughts, flight of ideas, pressured speech, intrusiveness Excessive reactivity 3 episodes per week Present for at least 12 months Onset before age 12 years and now 7-17 yrs old

27 Clinical Picture of SMD 27 A 10 yr old boy is angry all the time ; argues constantly; aggression to property (walls, doors, household items); police called 3 times last year; hits parents. Bossy with peers, few friends, fights w peers at school Enters on high doses of stimulant plus 2 atypical antipsychotic drugs, plus an alpha adrenergic drug and medication for sleep First mental health contact at age 3; one 3-wk hospital stay at 9 yrs old 9 medications tried in the past Dx: BP, ADHD, Anxiety Disorder, Mood Disorder

28 Longitudinal Course

29 Two Longitudinal Studies 29 Great Smokey Mountain Study (Brotman et al 2006) 1,420 children assessed at 9, 11, 13, 18 yrs old Interviewers assessed presence of symptoms, not just Dx Most common official diagnosis in those with proxy SMD: Anxiety disorders, disruptive disorders (ODD, ADHD, CD) 32% had no official diagnosis (didn t meet full criteria) Prevalence of SMD in the children was 3.2% Children in the Community Study (Leibenluft et al 2006; Stringaris, et. al 2010) 776 children seen at 13.8, 22, 30 years old Comparison of chronic versus episodic irritability

30 Outcome Data: Depression is the most likely 30 Great Smokey Mountain Study Only condition predicted by SMD was major depression SMD was a better predictor of Major Depression than depression in childhood No cases of bipolar disorder Children in the Community By age 30, chronic irritability in childhood predicted only Depression, Dysthymic disorder, Anxiety Disorder (not bipolar disorder or personality disorders)

31 Longitudinal follow-up of BD vs. SMD (median=28.4 months) 31 Rate of (hypo)manic or mixed episodes at follow-up Children with SMD did not develop BD Stringaris et al, JAACAP 2010

32 Mood in Behavioral Disorders 32 Behavioral disorders (or disruptive disorders) (such as ODD & ADHD) have an emotion/mood component and are not purely about behavior Mood problems are common in these conditions Treating mood problems could be critical to helping these individuals and may be important for their overall outcome

33 Summary of Prevalence, Course, and Diagnosis of SMD 33 SMD is very common.about 3.2% Chronic irritability predicts depression Displaying severe irritability is insufficient to make the diagnosis of a manic episode the diagnosis of a manic episode requires other symptoms, too

34 Family History

35 Rates of BD In Parents of BD vs Parents 35 of SMD Children 40 Brotman et al., % BD BD (n=33) SMD (n=30) OR 17.96, CI , p<.01; Chi-square= 6.32

36 Biological/Physiological Features

37 37 Task Example: Affective Posner

38 Posner Paradigm: Feedback 38 TASK 1: Baseline TASK 2: Contingency TASK 3: Contingency & Frustration

39 Affective Posner: Subjective Frustration 39 7 p=.03 p= BD (N= 35) Controls (N=26) SMD (N= 21) Rich et al, 2007

40 Executive Attention (P3 ERP Amplitude at Pz) 40 P3 amplitude at Pz Control (N=26) BD (N=41) SMD (N=23) 8 uv 6 4 * * 2 0 Task 1 Baseline Task 2 Win/Lose $ Task 3 Rigged Significant group x task interaction F(4,112) = 2.67, p=.04 Task 3: BPDs < controls (p=.029); BPDs < SMD Rich (p=.04) et al, 2007

41 Orienting Attention (N1 ERP) in SMD versus BP 41 Control (N=26) SMD (N=21) BPD (N=35) 8 * 6 * * uv 4 2 * * 0 N1 Frontal N1 Central N1 Temporal SMD have problems with initial attention orienting response * p<.05 Rich et al, 2007

42 42 Structural MRI and Functional MRI

43 Structural MRI and Functional MRI 43 No harmful radiation, no needles/injections

44 Face-Emotion Labeling Tasks 44 How hostile is this face? How afraid are you of this face? How wide is the nose?

45 Amygdala Activation: Differences in 45 Diagnostic Groups

46 46 How afraid are you? vs. How wide is nose? Left amygdala ROI, Neutral faces % signal change * * HC (37) ADHD (18) BD (43) SMD (29) Brotman et al, 2010

47 Other fmri Paradigms that show differences between SMD & BP 47 Gender Identification of neutral, angry, fearful faces Probablistic Response Reversal Motor Inhibition (stop signal paradigm) Response flexibility (change paradigm)

48 Chronic Irritability & Bipolar Disorder 48 Data indicate that severely, chronically irritable children with differ from those with BD in Outcome family history brain mechanisms

49 DSM5 Criteria for DMDD 49 A. Severe recurrent outbursts that are not consistent with developmental level B. Outbursts occur, on average, 3 times per week or more C. Angry or irritable most of the day, most days and is observable by others D. Present for at least 12 months without any period of 3 months or more without symptoms E. Irritability is observed in at least 2 settings F. Not before 6 years old or after 18 years old G. Excluded if only occurs during major depression or if better explained by another diagnosis (such as ASD, PTSD, Separation Anxiety Disorder and so on)

50 DMDD and SMD 50 Similar to, but not exactly the same as SMD Similar features Irritability shown by both grouchy, angry mood between outbursts outbursts of anger that are excessive Early age of onset Impairment as a result of irritability Differences: DMDD has onset by 10 years old, SMD by 12 DMDD does not require hyperarousal symptoms DMDD trumps ODD

52 Implications: Treatment of SMD 52 If SMD was the same as BD one would consider: Mood stablizers (e. g. anticonvulsant drugs or lithium) Antipsychotics (e.g. risperidone, aripiprazole, quetiapine) BUT since SMD is more like ADHD with anxiety or depression then one ought to treat what is there : stimulants (e.g. methylphenidate, dextroamphetamine) treatments for anxiety or depression such as SSRIs or CBT psychotherapy, or a combination of these

53 Implications: Treatment of SMD 53 There is a lot we do not know about treatment of Irritability and SMD But we can study treatments now that we can define what we mean by SMD Testable ideas Li was not helpful in SMD Environmental interventions were helpful but Study of benefit of stimulant plus SSRI for SMD is underway What role can non-pharmacological treatments play?

55 Assessment Tips 55 Offer examples from direct observation Interview : Parent & child separately Parent & child together Look at effects across different settings

56 Diagnosing Bipolar Disorder: I 56 It is all about the episodes Are there episodes that are clearly different from that individual s usual functioning (episode), or is there a fairly steady presence of irritable mood (DMDD)? In an episode, symptoms change/occur in a bundle with other symptoms, not in isolation The mood changes show across settings Question manic symptoms that only occur at home

57 Diagnosing Bipolar Disorder: II 57 Elevated mood, grandiosity can be tricky Developmental considerations are key Cultural considerations are important For example: the ambiguity of statements like He acts as if the rules don t apply to him. Decreased need for sleep insomnia

58 From: Sleep Problems in Children With Attention-Deficit/Hyperactivity Disorder: Prevalence and the Effect on the Child and Family Arch Pediatr Adolesc Med. 2008;162(4): doi: /archpedi Date of download: 5/14/2015 Copyright 2015 American Medical Association. All rights reserved.

59 Assessment of DMDD 59 Look for a routine pattern of outbursts at home, school and/or with peers Think about mood (anger and irritability) between outbursts Consider developmental level carefully Consider how parents and others make accommodations for the child s mood and irritability Think about impairment that is a consequence of irritability

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