Presenter: John Bailey, D.O., D.F.A.P.A. FOMA Annual Meeting---Weston, Florida

February 2017

The Color Purple Changes to a number of diagnostic

categories, and some re-categorization And…DMDD

Found in DSM 5 under “Depressive Disorders,” not anxiety or bipolar.

Portends adult anxiety and unipolar depression, NOT manic episodes in adult life

The irritability of DMDD tends to remain constant---as opposed to the episodic departure from baseline mood characteristic of bipolar mood episodes.

The two core sx are: temper tantrums (> 3 per wk), and a pervasive, very chronic daily irritable mood.

Dates back to DSM II and dx of ADD In DSM III (1980), mood lability sx removed

from ADD dx, and ODD dx created, but… Bipolar mania dx in children soared 44 fold in

outpatient settings, 7 fold in inpatient settings---and not all of these children appeared to actually have a reliable dx.

So DMDD looks a lot like ADD + ODD, and treatment strategies may be similar

Diagnosis imprecise Syndrome based on work in patients

described as “SMD” Invites criticism for “pathologizing” temper

tantrums Proposed criteria are almost certainly

premature Research hasn’t clarified boundaries between

DMDD, ADHD, Oppositional Defiant Disorder and developmentally acceptable behavior

More information needed on how the phenotype changes over the lifespan

American Academy of Child and Adolescent Psychiatry, March 30, 2010

Much of the research literature on which DMDD is based is actually based on “SMD.”

This was before chronic irritability and intermittent explosive episodes in children were recognized as precursors to life-long problems with depression.

Signs and Symptoms of DMDD DMDD symptoms typically begin

before the age of 10, but the diagnosis is not given to children under 6 or adolescents over 18. A child with DMDD experiences:

Irritable or angry mood most of the day, nearly every day

Severe temper outbursts (verbal or behavioral) at an average of three or more times per week that are out of keeping with the situation and the child’s developmental level

Trouble functioning due to irritability in more than one place (e.g., home, school, with peers)

To be diagnosed with DMDD, a child must have these symptoms steadily for 12 or more months.

296.99 ( F34.81)

A. 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 or provocation.

B. The temper outbursts are inconsistent with developmental level. C. The temper outbursts occur, on average, three or more times per week. D. The mood between temper outbursts is persistently irritable or angry most of the

day, nearly every day, and is observable by others (e.g., parents, teachers, peers).

E. Criteria A–D have been present for 12 or more months. Throughout that time, the individual has not had a period lasting 3 or more consecutive months without all of the symptoms in Criteria A–D.

F. Criteria A and D are present in at least two of three settings (i.e., at home, at school, with peers) and are severe in at least one of these.

G. The diagnosis should not be made for the first time before age 6 years or after age 18 years.

H. By history or observation, the age at onset of Criteria A–E is before 10 years. I. There has never been a distinct period lasting more than 1 day during which the

full symptom criteria, except duration, for a manic or hypomanic episode have been met.

Note: Developmentally appropriate mood elevation, such as occurs in the context of a highly positive event or its anticipation, should not be considered as a symptom of mania or hypomania.

J. The behaviors do not occur exclusively during an episode of major depressive disorder and are not better explained by another mental disorder (e.g., autism spectrum disorder, posttraumatic stress disorder, separation anxiety disorder, persistent depressive disorder [dysthymia]).

Note: This diagnosis cannot coexist with oppositional defiant disorder, intermittent explosive disorder, or bipolar disorder, though it can coexist with others, including major depressive disorder, attention-deficit/hyperactivity disorder, conduct disorder, and substance use disorders. Individuals whose symptoms meet criteria for both disruptive mood dysregulation disorder and oppositional defiant disorder should only be given the diagnosis of disruptive mood dysregulation disorder. If an individual has ever experienced a manic or hypomanic episode, the diagnosis of disruptive mood dysregulation disorder should not be assigned.

K. The symptoms are not attributable to the physiological effects of a substance or another medical or neurological condition.

When families avoid certain activities likely to provoke a temper tantrum---e.g. going out in public, or having other families and friends over.

Can result in underdx of DMDD if temper tantrums are accommodated. Accommodations made by parents or teachers are considered evidence of impairment.

Rare

Neither DMDD Nor Bipolar

Change from previous Behavior or self

Frequent

Child

Teen

First r/o Stressors: School: learning Problem, bullying Home: family problems, abuse

r/o mood d/o Depression Mania Anxiety d/o Drugs Psychosis

Chronic

Irritable Between Outbursts Fine til

frustrated

DMDD ADHD ODD

Gabrielle Carlson, M.D.

Higher prevalence in males Higher prevalence in school aged children

than teens: 2-3% prevalence among pre-school aged children 1-3% of 9-12 yr olds 0.12% of adolescents

Compared with Healthy Volunteers, brain areas of individuals with DMDD showed hypoactivity when presented with positive facial stimuli, and hyperactivity when presented with negative stimuli. [R limbic structures].

Date of download: 2/16/2017 Published by Oxford University Press 2015. This work is written by US

Government employees and is in the public domain in the US.This work is written by US Government employees and is in the public domain in the US.

From: Neural correlates of masked and unmasked face emotion processing in youth with severe mood dysregulation

Affective priming paradigm. (a) Non-aware condition. (b) Aware condition.

Figure Legend:

Soc Cogn Affect Neurosci. 2015;11(1):78-88. doi:10.1093/scan/nsv087

Date of download: 2/16/2017 Published by Oxford University Press 2015. This work is written by US

Government employees and is in the public domain in the US.This work is written by US Government employees and is in the public domain in the US.

From: Neural correlates of masked and unmasked face emotion processing in youth with severe mood dysregulation

Diagnosis × Emotion interaction in the right PHG. * P  < 0.05.

Figure Legend:

Soc Cogn Affect Neurosci. 2015;11(1):78-88. doi:10.1093/scan/nsv087

Date of download: 2/16/2017 Published by Oxford University Press 2015. This work is written by US

Government employees and is in the public domain in the US.This work is written by US Government employees and is in the public domain in the US.

From: Neural correlates of masked and unmasked face emotion processing in youth with severe mood dysregulation

Diagnosis × Emotion interaction in the right thalamus. * P  < 0.05.

Figure Legend:

Soc Cogn Affect Neurosci. 2015;11(1):78-88. doi:10.1093/scan/nsv087

Date of download: 2/16/2017 Published by Oxford University Press 2015. This work is written by US

Government employees and is in the public domain in the US.This work is written by US Government employees and is in the public domain in the US.

From: Neural correlates of masked and unmasked face emotion processing in youth with severe mood dysregulation

Diagnosis × Emotion interaction in the right STG. * P  < 0.05.

Figure Legend:

Soc Cogn Affect Neurosci. 2015;11(1):78-88. doi:10.1093/scan/nsv087

Psychostimulants Impact on decreasing aggression Good job on decreasing inattentive SE’s of ADHD Limited impact on daily irritability and temper Maximizing stimulant dosage can be an

important part of treating the irritability and aggression

ANTICONVULSANTS: Divalproex sodium (Depakote): Frequently used

to target aggression and rage associated with autism. Potentially useful, but low research evidence. Better if stimulant maximized before tx with AC [Blader, 2009]

Carbamazepine: Little evidence for DMDD like sx so far, though often used clinically. Minimally studied.

Lamotrigine: evidence in autism, bipolar I and II, and decrease aggression in Borderline Personality Disorder

Lithium: evidence for reducing aggression, but not the persistent

irritability of DMDD Note lithium ineffectiveness for targeting SMD SX

(Dickstein)

FGAs: Haldol and Thioridazine are the only FGAs specifically studied for aggression

SGAs: Risperidone and aripiprazole have evidence for

effectiveness in behaviors associated with autism. In Autism, risperadone and aripiprazole alone have strong evidence.

Risperidone is particularly effective in disorders involving irritability in general---not just DMDD

SSRI/SNRI Antidepressants: studies are in progress. SNRIs can be helpful for global sx of ADD but not aggression---evidence indicates small effect sizes

α2 agonists: clonidine and guanfacine. Moderate evidence for both in decreasing aggressive behavior associated with ADD

β blocker: Widely used. No RCT evidence. Trazodone: one study from 1992 (Zubieta

and Alessi) shows effectiveness in decreasing aggression.

So---there is a population of children for whom treating ADD, ODD with usu pharmacology and intervention is not enough.

These children appear to be @ risk for poorer outcomes into adulthood

DMDD children may benefit from more intensive behavioral interventions and behavioral analysis

Note: Disruptive Mood Dysregulation Disorder (DMDD) is a new

diagnosis in DSM-5 characterized by irritability and explosive outbursts. Due to an increase in the use of this diagnosis since its introduction to the DSM-5, the expert panel determined it appropriate to provide recommendations on the diagnosis and treatment of this condition.

Due to the current lack of evidence-based specific and suitable pharmacological treatment options for Disruptive Mood Dysregulation Disorder, clinical judgment is paramount in the choice of medications, dose, length of treatment, and measurement of treatment response. Medications are only part of the treatment plan and are provided in combination with psychosocial interventions which may include parent training, anger management, social skills, care managers, in-home services, psychiatric hospitalization, residential treatment and other supports determined on a case by case basis.

Comprehensive assessment: Systematic interview covering other psychiatric conditions in which irritability may be a presenting

symptom: ADHD ODD and/or conduct disorder Bipolar disorder (mania) Depressive disorders Anxiety disorders (including obsessive-compulsive disorder) PTSD and trauma related conditions Autism Spectrum Disorder Intermittent explosive disorder Psychosis Drug/alcohol use/abuse

Family history of psychopathology including depressive disorders, anxiety disorders and bipolar disorder (with specific assessment for mania).

Information from collateral sources (eg. teachers, caregivers) to establish duration of symptoms. Use rating scales to assess for psychiatric conditions as noted above. Refer to relevant sections in these

Practice Guidelines. Assess for other medical conditions or medications that may be contributing to symptoms. If other medical

conditions are present, make appropriate referrals to primary care or specialists to ensure conditions are treated adequately.

If symptoms are medication-induced, consider tapering or stopping the offending agent. Assess for psychosocial stressors (eg. conflict at home, classroom situation, bullying) that may be

contributing to the child’s symptoms (i.e. irritability, anger, temper outbursts disproportionate to the situation and more severe than the typical reaction of same-aged peers).

Assess for and rule out other DSM-5 diagnoses as noted above (eg. ADHD, ODD, bipolar disorder, etc.).

Assess and document the severity of symptoms (frequency, intensity, number and duration of outbursts and irritability) using rating scales. Recommended rating scales for irritability: Affective Reactivity Index (quick assessment, focuses on frequency of irritability

only) Child Behavior Checklist (comprehensive scale that includes irritability sub-scale) Aberrant Behavior Checklist (used in children with developmental disorders, has irritability sub-scale).

Note: The Child Behavior Checklist and Aberrant Behavior Checklist are not available in the public domain.

Recommended scales for aggression and outbursts:

Overt Aggression Scale-Modified (measures nature and severity of aggression)

Irritability Inventory (assesses triggers, behaviors, duration of outbursts and how the child feels after the outburst).

Note: The Irritability Inventory has not been widely used, and it is not available on the public domain.

For available clinical rating scales, refer to http://www.medicaidmentalhealth.org/.

Assess and document degree of impairment, which is based on the severity, frequency, and duration of outbursts.

Note: Once other medical and psychiatric conditions have been assessed or/ruled out, and treatment has been optimized for known conditions (medical, psychiatric) in which irritability and aggression may be presenting symptoms and for which there are evidence based treatments, if DSM-5 criteria are met for Disruptive Mood Dysregulation Disorder, that diagnosis may be made.

Level 1 The core symptoms of Disruptive Mood Dysregulation Disorder are

irritability, anger, aggression, and temper outbursts (verbal or behavioral/physical) that are disproportionate to the situation and significantly more severe than the typical reaction of same-aged peers. Irritability and aggression are distinct symptoms. Irritability is defined as becoming extremely angry with what most would feel is minor provocation (Copeland, et al., 2015). Aggression refers to hostile, injurious, or destructive behaviors.

1a. Address psychosocial stressors that are directly contributing to or worsening the child’s symptoms (eg. irritability, anger, aggression, temper outbursts).

1b. Address the severity of the child’s symptoms. If symptoms are mild, implement psychosocial interventions (eg.

targeted case management, crisis intervention programs, parent training).

If symptoms are moderate to severe (eg. child is removed from school, has been seen in emergency room or psychiatrically hospitalized), psychosocial interventions alone are unlikely to suffice. Consider interventions in Level 2.

Level 2 Currently, limited scientific evidence exists for the

use of medications for Disruptive Mood Dysregulation Disorder.

If irritability and outbursts continue to cause impairment after co-morbid disorders have been treated optimally, re-assess the diagnosis.

If symptoms persist, may consider use of treatments targeted toward aggression including atypical antipsychotics, mood stabilizers, alpha agonists, or antidepressants in conjunction with psychotherapeutic and psychosocial interventions. Refer to Table 9 on pg. 28 for dosing recommendations for aggression.

Not Recommended: Use of medications alone.

Kids with DMDD improve with stimulants and behavioral modification

There is some improvement if ADHD is optimally treated and mood stabilizers or SGA’s are added

SGA’s appear to work somewhat for “aggression,” aka, “mood swings,” aka “irritability.”

But: most children remain significantly impaired even if improved

Psychological interventions have some efficacy, but require motivation, and considerable effort.

Adleman NE J Am Acad Child Adolesc Psychiatry (2011 Nov) 50(11):1173-1185.e2 ISSN: 1527-5418

American Academy of Child and Adolescent Psychiatry, Mar 30 2015 Concerns re: DMDD diagnosis.

Blader JC, Carlson GA. Increased rates of bipolar disorder diagnoses among U.S. child, adolescent, and adult inpatients, 1996–2004. Biological psychiatry. 2007;62:107–114. [PMC free article][PubMed]

Blader JC, Schooler NR, Jensen PS, Pliszka SR, Kafantaris V. Adjunctive divalproex versus placebo for children with ADHD and aggression refractory to stimulant monotherapy. The American journal of psychiatry. 2009;166:1392–1401. [PMC free article] [PubMed]

Brotman MA , Schmajuk M , Rich BA , et al: Prevalence, clinical correlates, and longitudinal course of severe mood dysregulation in children. Biol Psychiatry 60(9):991–997, 2006

Carlson, G, Presentation to Best Practices Guidelines Expert Panel Meeting, Tampa. October 2016 Excerpts used with permission.

Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 5th ed. Arlington: American Psychiatric Association, 2013. Print.

2016 Florida Best Practice Psychotherapeutic Medication Guidelines for Adults (2016). The University of South Florida, Florida Medicaid Drug Therapy Management Program sponsored by the Florida Agency for Health Care Administration.

Leibenluft E. Severe mood dysregulation, irritability, and the diagnostic boundaries of bipolar disorder in youths. The American journal of psychiatry. 2011;168:129–142. [PMC free article][PubMed]

Ryan ND Severe irritability in youths: disruptive mood dysregulation disorder and associated brain circuit changes. Am J Psychiatry (2013 Oct) 170(10):1093-6 ISSN: 1535-7228

Tseng WL, Thomas LA, Harkins E, Pine DS, Leibenluft E, Brotman MA Neural correlates of masked and unmasked face emotion processing in youth with severe mood dysregulation. Soc Cogn Affect Neurosci (2016 Jan) 11(1):78-88 ISSN: 1749-5024

Leon Tourian, MD, MSc,1 Amélie LeBoeuf, MD, MSc,1 Jean-Jacques Breton, MD, MSc,2 David Cohen, MD, PhD,3 Martin Gignac, MD, FRCPC,4 Réal Labelle, PhD,5 Jean-Marc Guile, MD, MSc,6 and Johanne Renaud, MD, MSc, FRCPC1 Treatment Options for the Cardinal Symptoms of Disruptive Mood Dysregulation Disorder Can Acad Child Adolesc Psychiatry. 2015 Winter; 24(1): 41–54. Published online 2015 Mar 4. PMCID: PMC4357333 Language: English | French

Zubieta JK, Alessi NE. Acute and chronic administration of trazodone in the treatment of disruptive behavior disorders in children. Journal of Clinical Psychopharmacology. 1992;12(5):346–351.