diagnosis & assessment in pediatric …... diagnosis & assessment in pediatric...
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Diagnosis & Assessment in Pediatric Psychopharmacology
Joseph Biederman, MDProfessor of Psychiatry Harvard Medical School
Chief, Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD
Massachusetts General Hospital
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Disclosures 2018-2019
My spouse/partner and I have the following relevant financial relationships with commercial interests to disclose:
– Research support: Genentech, Headspace Inc., Lundbeck, Neurocentria Inc., Pfizer, Roche TCRC Inc., Shire Pharmaceuticals Inc., and Sunovion.
– Consulting fees: Akili, Jazz Pharma, and Shire– Royalties paid to the Department of Psychiatry at MGH, for a
copyrighted ADHD rating scale used for ADHD diagnoses: Bracket Global, Ingenix, Prophase, Shire, Sunovion, and Theravance
– Financial interest: Avekshan LLC, a company that develops treatments for ADHD. My interests were reviewed and are managed by MGH and Partners HealthCare in accordance with their COI policies
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Insel’s JAMA Editorial May 2014
• 50% of adults with a mental disorder reported onset by 14 years or younger
• Mental and substance abuse disorders remain the predominant noncommunicable disorders of young people in terms of burden of illness
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2013 CDC Major Report on Mental Illness in Youth
• 1 in 5 youth has a mental illness
• Estimated yearly cost: $247 billion
• Because of their high prevalence, early onset, their impact on the child, family, and community, and its associated enormous cost mental and behavioral disorders of the young represent a major public-health issue in the US (and across the world)
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Most Prevalent Mental Illnesses in Youth
• ADHD (11%)• Conduct disorder (3%) • Anxiety disorders (3-5%)• Depression (2%-4%)• ASD (1%-2%)• SUD (in prior yr 5%)• Alcohol abuse (in prior yr 4%)• Cigarette Dependence (prior month 3%)• Suicide remains a leading cause of death in youth
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• There are less than 7000 fully trained child and adolescent psychiatrists currently practicing in the US, despite estimates that over 30,000 would be required to meet the current demand.
• The need for services is projected to increase 100% by the year 2020, highlighting a growing mental health crisis.
• Increasing importance of the PCP in the management of children’s mental health problems
Problem: Limited Manpower
Center for Mental Health Services
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Problem: Prejudices and Misconceptions
• Pervasiveness of psychosocial and psychological hypotheses to explain childhood mental disorders
• Poor public acceptance for using pharmacotherapy in children– Bad Press– Frequent “alarming statistics” on the use of psychotropics
in children– Diagnostic Conundrums (i.e., DSM-V Temper Dysregulation
Disorder)– Diagnostic biases in the medical community (mental
illnesses do not exist; they are accounted by other conditions; their treatment not necessary; “cosmetic” pharmacotherapy)
Groopman, J. (2007, April 9). What’s Normal?
Diagnosing bipolar disorder in children. The
New Yorker, p. 28
Parens et al. N Engl J Med. 2010 May 20;362(20):1853-5
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June 19, 2006
'Off-Label' Antipsychotics—for Kids
Kalb, C. (2006, June 19). 'Off-Label' Antipsychotics—for Kids. Newsweek Health.
The statistics are staggering: a sixfold spike, between 1993 and 2002, in the number of doctor
visits in which kids and adolescents were prescribed antipsychotic drugs. Total tally in '02: 1.2
million. Antipsychotics are powerful drugs, typically used to treat severe mental illnesses like
schizophrenia in adults—and they're not FDA-approved for children. But increasingly, doctors
are prescribing newer generations of antipsychotics "off label" for a range of conditions in
young people, from mood disorders to behavioral problems and ADHD.
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Problem: Lack of FDA Approval for the Use of Many Psychotropics in Youth
• Absence of FDA approval is not synonymous with proscription of use
• Lack of FDA approval only denotes that the drug was not adequately studied for the particular condition, at a particular dose or for a particular age group
• When used off-label, risks, potential benefits and informed consent should be carefully documented
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Black Box Fatigue
• Cardiovascular risk/sudden death for stimulants
• Suicidality/activation for antidepressants and anticonvulsants
• Metabolic syndrome/ TD for neuroleptics
• General uncertainties about long-term effects of psychotropics
Cooper et al. N Engl J Med 2011
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• 78 out of 4,400 cases in controlled clinical trials on all antidepressants in pediatric patients suffered increases in suicidal ideation and/or self-harm
– 52 patients (3.8%) randomized to medications
– 26 patients (2.1%) randomized to placebo
• No patients committed suicide or seriously harmed self
FDA issues Black Box Warning: Suicide Risk with Antidepressant
AACAP Joint Meeting of the Psychopharmacologic Drugs Advisory Committee and the Pediatric Advisory Committee September 28, 2004
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% of high school students who felt sad or hopeless, who seriously considered attempting suicide, who made a suicide plan, and who attempted suicide
0
5
10
15
20
25
Seriously
considered
attempting suicide
Made a suicide
plan
Attempted suicide Suicide attempt
required medical
attention
9 10 11 12
Grade
SOURCE: United States, Youth Risk Behavior Survey, 1999.
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Antidepressant Medication and Suicide in Adolescents
11.546.51
73.15
6
0
10
20
30
40
50
60
70
80
AD Suicide
1990 2000
-0.23 (t=5.14, P<.001)
AD= Antidepressant rate per 1000 Medication Users
Olfson et al., (2003) AGP 60 (10): 978-982
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Simon et al. (2006) Am J Psychiatry (163):41-47
Rates of Suicide Attempts During the 3 Months Before and the 6 Months After Initial Antidepressant Prescription
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Am J Psychiatry 164:38A, June 2007
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Trends in the prescribing of psychotropic medications to preschoolers
• Main Findings
– Psychotropic medications prescribed for preschoolers increased dramatically from 1991-1995 with the preponderance of medications with off-label (unlabeled) indications.
– <2% of preschoolers receive various psychotropics
Zito et al JAMA. Feb 23;283(8):1025-30
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0
25
50
75
100
Diagnostic Categories
Types of Psychiatric Disorders in Preschoolers (N=200)
MGH Study of Preschoolers
Perc
ent
of
Sam
ple
Mood
43%
Multiple
Anxiety
28%
ADHD
86%
Disruptive
61%
Wilens et al. J Dev Behav Pediatr. 2002 Feb;23(1 Suppl):S31-6
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Disruptive
0
1
2
3
4
5
6
ADHD Mood Multiple
Anxiety
Mea
n A
ge o
f O
nse
t
Age of Onset of Psychopathology
Mean age at referral = 5.2 years
MGH Study of Preschoolers: Preliminary Study of Psychopathology
Diagnostic Categories
Wilens et al. J Dev Behav Pediatr. 2002 Feb;23(1 Suppl):S31-6
AAP News Release, October 16th 2011
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General Principles
• A successful pharmacotherapeutic intervention requires realistic expectations and initial diagnostic hypotheses with careful definition of target symptoms
– i.e., the treatment of insomnia is very different if driven by existential concerns, mania, psychosis or depression
• While psychotropics can be highly beneficial, their use is not universally successful
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General Principles
• The use of psychotropics should follow a careful evaluation of the child and the family
• Before beginning treatment, the family and the child need to be familiarized with the risks and benefits of such an intervention
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General Principles
• Treatment should be started at the lowest possible dose with frequent reevaluation during the initial phase of treatment
• Following a sufficient period of clinical stabilization (i.e.... 6-12 months) it is prudent to reevaluate the need for continued psychopharmacologic intervention
• This approach need to be considered when the clinical picture has fully stabilized
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General Issues: Adverse Effects
• Certain adverse effects can be anticipated based on known pharmacologic properties of the drug (i.e.., the anticholinergic effects of tricyclic antidepressants), while others, generally rare, are unexpected (idiosyncratic) and are difficult to anticipate
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Components of the Diagnostic Process
• Psychiatric Assessment
• Cognitive Assessment
• Assessment of School Functioning
• Psychosocial Assessment
• Laboratory Assessments (when indicated)
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Diagnostic Process:Cognitive Assessment
• Estimates of IQ• Estimates of EFDs (i.e, working memory,
processing speed)• Estimates of academic performance:
Achievement in math and reading• Search for discrepancies between expected and
actual functioning• Distinguish Low achievement from
Underachievement– Example: a brilliant child that is performing averagely
in school may be underachieving
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Diagnostic Process:Psychosocial Evaluation
– Evaluation of the family environment
• Marital discord
• Parenting difficulties
• Separation and divorce
• Custodial parent
• Guardianship
• Potential issues of abuse and neglect
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Psychosocial Adversity
• Low SES (poverty)
• Family conflict
• Single parent homes
• Parental psychopathology
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Findings from Rutter Study
0
2
4
6
8
10
12
1 2 4
Od
ds
Rat
io
Number of Indicators of Adversity
Risk for Childhood Mental Disturbance
Biederman et al. Am J Psychiatry. 2002 Sep;159(9):1556-62
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The Challenge of Psychopathology vs. Stress Reaction
Normal Reaction
Adjustment Disorder
Major Psychiatric Disorders (such as Major Depressive Disorder or Anxiety Disorder)
Stress
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Diagnostic Process:Psychosocial Evaluation
• Social Functioning
– Relationship with peers
– Relationship with parents
– Use of leisure time
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Diagnostic Process:Psychosocial Evaluation
• Social Functioning Assessment
– Anamnesis
– Questionnaires and Rating Scales
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Diagnostic Process: School Functioning
• School Functioning
– School and grade placement
– Teacher information
– Parent-based school information
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Diagnostic Process: School Functioning
• Indices of school dysfunction
– Repeated grades
– Placement in special classes
– Need for Tutoring
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Diagnostic Process: School Functioning
• Parent-based school information
– Parent-teacher conferences
– Teacher reports
– Teacher complaints
– Observation
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Indications for Major Drug Classes
• Stimulants
• Antidepressants
• Antipsychotics
• Mood stabilizers
• Anxiolytics
• Alpha adrenergic compounds
• Beta blockers
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Indications for Major Drug Classes
• Stimulants
– ADHD
– Narcolepsy
– Tx resistant depression
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Indications for Major Drug Classes
• Antidepressants
– Depressive disorders
– Anxiety disorders
– OCD (serotonergic)
– ADHD (noradrenergic, dopaminergic)
– Enuresis (TCAs)
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Antidepressants Best for Anxiety Disorders
Source: Journal of the American Medical Association. April 18, 2007.
Perc
enta
ge o
f Yo
uth 50
3239
69
52
61
0
10
20
30
40
50
60
70
80
Major Depressive
Disorder
Obsessive
Compulsive Disorder
Anxiety Disorders
Antidepressants
Placebo
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March et al. JAMA. (2004) 292 (7):807-820.
Treatment of Adolescent DepressionEffect Size for CDRS (ITT)
-0.2
0
0.2
0.4
0.6
0.8
1
1.2
COMB FLX CBT
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• Yet, the FDA did not provide any guidance for dosing limitations in pediatric patients
• If children were to be at the same or higher risk for Citalopram associated QTc prolongations as adults, such risk would require EKG monitoring in children prescribed doses >0.5 mg/kg 940 mg for an 80 kg adult).
http://www.fda.gov/Drugs/DrugSafety/ucm269086.htm
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SSRIs and QTc Prolongations: Summary of Pediatric Data
• Using an electronic medical record, mean QTc intervals were in the normal range for all antidepressants
• No single antidepressant was associated with a significantly greater QTc than others
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Indications for Major Drug Classes
• Antipsychotics (atypical)
– Psychotic disorders
– Tourette’s disorder
– Bipolar disorder
– Dysphoric dyscontrol
– Augmentation of antidepressants
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Indications for Major Drug Classes
• Mood stabilizers
– Bipolar disorder
– Tx refectory depression
– Dysphoric dyscontrol
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Indications for Major Drug Classes
• Anxiolytics
– Anxiety disorders
– Augmentation of treatments for other disorders (BPD, depression, TS)
– Severe situational anxiety
– Tourette’s syndrome (high potency BZDs)
– Stimulant induced anxiety
– Insomnia
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Indications for Major Drug Classes
• Alpha Adrenergic Compounds (clonidine, guanfacine)– TS/Tics
– ADHD
– Dyscontrol
– SIB
– Augmentation
– Treatment emergent adverse effects (I.e., stimulant-induced insomnia
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Indications for Major Drug Classes
• Beta Blockers
– Akathisia
– Stage fright
– Tremor
– Dyscontrol
– SIB
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Indications for Combined Pharmacotherapy
• Comorbidity
• Treatment resistant cases: Augmentation
• Treatment emergent adverse effects
• Poor tolerability with therapeutic doses of individual medicines
Wilens et al. JAACAP. 1995 Jan;34(1):110-2
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Combined Pharmacotherapy
• Treatment resistant cases
– Augmentation
– Less than satisfactory response to a single agent
– Potential synergy of combined agents for certain disorders
• Combined Tx may permit the use of lower doses of two agents reducing the adverse effect profile associated with higher doses of a single agent
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Combined Pharmacotherapy
• Comorbidity
– High rates of psychiatric comorbidity in childhood psychiatric disorders
– Irrespective of etiology, different disorders require different treatments
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Combined Pharmacotherapy
• Vast array of potential combinations
• Clinicians should become familiar with potential psychopharmacological combination regimens
– adverse effects [i.e., excessive sedation]
– drug-drug interactions [i.e.,fluoxetine plus TCAs]
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Combined Pharmacotherapy
• Simple cases: monotherapy could be sufficient and should be preferred
• Complex cases: monotherapy may be insufficient and combined pharmacotherapy needs to be considered