Transcript Psychiatric Medications and Child Welfare

Terry Lee, MD
[email protected]
UW School of Medicine Department of Psychiatry
Developmentally-Informed Representation
of Young Children in Child Welfare
October 16, 2015
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Psychiatry resources
Child welfare and psychiatric medications: appropriate or
inappropriate?
Bench card
Questions to ask psychiatrists
What some other states are doing
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aacap.org: American Academy of Child and
Adolescent Psychiatry (AACAP)—main child
psychiatry organization
◦ Facts for Families
◦ Practice Parameters
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cebc4cw.org: California Evidence-Based
Clearinghouse for Child Welfare—CW resources,
rating scales, assessment tools, webinars,
resources
nlm.nih.gov/medlineplus/: Medline Plus—
medication information
ohiomindsmatter.org: Ohio Minds Matter—online
toolkit for consumers and stakeholders to
improve psychiatric prescribing to young people
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Youth in foster care prescribed psychiatric
medications at 2-10 times the rate of nonfoster youth on Medicaid (MMDLN, 2010;
Raghavan, 2005; Zito, 2008)
◦ Any psychiatric medication
◦ Multiple psychiatric medications at the same time
◦ Children < 5 years old
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Evaluations and follow-ups are too short
Too quick to put kids on meds
Too many kids on meds
Too many meds prescribed
Doses are too high
Kids turned into “zombies”
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Youth involved with child welfare system have
higher rates of MH needs:
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Maltreatment/trauma
Removal from home, family, and ecology
Multiple placements, disrupted attachments
Poverty
Intrauterine exposures, genetic risks
Entry into foster care also:
◦ Provides access to Medicaid
◦ Systematic screening for behavioral health needs
◦ Advocacy for behavioral health needs
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Insufficient time for proper assessment
Limited information on youth history and
current functioning
Poor continuity of care
Lack of critical clinical feedback to inform
psychiatrist decision-making
Ineffective advocacy
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Unrealistic hopes that medication will
stabilize a complex psychosocial situation
Under-recognition of trauma etiology in
formulating complex presentations
Lack of commitment of resources to parent
skills training, especially if permanency is
unclear
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Limited access to effective psychosocial
interventions
Limited access to effective psychiatric
prescribing practices
Limited integration of psychiatric and
psychosocial treatments
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Foster youth 6-12 years-old
49% of youth diagnosed with ADHD had not
received psychotropics in the previous year
80% of youth identified with severe
psychiatric disorder not recommended for
medication evaluation in previous year
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National longitudinal survey
Youth and families referred to child welfare
◦ Completed investigations
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Two groups of children (0-14 years-old)
randomly chosen between October 1999 and
December 2000
◦ 5,504 youth entering the system
◦ 727 youth in out-of-home placement>12 months
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Evaluated at baseline and 12 months
Child Behavior Check List
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47.9% of youth scored in the clinical range on the
CBCL
◦ 39.3 % of youth in kinship care
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Youth with strong evidence of mental health
need (CBCL) were more likely to receive help, but
only ¼ had received any care in the previous 12
months
Factors relating to increased likelihood of
services:
◦ Preschoolers: sexual abuse (versus neglect)
◦ Elementary school age: Caucasian and living out-ofhome
◦ Adolescents: out-of-home and parent with severe
mental illness
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Assessed 5 domains: cognition, behavior,
communication, social skills and adaptive
functioning
Developmental and/or behavioral health needs:
◦ Toddlers (0-2 years-old): 41.8%
◦ Preschoolers (3-5 years-old): 68.1%
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Youth with need receiving services: 22.7%
Factors relating to decreased likelihood of
services:
◦ Remaining at home
◦ 0-2 years-old
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Children 12-36 months old with behavioral
health needs
◦ Only 19.2% received any type of behavioral health
service, including parent skills training related to
mental health problems
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Youth 2-15 years-old
Need defined by CBCL clinical range: 46.8% of
youth
75.8 % had accessed outpatient mental health
services, 24.2% had not received services
Predictors of receiving services: higher CBCL
scores, older age, history of sexual abuse
Lesser use of services: history of neglect,
African-American race/ethnicity
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African-American youth
Victims of neglect
Youth remaining at home or placed in kinship
care
Utilize systematic screening!
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Help courts ask the right questions
Help child welfare workers prepare and have
specific information in court
Mental health system and child psychiatrists
are still responsible for providing good
mental health and psychiatric care
But court can provide oversight and advocacy
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How was the diagnosis made? Did you use
information from other informants, like the school?
What is known about how helpful this medication is
for other children who have a similar condition to
my child’s?
How will the medication help my child? How long
before I see improvement? When will it work?
What are the side effects that commonly occur with
this medication?
Are there any serious side effects?
Is this medication addictive? Can it be abused?
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Who will be monitoring my child’s response
to medication and make dosage changes if
necessary? How often will progress be
checked and by whom?
Are there any other medications or foods
which my child should avoid while taking the
medication?
Are there interactions between this
medication and other medications
(prescription and/or over-the-counter) my
child is taking?
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Are there any activities that my child should
avoid while taking the medication? Are any
precautions recommended for other
activities?
How long will my child need to take this
medication? How will the decision be made
to stop this medication?
What do I do if a problem develops (e.g. if my
child becomes ill, doses are missed or side
effects develop)?
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What is the cost of the medication (generic
versus brand name)?
Are there any psychosocial (non-medication)
treatments that can help? How do they
compare to medication treatments?
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Very effective for ADHD, including long term
Relatively rapid onset of action
On-task behavior by all raters
Compliance as rated by teachers
Peer nominated rankings of social standing
Parent-child interactions
Attention during sports activities
Performance on paper-and-pencil and
computerized tests of attention, math, short-term
memory tasks, problem-solving, accuracy
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Appetite suppression
Sleep disturbance
Elevated pulse and blood pressure
Tics
Obsessive-compulsive behavior
Loss of spontaneity
Abuse potential
◦ More tightly controlled prescribing (Schedule II
medication)
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Long term
◦ Shorter height
◦ Lighter weight
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Took stimulants without prescription
o 5-9% of elementary through high school age
o 5-35% of college age individuals
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16-29% of youth prescribed stimulants who
were asked to sell, give or trade their
stimulants
Cognitive enhancers? E.g. NY Times 4/18/15:
“Workers Seeking Productivity in a Pill Are
Abusing ADHD Drugs”
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Concerta (OROS-methylphenidate)
Adderall XR (mixed amphetamine salts
extended release)
Dexedrine Spansules (dextroamphetamine
spansules)
Ritalin LA, SR (methylphendiate)
Metadate (methylphenidate)
Focalin XR (dex-methylphenidate extended
release)—isomer that provides most of the
positive effect
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Quillavent XR: long-acting liquid
methylphenidate
Daytrana (methylphenidate transdermal patch)
◦ Take off to stop action at some point
◦ Can be taken off and
 reattached (on someone else?)
 Extract methylphenidate ?
 To deliver 30 mg, 82.5 mg in patch
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Vyvanse (lisdexamfetamine)-prodrug:
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Aptensio XR (methylphenidate MLR)-long-acting
(12 hours) formulation
◦ must be ingested to activate –less likely to be diverted
and ingested by alternate route (snorting or injecting)?
◦ not any more effective
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Methylphenidate total dose > 120 mg/24
hours
Amphetamine total dose > 60 mg/24 hours
Lisdexamfetamine total dose > 70 mg/24
hours
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Atomoxetine (Strattera)*
Alpha Agonists—primarily treat hyperactivity
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Guanfacine XR (Intuniv)*
Clonidine XR (Kapvay)*
Guanfacine (Tenex)
Clonidine (Catapress)
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Buproprion (Wellbutrin)
Modafinil (Provigil)
Imipramine
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*FDA-approved for ADHD
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Atomoxetine (Strattera) not as effective as
stimulants
Pros
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Effective throughout the day?
Not Schedule II medication
No increase in tics
Less sleep disruption and appetite suppression
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Cons
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FDA black box warning for suicidal ideation
Rare, severe liver injury
Very rare sudden cardiac death at therapeutic doses
Increase blood pressure and pulse—less than
stimulants
Weight loss—less than stimulants
Effects on growth?
Nausea and vomiting
Headache
Sedation
Lightheadedness and dizziness
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Helps decrease hyperactivity
Support for adding to stimulants for further
effect
Decreases tics
Helps with sleep (sedating)
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Sedating
Dizziness upon standing
Lower blood pressure and pulse
Tolerance develops to above 3 bullets
Rebound hypertension if stopped suddenly
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Fluoxetine (Prozac)
Sertraline (Zoloft)
Citalopram (Celexa)
Paroxetine (Paxil)
Escitalopram (Lexapro)
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Goes beyond “statistical significance”
The number of patients who must receive the
treatment to get a response that is
attributable to active treatment
More effective treatments will have a lower
NNT
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Meta-analysis of SSRI NNT for youth
disorders (Bridge, et al; 2007)
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Anxiety disorders (adjusted): 4 (95% CI 3-6)
Depression: 10 (95% CI 7-15)
OCD: 6 (95% 4-8)
(for comparison, stimulant for ADHD NNT typically
range from 1.5-3)
Effective for youth PTSD?
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Negative Effects
◦ Slight increase in suicidal ideation, especially for
youth with depression: 2%?
◦ Induce mania? If youth has bipolar disorder
◦ Activation, insomnia or irritability—usually transient
◦ Sedation
◦ Gastrointestinal symptoms
◦ Headache
◦ Increased bleeding risk—less common
◦ Apathy—sometimes a sign of too high a dose
◦ Decreased libido—rare in adolescents
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Positive effects
◦ Effective for classic bipolar disorder
◦ Mild short term positive effects for other disorders
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Negative effects
Weight gain
Acne
Sedation—may be transient
Tremor—may be transient
Increased thirst
Depressed thyroid function, which may lead to
hypothyroidism
◦ Kidney effects, usually insignificant
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Positive Effects
◦ Anti-seizure medication
◦ Effective in classic or “real” bipolar disorder—the
type seen in adults and post-pubertal youth
◦ Mild positive effects on (controversial) pediatric
bipolar disorder
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Serious Negative Effects
◦ Hormone-like effects, including increased rate of
Polycystic Ovaries in females
◦ Neural Tube Defects increased in children of women
taking Depakote during pregnancy
◦ Serious but rare
 Hepatoxicity-potentially fatal liver damage
 Pancreatitis-potentially fatal (~2 per 1,000 patient
years)
 Severe bone marrow suppression
 Withdrawal seizures if stopped suddenly
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Negative Effects
◦ Common—usually temporary
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Nausea
Sedation
Dizziness
Weight gain
Vomiting
Weakness
Gastrointestinal symptoms
Rash
Mild elevation of liver enzymes
Mild suppression of bone marrow function, such as platelet
function, which can lead to easy bruising or nose bleeds
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Olanzapine (Zyprexa)
Risperidone (Risperdal)
Quetiapine (Seroquel)
Ziprasidone (Geodon)
Aripiprazole (Abilify)
Asenapine (Saphris)
Iloperidone (Fanapt)
Lurasidone (Latuda)
Paliperidone (Invega)
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Positive Effects
◦ Effective for psychosis
◦ Effective for classic mania and bipolar disorder
◦ Less effective for controversial pediatric bipolar
disorder
◦ Moderately effective for tics and Tourette’s Disorder
◦ In the short term, unlikely to have irreversible
negative effects
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Negative Effects
◦ Common
 Sedation
 Weight gain (depending on which antipsychotic, 9.718.7 pounds in ~11 weeks in one study (Correll et al,
2009))
 Dyslipidemias
 Glucose intolerance, which may lead to diabetes
 Extra-pyramidal side effects (EPS)-muscle stiffness,
sometimes with tremor
 Akathisia-inner restlessness associated with urge to
keep moving
 Blurred vision
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Negative Effects
◦ Less common
 Diabetes
 Acute dystonia-temporary and non-fatal, but very
uncomfortable, muscle spasm when starting
antipsychotic medication
◦ Rare but serious
 Tardive dyskinesia-irreversible movement disorder
 Neuroleptic Malignant Syndrome-muscle rigidity,
fever, autonomic instability and altered mental status
which, in rare instances, may lead to death
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Olanzapine (Zyprexa)
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Risperidone (Risperdal)
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Quetiapine (Seroquel)
◦ More sedating
◦ A little more effective for psychosis
◦ More weight gain
◦ Less sedating
◦ More prone to stiffness, restlessness, acute dystonia and
tardive dyskinesia
◦ More prone to hyperprolactinemia
◦ More prone to galactorrhea, gynecomastia
◦ Usually very sedating, initially
◦ FDA warning about cataracts, but not a problem
◦ More weight gain
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Ziprasidone (Geodon)
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Less weight gain
Less glucose intolerance and lipid problems
Less sedating
Rare cardiac conduction problems
Aripiprazole (Abilify)
◦ Mild to moderate weight gain
◦ Mildly to moderately sedating
◦ Mild muscle stiffness and restlessness
EPS
Anticholin
ergic
Elevated
prolactin
Orthostasis
QTC increase
(heart)
Sedation
Weight
gain
Risperidone
0/+
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0
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Olanzapine
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0
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++++
Quetiapine
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+
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+
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Ziprasidone
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+
+
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+
+
Aripiprazole
0/+
0
0/+
+
0
+
+/++
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338 youth
4-19 years-old
1 week or less of antipsychotic medication
treatment
272 had one post-baseline assessment
205 completed the 12 week study
15 youth who refused or were non-compliant
served as controls
10.8 weeks median treatment
length
Mean Weight Gain (pounds)
Olanzapine (Zyprexa)
18.7*
Quetiapine (Seroquel)
13.42*
Risperidone (Risperdal)
11.6*
Aripiprazole (Abilify)
9.68*
Control (refused meds)
0.44
10.8 weeks median treatment
length
Mean Waist Circumference Gain
(inches)
Olanzapine (Zyprexa)
3.37*
Quetiapine (Seroquel)
2.07*
Risperidone (Risperdal)
2.01*
Aripiprazole (Abilify)
2.13*
Control (refused meds)
0.28
10.8 weeks median treatment
length
Total Cholesterol Gain
Olanzapine (Zyprexa)
15.58*
Quetiapine (Seroquel)
9.05*
Risperidone (Risperdal)
3.46
Aripiprazole (Abilify)
3.75
Control (refused meds)
2.38
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Five-fold increase from 1993-2002 in the
prescription of antipsychotics in youth
18.3% of visits (2000-2) to psychiatrist
involve prescription of antipsychotic
medication
Diagnoses:
◦ Disruptive behavior disorder 37.8%
◦ Mood disorder 31.8%
◦ Pervasive developmental disorder or mental
retardation 17.3%
◦ Psychotic disorder 14.2%
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Youth on Medicaid four times more likely to
receive antipsychotic medication than youth
with private insurance (Olfson, 2009)
75% off-label (non-FDA approved)
prescribing
$7.9 billion on antipsychotics (2006), largest
medication expenditure for Medicaid
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Oppositional-Defiant Disorder Lifetime
Additional Disorders:
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Impulse Control Disoders-68.2%
Anxiety Disorders-62.3%
Substance Use Disorders-47.2%
Mood Disorders-45.8%
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Some short term effectiveness for many
psychiatric medication classes and disruptive
behavior (oppositional-defiant disorder and
conduct disorder)
Transient sedative effect?
Psychosocial interventions are the most
effective treatments for disruptive behavior
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Aggression (though consider comorbid
condition)
Rule-breaking, noncompliant behavior,
missing curfew
Temper tantrums
Psychosocial interventions are the most
effective for the above behaviors
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Over- or under-diagnosed?
◦ Evidence of both in the United States
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Approximately 5-10% of youth in the United
States
Approximately 3-5% in the rest of the world,
though higher in post-industrialized
countries
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Driving: youth with ADHD compared to those
without (American Academy of Pediatrics,
2006)
◦ 2-4 times as likely to have a motor vehicle accident
◦ More likely to have repeat traffic citations
◦ More likely to have licenses suspended or revoked
◦ Driving performance improves with stimulant
medication
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More boys than girls affected
Girls tend to have primarily inattentive type,
which may lead to under-diagnosis, but still
more boys with ADHD
Some ADHD is due to CNS immaturity
◦ Some youth will “grow out” of symptoms
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However, for others, hyperactivity will
diminish, but inattentiveness and impulsivity
will continue
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Diagnosing
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Symptoms in 2 settings
Don’t count on doctor’s office evaluation
Obtain feedback from school
Use rating forms to help
◦ Double-blind placebo-controlled medication trials
to assess medication effectiveness?
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Best for most people with ADHD
◦ ~2/3 will respond
◦ Largest effect size of psychiatric medications in
youth
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Schedule II medication—abuse and addiction
potential
◦ All medications need to monitored closely,
especially stimulants
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More than 300 randomized controlled trials
demonstrating effectiveness of stimulants for
ADHD
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Effect Size meta-analysis—up to 15 studies
met criteria for inclusion (Oord, et al; 2007)
◦ methylphenidate versus
◦ psychosocial treatment versus
◦ combined methylphenidate and psychosocial
treatment
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Goes beyond “statistical significance”
For following study, Cohen’s D used:
ES=(pretreatment mean-post-treatment
mean)/pooled standard deviation
Cohen’s guidelines for effect size:
◦ Small: 0.20
◦ Medium: 0.50
◦ Large: 0.80
Psychosocial
Methylphenidate
Combined
ADHD-parent
0.87
1.53
1.89
ADHD-teacher
0.75
1.83
1.77
ODD-parent
0.66
0.61
1.23
ODD-teacher
0.43
1.08
0.92
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Mild ADHD can be treated with psychosocial
interventions alone
Uncomplicated ADHD can be treated with
medication only
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Combination of behavior therapy and
medications showed more improvement than
youth treated with behavior therapy alone
(MTA, 1999)
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25,656 adults in Sweden with ADHD
Followed for 3 years
Compliance with ADHD meds:
◦ Males-32% reduction in criminality
◦ Females-41% reduction in criminality
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Compliance with SSRI’s not associated with
reduction in criminality
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Common childhood psychiatric disorder
6-20% prevalence based on large epidemiological
studies (Costello, 2004)
CBT:
◦ Coping Cat (Kendall, 1990) (14-18 sessions) with several
variations, is most widely used and studied for youth
with anxiety disorders
◦ Demonstrated long term effectiveness: 2-5 years
◦ However, up to 20-50% of youth may continue to have
anxiety symptoms after child-focused CBT (Barrett,
1996; Kendall, 1997)
◦ Additional benefit from additional family involvement in
treatment (Barrett, 1996; Cobham, 1998)
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Medications: SSRI’s have demonstrated short
term efficacy in randomized, placebocontrolled trials (Connolly, 2007; Reinblatt
and Riddle, 2007)
◦ NNT=3-4
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Response rates range from 61-90% for
separation anxiety, social phobia and
generalized anxiety
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Seven academic sites
488 children
◦ Racially and ethnically diverse
◦ But despite intense outreach, did not include the
most socioeconomically disadvantaged children
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7-17 years old
Anxiety Disorders lumped together:
separation anxiety, generalized anxiety and
social phobia
Less severe comorbid conditions permitted
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Treatments:
◦ 14 sessions of cognitive behavioral therapy (CBT)
(weekly parent check-in, and 2 parent only
sessions)
◦ Sertraline (Zoloft) up to 200 mg/day
◦ Combination CBT and sertraline
◦ Placebo
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Results (at 12 weeks)—Very Much or Much
Improved on Clinician Global ImpressionImprovement (CGI) scale:
◦ CBT 59.7% (improved later in treatment, fewer side
effects)
◦ Sertraline 54.9% (improved earlier in treatment)
◦ Combination CBT and sertraline 80.7%
◦ Placebo 23.7%
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Clinical Global Impression-Improvement Scale
Response Rates
◦ Combination(81%)>CBT(60%)=sertraline(55%)
>placebo(24%)
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Pediatric Anxiety Rating Scale
◦ Combination>sertraline=CBT>placebo
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Mean sertraline dose at final visit:
◦ Combination: 134 mg/day
◦ Sertraline only: 146 mg/day
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Adverse events
◦ No differences between sertraline and placebo
groups, including suicidal and homicidal ideation
◦ No child in study attempted suicide
◦ CBT group<sertraline group: insomnia, fatigue,
sedation and restlessness/fidgeting
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Major Depression
◦ 2.5% of children
◦ 8.3% of adolescents (Birmaher, 1996)
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439 youth 12-17 years old
Moderate to severe depression
13 academic centers
12 weeks of treatment
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Fluoxetine (Prozac) alone
Cognitive-Behavioral Therapy (CBT) alone
Combined fluoxetine and CBT
Placebo
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Response rate
◦ Combined (fluoxetine and CBT) 71% (faster rate of
improvement)
◦ Fluoxetine (Prozac) 61%
◦ Cognitive-Behavioral Therapy (CBT) 43%
◦ Placebo 35%
For severely depressed, response rate for
combination therapy no different than medication
alone
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Children’s Depression Rating Scale-Revised
◦ Combination>fluoxetine>CBT
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Clinical Global Impression-Improvement Scale
◦ Combination=fluoxetine>CBT=placebo
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Suicidal Thinking Decrease
◦ Present in 29% of youth at baseline
◦ All groups showed improvement, combination
therapy showed the most
◦ Combo>CBT=placebo=fluoxetine
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More chronic and treatment-resistant youth
12 weeks
334 adolescents
12-18 years-old
Did not respond to 2 month trial of SSRI
Randomized to:
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A different SSRI
A different SSRI with CBT
Venlafaxine (SNRI)
Venlafaxine with CBT
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Response rates
◦ Medication switch and CBT (54.8%) > medication switch
alone (40.5%)
◦ No differences in response between a different SSRI and
SNRI
◦ 24-week follow-up: 38.9% of youth remitted, regardless
of initial treatment group
◦ 72-week follow-up: 61.1% of youth remitted, regardless
of initial treatment group
◦ However,
 Among responders at week 12, 19.6% had relapse by week
24
 Among week 24 remitters, 25.4% relapsed within one year
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British study
208 youth
11-17 years-old
Non-responders to psychosocial Brief Initial
Intervention (BII)—a 2 week psychoeducation
intervention
After non-response to BII, randomized to:
◦ SSRI and CBT, or
◦ SSRI (with Active Clinical Care (ACC)—seeing psychiatrist)
for medication


12 week treatment phase
16 week maintenance phase




Follow-up assessments at 6, 12 and 28
weeks
208 randomized patients, 200 completed 12
week trial
174 followed-up at 28 weeks
Severely depressed group

After no response to a 2 week psychoeducational intervention, throughout the study
(6, 12 & 28 weeks): no difference between
groups (SSRI only versus SSRI+CBT) in:
◦ Depression Scales
◦ Functional Measures (Health of the Nation Outcome
Scales for Children and Adolescents)
◦ Global Measures



SSRI+CBT more expensive than SSRI only
Both groups improved on all measures
No increase in suicidal thoughts or self-harm
behaviors


Children with significant PTSD symptoms
without meeting full diagnostic criteria have
similar functional impairments to those with
the full disorder (Carrion, et al; 2002)
Trauma Focused Cognitive Behavioral
Therapy (TF-CBT) is a relatively well-studied
treatment for childhood PTSD


Review of 6 RCTs of TF-CBT for sexually
abused and/or multiply traumatized children
(Cohen, et al; 2004)
TF-CBT superior to control or comparison:
◦ Decreasing PTSD symptoms
◦ Improved depression, anxiety and externalizing
behavior
◦ However, continued significant PTSD diagnosis in
approximately 20% of sample

Adults
◦ SSRIs shown superior to placebo in reducing PTSD
symptoms in RCTs (Brady, 2000; Davidson, 2003;
Connor, 1999)
◦ Prazosin shown to be superior to placebo for
combat vets (Raskind, 2003; 2007)

Youth
◦ No good controlled medication data





24 girls (wanted larger sample, but FDA
“black box warning” came out)—calculated 64
subjects needed to find medium effect size
10-17 years-old
All experienced sexual abuse
Non-offending caregiver participated
12 weeks of treatment
◦ TF-CBT + placebo, versus
◦ TF-CBT + sertraline (Zoloft)


No difference between groups on K-SADSPL-PTSD scales: Re-experiencing, Avoidance,
Hyper-arousal, Total Symptoms ~medium
effect sizes (d): 0.40, 0.48, 0.53 and 0.53
respectively
No clinically meaningful differences on other
measures, including PTSD diagnosis, Global
Impairment Status (CGAS), SCARED, Mood
and Feelings Questionnaire (MFQ), CBCL, BDI

Statistically significant differences on
Children’s Global Assessment Scale (CGAS)
◦ Favoring TF-CBT+ sertraline: 66.64 (10.12) versus
59.55 (9.70)
◦ Clinically significant?
◦ Biggest change between groups occurred at weeks
3 and 5, when medication would be expected to
have effect

Effect of larger study?


Controversial
Regardless of what diagnosis is given, these
youth diagnosed with Bipolar Disorder
present with very concerning behaviors and
symptoms



DSM diagnosis
Also known as manic-depressive illness
Characterized by episodes:
◦ highs (mania)
◦ lows (depression)

Episodes are a change from baseline mood


A distinct period of abnormally and persistently
elevated, expansive, or irritable mood, lasting at
least 1 week
During the episode, 3 or more of following
symptoms
◦
◦
◦
◦
◦
◦
◦
Inflated self-esteem or grandiosity
Decreased need for sleep
More talkative than usual or pressured speech
Flight of ideas or racing thoughts
Distractibility
Increased in goal-directed activity
Excessive involvement in pleasurable activities that have
a high potential for painful consequences

Youth (0-19 years old)
◦ 25 visits per 100,000 (1994-5)
◦ 1003 visits per 100,00 (2002-3)
◦ 40 fold increase

Adult (20 years old and above)
◦ 905 visits per 100,000 (1994-5)
◦ 1679 visits per 100,000 (2002-3)
◦ Almost double

Need to distinguish between “Real” or “Classic” Bipolar
Disorder versus controversial
“Pediatric Bipolar Disorder” chronic non-episodic
irritability

5X increase in bipolar disorder if one parent
has bipolar disorder (LaPalme, 1997)
◦ However, prevalence is still only 5%, lower than
ADHD

Presence of bipolar disorder in more distant
relatives does not appear to increase risk

United Kingdom:
◦ 0 cases of preadolescent mania in large
epidemiological study
◦ 0 cases of 2500 hospital-referred youth (<10) over
10 years
◦ In one study in the United States, 30% of all youth
admitted to a psychiatric unit were diagnosed with
Pediatric Bipolar Disorder (Carlson & Youngstrom,
2003)




Holland (teens): 1.9% mania, 0.9% hypomania
in epidemiological study
Denmark (<15 yo): 1.2% of inpatients
Ireland (>14 yo): 2.2 cases/100,000 youth
per year-epidemiologic study
Finland:
◦ Annual rate of all hospitalized patients: 0.03%
◦ 1.7% of 475 hospitalized patients 2-18 years-old

Spain: 4% of 714 outpatients <18 years-old

Pre-Adolescent Bipolar Disorder is nonexistent or very rare in Australia, Brazil,
China, India, Israel, Japan, New Zealand,
Russia and Turkey
Pediatric Bipolar Disorder
Medication Response

Youth with
◦ DSM IV mania
◦ YMRS>16


Stabilized on lithium alone (some required
adjunctive antipsychotic initially, which was
then stopped): 33% decline in YMRS
Then randomized to placebo or lithium for
2 weeks (3 day taper for placebo group)

“This study does not support a large effect
for lithium continuation treatment of
adolescents with acute mania, mostly due to
the unexpectedly high rate of exacerbations
in the group that continued on lithium.”


Divalproex no better than placebo on YMRS
or secondary measures on during the 4 week
double-blind study (slight improvements in
both groups, but not statistically significant)
66 patients began long term study (from 151
randomized), with 20 receiving 6 months of
divalproex treatment
◦ Average of 2.2 point decrease in YMRS (>20 to
enter study)

“The results of the study do not support the
use of divalproex (Depakote) ER in the
treatment of youth with bipolar I disorder,
mixed or manic state.”

112 kids
◦ 7-12 years old (N=73)
◦ 13-18 years old (N=42)


3-14 day baseline phase
7 week double blind phase
◦ 2 week titration
◦ 4 week maintenance
◦ 1 week titration-down

Mean oxcarbamazepine dose
◦ 7-12 years old: 1200 mg/day
◦ 13-18 years old: 2040 mg/day

“Oxcarbazepine is not significantly superior
to placebo in the treatment of bipolar
disorder in youths.”


30 adolescents diagnosed with BMD, on
divalproex (Depakote or DVP) 20 mg/kg
Randomized to add-on
◦ quetiapine (Seroquel) mean dose 432 mg/day or
◦ placebo for 6 weeks

Completion rate

Response rates (YMRS reduction >50%)
◦ 53% for quetiapine and DVP (not for SE’s(?))
◦ 93% placebo and DVP
◦ 87% divalproex and quetiapine group
◦ 53% divalproex and placebo group





Risperidone (Risperdal) superior to placebo in 3
week study (Haas et al, 2009)
Quetiapine (Seroquel) superior to placebo in 3 week
study (Delbello et al, 2007)
Aripiprazole (Abilify) superior to placebo in 4 week
study (Findling et al, 2009)
Olanzapine (Zyprexa) superior to placebo in 3 week
study (Tohen et al, 2007) (average weight gain 8.14
pounds for olanzapine vs 0.66 for placebo)
Controlled long term studies are limited






Early in development and testing
Utilize psychoeducation, individual and family
techniques for mood and behavioral regulation
MultiFamily Psychoeducation Group (Fristad et al,
2002)
Child and Family Focused Cognitive Behavioral
Therapy (CFF-CBT) (Pavuluri et al, 2004)
Group CFF-CBT (West et al, 2009)
Family Focused Therapy (Miklowitz et al, 2008)



The construct of Pediatric Bipolar Disorder is
controversial
Regardless of diagnosis, pre-pubertal youth
diagnosed with Bipolar Disorder present with
a number of behavioral health challenges and
poor psychosocial functioning
Prepubertal bipolar disorder is rare or
nonexistent outside of the United States



There is little to no evidence to generalize
what is known about adult “Classic” Bipolar
Disorder to Pediatric Bipolar Disorder
There is little to no evidence that preadolescent youth diagnosed with Pediatric
Bipolar Disorder grow up to have “Classic”
adult Bipolar Disorder
Bipolar Diagnosis requires:
◦ Episodic quality
◦ Change from baseline



Mood stabilizer medications that are effective for
treating “Classic” adult Bipolar Disorder have not
been shown to be more effective than placebo for
youth diagnosed with Pediatric Bipolar Disorder
Atypical antipsychotics have been shown to be
more effective than placebo in the short-term,
but it is not clear if this is a specific or longlasting effect
Psychosocial interventions based on skills
training have some effectiveness in Pediatric
Bipolar Disorder, but these are generally nonspecific interventions

Emphasizes that bipolar disorder is:
◦ Episodic
◦ Change from baseline







Persistent irritability
Severe behavioral outbursts 3 or more times
per week for more than 1 year
Mood between outbursts is persistently
negative
Observable by others
Present in at least 2 settings
Before age 10 years
Developmental age of at least 6 years
Anxiety
ODD
CD
ADHD
MDD
TDD?
BMD
IED
PTSD
Anxiety
MDD
ODD TDD?
PTSD
BMD
IED
CD
ADHD




Symptoms are common among clinic-referred
youth
Difficult to differentiate from OppositionalDefiant Disorder and Conduct Disorder
DMDD diagnosis was not stable over time
Not associated with youth mood or anxiety
disorders or parent history of mood or
anxiety disorders



Is there enough evidence to justify creating a
new diagnosis?
Consequences of creating a diagnosis
prematurely?
How is the rest of the world dealing with this?




Develop policies or guidelines for
psychotropics in child welfare (4/5 of states)
Provide education, training and consultation
to stakeholders
Track provider trends
Establish “flags” for further review, such as
young age, multiple meds, 2 meds from same
class, high doses, PRN meds, etc (2/3 of
states)

Second Opinion: All Medicaid-insured youth
◦ Psychotropic prescriptions exceeding dose-age and
polypharmacy limits are flagged by pharmacy; SCH
child psychiatry consultants review prescriber’s
clinical reasoning for prescription, and approve or
disapprove, and provide clinical suggestions

Partnership Access Line (PAL): Available to
any primary care provider in the state
◦ Primary provider can call PAL and consult with SCH
child psychiatrist; PAL strives to respond within 15
minutes during the workweek

Foster Care Assessment Program (FCAP):
Child welfare social workers may request
◦ Comprehensive multidisciplinary assessment
(psychological, pediatric, psychiatric, social work,
cultural)
◦ Addresses safety, permanency, and well-being
◦ 6 month follow-up

House Bill 1879
◦ Requires review of psychotropic medications to all
children under 5 and establish one or more
mechanisms to evaluate the appropriateness of
psychiatric medications
◦ Requires expert child psychiatry second opinion
review of all antipsychotic prescriptions to foster
youth under 18 years old
 30 days’ medication can be presented pending review
 Review must include discussion of psychosocial
interventions

Contract all foster health care, including
mental health care, to a single managed care
organization (MCO)



Central authority—some health care provider,
child psychiatrists in Illinois—approve all
psychiatric medication consents for youth in
foster care
Standing prn orders not allowed in Illinois; all
emergency medications are reviewed
Consultation available


DCF provides regular reports to court include
updates on youth’s medical and behavioral
status, including psychiatric medication
management and all pertinent medical
records
Court may order DCF to obtain a second
opinion about psychiatric care from the
MedConsult line at the University of Florida