and Child Welfare Terry Lee MD drterryuwedu UW School of Medicine Department of Psychiatry DevelopmentallyInformed Representation of Young Children in Child Welfare October 16 2015 Psychiatry resources ID: 777320
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Slide1
Psychiatric Medications andChild Welfare
Terry Lee, MD
drterry@uw.edu
UW School of Medicine Department of Psychiatry
Developmentally-Informed Representation
of Young Children in Child Welfare
October 16, 2015
Slide2Psychiatry resourcesChild welfare and psychiatric medications: appropriate or inappropriate?Bench cardQuestions to ask psychiatristsWhat some other states are doing
Overview
Slide3aacap.org: American Academy of Child and Adolescent Psychiatry (AACAP)—main child psychiatry organization
Facts
for
Families
Practice Parameterscebc4cw.org: California Evidence-Based Clearinghouse for Child Welfare—CW resources, rating scales, assessment tools, webinars, resources nlm.nih.gov/medlineplus/: Medline Plus—medication informationohiomindsmatter.org: Ohio Minds Matter—online toolkit for consumers and stakeholders to improve psychiatric prescribing to young people
Psychiatry Resources
Slide4Youth in the Child Welfare System and Mental Health Needs/Psychiatric Medications
Slide5National DataYouth in foster care prescribed psychiatric medications at 2-10 times the rate of non-foster youth on Medicaid (MMDLN, 2010; Raghavan
, 2005;
Zito
, 2008)
Any psychiatric medicationMultiple psychiatric medications at the same timeChildren < 5 years old
Slide6Evaluations and follow-ups are too shortToo quick to put kids on medsToo
many
kids
on
medsToo many meds prescribedDoses are too highKids turned into “zombies”Stakeholder Concerns About Psychiatric Medications in Child Welfare (McMillen, 2006)
Slide7Factors Contributing to Increased Prescribing of Psychiatric Medications to Youth Involved with the Child Welfare System
Slide8Causes: Good Reasons for Increased PrescribingYouth involved with child welfare system have higher rates of MH needs:
M
altreatment/trauma
Removal from home, family, and ecology
Multiple placements, disrupted attachmentsPovertyIntrauterine exposures, genetic risksEntry into foster care also:Provides access to MedicaidSystematic screening for behavioral health needsAdvocacy for behavioral health needs
Slide9Insufficient time for proper assessmentLimited information on youth history and current functioningPoor continuity of care
Lack
of critical clinical feedback to inform psychiatrist decision-
making
Ineffective advocacyFactors Potentially Contributing to Inappropriate Psychotropic Prescribing
Slide10Unrealistic hopes that medication will stabilize a complex psychosocial situationUnder-recognition of trauma etiology in formulating complex presentationsLack of commitment of resources to parent skills training, especially if permanency is unclear
Factors Potentially Contributing to
Inappropriate
Psychotropic Prescribing
Slide11Limited access to effective psychosocial interventionsLimited access to effective psychiatric prescribing practicesLimited integration of psychiatric and psychosocial treatments
Factors Potentially Contributing to
Inappropriate
Psychotropic Prescribing
Slide12Evidence of Unmet or Underserved Mental Health Needs Too
Slide13Foster youth 6-12 years-old49% of youth diagnosed with ADHD had not received psychotropics in the previous year80% of youth identified with severe psychiatric disorder not recommended for medication evaluation in previous year
LA County CW Youth, Psychotropics and MH Needs (Zima, 1999a & 1999b)
Slide14National longitudinal surveyYouth and families referred to child welfareCompleted investigationsTwo groups of children (0-14 years-old) randomly chosen between October 1999 and December 20005,504 youth entering the system
727 youth in out-of-home placement>12 months
Evaluated at baseline and 12 months
Child Behavior Check List
National Survey of Child and Adolescent Well-Being (NSCAW)
Slide1547.9% of youth scored in the clinical range on the CBCL 39.3 % of youth in kinship careYouth 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 monthsFactors relating to increased likelihood of services:
Preschoolers: sexual abuse (versus neglect)
Elementary school age: Caucasian and living out-of-home
Adolescents: out-of-home and parent with severe mental illness
NSCAW 2-14 Years-Old (Burns, 2004)
Slide16Assessed 5 domains: cognition, behavior, communication, social skills and adaptive functioningDevelopmental and/or behavioral health needs:Toddlers (0-2 years-old): 41.8%Preschoolers (3-5 years-old): 68.1%
Youth with need receiving services: 22.7%
Factors relating to decreased likelihood of services:
Remaining at home
0-2 years-oldNSCAW <6 Years-Old (Stahmer, 2005)
Slide17Children 12-36 months old with behavioral health needsOnly 19.2% received any type of behavioral health service, including parent skills training related to mental health problemsNSCAW II (
Horwitz
, 2012)
Slide18Youth 2-15 years-oldNeed defined by CBCL clinical range: 46.8% of youth75.8 % had accessed outpatient mental health services, 24.2% had not received servicesPredictors of receiving services: higher CBCL scores, older age, history of sexual abuseLesser use of services: history of neglect, African-American race/ethnicity
NSCAW Out-of-Home for ~1 Year (Leslie, 2004)
Slide19African-American youthVictims of neglectYouth remaining at home or placed in kinship careUtilize systematic screening!
Youth at Risk for Underserved Mental Health Needs
Slide20Help courts ask the right questionsHelp child welfare workers prepare and have specific information in courtMental health system and child psychiatrists are still responsible for providing good mental health and psychiatric careBut court can provide oversight and advocacy
Psychiatric Medication Bench Card
Slide21Some Possible Questions to ask a Child Psychiatrist
Slide22How 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?
Questions to Ask About Psychiatric Medications (Adapted from Facts for Families, AACAP, 2004)
Slide23Who 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?
Questions to Ask About Psychiatric Medications (Adapted from Facts for Families, AACAP, 2004)
Slide24Are 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)?
Questions to Ask About Psychiatric Medications (Facts for Families, AACAP, 2004)
Slide25What 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?
Questions to Ask About Psychiatric Medications (Adapted from Facts for Families, AACAP, 2004)
Slide26Consider Psychiatric Medication Benefit
relative to
Risk
Slide27Psychiatric Medication Classes
Slide28Very effective for ADHD, including long termRelatively rapid onset of actionOn-task behavior by all ratersCompliance 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, accuracyStimulant Positive Effects
Slide29Appetite suppressionSleep disturbance
Elevated pulse and blood pressure
Tics
Obsessive-compulsive behavior
Loss of spontaneityAbuse potentialMore tightly controlled prescribing (Schedule II medication)Long term
Shorter height
Lighter weight
Stimulant Negative Effects
Slide30Took stimulants without prescription5-9% of elementary through high school age
5-35% of college age individuals
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”
Stimulant Diversion (
Wilens
, 2008)
Slide31Concerta (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
Stimulants
Slide32Quillavent 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 patchVyvanse (lisdexamfetamine)-prodrug:
must be ingested to activate –less likely to be diverted and ingested by alternate route (snorting or injecting)?
not any more effective
Aptensio
XR (methylphenidate MLR)-long-acting (12 hours) formulation
Relatively Newer Long-Acting Stimulants
Slide33Methylphenidate total dose > 120 mg/24 hoursAmphetamine total dose > 60 mg/24 hoursLisdexamfetamine total dose > 70 mg/24 hours
Washington State Medicaid Second Opinion Dose Thresholds (>4
yo
)
Slide34Atomoxetine (Strattera)*Alpha
Agonists—primarily
treat hyperactivity
Guanfacine
XR (Intuniv)*Clonidine XR (Kapvay)*Guanfacine (Tenex)
Clonidine
(
Catapress
)
Buproprion
(
Wellbutrin
)
Modafinil
(
Provigil
)
Imipramine
*FDA-approved for ADHD
Non-Stimulant Medications for ADHD
Slide35Atomoxetine (Strattera) not as effective as stimulantsProsEffective throughout the day?Not Schedule II medicationNo increase in tics
Less sleep disruption and appetite suppression
Atomoxetine for ADHD
Slide36ConsFDA 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 stimulantsEffects on growth?Nausea and vomiting
Headache
Sedation
Lightheadedness and dizziness
Atomoxetine for ADHD
Slide37Helps decrease hyperactivitySupport for adding to stimulants for further effectDecreases ticsHelps with sleep (sedating)
Positive Effects of Alpha-Agonists for ADHD
Slide38SedatingDizziness upon standingLower blood pressure and pulseTolerance develops to above 3 bulletsRebound hypertension if stopped suddenly
Negative Effects of Alpha-Agonists for ADHD
Slide39Fluoxetine (Prozac)Sertraline (Zoloft)Citalopram (Celexa)Paroxetine (Paxil)Escitalopram (Lexapro)
Some Specific Serotonin Reuptake Inhibitors (SSRIs)
Slide40Goes beyond “statistical significance”The number of patients who must receive the treatment to get a response that is attributable to active treatmentMore effective treatments will have a lower NNT
Number Needed to Treat (NNT)
Slide41Meta-analysis of SSRI NNT for youth disorders (Bridge, et al; 2007)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?
Specific Serotonin Reuptake Inhibitors (SSRIs)
Slide42Negative EffectsSlight increase in suicidal ideation, especially for youth with depression: 2%?Induce mania? If youth has bipolar disorderActivation, insomnia or irritability—usually transientSedation
Gastrointestinal symptoms
Headache
Increased bleeding risk—less common
Apathy—sometimes a sign of too high a doseDecreased libido—rare in adolescentsSpecific Serotonin Reuptake Inhibitors (SSRIs)
Slide43Positive effectsEffective for classic bipolar disorder
Mild short term positive effects for other disorders
Negative effects
Weight gain
AcneSedation—may be transientTremor—may be transient
Increased thirst
Depressed thyroid function, which may lead to hypothyroidism
Kidney effects, usually insignificant
Lithium Carbonate (LiCO3)
Slide44Positive EffectsAnti-seizure medicationEffective in classic or “real” bipolar disorder—the type seen in adults and post-pubertal youthMild positive effects on (controversial) pediatric bipolar disorder
Divalproex
(
Depakote
)
Slide45Serious Negative EffectsHormone-like effects, including increased rate of Polycystic Ovaries in femalesNeural 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 suppressionWithdrawal seizures if stopped suddenlyDivalproex (Depakote)
Slide46Negative EffectsCommon—usually temporary
Nausea
Sedation
Dizziness
Weight gainVomitingWeaknessGastrointestinal 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
Divalproex
(
Depakote
)
Slide47Olanzapine (Zyprexa)
Risperidone (
Risperdal
)
Quetiapine (Seroquel)Ziprasidone (Geodon)Aripiprazole (Abilify)
Asenapine
(
Saphris
)
Iloperidone
(
Fanapt
)
Lurasidone
(
Latuda
)
Paliperidone
(
Invega
)
Atypical Antipsychotics
Slide48Positive EffectsEffective for psychosisEffective for classic mania and bipolar disorderLess effective for controversial pediatric bipolar disorderModerately effective for tics and Tourette’s Disorder
In the short term, unlikely to have irreversible negative effects
Atypical Antipsychotics
Slide49Negative EffectsCommon
Sedation
Weight gain (depending on which antipsychotic, 9.7-18.7 pounds in ~11 weeks in one study (
Correll
et al, 2009))DyslipidemiasGlucose intolerance, which may lead to diabetesExtra-pyramidal side effects (EPS)-muscle stiffness, sometimes with tremorAkathisia-inner restlessness associated with urge to keep moving
Blurred vision
Atypical Antipsychotics
Slide50Negative EffectsLess commonDiabetesAcute dystonia-temporary and non-fatal, but very uncomfortable, muscle spasm when starting antipsychotic medicationRare but seriousTardive dyskinesia-irreversible movement disorder
Neuroleptic Malignant Syndrome-muscle rigidity, fever, autonomic instability and altered mental status which, in rare instances, may lead to death
Atypical Antipsychotics
Slide51Olanzapine (Zyprexa)
More sedating
A little more effective for psychosis
More weight gain
Risperidone (Risperdal)Less sedatingMore prone to stiffness, restlessness, acute dystonia
and tardive dyskinesia
More prone to
hyperprolactinemia
More prone to
galactorrhea
,
gynecomastia
Quetiapine
(
Seroquel
)
Usually very sedating, initially
FDA warning about cataracts, but not a problem
More weight gain
Individual Atypical Antipsychotic Effects
Slide52Ziprasidone (Geodon)Less weight gainLess glucose intolerance and lipid problemsLess sedatingRare cardiac conduction problemsAripiprazole (Abilify)
Mild to moderate weight gain
Mildly to moderately sedating
Mild muscle stiffness and restlessness
Individual Atypical Antipsychotic Effects
Slide53Atypical Antipsychotic Side Effects (adapted from Pappadopulos, 2002; Marder, 2003;
Potkin
, 2003)
Anti-cholinergic
Elevated prolactinEPS
Orthostasis
QTC increase (heart)
Sedation
Weight gain
Risperidone
0/+
+++
++
++
0
+
+++
Olanzapine
+++
++
+
++
0
+++
++++
Quetiapine
++
+
++
++
+
++
++
Ziprasidone
++
+
+
+
++
+
+
Aripiprazole
0/+
0
0/+
+
0
+
+/++
Slide54338 youth4-19 years-old1 week or less of antipsychotic medication treatment272 had one post-baseline assessment205 completed the 12 week study15 youth who refused or were non-compliant served as controls
Cardiometabolic
Risk of Antipsychotic Medications (
Correll
, 2009)
Slide5510.8 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
Cardiometabolic
Risk of Antipsychotic Medications (
Correll
,
2009
)
Slide5610.8 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
Cardiometabolic
Risk of Antipsychotic Medications (
Correll
,
2009
)
Slide5710.8 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
Cardiometabolic
Risk of Antipsychotic Medications (
Correll
,
2009
)
Slide58Five-fold increase from 1993-2002 in the prescription of antipsychotics in youth18.3% 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%
Children on Antipsychotics (
Olfson
, 2006)
Slide59Youth 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
Youth on Medicaid and Antipsychotics
Slide60Some Common Childhood Psychiatric Disorders and Diagnoses
Slide61ADHD Comorbidity (MTA Study)
Slide62Oppositional-Defiant Disorder Lifetime Additional Disorders:Impulse Control Disoders-68.2%Anxiety Disorders-62.3%Substance Use Disorders-47.2%
Mood Disorders-45.8%
National Comorbidity Survey Replication (Nock, 2007)—Adult Epidemiological Study
Slide63Some 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
Psychiatric Medications for Disruptive Behavior
Slide64Aggression (though consider comorbid condition)Rule-breaking, noncompliant behavior, missing curfewTemper tantrumsPsychosocial interventions are the most effective for the above behaviors
Limited or No Long-Term Medication Efficacy For:
Slide65Over- or under-diagnosed?Evidence of both in the United StatesApproximately 5-10% of youth in the United StatesApproximately 3-5% in the rest of the world, though higher in post-industrialized countries
Attention-Deficit/Hyperactivity Disorder (ADHD)
Slide66Driving: youth with ADHD compared to those without (American Academy of Pediatrics, 2006)2-4 times as likely to have a motor vehicle accidentMore likely to have repeat traffic citationsMore likely to have licenses suspended or revoked
Driving performance improves with stimulant medication
Attention-Deficit/Hyperactivity Disorder (ADHD)
Slide67More boys than girls affectedGirls tend to have primarily inattentive type, which may lead to under-diagnosis, but still more boys with ADHDSome ADHD is due to CNS immaturitySome youth will “grow out” of symptoms However, for others, hyperactivity will diminish, but inattentiveness and impulsivity will continue
Attention-Deficit/Hyperactivity Disorder (ADHD)
Slide68DiagnosingSymptoms in 2 settingsDon’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?
Attention-Deficit/Hyperactivity Disorder (ADHD)
Slide69Best for most people with ADHD~2/3 will respond
Largest effect size of psychiatric medications in youth
Schedule II medication—abuse and addiction potential
All medications need to monitored closely, especially stimulants
More than 300 randomized controlled trials demonstrating effectiveness of stimulants for ADHDStimulants
Slide70Effect 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
Attention-Deficit/Hyperactivity Disorder Treatment Effectiveness
Slide71Goes beyond “statistical significance”For following study, Cohen’s D used: ES=(pretreatment mean-post-treatment mean)/pooled standard deviationCohen’s guidelines for effect size:Small: 0.20Medium: 0.50
Large: 0.80
Effect Size
Slide72Psychosocial
Methylphenidate
Combined
ADHD-parent
0.871.531.89
ADHD-teacher
0.75
1.83
1.77
ODD-parent
0.66
0.61
1.23
ODD-teacher
0.43
1.08
0.92
ADHD Treatment Effect Size Meta-analysis—up to 15 studies sampled (
Oord
, et al; 2007)
Slide73Mild ADHD can be treated with psychosocial interventions aloneUncomplicated ADHD can be treated with medication onlyAACAP Guidelines
Slide74Combination of behavior therapy and medications showed more improvement than youth treated with behavior therapy alone (MTA, 1999)
Comorbid ADHD and Disruptive Behavior
Slide7525,656 adults in Sweden with ADHDFollowed for 3 yearsCompliance with ADHD meds:Males-32% reduction in criminalityFemales-41% reduction in criminalityCompliance with SSRI’s not associated with reduction in criminality
ADHD and Adult Criminality (Lichtenstein, 2012)
Slide76Common childhood psychiatric disorder6-20% 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)
Childhood Anxiety Disorders
Slide77Medications: SSRI’s have demonstrated short term efficacy in randomized, placebo-controlled trials (Connolly, 2007; Reinblatt and Riddle, 2007)NNT=3-4Response rates range from 61-90% for separation anxiety, social phobia and generalized anxiety
Childhood Anxiety Disorders
Slide78Seven academic sites488 childrenRacially and ethnically diverseBut despite intense outreach, did not include the most socioeconomically disadvantaged children7-17 years old
Anxiety Disorders lumped together: separation anxiety, generalized anxiety and social phobia
Less severe comorbid conditions permitted
Child and Adolescent Anxiety Multimodal Treatment Study (CAMS) (Walkup, 2008)
Slide79Treatments:14 sessions of cognitive behavioral therapy (CBT) (weekly parent check-in, and 2 parent only sessions)Sertraline (Zoloft) up to 200 mg/dayCombination CBT and sertraline
Placebo
Child and Adolescent Anxiety Multimodal Treatment Study (CAMS) (Walkup, 2008)
Slide80Results (at 12 weeks)—Very Much or Much Improved on Clinician Global Impression-Improvement (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%
Child and Adolescent Anxiety Multimodal Treatment Study (CAMS) (Walkup, 2008)
Slide81Clinical Global Impression-Improvement Scale Response RatesCombination(81%)>CBT(60%)=sertraline(55%) >placebo(24%)Pediatric Anxiety Rating ScaleCombination>sertraline=CBT>placeboMean sertraline dose at final visit:
Combination: 134 mg/day
Sertraline only: 146 mg/day
Child and Adolescent Anxiety Multimodal Treatment Study (CAMS) (Walkup, 2008)
Slide82Adverse eventsNo differences between sertraline and placebo groups, including suicidal and homicidal ideationNo child in study attempted suicideCBT group<sertraline group: insomnia, fatigue, sedation and restlessness/fidgeting
Child and Adolescent Anxiety Multimodal Treatment Study (CAMS) (Walkup, 2008)
Slide83Clinical Global Impression-Improvement Scale (Walkup, 2008)
Slide84Pediatric Anxiety Rating Scale (Walkup, 2008)
Slide85Major Depression2.5% of children8.3% of adolescents (Birmaher, 1996)
Childhood Depressive Disorders
Slide86439 youth 12-17 years oldModerate to severe depression13 academic centers12 weeks of treatment Fluoxetine
(Prozac) alone
Cognitive-Behavioral Therapy (
CBT
) aloneCombined fluoxetine and CBTPlaceboTreatment of Adolescents with Depression Study (TADS) (March, 2004)
Slide87Response rateCombined (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 aloneTreatment of Adolescents with Depression Study (TADS) (March, 2004)
Slide88Children’s Depression Rating Scale-RevisedCombination>fluoxetine>CBTClinical Global Impression-Improvement ScaleCombination=fluoxetine>CBT=placebo
Suicidal Thinking Decrease
Present in 29% of youth at baseline
All groups showed improvement, combination therapy showed the most
Combo>CBT=placebo=fluoxetineTreatment of Adolescents with Depression Study (TADS) (March, 2004)
Slide89TADS Children’s Depression Rating Scale-Revised Scores (March, 2004)
Slide90TADS Suicide Questionnaire-JHS Version (March, 2004)
Slide91More chronic and treatment-resistant youth12 weeks334 adolescents12-18 years-oldDid not respond to 2 month trial of SSRIRandomized to:A different SSRI
A different SSRI with CBT
Venlafaxine (SNRI)
Venlafaxine with CBT
Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) (Brent, 2008)
Slide92Response ratesMedication 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 24Among week 24 remitters, 25.4% relapsed within one year
Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) (Brent, 2008)
Slide93British study208 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, orSSRI (with Active Clinical Care (ACC)—seeing psychiatrist) for medication
12 week treatment phase
16 week maintenance phase
Adolescent Depression Antidepressant and Psychotherapy Trial (ADAPT) (
Goodyer
, 2008)
Slide94Follow-up assessments at 6, 12 and 28 weeks208 randomized patients, 200 completed 12 week trial174 followed-up at 28 weeksSeverely depressed group
Adolescent Depression Antidepressant and Psychotherapy Trial (ADAPT) (
Goodyer
, 2008)
Slide95After no response to a 2 week psycho-educational 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 onlyBoth groups improved on all measuresNo increase in suicidal thoughts or self-harm behaviors
Adolescent Depression Antidepressant and Psychotherapy Trial (ADAPT) (
Goodyer
, 2008)
Slide96Children 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
Childhood Trauma
Slide97Review 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 symptomsImproved depression, anxiety and externalizing behavior
However, continued significant PTSD diagnosis in approximately 20% of sample
Childhood Trauma
Slide98AdultsSSRIs 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 dataPTSD and Psychiatric Medication Treatment
Slide9924 girls (wanted larger sample, but FDA “black box warning” came out)—calculated 64 subjects needed to find medium effect size10-17 years-oldAll experienced sexual abuseNon-offending caregiver participated12 weeks of treatment
TF-CBT + placebo, versus
TF-CBT + sertraline (Zoloft)
Pilot randomized controlled trial of combined trauma-focused CBT and sertraline for childhood PTSD symptoms (Cohen, 2007)
Slide100No difference between groups on K-SADS-PL-PTSD scales: Re-experiencing, Avoidance, Hyper-arousal, Total Symptoms ~medium effect sizes (d): 0.40, 0.48, 0.53 and 0.53 respectivelyNo clinically meaningful differences on other measures, including PTSD diagnosis, Global Impairment Status (CGAS), SCARED, Mood and Feelings Questionnaire (MFQ), CBCL, BDI
Pilot randomized controlled trial of combined trauma-focused CBT and sertraline for childhood PTSD symptoms (Cohen, 2007)
Slide101Statistically 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?
Pilot randomized controlled trial of combined trauma-focused CBT and sertraline for childhood PTSD symptoms (Cohen, 2007)
Slide102ControversialRegardless of what diagnosis is given, these youth diagnosed with Bipolar Disorder present with very concerning behaviors and symptoms
Pediatric Bipolar Disorder
Slide103DSM diagnosisAlso known as manic-depressive illnessCharacterized by episodes:highs (mania) lows (depression)Episodes are a change from baseline mood
What is Bipolar Disorder?
Slide104Mood Graph
Slide105A 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 speechFlight of ideas or racing thoughtsDistractibility
Increased in goal-directed activity
Excessive involvement in pleasurable activities that have a high potential for painful consequences
Mania (abbreviated criteria; see DSM IV for full criteria)
Slide106Brief Clip of Depiction of Manic-like (?) Behavior, with Caveat
Slide107Youth (0-19 years old)25 visits per 100,000 (1994-5)1003 visits per 100,00 (2002-3)40 fold increaseAdult (20 years old and above)
905 visits per 100,000 (1994-5)
1679 visits per 100,000 (2002-3)
Almost double
Increase in Outpatient Rates of Diagnosis of Bipolar Disorder from 1994-5 to 2002-3 (Moreno et al, 2007)
Slide108National trends in visits with a diagnosis with bipolar disorder as a percentage of total office-based visits by youth (0-19 years old) and adults (>19 years old)
Slide109Mood Graph
Slide110Mood Graph
Slide111Different definitions and criteria for bipolar disorder complicate interpretation of research
Need to distinguish between “Real” or “Classic” Bipolar Disorder versus controversial
“Pediatric Bipolar Disorder” chronic non-episodic irritability
Slide1125X increase in bipolar disorder if one parent has bipolar disorder (LaPalme, 1997)However, prevalence is still only 5%, lower than ADHDPresence of bipolar disorder in more distant relatives does not appear to increase risk
Family History of Bipolar Disorder?
Slide113Is Pre-Adolescent Bipolar Disorder a World-Wide Phenomenon?
Slide114United Kingdom: 0 cases of preadolescent mania in large epidemiological study 0 cases of 2500 hospital-referred youth (<10) over 10 yearsIn one study in the United States, 30% of all youth admitted to a psychiatric unit were diagnosed with Pediatric Bipolar Disorder (Carlson & Youngstrom, 2003)
Rates of Youth Bipolar Disorder in Other Countries (
Soutullo
et al, 2005)
Slide115Holland (teens): 1.9% mania, 0.9% hypomania in epidemiological studyDenmark (<15 yo): 1.2% of inpatientsIreland (>14 yo): 2.2 cases/100,000 youth per year-epidemiologic studyFinland: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
Rates of Youth Bipolar Disorder in Other Countries (Soutullo, et al; 2005)
Slide116Pre-Adolescent Bipolar Disorder is non-existent or very rare in Australia, Brazil, China, India, Israel, Japan, New Zealand, Russia and TurkeyPediatric Bipolar Disorder: A Global Perspective (
Diler
(
ed
) 2007)
Slide117I don’t care what you call it, it’s what you do about that’s important
Pediatric Bipolar Disorder Medication Response
Slide118Pediatric Bipolar Disorder Medication Response?
Slide119Youth withDSM IV mania YMRS>16Stabilized 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)
Lithium Treatment of Acute Mania in Adolescents: A Placebo-Controlled Discontinuation Study (
Kafantaris
, 2004)
Slide120Lithium Treatment of Acute Mania in Adolescents: A Placebo-Controlled Discontinuation Study (Kafantaris, 2004)
Slide121Lithium Treatment of Acute Mania in Adolescents: A Placebo-Controlled Discontinuation Study (Kafantaris, 2004)
Slide122Lithium Treatment of Acute Mania in Adolescents: A Placebo-Controlled Discontinuation Study (Kafantaris, 2004)
“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.”
Slide123Divalproex 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)
Double-Blind, Randomized Placebo-Controlled Trial of
Divalproex in Treatment of Bipolar Disorder in Children and Adolescents (Wagner et al, 2009)
Slide124Double-Blind, Randomized Placebo-Controlled Trial of Divalproex in Treatment of Bipolar Disorder in Children and Adolescents (Wagner et al, 2009)
Slide125Double-Blind, Randomized Placebo-Controlled Trial of Divalproex in Treatment of Bipolar Disorder in Children and Adolescents (Wagner et al, 2009)
Slide126Double-Blind, Randomized Placebo-Controlled Trial of Divalproex in Treatment of Bipolar Disorder in Children and Adolescents (Wagner et al, 2009)
“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.”
Slide127Multisite Oxcarbazepine (Trileptal) Randomized Controlled Trial
(Wagner, 2006)
112 kids
7-12 years old (N=73)
13-18 years old (N=42)3-14 day baseline phase7 week double blind phase2 week titration4 week maintenance
1 week titration-down
Mean
oxcarbamazepine
dose
7-12 years old: 1200 mg/day
13-18 years old: 2040 mg/day
Slide128Multisite Oxcarbazepine (Trileptal) Randomized Controlled Trial (Wagner, 2006)
Slide129Multisite Oxcarbazepine (Trileptal) Randomized Controlled Trial for Pediatric Bipolar Disorder
(Wagner, 2006)
“
Oxcarbazepine
is not significantly superior to placebo in the treatment of bipolar disorder in youths.”
Slide13030 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 weeksCompletion rate53% for quetiapine and DVP (not for SE’s(?))93% placebo and DVPResponse rates (YMRS reduction >50%)87%
divalproex
and
quetiapine
group
53%
divalproex
and placebo group
Quetiapine
Add-On Treatment for BMD in Adolescents (
Delbello
, 2002)
Slide131Quetiapine Add-On Treatment for BMD in Adolescents (Delbello et al, 2002)
Slide132Risperidone (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
Atypical Antipsychotics and Acute Treatment of Manic or Mixed Symptoms with FDA Approval >10 or 13 years old
Slide133Early in development and testingUtilize 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)
Psychosocial Interventions for Pediatric Bipolar Disorder
Slide134The construct of Pediatric Bipolar Disorder is controversialRegardless of diagnosis, pre-pubertal youth diagnosed with Bipolar Disorder present with a number of behavioral health challenges and poor psychosocial functioningPrepubertal bipolar disorder is rare or nonexistent outside of the United States
Bipolar Disorder Summary
Slide135There is little to no evidence to generalize what is known about adult “Classic” Bipolar Disorder to Pediatric Bipolar DisorderThere is little to no evidence that pre-adolescent youth diagnosed with Pediatric Bipolar Disorder grow up to have “Classic” adult Bipolar DisorderBipolar Diagnosis requires:Episodic quality
Change from baseline
Bipolar Disorder Summary
Slide136Mood 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 long-lasting effect
Psychosocial interventions based on skills training have some effectiveness in Pediatric Bipolar Disorder, but these are generally non-specific interventions
Bipolar Disorder Summary
Slide137Emphasizes that bipolar disorder is:EpisodicChange from baseline
DSM 5
Slide138Persistent irritabilitySevere behavioral outbursts 3 or more times per week for more than 1 yearMood between outbursts is persistently negativeObservable by othersPresent in at least 2 settingsBefore age 10 years
Developmental age of at least 6 years
DSM 5: Disruptive Mood Dysregulation Disorder
Slide139Need for DMDD?
ODD
BMD
CD
IED
MDD
PTSD
Anxiety
ADHD
TDD?
Slide140Need for DMDD?
ODD
BMD
CD
IED
MDD
PTSD
Anxiety
ADHD
TDD?
Slide141Symptoms are common among clinic-referred youthDifficult to differentiate from Oppositional-Defiant Disorder and Conduct DisorderDMDD diagnosis was not stable over timeNot associated with youth mood or anxiety disorders or parent history of mood or anxiety disorders
DMDD (
Axelson
, 2012)
Slide142Is 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?
New DSM 5 Diagnosis: Disruptive Mood Dysregulation Disorder (DMDD)
Slide143State are Developing Guidelines and Protocols for Psychotropics and the Child Welfare System (Naylor, 2007; Leslie, 2010; Medicaid Medicaid Directors Learning Network, 2010)
Slide144Develop policies or guidelines for psychotropics in child welfare (4/5 of states)Provide education, training and consultation to stakeholdersTrack provider trendsEstablish “flags” for further review, such as young age, multiple meds, 2 meds from same class, high doses, PRN meds,
etc
(2/3 of states)
State Strategies for Psychotropics and Child Welfare
Slide145Second Opinion: All Medicaid-insured youthPsychotropic 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 suggestionsPartnership 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
Washington State
Slide146Foster Care Assessment Program (FCAP): Child welfare social workers may requestComprehensive multidisciplinary assessment (psychological, pediatric, psychiatric, social work, cultural) Addresses safety, permanency, and well-being6 month follow-up
Washington State
Slide147House Bill 1879Requires review of psychotropic medications to all children under 5 and establish one or more mechanisms to evaluate the appropriateness of psychiatric medicationsRequires 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
Washington State
Slide148Contract all foster health care, including mental health care, to a single managed care organization (MCO)Texas and Other States; Washington soon
Slide149Central authority—some health care provider, child psychiatrists in Illinois—approve all psychiatric medication consents for youth in foster careStanding prn orders not allowed in Illinois; all emergency medications are reviewedConsultation available
Illinois and Other States
Slide150DCF provides regular reports to court include updates on youth’s medical and behavioral status, including psychiatric medication management and all pertinent medical recordsCourt may order DCF to obtain a second opinion about psychiatric care from the MedConsult line at the University of Florida
Florida and Other States
Slide151Questions?