Transcript Advair Use in Arkansas Medicaid

Improving Medication Prescribing for Arkansas
Children Through Off-label Education
IMPACT Off-label Education
Update on Depression and Anxiety in
Children and Adolescents
UAMS College of Pharmacy
Evidence-based Prescription Drug Program
UAMS College of Medicine
Division of Child and Adolescent Psychiatry
Goals
Review anxiety and depression prevalence
and recommendations
Discuss recently completed clinical trials and
consensus national treatment guidelines
Review FDA advisory on “suicidality”
Examine treatment patterns in Arkansas
Medicaid
Provide points of access to useful resources
Anxiety in Children
Anxiety in Children
Fear and worry can be normal, but excessive
anxiety causes impairment
Prevalence in children is reported between
6% and 20%
Anxiety can be recognized at young ages,
and may recur or persist to adulthood
Association with poor problem-solving, low
self-esteem, negative self perceptions
Source: AACAP Practice Parameter for the Assessment and Treatment of Children
and Adolescents With Anxiety Disorders, 2007
Anxiety in Children
Anxiety in children predicts:
Adult anxiety
Major depression
Suicide attempts
Psychiatric hospitalization
Source: APA Report of the Working Group on Psychotropic Medications for Children
and Adolescents, 2007
Anxiety in Children
Includes, generalized anxiety, separation
anxiety, social phobia (and selective mutism),
obsessive compulsive disorder, specific
phobias, panic disorder, PTSD
Separate guidelines for OCD and PTSD in
children are available by the AACAP
Anxiety can be a family phenomenon
Source: AACAP Practice Parameter for the Assessment and Treatment of Children
and Adolescents With Anxiety Disorders, 2007
Anxiety in Children
Screening tools for children exist
A positive screen is not a diagnosis – but an
indication for more formal assessment
Consider overlap or overlay of physical ills
Comorbid conditions should be evaluated and
effectively treated
Early assessment and intervention may
improve long-term outlook
Source: AACAP Practice Parameter for the Assessment and Treatment of Children
and Adolescents With Anxiety Disorders, 2007
Anxiety in Children - Treatments
Treatment Guideline considerations:
Multiple treatment modalities
Severity of impairment
Psychotherapy – especially Cognitive
Behavioral Therapy (CBT)
Pharmacotherapy with SSRIs
Short-term helpful, long-term unknown
Pharmacotherapy with other agents
Source: AACAP Practice Parameter for the Assessment and Treatment of Children
and Adolescents With Anxiety Disorders, 2007
Anxiety in Children - Treatments
Psychotherapy (CBT) is consensus first-line
approach
56% remission vs. 34% remission on wait-list control
SSRI are helpful, but no comparisons
Sertraline and fluoxetine have supportive trials
Fluvoxamine more useful if no baseline depression
Paroxetine useful, but not recommended due to
safety concerns/”suicidality” association
Combined CBT with sertraline trial is recently
published – NIMH CAMS trial
Source: APA Report of the Working Group on Psychotropic Medications for Children
and Adolescents, 2007
Anxiety in Children - Treatments
TCAs – Imipramine has mixed data. Risks
(esp. CV) limit use – no longer supported
Benzodiazepines – not supported alone in
children or adolescents. Avoid with history of
substance use
SNRIs – limited information on venlafaxine
ER
Buspirone – no published data
Sources: APA Report of the Working Group on Psychotropic Medications for
Children and Adolescents, 2007. AACAP Practice Parameter for the Assessment and
Treatment of Children and Adolescents With Anxiety Disorders, 2007
Anxiety in Children
Major Points:
Screen, evaluate and intervene early
Refer for evaluation and psychotherapy
SRI role – likely second-line or adjunct:
 Fluoxetine, fluvoxamine, sertraline supported
 Paroxetine good anxiety data, but suicide warnings in teens
 Some ER venlafaxine support, though less than SSRIs
New study from NIMH on CBT vs. sertraline
vs. combination
Depression in Children
Depression in Children
Prevalence estimated at 2.5% of children,
8.3% of adolescents
Anxiety is often associated
Suicidal thoughts are reported by 40 to 80%
of depressed youth; attempts may be as high
as 35%
Depression marks significant risks for
recurrence, substance abuse, teen
pregnancy…
Source: PhysiciansMedGuide The Use of Medication in Treating Childhood and
Adolescent Depression: Information for Physicians, 2007
Depression in Children
Younger Children
Somatic complaints
Psychomotor agitation
Mood-congruent
hallucinations
School refusal
Anxiety related issues
Older Children
Esteem issues,
boredom, apathy
Substance use
Change in weight,
eating, sleep
Excess sleep/depressed
affect
Aggression/antisocial
behavior
Source: GLAD-PC Toolkit available at www.GLAD-PC.org
Depression in Children
Recent Trial Information
TADS Study Results:
Therapy
Improvement/Response Rate
Week 12
Week 18 Week 36
CBT+Fluoxetine
71%
85%
86%
Fluoxetine
61%
69%
81%
CBT
Placebo
43%
35%
65%
81%
Source: TADS Team Treatment for Adolescents with Depression Study (TADS) – Longterm Effectiveness and Safety Outcomes. Arch Gen Psychiatry. 2007; 64(10) 1132-1144
Depression in Children
Recent Trial Information
TADS Study Suicide Event Screening Results
Treatment
Positive Suicide Event Screening
Baseline
Week 12
Week 36
CBT+Fluoxetine
42/106
8/90
2/79
Fluoxetine
28/107
18/97
10/73
CBT
27/107
5/91
3/76
Fluoxetine differed significantly from both other
treatments at weeks 12 and 36
Source: TADS Team Treatment for Adolescents with Depression Study (TADS) – Longterm Effectiveness and Safety Outcomes. Arch Gen Psychiatry. 2007; 64(10) 1132-1144
Depression in Children
Recent Trial Information
TORDIA trial – resistant depression/poor
treatment response in adolescents
Entering subjects had prior SSRI treatment
+/- CBT, high rate of suicidal thoughts
Tested changing medication vs. changing
medication with CBT
Postulated changing to an SNRI after an
SSRI may increase response rate
Source: Brent, et. al. Switching to Another SSRI or to Venlafaxine With or Without Cognitive Behavioral
Therapy for Adolescents With SSRI-ResistantDepression. JAMA. 2008;299(8):901-913
Depression in Children
Recent Trial Information
Initially treated with at least 40mg fluoxetine
(or equivalent)
Switched to SSRI, SSRI+CBT, SNRI, or
SNRI+CBT
SNRI was venlafaxine ER
Initial SSRIs were fluoxetine or paroxetine
After FDA warnings, paroxetine was dropped,
and citalopram was substituted.
Source: Brent, et. al. Switching to Another SSRI or to Venlafaxine With or Without Cognitive Behavioral
Therapy for Adolescents With SSRI-ResistantDepression. JAMA. 2008;299(8):901-913
Depression in Children
Recent Trial Information
Best responses occurred with switch from
SSRI to either arm with CBT
ER venlafaxine was no better than a change
from one SSRI to another
CBT showed site variations, but robust and
durable improvement
ER venlafaxine had higher rates of
cardiovascular and other side effects.
Source: Brent, et. al. Switching to Another SSRI or to Venlafaxine With or Without Cognitive Behavioral
Therapy for Adolescents With SSRI-ResistantDepression. JAMA. 2008;299(8):901-913
Depression in Children - Treatments
Fluoxetine plus CBT has best evidence of
success. Consistent benefits and FDA
approved down to age 8 (7 for OCD)
Non-responders to SSRI alone, may benefit
from addition of CBT with change in SSRI
Most medication trials have serious flaws/
limitations
Several psychotherapy approaches may help
Sources: APA Report of the Working Group on Psychotropic Medications for Children and Adolescents, 2007.
Brent, et. al. Switching to Another SSRI or to Venlafaxine With or Without Cognitive Behavioral Therapy for Adolescents
With SSRI-ResistantDepression. JAMA. 2008;299(8):901-913
Depression in Children
Major Points:
Screen, evaluate and intervene early
Refer for evaluation and psychotherapy
SRI role – likely first-line in combination:
 Fluoxetine was the only approved agent, still a good starting
point
 Monitoring is key
 Shorter half-life agents seem problematic
Watch for more from NIMH:
 Antidepressant Safety in Kids (ASK)
 Treatment of Adolescent Suicide Attempters (TASA)
FDA “Suicidality” Warnings,
Antidepressants, and Young People
FDA and “Suicidality”
“Suicidality” links thoughts of suicide and
suicide attempts
60% of completed suicides are thought to be
in patients with depression
FDA warning based on 23 studies of nine
medications, none with a completed suicide
Monitoring for thoughts, plans and attempts
is important with any treatment
Source: PhysiciansMedGuide The Use of Medication in Treating Childhood and
Adolescent Depression: Information for Physicians, 2007
FDA and “Suicidality” Timeline
June 2003 – FDA issues warnings specific to
paroxetine and increased rate of suicide
reports
December 2003 – EU/UK agencies advise not
to use most SSRI/SNRIs in patients under 18
October 2004 – FDA “black box” warning
relating to children and adolescents on all
agents
December 2006 – FDA warning extended to
young adults
Selective Reuptake Inhibitors
Uses are anxiety and depression
Reasonable evidence, some very recent
Recent controversy – “suicidality” link
FDA statements in 2003 and 2004
Subsequent drop in youth SSRI use of 22% from
2003 to 2005 reported
2003 to 2004 suicide rate increases
10-14 YO females – 56 to 94 or .95/100K (+75%)
15-19 YO females – 265 to 365 or 3.52/100K (+32%)
15-19 YO males – 1,222 to 1,345 or 12.65/100K (+9%)
Sources: Gibbons, et al. Early Evidence on the Effects of Regulators’ Suicidality Warnings on SSRI Prescriptions and Suicide in
Children and Adolescents. Am J Psychiatry 2007; 164:1356–1363.
CDC Suicide Trends among Youths and Young Adults aged 10 to 24 years – United States,1990 to 2004. MMWR. 2007
56(35);905-908.
“Suicidality” Warning Impact
Gibbons commercially available data show:
no prescribing gain or drop between 2003 and 2004
22% prescribing drop between 2004 and 2005
Olfson reported on pharmacy claims data:
Rapid annualized increases in SSRI use in children
prior to paroxetine warnings (May 2002 to June 2003)
Significant drop (mostly due to paroxetine) seen after
paroxetine warning (June 2003 to October 2004)
Stable/no significant drop after black box warning
(October 2004 through Dec 2005)
Sources: Gibbons, et al. Early Evidence on the Effects of Regulators’ Suicidality Warnings on SSRI
Prescriptions and Suicide in Children and Adolescents. Am J Psychiatry 2007; 164:1356–1363.
Olfson, et. al. Effects of Food and Drug Administration Warnings on Antidepressant Use in a National
Sample, Arch Gen Psychiatry 2008;65(1): 94-101.
“Suicidality” in Practice
Screening does not increase risks
or cause suicidal thoughts
Failing to screen may lead to
missing vital information
“Suicidality” in Practice
When starting Tx, FDA recommends
weekly assessment for first four weeks
twice weekly assessment for four weeks,
then (minimally) at the end of 12 weeks
Practically, this can be individualized
Formal assessment tools available
Suicide risk and assessment plan
should be documented
Anxiety and Depression Treatment
Trends in Arkansas Medicaid
Treatment Pattern Trends
Arkansas Medicaid claims data are robust
(half of all children in the state)
We include only continuously enrolled
Medicaid and ARKids recipients which
corrects for variations in total enrollment over
time.
Prevalence can be grouped by recipient age:
Preschool – one year to age six
Primary School – six years to age 12
Adolescent – 12 years to age 18
Recent Initial Treatment Trends
 777 newly diagnosed/
20%
treated Medicaid
recipients under 18 from
April – Oct 2008
 Treatment patterns
12%
identified by CPT codes
and pharmacy claims paid
 No severity indicator, but
all had no treatment in
Counseling Only
prior six months
Medication Only
68%
Combined
Persistence Of Treatment
Counseling Visits
Prescriptions
Dispensed
Same 777 newly
diagnosed/treated
children
Question: How many
received more than two
claims for either
intervention?
Answer: About 70% Possibly better
persistence with
counseling
None
1-2
3 or
more
122 406
None
1-2
89
23
43
3 or
More
68
9
27
Preschool Prevalence Trends
1.2%
1.0%
0.8%
0.6%
0.4%
0.2%
0.0%
2
0_
0
0
7
2
1_
0
0
1
2
1_
0
0
7
2
2_
0
0
1
2
2_
0
0
7
2
3_
0
0
1
2
3_
0
0
Newer Antidepressants
Tri/Tetracyclics
Source: Arkansas Medicaid claims data, EBRx analysis
7
2
4_
0
0
1
2
4_
0
0
7
2
5_
0
0
1
2
5_
0
0
7
2
6_
0
0
1
2
6_
0
0
7
2
7_
0
0
ADHD Medications
Atypical Antipsychotics
1
Grade School Prevalence Trends
12%
10%
8%
6%
4%
2%
0%
2
0_
0
0
7
2
1_
0
0
1
2
1_
0
0
7
2
2_
0
0
1
2
2_
0
0
7
2
3_
0
0
1
2
3_
0
0
Newer Antidepressants
Tri/Tetracyclics
Source: Arkansas Medicaid claims data, EBRx analysis
7
2
4_
0
0
1
2
4_
0
0
7
2
5_
0
0
1
2
5_
0
0
7
2
6_
0
0
1
2
6_
0
0
7
2
7_
0
0
ADHD Medications
Atypical Antipsychotics
1
Adolescent Prevalence Trends
10%
9%
8%
7%
6%
5%
4%
3%
2%
1%
0%
2
0_
0
0
7
2
1_
0
0
1
2
1_
0
0
7
2
2_
0
0
1
2
2_
0
0
7
2
3_
0
0
1
2
3_
0
0
Newer Antidepressants
Tri/Tetracyclics
Source: Arkansas Medicaid claims data, EBRx analysis
7
2
4_
0
0
1
2
4_
0
0
7
2
5_
0
0
1
2
5_
0
0
7
2
6_
0
0
1
2
6_
0
0
7
2
7_
0
0
ADHD Medications
Atypical Antipsychotics
1
Newer Antidepressant Use Patterns
Four Groups of SSRI/SNRI medications
FDA approved – fluoxetine*
Supported with some evidence:
 Anxiety – sertraline, fluvoxamine
 Depression – citalopram, ER venlafaxine
No adequate/supportive trials
 Buproprion, duloxetine, escitalopram*, mirtazepine, nefazodone
Negative information – paroxetine
* During the periods reviewed. Escitalopram was FDA approved in March 09,
but at this time, studies are not yet available.
Pattern of Medication Treatment in Arkansas
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
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02
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02
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Approved
03
20
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03
20
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Supported
04
20
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04
20
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Negative
05
20
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05
20
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06
20
No Support
l-D
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06
20
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Ja
07
20
What we know now
Some decrease in prevalence of medication
use after FDA warnings – but now stable
Almost half of Arkansas children treated with
medication did not receive an evidencesupported SSRI/SNRI
Still need more data on children and
adolescents receiving counseling alone or
combined with SSRI
Depression and Anxiety
in Children and Adolescents
Take Home Points
Depression and Anxiety
in Children and Adolescents
Anxiety and depression are common in
children and adolescents
Earlier awareness/intervention may prevent
negative events
Screening tools are available, easy to use,
and facilitate recognition
Practice guidelines and recent evidence
should inform treatment decisions
Anxiety Recommendations
Counseling can help define diagnosis and is a
first-line treatment
Limited SSRI/SNRI support
Fluoxetine appears to be best supported
Sertraline with CBT for anxiety
Fluvoxamine (only if no depression present)
Maybe ER venlafaxine, but CV effects are limiting
Paroxetine good for anxiety, but specific suicide risk
Other pharmacotherapy not supported
Depression Recommendations
Counseling can help define diagnosis and is a
first-line treatment
Frequent suicidality screening
CBT plus fluoxetine – best practice
Fluoxetine alone caries suicidality risk
Other SSRI/SNRI agents with published data
Citalopram
Venlafaxine ER – higher side effects than SSRIs
Other pharmacotherapy not supported
SSRI/SNRI Adverse Effects
Serious Adverse Effects
Serotonin Syndrome
Akathisia
Hypomania
Discontinuation
syndromes
Common Adverse Effects
GI effects (dry mouth,
constipation, diarrhea)
Sleep disturbance
Irritability
Disinhibition
Agitation/jitteriness
Headache
Recommendations
CBT is a first-line approach with or without
medication
Foster a relationship with a psychologist to
refer and communicate about your patients
Identify and use screening tools
Remember fluoxetine dosing:
Younger children - 10mg daily, cautious titration
Older children - 10mg initially with titration to 20mg
after 2 weeks
Limited experience above 20mg
Recommendations
Use GLAD-PC materials for depression or
other screening tools for anxiety
If treating with SSRIs, establish, document
and monitor a safety/suicidal thoughts plan
ParentsMedGuide.org has useful information
on pharmacologic treatment for obtaining
informed consent
IMPACT Off-label Education
If this was helpful to you:
Make time for AFMC to bring you more
materials/resources
AFMC will have tool-kit items and other free
resources
Web-based curricula/resource pages
available at: COP.UAMS.EDU/OffLabel
Hows and Whys of the Project
Project Funding
Attorney General Consumer Prescriber
Education Grant Program
Settlement paid for off-label promotion of
Neurontin(gabapentin)
Arkansas received $370,000 of this grant.
Focus: SSRI and SNRI medication use in
children and adolescents
IMPACT Off-label Education
The concept:
 Use techniques and tools of the industry
 Provide up-to-date evidence-based information on off-label
medication uses in children
 Report our results
Pharmaceutical representative discussion of uses not
FDA approved is prohibited by federal law
Physician-to-physician communication is not
restricted, but usually only available with corporate
sponsorship
Off-label Uses:
Finding information on appropriate, safe and
helpful off-label uses is a challenge
Sometimes, national meetings have
reasonably authoritative presentations
Usually manufacturers have more
information, but they don’t always share
Pediatric medication trials have special
challenges, so there is much off-label use
Why SSRI/SNRIs?
Mental health medications stand out for offlabel uses in children
2006 Medicaid data analysis revealed high
use of SSRIs/SNRIs in children
General interest, need and utility:
Current controversy/new data
Low industry noise level – only a few brand players
Stable category for analysis of our program
IMPACT Off-label Education
Drug Category
Children
Treated
SSRIs/SNRIs
12,297
1,465
56,395
$3,533,620
Tri/Tetra
6,486
989
23,607
$273,276
11,974
945
69,229
$19,672,764
327
132
1,654
$48,921
972
353
2,555
$231,427
Newer
Antipsychotic
Older
Antipsychotic
Newer Sleep
Aids
Prescriber Prescription
Count
Count
Paid Amounts
Source: Arkansas Medicaid MIS, Calendar Year 2006, Children under age 18 years.
Our Information Sources
American Academy of Child and Adolescent
Psychiatry
American Psychiatric Association
American Psychological Association
Agency for Healthcare Research and Quality
Centers for Disease Control
NIMH funded Treatment for Adolescents with
Depression Study (TADS)
GLAD-PC project
Other recent peer-reviewed reports
Thank you for your interest
Screening/Monitoring Tools
Anxiety (for 8 yo and up)
Multidimensional Anxiety Scale for Children
Screen for Child Anxiety Related Emotional
Disorders
Depression
Columbia Depression Scale
Beck Depression Inventory
Children’s Depression Rating Scale – Revised
Reynold’s Adolescent Depression Scale