Advair Use in Arkansas Medicaid

1
(No Transcript)
2
Improving Medication Prescribing for Arkansas
Children Through Off-label EducationIMPACT
Off-label EducationUpdate 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

3
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

4
Anxiety in Children
5
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
6
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
7
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
8
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
9
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
10
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
11
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
12
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

13
Depression in Children
14
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
15
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
16
Depression in ChildrenRecent Trial Information

• TADS Study Results

Therapy Improvement/Response Rate Improvement/Response Rate Improvement/Response Rate
Therapy Week 12 Week 18 Week 36
CBTFluoxetine 71 85 86
Fluoxetine 61 69 81
CBT 43 65 81
Placebo 35
Source TADS Team Treatment for Adolescents
with Depression Study (TADS) Long-term
Effectiveness and Safety Outcomes. Arch Gen
Psychiatry. 2007 64(10) 1132-1144
17
Depression in ChildrenRecent Trial Information

• TADS Study Suicide Event Screening Results

Treatment Positive Suicide Event Screening Positive Suicide Event Screening Positive Suicide Event Screening
Treatment Baseline Week 12 Week 36
CBTFluoxetine 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) Long-term
Effectiveness and Safety Outcomes. Arch Gen
Psychiatry. 2007 64(10) 1132-1144
18
Depression in ChildrenRecent 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.
2008299(8)901-913
19
Depression in ChildrenRecent Trial Information

• Initially treated with at least 40mg fluoxetine
  (or equivalent)
• Switched to SSRI, SSRICBT, SNRI, or SNRICBT
• 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.
2008299(8)901-913
20
Depression in ChildrenRecent 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.
2008299(8)901-913
21
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.
2008299(8)901-913
22
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)

23
FDA Suicidality Warnings, Antidepressants, and
Young People
24
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
25
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

26
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 16413561363.
CDC Suicide Trends among Youths and Young
Adults aged 10 to 24 years United States,1990
to 2004. MMWR. 2007 56(35)905-908.
27
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 16413561363.
Olfson, et. al. Effects of Food and Drug
Administration Warnings on Antidepressant Use in
a National Sample, Arch Gen Psychiatry
200865(1) 94-101.
28
Suicidality in Practice

• Screening does not increase risks or cause
  suicidal thoughts
• Failing to screen may lead to missing vital
  information

29
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

30
Anxiety and Depression Treatment Trends in
Arkansas Medicaid
31
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

32
Recent Initial Treatment Trends

• 777 newly diagnosed/ treated Medicaid recipients
  under 18 from April Oct 2008
• Treatment patterns identified by CPT codes and
  pharmacy claims paid
• No severity indicator, but all had no treatment
  in prior six months

33
Persistence Of Treatment

• 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

Counseling Visits Counseling Visits Counseling Visits Counseling Visits
Prescriptions Dispensed None 1-2 3 or more
Prescriptions Dispensed None 122 406
Prescriptions Dispensed 1-2 89 23 43
Prescriptions Dispensed 3 or More 68 9 27
34
Preschool Prevalence Trends
Source Arkansas Medicaid claims data, EBRx
analysis
35
Grade School Prevalence Trends
Source Arkansas Medicaid claims data, EBRx
analysis
36
Adolescent Prevalence Trends
Source Arkansas Medicaid claims data, EBRx
analysis
37
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.

38
Pattern of Medication Treatment in Arkansas
39
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 evidence-supported
  SSRI/SNRI
• Still need more data on children and adolescents
  receiving counseling alone or combined with SSRI

40
Depression and Anxiety in Children and
Adolescents

• Take Home Points

41
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

42
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

43
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

44
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

45
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

46
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

47
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

48
Hows and Whys of the Project
49
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

50
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

51
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 dont always share
• Pediatric medication trials have special
  challenges, so there is much off-label use

52
Why SSRI/SNRIs?

• Mental health medications stand out for off-label
  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

53
IMPACT Off-label Education
Drug Category Children Treated Prescriber Count PrescriptionCount Paid Amounts
SSRIs/SNRIs 12,297 1,465 56,395 3,533,620
Tri/Tetra 6,486 989 23,607 273,276
Newer Antipsychotic 11,974 945 69,229 19,672,764
Older Antipsychotic 327 132 1,654 48,921
Newer Sleep Aids 972 353 2,555 231,427
Source Arkansas Medicaid MIS, Calendar Year
2006, Children under age 18 years.
54
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

55
Thank you for your interest
56
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
• Childrens Depression Rating Scale Revised
• Reynolds Adolescent Depression Scale