Transcript Depression and Bipolar Disorder in Children and Adolescents

Adolescent Mood Disorders:
Management and Medication
David C. Rettew, M.D.
Associate Professor of Psychiatry and Pediatrics
Director, Pediatric Psychiatry Clinic
UVM College of Medicine
Conflicts of Interest
None
Will be discussing off-label uses of
some medications
Objectives
• Brief outline of adolescent mood
disorders
• General assessment and treatment
strategies
• Update on antidepressants and
suicidality
• Bipolar disorder controversy
Understanding Psychiatric Disorders
(New School)
Genetics
Prenatal environment
Attachment
Temperament
Parenting
Exposures
SES
Phenotype
Comprehensive
Treatment
Pediatric Depression
Diagnosis: 5 of 9 - Distinct 2 Week Period)
• Depressed mood
(Irritability)
• Anhedonia
• Weight change
(Failure to make
expected gains)
• Sleeping Disturbance
• Psychomotor
Agitation/Retardation
• Energy Loss
• Guilt/Worthlessness
• Concentration
Impairment/Indecisive
• Suicidal
Thoughts/Recurrent
Thoughts of Death
Dysthymia
• Long, term mood symptoms
• More chronic (most days for at least
a year), less intense
• Need 2 neurovegetative symptoms
• Studies show equivalent or even
greater impairment compared to
depression
USA Teen Suicide Rates 1988-2004
Note: 2005 data (Bridge et al., JAMA 2008) shows a
Reduction of 5.3% from 2004 but still above earlier levels
Predictors of Suicidal Behavior
• Prior attempts
• Other psychiatric disorders
• Impulsivity/aggression
• Availability of firearms
• Exposure to negative events
• Family history of suicidal behavior
• Substance abuse
• Attempt:completion ratio about
6000:1 in girls and 400:1 in boys
Pediatric Depression
Comorbidity
80
70
60
50
40
Prevalence
30
20
10
0
ADHD
ODD
Anxiety
Conduct
Spencer T, MGH Study of Depression
Assessment and Treatment
Overall Assessment Plan
Visit 1
Is there a problem?
Safety assessment
Other medical
conditions
Distribute general rating
scale
Visit 3 and Beyond
Track progress
Check gaps and
assumptions
Visit 2
Review general rating
scale
Establish primary
diagnosis
Initial treatment plan
From D Rettew, OCD in the Primary Care Setting, 2007
Broad Based Rating Scales
General Treatment Guidelines
• Medication
• Environment
– Sleep, structure, media
• Psychotherapy (evidence based)
• Parents
• School
• Resources
Guidelines for Treatment of Adolescent
Depression in Primary Care (GLAD-PC)
• Expert consensus
driven guidelines
published in
Pediatrics (2007)
• Conducted focus
groups, surveys,
literature reviews,
http://www.glad-pc.org/documents/GLAD-PCToolkit.pdf
GLAD-PC Recommendations
Identification
• Patients at risk for depression should be
identified and systematically monitored
Assessment/Diagnosis
• High-risk adolescents should be evaluated for
depression as well as those with a chief
complaint of emotional problems
• Clinicians should use standardized tools to aid
in the assessment
GLAD-PC Recommendations
Assessment Tools
• Reliance on presenting
complaint or family
concerns underidentify
cases
• No “gold standard”
screening tool
– Beck Depression Inventory
– Reynolds Adolescent
Depression Scale
– Mood and Feelings
Questionnaire
– Kutcher Adolescent
Depression Scale
GLAD-PC Recommendations
Assessment should include…
•Interviews with family members
•Degree of impairment across
domains
•Other psychiatric conditions
GLAD-PC Recommendations
Initial Management
• Educate patient and family about
depression
• Outline confidentiality and its limits
• Develop a treatment plan with
specific goals in key areas of
functioning
• Establish links with resources (mental
health, family members)
• Develop a safety plan – contract?
GLAD-PC Recommendations
Further Management
• Mild depression – consider active
support and monitoring
• Moderate/severe/complicated –
consider consultation with a mental
health specialist
• Establish roles of primary care and
mental health specialist with family
• Recommend scientifically tested
treatments
• Monitor for adverse effects of treatment
Severity of Depression
GLAD-PC Recommendations
Further Management
• Continue to track outcomes and
functional targets
• Reassess diagnosis and treatment if no
response in 6-8 weeks
• Consider consultation with mental
health professional if treatments
produced only partial response
• Ensure adequate management
First Line Treatment
Moderate/Severe Depression
• Cognitive Behavioral Therapy
• Interpersonal Therapy
• Antidepressants
• Both
Pharmacotherapy
• Response 40-70% with medications
vs 30-60% for placebo
• Remission with medications lower
(30-40%)
• Little efficacy evidence for non SSRIs
• Bupropion effective in open trials
Medications in Depression
Med
Start Dose
Max
FDA
Generics
Citalopram
10mg
60mg
N
Y
Fluoxetine
10mg
60mg
Y
Y
Fluvoxamine 25mg
300mg
N
Y
Sertraline
200mg
N
Y
12.5-25mg
Pharmacotherapy Tips
• Half life of antidepressants often
shorter in children and adolescents
– Watch for withdrawal symptoms on qd
dosing
• Goal for remission at 12 weeks
(consider switch if no or little
response at 8 weeks)
Text of Black Box Warning 2/05
Proposed Mechanisms of
Increased Suicidal Behavior
• Medication adverse affects:
insomnia, agitation, irritability
• Switching patients with bipolar
disorder
• Acute effects on serotonin that differ
from long-term effects
• Greater comfort in disclosing ideation
Criticism of Data
• Significant differences found only when
combine suicidal thoughts and behavior and
combine depressive and anxiety disorders
• Signal only for spontaneously reported
suicidality
• No increase in ‘emergence’ or ‘worsening’ or
suicidal symptoms when systematically
assessed
• Overall rate lower than found in community
samples
• No actual suicides
Change in Youth
Antidepressant Prescribing
Psychiatric News, September 2005
Official Monitoring Guidelines
FDA
Once per week x 4
weeks
Every 2 weeks for next 8
weeks
At end of week 12 and
regularly thereafter
More often if problems
or questions arise
No scales
recommended
AACAP
www.parentsmedguide.org
www.aacap.org
Fluoxetine alone, or
Fluoxetine + CBT, or CBT
alone as 1st line
Monitor consistent with FDA
guidelines (though no
specific data to support
such frequency of
contact)
From: “FDA Proposed Medication Guide: About Using Antidepressants in Children or
Teenagers” (Center for Drug Evaluation and Research)
http://www.fda.gov/cder/drug/antidepressants/SSRIMedicationGuide.htm
Completed Suicides in NYC
• 41 NYC suicides in children less than 18
• Antidepressants (bupropion and sertraline)
detected in 1/38 (2.8%) available cases
JAACAP, Sept 2006
Recent Meta-Analysis
Bridge et al., JAMA 2007
• Covered 27 controlled studies in depression
and anxiety
• MDD medication response vs placebo: 61% vs
50%
• Less response for younger children, except with
fluoxetine
• Suicidality on medications vs placebo: 2% vs 1%
(statistically significant across all disorders but
not MDD alone)
• More efficacy with shorter depression duration
• Concluded a favorable benefit to risk
comparison for cautious use as first line
treatment
Suicide Rates by County
Gibbons et al, AJP, 2006
• Highest rates often in rural western areas and
lowest in most major cities
• More SSRI Rxs, less suicides even after
controlling for mental health care and income
Treatment for Adolescents with
Depression Study (TADS) – JAMA, 2004
• Funded by NIMH (not pharmaceutical
company)
• 439 subjects aged 12-17 from 13 sites
• Randomized to CBT, fluoxetine (10-40mg),
combination, or placebo
• Short term (12 week) and long term followup (36 weeks)
• Suicidal ideation in 29% - “severe”
suicidality exclusionary criteria
TADS Study
Acute Response
80
70
60
50
Combination
Fluox
CBT
Placebo
40
30
20
10
0
% Response
Combin, Fluox > CBT, Placebo
More med response for
more severely affected
TADS Study
Sustained Response
• At 36 weeks, 80% of acutely
nonresponding patients had
achieved definite or probably
sustained response (didn’t differ by
treatment type)
• If did get sustained response, most
kept it (80%)
– BUT higher loss of response in fluoxetine
group 26% compared to CBT 3%
Rodhe et al., Arch Gen Psychiatry, April, 2008
TADS Followup
TADS summary
• CBT can work very well but can take
a little longer
• If you get better with CBT, you are
very likely to stay that way
• Medications may result in better
acute response but also more
relapses without other interventions
Summary
• Depression in children and adolescents is
a serious problem with potentially
disastrous outcomes
• Practical and effective approaches to
assessment and treatment have now
been organized
• Several well supported treatment
options exist both pharmacologically
and nonpharmacologically
• Antidepressants should be respected,
but not feared
Major References
• GLAD-PC: Zuckerbrot et al., Pediatrics,
120:e1299-1312, 2007
• AACAP Parameters: Birhamer et al., J
Am Acad Child Adolsc Psychiat,
46:1503-1527, 2007
• www.Parentsmedguide.org
• TADS study: March et al., JAMA,
292:807-820, 2004
Pediatric Bipolar Disorder
• One of most
controversial topics in
child psychiatry
• Underdiagnosed vs.
Overdiagnosed?
• In forefront of
physician/pharma
discussions
Pediatric Bipolar Disorder
Criteria Overlap with ADHD
• Distractibility
• Increased
activity/psychomo
tor agitation
• Grandiosity
• Flight of ideas
• Activities with
painful
consequences
• Sleep decrease
• Talkativeness
In children, characterized by ultradian cycling in about
75% and prominent suicidality in about 25%
Proposed New Categories
Liebenluft et al., 2003
• Narrow: Mood elevation + duration
• Intermediate:
– Clear symptoms but 1-3 day duration OR
– Clear episodes but irritable
• Broad: Chronic, nonepisodic, irritability
Dilemma in Pediatric Bipolar
Disorder
Special Communication
JAACAP, March 2005
The FIND Threshold
JAACAP, 2005
• Frequency – most days in a week
• Intensity – extreme disturbance in
one setting or moderate
disturbance in two
• Number – 3 or more times a day
• Duration – occur 4 or more hours a
day total
Psychopharmacology
Bipolar 1 in acute phase – No psychosis
• Adequate trial means 4-6 weeks at therapeutic blood
level or therapeutic dose (perhaps 8 weeks for lithium)
• Start with mood stablizer (lithium, valproate,
carbamazapine) or atypical antipsychotic (risperidone,
olanzapine, quetiapine) monotherapy
• If no response, switch
• If partial response, augment
• Consensus panel did not/could not favor particular
agent
• Trials of lamotragine (Lamictal), oxcarbazepine
(Trileptal), ziprasidone (Geodon), aripiprazole (Abilify)
recommended only after combination treatment fails
Antipsychotic FDA Approvals
in Pediatrics
• Risperidone (Risperdal): Schizophrenia (age 1317) Bipolar Disorder (age 10-17); Autism
irritabiltiy/aggression (age 5-16)
• Aripiprazole (Abilify): Bipolar Disorder (ages 1017)
• Olanzapine (Zyprexa): None
• Quetiapine (Seroquel): None
• Ziprasidone (Geodon): None
Risks of Treatment
Informed Consent
• Weight gain and
diabetes – new
monitoring protocol
published by ADA,
2004
• Cognitive dulling
• Polycystic Ovarian
Syndrome
• Hypothyroidism
• Abnormal involuntary
movements
• Liver disease
• Pancreatitis
• Prolactin elevation
• Cardiac effects??
• Neuroleptic
malignant syndrome
ADA Protocol Prior to Using
Atypical Antipsychotics
• Personal and family
history of obesity,
diabetes, dyslipidemia,
hypertension,
cardiovascular disease
• Weight, height, BMI,
• Waist circumference
at umbilicus
• Blood pressure
• Fasting glucose
• Fasting lipid profile
• Reassess at 4, 8, and
12 weeks
• Switch agents if gains
> 5% of body weight
My Treatment Approach
• If meets criteria for narrowly
phenotype then proceed directly to
bipolar treatment
• If broad phenotype, attempt nonmedication and treatment of other
conditions first
11 Reasons for why “the medicine is
not working”
• Diurnal Variation
• Nonpsychiatric
Causes
• Dose and Duration
of Treatment
• Comorbidity
(child)
• Comorbidity
(parent)
• Medication Side
Effects
• Compliance
• Multinformant
Variation
• Substance abuse
• Medication
Limitations
• Lack of
Commitment
THANK YOU
Questions and Discussion