Transcript Update on the Diagnosis and Treatment of Juvenile Mood

Basic Management of Juvenile
Mood Disorders
Jeffrey I. Hunt, MD
Alpert Medical School of Brown University
The Clinical Challenge
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Juveniles often present with depression and other
disturbances in their mood
Mood disorders in juveniles are complex and not
well understood
Many juveniles with mood symptoms are being
treated by their primary care physician or clinician
Antidepressants, while very helpful in some, can
cause rapid deterioration in others
Major Depression is Common in
Juveniles
Prevalence 2% in children and 4% to 8% in
adolescents
 Male:Female ratio 1:1 during childhood and
1:2 during adolescence
 Cumulative prevalence is 20% by age 18
 Increase in risk for younger generations is
suggested
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( Kashani et al., 1987; Kovacs, 1994; Lewinsohn et al., 1994)
Juvenile Major Depression: Clinical
Presentation
Pervasive change in mood: depressed or irritable
 Loss of interest or pleasure
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Dysthymia: 1 vs 2 year criterion)
Sleep Disturbance
Irritability (core symptom in youth)
Guilt
Energy
Concentration
Appetite
Psychomotor Agitation or Retardation
Suicidality
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Juvenile Major Depression: Clinical
Presentation
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“Children are not little adults”
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Younger children: more anxiety (especially separation), somatic
symptoms, auditory hallucinations, temper tantrums and behavioral
problems
Middle / late childhood: dysphoria, low self-esteem, guilt,
hopelessness, “burden on family”
Adolescents: sleep and appetite changes, suicidality,
neurovegetative symptoms, irritability, explosive and conduct
symptoms, “acting out”, and substance abuse
Juvenile MDD: Age-related changes
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Biological
 Sexual maturation and hormonal changes
 Differential ontogeny of neural pathways:
• Serotonergic pathways mature earlier on
• Noradrenergic pathways continue development
into young adulthood
Environmental
 Social and academic expectations
 Increased exposure to adverse life events, stressors
and losses
 Increased autonomy and abstract thinking
Juvenile Depression: Clinical Course
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Duration of episode is 7 months to 2 years for
clinically referred samples
After successful acute therapy 40% to 60%
experience a relapse
Probability of recurrence is 20% to 60% by 2
years and 70% by five years
( Emslie, 1997; Kovacs, 1996; Lewinsohn 1994)
Juvenile Major Depression:
Sequelae
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Untreated MDD may affect social, emotional, cognitive,
and interpersonal skills and the attachment bond between
parent and child
Juveniles with MDD are at higher risk for substance abuse,
physical illness, poor academic functioning
Protracted, chronic course in ~10% of cases.
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Earlier onset, number and severity of prior episodes, poor compliance,
psychosocial adversity, psychiatric illness in parents, adverse life events
20% to 40% of adolescents may develop bipolar disorder
within 5 years
MDD is a major cause of suicide attempts and completion
 Third leading cause of death among 15-24 year olds in
US
( Kovacs, 1996; Birmaher, 1996; Brent, 1995, Geller 1997 )
Juvenile Major Depression:
Comorbidity
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Dysthymia (“double depression”)
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Dysthymia as “gateway” disorder
Anxiety disorders (often precedes depression in youth)
Disruptive disorders (attention deficit, oppositional defiant,
conduct)
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Substance abuse
Somatoform disorders
Personality disorders or traits (teenagers)
Juvenile Major Depression:
Comorbidity
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Bipolar Disorder
 MDD may be the first presentation of
underlying Bipolar Disorder
 “False” unipolar depression
 Mixed states are common in youngsters
 “Switch” rates are reported to range between
25- 40%
 Legitimate “switches” may be hard to interpret
in the face of treatment or concurrent substance
use
Look for Mania before Initiating
Treatment for Depression
Many juveniles with bipolar disorder
present initially with severe depression and
histories of being “moody”
 Children and adolescents with unipolar
depression may be irritable but usually are
not labile and don’t have periods of
elevated “giddy” moods
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Cycles of Affective Disorder
Stahl, 2000
DSM-IV Diagnosis of Mania
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Distinct period of
abnormally and
persistently elevated,
expansive, or irritable
mood
Distractibility
Increased physical activity
or goal directed activity
Grandiosity
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Flight of ideas
Activities showing poor
judgement
Sleep, decrease need for
Talkativeness
Bipolar depressive symptoms in
juveniles
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Many physical complaints
Frequent absenteeism from school
Poor school performance
Talk of running away from home
Complaining
Unexplained crying
Social isolation
Extreme sensitivity to rejection/failure
see www.nimh.nih.gov/publicat/childnotes.cfm for review publication
No. 00-4778 Child and Adolescent Bipolar Disorder, Aug 2000
How Broad is the Spectrum?
Angst and Gamma, 2002
Narrow Phenotype of Juvenile
Mania
Leibenluft,
Charney, et al.,
2003
Intermediate Phenotype of
Juvenile Mania
Leibenluft, Charney, et al., 2003
Broad Phenotype of Juvenile Mania: Severe Mood
and Behavioral Dysregulation
Leibenluft,
Charney, et al.,
2003
How fast can moods change?
Rapid Cycling
Stahl, 2000
Practical Assessment of Mood
Disorders
Juvenile Mood Disorders: Assessment
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Diagnostic interviews of child/adolescent and
parents ( separate and conjoint)
Utilize collateral informants such as teachers
Family History
Psychosocial Stressors
Review for comorbidity
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Diagnosis is based upon DSM-IV criteria
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Helpful Tools in Diagnosis of
Mood Disorders
Child Behavior Checklist
 Beck Depression Inventory
 Children’s Depression Inventory
 Young Mania Rating Scale
 K-SADS Mania Rating Scale
 Mood Disorder Questionnaire
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Helpful web site: www.schoolpsychiatry.org
Differentiating Between Unipolar and
Bipolar Disorders
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Be suspicious for Bipolar Disorder when there is:
Abrupt onset of any mood symptoms
 Positive FH in 1st degree relatives or if
present in 2nd and 3rd degree relatives
 1st episode of any mood disturbance in
adolescence with psychotic features
 Distinct and repeated cycles of
depression
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Missing the Diagnosis of Bipolar
Disorder
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Failure to consider full spectrum of the disorder
 Broad spectrum of bipolar may be up to 2%-11%
prevalence
Tendency to focus on acute presenting picture instead of
longitudinal history
Over-reliance on patient’s self presented history, rather
than careful interview of family
Atypical presentation in juveniles
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classic euphoria may not be present
High prevalence of co-morbid conditions leads to
confusion
Juvenile Mood Disorders: Overall Treatment
Least-restrictive setting in continuum of
care
 Outpatient, home-based, partial hospital,
inpatient
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Suicidal risk
 Medical, substance abuse and psychiatric
comorbidity
 Family involvement, protective services
involvement
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Treatment of Juvenile Mood
Disorders
Major Depression
 SSRIs
 Cognitive Behavior Therapy and
Interpersonal Psychotherapy
 Bipolar Disorders
 Mood stabilizers
 Atypical antipsychotics
 Interpersonal Social Rhythms Therapy
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Juvenile MDD: Psychotherapy
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Psycho-education
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Cognitive-Behavioral Treatment (CBT)
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“Is it adolescence or is it depression?”
Cognitive distortions, generalization, overattribution
Interpersonal Psychotherapy (IPT)
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Areas of loss and grief, interpersonal roles and disputes,
role transitions
Juvenile MDD: Pharmacotherapy
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Medication not first-line, except when:
 Severe symptoms or suicidal risk
 Psychotic and certain (non-rapid cycling)
bipolar depressions
 Symptoms prevent participation in
psychotherapy
 Adequate psychotherapy trial ineffective
 Chronic or recurrent depression
Efficacy of Antidepressants for Treating
Pediatric major Depressive Disorder: Positive
Studies
Medication Duration
Number
Fluoxetine
48 flx 48 pb 58%vs. 32%
8 wks
Response
p=.013
Fluoxetine
9 wks
Paroxetine
8 wks
Sertraline
10 wks
Nefazodone 8 wks
209flx
210pb
93par,
95imp, 87pb
189sert
187pb
99 nef
96pb
65%vs.53%
p=.09
63%vs.
50%vs46%
p=.02
69%vs. 59%
p=.05
62%vs42%
p=.005
Reference
Emslie et al.,
1997
Emslie et al.,
2002
Keller et al.,
2001
Wagner et al.,
2003
Emslie et al,
2002
Efficacy of Antidepressants for Treating
Pediatric Major Depressive Disorder:
Negative Studies
 Paroxetine: 2 studies (N=489) from UK
 Citalopram: 2 studies (N=418) from US and
UK
 Mirtazepine: 1 study (N=250)
 Venlafaxine: 2 studies (N=354)
SSRIs: Practical Issues in Treatment
of Major Depression
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Start with fluoxetine
 5 to 10 mg/day in first week titrate to 10 to 20
mg/day over next 2 weeks depending on
age/weight
 Treat with adequate and tolerable doses for at
least 4 weeks
 If no improvement by 4 weeks consider
gradual increase in dose up to 30 to 40 mg/day
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Monitor pt. very closely during this titration !
Cognitive-behavioral therapy also recommended
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Depending upon age, weight, tolerance
The Treatment for
Adolescents with
Depression Study
2004
The Treatment for
Adolescents With
Depression Study
2004
FDA Regulations for
Antidepressant Use in Children
and Adolescents
BLACK BOX WARNING
Suicidality in Children and Adolescents
Suicidality in Children and Adolescents
Antidepressants increase the risk of suicidal thinking and behavior
(suicidality) inincrease
childrenthe
with
major
depressive
disorder(MDD)
and
other
Antidepressants
risk
of suicidal
thinking
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(suicidality)
disorders.
Anyone considering
the use
of other
_____psychiatric
or any other
in psychiatric
children with
major depressive
disorder(MDD)
and
antidepressant
a child or adolescent
must balanced
this antidepressant
risk with the in a
disorders.
Anyoneinconsidering
the use of _____
or any other
clinical
need. Patients
are started
onwith
therapy
should need.
be observed
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child
or adolescent
must who
balanced
this risk
the clinical
Patients
who
clinical
suicidality,
or unusual
changes
in behavior.
Families
arefor
started
onworsening,
therapy should
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for clinical
worsening,
and caregivers
should
be advised
of the need
for close
and be
suicidality,
or unusual
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in behavior.
Families
and observation
caregivers should
communication
the prescriber.
_____is
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in prescriber.
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advised
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for close
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_____is
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for use inwith____.
pediatric patients except for patients with____.
Pooled
analyses
short-term
weeks)
placebo-controlled
trials
nine
Pooled
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of of
short-term
(4 (4
to to
16 16
weeks)
placebo-controlled
trials
of of
nine
antidepressant
drugs
(SSRIs
and
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children
and
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(SSRIs
and
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in in
children
and
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with
MDD,
MDD,
OCD,psychiatric
or other psychiatric
ofinvolving
24 trials involving
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(a total of(a24total
trials
over 440 over
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have revealed
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representing
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have revealed
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adverse
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representing
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suicidalorthinking
behavior (suicidality)
the
first few
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during the during
first few
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treatment
in antidepressants.
those receiving antidepressants.
The
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The average risk
of such
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ontwice
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wasplacebo
4%, twice
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No suicides
occurred
4%,
riskthe
of 2%.
No suicides
occurred
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FDA Recommended Guidelines
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After starting an antidepressant, your child should
generally see his/her healthcare provider:
 Once a week for the first 4 weeks
 Every 2 weeks for the next 4 weeks
 After taking the antidepressant for 12 weeks
 After 12 weeks, follow your healthcare provider’s
advice about how often to come back
 More often if problems or questions arise
• FDA Medication guide
http://www.fda.gov/cder/drug/antidepressants/default.htm
What to Look for:
Anxiety
 Agitation
 Panic attacks
 Insomnia
 Irritability
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Hostility
 Impulsivity
 Akathisia
 Hypomania
 Mania
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Mixed Impact of Black Box
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Prescriptions for antidepressants have dropped by
20% for those 18 y/o and younger since 2004
when FDA initial warnings were published
Increased suicide rate
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? Due to decrease in antidepressant use Gibbons et al., Am J
Psychiatry 164:1356-1363, September 2007
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Antidepressant treatment study
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antidepressant use in juveniles significantly associated
with suicide attempts/deaths Olfson et al., Arch Gen
Psychiatry. 2006;63:865-872
Treatment of Juvenile Depression with
Antidepressants: Rationale for Continued Use
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American College of Neuropsychopharmacolgy Task
Force Report ( January 2004)
 Suicide occurs most often in untreated depression
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Confirmed by autopsy studies
Several SSRI trials showed efficacy in treating
depression
SSRI did not increase risk of suicide or suicidal
thinking in youths based upon strong evidence from
clinical trials, epidemiology, and autopsy studies
Increase use of SSRI worldwide led to decline in 33%
decline in youth suicide in the last 15 years
SSRIs: Side Effects
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ABCs of SSRIs
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Activation / Akathisia
Bipolar switching
Cytochrome P450-based interactions. Common:
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FLUOX / PAR: CYP 2D6 (TCAs)
FLUV: CYP 2C9 (Phenytoin)
FLUV: CYP 1A1/2 (Theophylin)
Discontinuation syndrome
Evolving Psychopathology
Long Term Management in
Treatment of Major Depression
Continuation therapy recommended for all
patients for at least 6 to 12 months
 Maintenance treatment may be indicated for
some patients with > 2 or 3 discrete
episodes of depression
 Combined meds +psychotherapy therapy
likely will lead to best outcomes
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Always be vigilant for emergence
of mania!!
Can occur any time from few hours to many
weeks later
 Initial agitation sometimes difficult to
distinguish from manic symptoms
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What happens if a “switch
occurs”
Refer to psychiatrist if possible
 Monitor patient very closely
 Educate caregivers
 Re-evaluate diagnosis
 Taper and discontinue SSRI
 Consider mood stabilizer
 Consider more intensive level of care
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Summary
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Mood disorders are common in children and adolescents
Differentiating between unipolar depression and bipolar
disorder is vital prior to initiating treatment with
antidepressants
Effective treatments of mood disorders are emerging but
controversies remain
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Close monitoring of patients is imperative when antidepressants
are used
Important for MD and allied mental health clinicians to optimally
communicate with each other on shared patients
Primary care physicians and other mental health clinicians
are having to manage these complex children and
adolescents with little training or support