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Basic Management of Juvenile Mood Disorders

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Title: Basic Management of Juvenile Mood Disorders


1
Basic Management of Juvenile Mood Disorders
  • Jeffrey I. Hunt, MD
  • Alpert Medical School of Brown University

2
The Clinical Challenge
  • 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

3
Major Depression is Common in Juveniles
  • Prevalence 2 in children and 4 to 8 in
    adolescents
  • MaleFemale ratio 11 during childhood and 12
    during adolescence
  • Cumulative prevalence is 20 by age 18
  • Increase in risk for younger generations is
    suggested
  • ( Kashani et al., 1987 Kovacs,
    1994 Lewinsohn et al., 1994)

4
Juvenile Major Depression Clinical Presentation
  • Pervasive change in mood depressed or irritable
  • Loss of interest or pleasure
  • Dysthymia 1 vs 2 year criterion)
  • Sleep Disturbance
  • Irritability (core symptom in youth)
  • Guilt
  • Energy
  • Concentration
  • Appetite
  • Psychomotor Agitation or Retardation
  • Suicidality

5
Juvenile Major Depression Clinical Presentation
  • Children are not little adults
  • 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

6
Juvenile MDD Age-related changes
  • 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

7
Juvenile Depression Clinical Course
  • 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)

8
Juvenile Major Depression Sequelae
  • 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.
  • 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 )

9
Juvenile Major Depression Comorbidity
  • Dysthymia (double depression)
  • Dysthymia as gateway disorder
  • Anxiety disorders (often precedes depression in
    youth)
  • Disruptive disorders (attention deficit,
    oppositional defiant, conduct)
  • Substance abuse
  • Somatoform disorders
  • Personality disorders or traits (teenagers)

10
Juvenile Major Depression Comorbidity
  • 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

11
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
    dont have periods of elevated giddy moods

12
Cycles of Affective Disorder
Stahl, 2000
13
DSM-IV Diagnosis of Mania
  • Distinct period of abnormally and persistently
    elevated, expansive, or irritable mood
  • Distractibility
  • Increased physical activity or goal directed
    activity
  • Grandiosity
  • Flight of ideas
  • Activities showing poor judgement
  • Sleep, decrease need for
  • Talkativeness

14
Bipolar depressive symptoms in juveniles
  • 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

15
How Broad is the Spectrum?
16
Angst and Gamma, 2002
17
Narrow Phenotype of Juvenile Mania
Leibenluft, Charney, et al., 2003
18
Intermediate Phenotype of Juvenile Mania
Leibenluft, Charney, et al., 2003
19
Broad Phenotype of Juvenile Mania Severe Mood
and Behavioral Dysregulation
Leibenluft, Charney, et al., 2003
20
How fast can moods change?
21
Rapid Cycling
Stahl, 2000
22
Practical Assessment of Mood Disorders
23
Juvenile Mood Disorders Assessment
  • Diagnostic interviews of child/adolescent and
    parents ( separate and conjoint)
  • Utilize collateral informants such as teachers
  • Family History
  • Psychosocial Stressors
  • Review for comorbidity
  • Diagnosis is based upon DSM-IV criteria

24
Helpful Tools in Diagnosis of Mood Disorders
  • Child Behavior Checklist
  • Beck Depression Inventory
  • Childrens Depression Inventory
  • Young Mania Rating Scale
  • K-SADS Mania Rating Scale
  • Mood Disorder Questionnaire
  • Helpful web site www.schoolpsychiatry.org

25
Differentiating Between Unipolar and Bipolar
Disorders
  • 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

26
Missing the Diagnosis of Bipolar Disorder
  • 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 patients self presented
    history, rather than careful interview of family
  • Atypical presentation in juveniles
  • classic euphoria may not be present
  • High prevalence of co-morbid conditions leads to
    confusion

27
Juvenile Mood Disorders Overall Treatment
  • Least-restrictive setting in continuum of care
  • Outpatient, home-based, partial hospital,
    inpatient
  • Suicidal risk
  • Medical, substance abuse and psychiatric
    comorbidity
  • Family involvement, protective services
    involvement

28
Treatment of Juvenile Mood Disorders
  • Major Depression
  • SSRIs
  • Cognitive Behavior Therapy and Interpersonal
    Psychotherapy
  • Bipolar Disorders
  • Mood stabilizers
  • Atypical antipsychotics
  • Interpersonal Social Rhythms Therapy

29
Juvenile MDD Psychotherapy
  • Psycho-education
  • Is it adolescence or is it depression?
  • Cognitive-Behavioral Treatment (CBT)
  • Cognitive distortions, generalization,
    overattribution
  • Interpersonal Psychotherapy (IPT)
  • Areas of loss and grief, interpersonal roles and
    disputes, role transitions

30
Juvenile MDD Pharmacotherapy
  • 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

31
Efficacy of Antidepressants for Treating
Pediatric major Depressive Disorder Positive
Studies
32
Efficacy of Antidepressants for Treating
Pediatric Major Depressive Disorder Negative
Studies
  • Paroxetine 2 studies (N489) from UK
  • Citalopram 2 studies (N418) from US and UK
  • Mirtazepine 1 study (N250)
  • Venlafaxine 2 studies (N354)

33
SSRIs Practical Issues in Treatment of Major
Depression
  • 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
  • Depending upon age, weight, tolerance
  • Monitor pt. very closely during this titration !
  • Cognitive-behavioral therapy also recommended

34
The Treatment for Adolescents with Depression
Study 2004
35
The Treatment for Adolescents With Depression
Study 2004
36
FDA Regulations for Antidepressant Use in
Children and Adolescents
37
BLACK BOX WARNING

Suicidality in Children and Adolescents Antidepressants increase the risk of suicidal thinking and behavior (suicidality) in children with major depressive disorder(MDD) and other psychiatric disorders. Anyone considering the use of _____ or any other antidepressant in a child or adolescent must balanced this risk with the clinical need. Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. _____is not approved for use in pediatric patients except for patients with____. Pooled analyses of short-term (4 to 16 weeks) placebo-controlled trials of nine antidepressant drugs (SSRIs and others) in children and adolescents with MDD, OCD, or other psychiatric disorders (a total of 24 trials involving over 440 patients) have revealed a greater risk of adverse events representing suicidal thinking or behavior (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such events on drug was 4, twice the placebo risk of 2. No suicides occurred in these trials
Suicidality in Children and Adolescents Antidepre
ssants increase the risk of suicidal thinking and
behavior (suicidality) in children with major
depressive disorder(MDD) and other psychiatric
disorders. Anyone considering the use of _____ or
any other antidepressant in a child or adolescent
must balanced this risk with the clinical need.
Patients who are started on therapy should be
observed closely for clinical worsening,
suicidality, or unusual changes in behavior.
Families and caregivers should be advised of the
need for close observation and communication with
the prescriber. _____is not approved for use in
pediatric patients except for patients
with____. Pooled analyses of short-term (4 to 16
weeks) placebo-controlled trials of nine
antidepressant drugs (SSRIs and others) in
children and adolescents with MDD, OCD, or other
psychiatric disorders (a total of 24 trials
involving over 440 patients) have revealed a
greater risk of adverse events representing
suicidal thinking or behavior (suicidality)
during the first few months of treatment in those
receiving antidepressants. The average risk of
such events on drug was 4, twice the placebo
risk of 2. No suicides occurred in these trials
38
FDA Recommended Guidelines
  • 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 providers
    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

39
What to Look for
  • Anxiety
  • Agitation
  • Panic attacks
  • Insomnia
  • Irritability
  • Hostility
  • Impulsivity
  • Akathisia
  • Hypomania
  • Mania

40
Mixed Impact of Black Box
  • 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
  • ? Due to decrease in antidepressant use Gibbons
    et al., Am J Psychiatry 1641356-1363, September
    2007
  • Antidepressant treatment study
  • antidepressant use in juveniles significantly
    associated with suicide attempts/deaths Olfson
    et al., Arch Gen Psychiatry. 200663865-872

41
Treatment of Juvenile Depression with
Antidepressants Rationale for Continued Use
  • American College of Neuropsychopharmacolgy Task
    Force Report ( January 2004)
  • Suicide occurs most often in untreated depression
  • 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

42
SSRIs Side Effects
  • ABCs of SSRIs
  • Activation / Akathisia
  • Bipolar switching
  • Cytochrome P450-based interactions. Common
  • FLUOX / PAR CYP 2D6 (?TCAs)
  • FLUV CYP 2C9 (?Phenytoin)
  • FLUV CYP 1A1/2 (?Theophylin)
  • Discontinuation syndrome
  • Evolving Psychopathology

43
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 gt 2 or 3 discrete episodes of
    depression
  • Combined meds psychotherapy therapy likely will
    lead to best outcomes

44
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

45
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

46
Summary
  • 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
  • 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
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