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