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
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
( 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 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)
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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 %
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 don’t 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 for review publication No 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
Children’s Depression Inventory
Young Mania Rating Scale
K-SADS Mania Rating Scale
Mood Disorder Questionnaire
Helpful web site:

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 patient’s 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 (N=489) from UK
Citalopram: 2 studies (N=418) from US and UK
Mirtazepine: 1 study (N=250)
Venlafaxine: 2 studies (N=354)

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
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

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 provider’s advice about how often to come back
More often if problems or questions arise
FDA Medication guide

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 164: , September 2007
Antidepressant treatment study
antidepressant use in juveniles significantly associated with suicide attempts/deaths Olfson et al., Arch Gen Psychiatry. 2006;63:

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 > 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