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Basic Management of Juvenile Mood Disorders. Jeffrey I. Hunt, MD Alpert Medical School of Brown University. The Clinical Challenge. Juveniles often present with depression and other disturbances in their mood Mood disorders in juveniles are complex and not well understood

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Basic management of juvenile mood disorders

Basic Management of Juvenile Mood Disorders

Jeffrey I. Hunt, MD

Alpert Medical School of Brown University


The clinical challenge
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


Major depression is common in juveniles
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)


Juvenile major depression clinical presentation
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


Juvenile major depression clinical presentation1
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


Juvenile mdd age related changes
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


Juvenile depression clinical course
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)


Juvenile major depression sequelae
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 )


Juvenile major depression comorbidity
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)


Juvenile major depression comorbidity1
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


Look for mania before initiating treatment for depression
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



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

DSM-IV Diagnosis of Mania


Bipolar depressive symptoms in juveniles
Bipolar depressive symptoms in juveniles expansive, or irritable mood

  • 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
How Broad is the Spectrum? expansive, or irritable mood


Angst and Gamma, 2002 expansive, or irritable mood


Narrow phenotype of juvenile mania
Narrow Phenotype of Juvenile Mania expansive, or irritable mood

Leibenluft, Charney, et al., 2003


Intermediate phenotype of juvenile mania
Intermediate Phenotype of Juvenile Mania expansive, or irritable mood

Leibenluft, Charney, et al., 2003


Broad phenotype of juvenile mania severe mood and behavioral dysregulation
Broad Phenotype of Juvenile Mania: Severe Mood and Behavioral Dysregulation

Leibenluft, Charney, et al., 2003


How fast can moods change
How fast can moods change? Behavioral Dysregulation


Rapid cycling
Rapid Cycling Behavioral Dysregulation

Stahl, 2000


Practical assessment of mood disorders

Practical Assessment of Mood Disorders Behavioral Dysregulation


Juvenile mood disorders assessment
Juvenile Mood Disorders: Assessment Behavioral Dysregulation

  • 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


Helpful tools in diagnosis of mood disorders
Helpful Tools in Diagnosis of Mood Disorders Behavioral Dysregulation

  • 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: www.schoolpsychiatry.org


Differentiating between unipolar and bipolar disorders
Differentiating Between Unipolar and Bipolar Disorders Behavioral Dysregulation

  • 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


Missing the diagnosis of bipolar disorder
Missing the Diagnosis of Bipolar Disorder Behavioral Dysregulation

  • 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


Juvenile mood disorders overall treatment
Juvenile Mood Disorders: Overall Treatment Behavioral Dysregulation

  • 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


Treatment of juvenile mood disorders
Treatment of Juvenile Mood Disorders Behavioral Dysregulation

  • Major Depression

    • SSRIs

    • Cognitive Behavior Therapy and Interpersonal Psychotherapy

  • Bipolar Disorders

    • Mood stabilizers

    • Atypical antipsychotics

    • Interpersonal Social Rhythms Therapy


Juvenile mdd psychotherapy
Juvenile MDD: Psychotherapy Behavioral Dysregulation

  • 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


Juvenile mdd pharmacotherapy
Juvenile MDD: Pharmacotherapy Behavioral Dysregulation

  • 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
Efficacy of Antidepressants for Treating Pediatric major Depressive Disorder: Positive Studies


Efficacy of antidepressants for treating pediatric major depressive disorder negative studies
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
SSRIs: Practical Issues in Treatment of Major Depression Depressive Disorder: Negative Studies

  • 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


The Treatment for Depressive Disorder: Negative Studies

Adolescents with

Depression Study

2004


The Treatment for Depressive Disorder: Negative Studies

Adolescents With

Depression Study

2004



Black box warning
BLACK BOX WARNING Adolescents

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


Fda recommended guidelines
FDA Recommended Guidelines Adolescents

  • 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 Adolescents

Agitation

Panic attacks

Insomnia

Irritability

Hostility

Impulsivity

Akathisia

Hypomania

Mania

What to Look for:


Mixed impact of black box
Mixed Impact of Black Box Adolescents

  • 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 useGibbons et al., Am J Psychiatry 164:1356-1363, September 2007

  • Antidepressant treatment study

    • antidepressant use in juveniles significantly associated with suicide attempts/deathsOlfson et al., Arch Gen Psychiatry. 2006;63:865-872


Treatment of juvenile depression with antidepressants rationale for continued use
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


Ssris side effects
SSRIs: Side Effects Rationale for Continued Use

  • 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


Long term management in treatment of major depression
Long Term Management in Treatment of Major Depression Rationale for Continued Use

  • 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


Always be vigilant for emergence of mania
Always be vigilant for emergence of mania!! Rationale for Continued Use

  • Can occur any time from few hours to many weeks later

  • Initial agitation sometimes difficult to distinguish from manic symptoms


What happens if a switch occurs
What happens if a Rationale for Continued Use “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


Summary
Summary Rationale for Continued Use

  • 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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