Basic Management of Juvenile Mood Disorders

Jeffrey I. Hunt, MDJeffrey I. Hunt, MD Alpert Medical School of Brown UniversityAlpert Medical School of Brown University

The Clinical Challenge

Juveniles often present with depression and other Juveniles often present with depression and other disturbances in their mooddisturbances in their mood

Mood disorders in juveniles are complex and not Mood disorders in juveniles are complex and not well understoodwell understood

Many juveniles with mood symptoms are being Many juveniles with mood symptoms are being treated by their primary care physician or cliniciantreated by their primary care physician or clinician

Antidepressants, while very helpful in some, can Antidepressants, while very helpful in some, can cause rapid deterioration in otherscause rapid deterioration in others

Major Depression is Common in Juveniles Prevalence 2% in children and 4% to 8% in Prevalence 2% in children and 4% to 8% in

adolescentsadolescents Male:Female ratio 1:1 during childhood and Male:Female ratio 1:1 during childhood and

1:2 during adolescence1:2 during adolescence Cumulative prevalence is 20% by age 18Cumulative prevalence is 20% by age 18 Increase in risk for younger generations is Increase in risk for younger generations is

suggested suggested ( Kashani et al., 1987; Kovacs, 1994; Lewinsohn et al., 1994)( Kashani et al., 1987; Kovacs, 1994; Lewinsohn et al., 1994)

Juvenile Major Depression: Clinical Presentation

Pervasive change in mood: depressed or irritablePervasive change in mood: depressed or irritable Loss of interest or pleasure Loss of interest or pleasure

Dysthymia: 1 vs 2 year criterion)Dysthymia: 1 vs 2 year criterion) SSleep Disturbanceleep Disturbance IIrritability rritability (core symptom in youth)(core symptom in youth) GGuilt uilt EEnergy nergy CConcentration oncentration AAppetite ppetite PPsychomotor Agitation or Retardation sychomotor Agitation or Retardation SSuicidalityuicidality

Juvenile Major Depression: Clinical Presentation

““Children are not little adultsChildren are not little adults”” Younger children: more anxiety (especially separation), somatic Younger children: more anxiety (especially separation), somatic

symptoms, auditory hallucinations, temper tantrums and symptoms, auditory hallucinations, temper tantrums and behavioral problemsbehavioral problems

Middle / late childhood: dysphoria, low self-esteem, guilt, Middle / late childhood: dysphoria, low self-esteem, guilt, hopelessness, hopelessness, ““burden on familyburden on family””

Adolescents: sleep and appetite changes, suicidality, Adolescents: sleep and appetite changes, suicidality, neurovegetative symptoms, irritability, explosive and conduct neurovegetative symptoms, irritability, explosive and conduct symptoms, symptoms, ““acting outacting out””, and substance abuse, and substance abuse

Juvenile MDD: Age-related changes

BiologicalBiological Sexual maturation and hormonal changesSexual maturation and hormonal changes Differential ontogeny of neural pathways: Differential ontogeny of neural pathways:

• Serotonergic pathways mature earlier onSerotonergic pathways mature earlier on• Noradrenergic pathways continue development Noradrenergic pathways continue development

into young adulthoodinto young adulthood EnvironmentalEnvironmental

Social and academic expectationsSocial and academic expectations Increased exposure to adverse life events, stressors Increased exposure to adverse life events, stressors

and lossesand losses Increased autonomy and abstract thinkingIncreased autonomy and abstract thinking

Juvenile Depression: Clinical Course

Duration of episode is 7 months to 2 years for Duration of episode is 7 months to 2 years for clinically referred samplesclinically referred samples

After successful acute therapy 40% to 60% After successful acute therapy 40% to 60% experience a relapseexperience a relapse

Probability of recurrence is 20% to 60% by 2 Probability of recurrence is 20% to 60% by 2 years and 70% by five yearsyears and 70% by five years

( Emslie, 1997; Kovacs, 1996; Lewinsohn 1994)( Emslie, 1997; Kovacs, 1996; Lewinsohn 1994)

Juvenile Major Depression: Sequelae Untreated MDD may affect social, emotional, cognitive, and Untreated MDD may affect social, emotional, cognitive, and

interpersonal skills and the attachment bond between parent and interpersonal skills and the attachment bond between parent and childchild

Juveniles with MDD are at higher risk for substance abuse, Juveniles with MDD are at higher risk for substance abuse, physical illness, poor academic functioningphysical illness, poor academic functioning

Protracted, chronic course in ~10% of cases.Protracted, chronic course in ~10% of cases. Earlier onset, number and severity of prior episodes, poor compliance, Earlier onset, number and severity of prior episodes, poor compliance,

psychosocial adversity, psychiatric illness in parents, adverse life eventspsychosocial adversity, psychiatric illness in parents, adverse life events

20% to 40% of adolescents may develop bipolar disorder within 20% to 40% of adolescents may develop bipolar disorder within 5 years5 years

MDD is a major cause of suicide attempts and completionMDD is a major cause of suicide attempts and completion Third leading cause of death among 15-24 year olds in USThird leading cause of death among 15-24 year olds in US

( Kovacs, 1996; Birmaher, 1996; Brent, 1995, Geller 1997 )( Kovacs, 1996; Birmaher, 1996; Brent, 1995, Geller 1997 )

Juvenile Major Depression: Comorbidity Dysthymia (Dysthymia (““double depressiondouble depression””) )

Dysthymia as Dysthymia as ““gatewaygateway”” disorder disorder Anxiety disorders Anxiety disorders (often precedes depression in youth)(often precedes depression in youth)

Disruptive disorders Disruptive disorders (attention deficit, oppositional defiant, (attention deficit, oppositional defiant, conduct)conduct)

Substance abuseSubstance abuse Somatoform disorders Somatoform disorders Personality disorders or traits (teenagers)Personality disorders or traits (teenagers)

Juvenile Major Depression: Comorbidity Bipolar DisorderBipolar Disorder

MDD may be the first presentation of MDD may be the first presentation of underlying Bipolar Disorder underlying Bipolar Disorder

““FalseFalse”” unipolar depression unipolar depression Mixed states are common in youngstersMixed states are common in youngsters ““SwitchSwitch”” rates are reported to range between rates are reported to range between

25- 40%25- 40% Legitimate Legitimate ““switchesswitches”” may be hard to interpret may be hard to interpret

in the face of treatment or concurrent substance in the face of treatment or concurrent substance useuse

Look for Mania before Initiating Treatment for Depression Many juveniles with bipolar disorder Many juveniles with bipolar disorder

present initially with severe depression and present initially with severe depression and histories of being histories of being ““moodymoody””

Children and adolescents with unipolar Children and adolescents with unipolar depression may be irritable but usually are depression may be irritable but usually are not labile and donnot labile and don’’t have periods of elevated t have periods of elevated ““giddygiddy”” moods moods

Cycles of Affective Disorder

Stahl, 2000

DSM-IV Diagnosis of Mania

Distinct period of Distinct period of abnormally and abnormally and persistently elevated, persistently elevated, expansive, or irritable expansive, or irritable moodmood

DDistractibility istractibility IIncreased physical activity ncreased physical activity

or goal directed activity or goal directed activity GGrandiosityrandiosity

FFlight of ideaslight of ideas AActivities showing poor ctivities showing poor

judgement judgement SSleep, decrease need forleep, decrease need for TTalkativenessalkativeness

Bipolar depressive symptoms in juveniles Many physical complaintsMany physical complaints Frequent absenteeism from schoolFrequent absenteeism from school Poor school performance Poor school performance Talk of running away from homeTalk of running away from home ComplainingComplaining Unexplained cryingUnexplained crying Social isolationSocial isolation Extreme sensitivity to rejection/failureExtreme sensitivity to rejection/failure see www.nimh.nih.gov/publicat/childnotes.cfm for review publication No. 00-see www.nimh.nih.gov/publicat/childnotes.cfm for review publication No. 00-

4778 4778 Child and Adolescent Bipolar Disorder, Aug 2000Child 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

Diagnostic interviews of child/adolescent and Diagnostic interviews of child/adolescent and parents ( separate and conjoint)parents ( separate and conjoint)

Utilize collateral informants such as teachersUtilize collateral informants such as teachers Family HistoryFamily History Psychosocial StressorsPsychosocial Stressors Review for comorbidityReview for comorbidity Diagnosis is based upon DSM-IV criteriaDiagnosis is based upon DSM-IV criteria

Helpful Tools in Diagnosis of Mood Disorders Child Behavior ChecklistChild Behavior Checklist Beck Depression InventoryBeck Depression Inventory ChildrenChildren’’s Depression Inventorys Depression Inventory Young Mania Rating ScaleYoung Mania Rating Scale K-SADS Mania Rating ScaleK-SADS Mania Rating Scale Mood Disorder QuestionnaireMood Disorder Questionnaire Helpful web site: www.schoolpsychiatry.orgHelpful web site: www.schoolpsychiatry.org

Differentiating Between Unipolar and Bipolar Disorders Be suspicious for Bipolar Disorder when there is:Be suspicious for Bipolar Disorder when there is:

Abrupt onset of any mood symptomsAbrupt onset of any mood symptoms Positive FH in 1st degree relatives or if Positive FH in 1st degree relatives or if

present in 2nd and 3rd degree relativespresent in 2nd and 3rd degree relatives 1st episode of any mood disturbance in 1st episode of any mood disturbance in

adolescence with psychotic featuresadolescence with psychotic features Distinct and repeated cycles of Distinct and repeated cycles of

depressiondepression

Missing the Diagnosis of Bipolar Disorder Failure to consider full spectrum of the disorder Failure to consider full spectrum of the disorder

Broad spectrum of bipolar may be up to 2%-11% Broad spectrum of bipolar may be up to 2%-11% prevalenceprevalence

Tendency to focus on acute presenting picture instead of Tendency to focus on acute presenting picture instead of longitudinal historylongitudinal history

Over-reliance on patientOver-reliance on patient’’s self presented history, rather s self presented history, rather than careful interview of familythan careful interview of family

Atypical presentation in juvenilesAtypical presentation in juveniles classic euphoria may not be presentclassic euphoria may not be present

High prevalence of co-morbid conditions leads to High prevalence of co-morbid conditions leads to confusion confusion

Juvenile Mood Disorders: Overall Treatment

Least-restrictive setting in continuum of careLeast-restrictive setting in continuum of care Outpatient, home-based, partial hospital, Outpatient, home-based, partial hospital,

inpatientinpatient Suicidal riskSuicidal risk Medical, substance abuse and psychiatric Medical, substance abuse and psychiatric

comorbiditycomorbidity Family involvement, protective services Family involvement, protective services

involvementinvolvement

Treatment of Juvenile Mood Disorders Major DepressionMajor Depression

SSRIsSSRIs Cognitive Behavior Therapy and Cognitive Behavior Therapy and

Interpersonal Psychotherapy Interpersonal Psychotherapy Bipolar DisordersBipolar Disorders

Mood stabilizersMood stabilizers Atypical antipsychoticsAtypical antipsychotics Interpersonal Social Rhythms TherapyInterpersonal Social Rhythms Therapy

Juvenile MDD: Psychotherapy

Psycho-educationPsycho-education ““Is it adolescence or is it depression?Is it adolescence or is it depression?””

Cognitive-Behavioral Treatment (CBT) Cognitive-Behavioral Treatment (CBT) Cognitive distortions, generalization, overattributionCognitive distortions, generalization, overattribution

Interpersonal Psychotherapy (IPT)Interpersonal Psychotherapy (IPT) Areas of loss and grief, interpersonal roles and Areas of loss and grief, interpersonal roles and

disputes, role transitionsdisputes, role transitions

Juvenile MDD: Pharmacotherapy

Medication not first-line, except when:Medication not first-line, except when: Severe symptoms or suicidal riskSevere symptoms or suicidal risk Psychotic and certain (non-rapid cycling) Psychotic and certain (non-rapid cycling)

bipolar depressionsbipolar depressions Symptoms prevent participation in Symptoms prevent participation in

psychotherapypsychotherapy Adequate psychotherapy trial ineffectiveAdequate psychotherapy trial ineffective Chronic or recurrent depressionChronic or recurrent depression

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

Efficacy of Antidepressants for Treating Pediatric Major Depressive Disorder: Negative Studies Paroxetine: 2 studies (N=489) from UK Paroxetine: 2 studies (N=489) from UK Citalopram: 2 studies (N=418) from US and Citalopram: 2 studies (N=418) from US and

UKUK Mirtazepine: 1 study (N=250)Mirtazepine: 1 study (N=250) Venlafaxine: 2 studies (N=354) Venlafaxine: 2 studies (N=354)

SSRIs: Practical Issues in Treatment of Major Depression Start with fluoxetineStart with fluoxetine

5 to 10 mg/day in first week titrate to 10 to 20 5 to 10 mg/day in first week titrate to 10 to 20 mg/day over next 2 weeks depending on age/weightmg/day over next 2 weeks depending on age/weight

Treat with adequate and tolerable doses for at least Treat with adequate and tolerable doses for at least 4 weeks4 weeks

If no improvement by 4 weeks consider gradual If no improvement by 4 weeks consider gradual increase in dose up to 30 to 40 mg/day increase in dose up to 30 to 40 mg/day

Depending upon age, weight, toleranceDepending upon age, weight, tolerance Monitor pt. very closely during this titration !Monitor pt. very closely during this titration !

Cognitive-behavioral therapy also recommendedCognitive-behavioral therapy also recommended

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 WARNINGSuicidality 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

FDA Recommended Guidelines After starting an antidepressant, your child should After starting an antidepressant, your child should

generally see his/her healthcare provider:generally see his/her healthcare provider: Once a week for the first 4 weeksOnce a week for the first 4 weeks Every 2 weeks for the next 4 weeksEvery 2 weeks for the next 4 weeks After taking the antidepressant for 12 weeksAfter taking the antidepressant for 12 weeks After 12 weeks, follow your healthcare providerAfter 12 weeks, follow your healthcare provider ’’s s

advice about how often to come backadvice about how often to come back More often if problems or questions ariseMore often if problems or questions arise

• FDA Medication guide FDA Medication guide http://www.fda.gov/cder/drug/antidepressants/default.htm

What to Look for:

AnxietyAnxiety AgitationAgitation Panic attacksPanic attacks InsomniaInsomnia IrritabilityIrritability

HostilityHostility ImpulsivityImpulsivity AkathisiaAkathisia HypomaniaHypomania ManiaMania

Mixed Impact of Black Box

Prescriptions for antidepressants have dropped by Prescriptions for antidepressants have dropped by 20% for those 18 y/o and younger since 2004 20% for those 18 y/o and younger since 2004 when FDA initial warnings were publishedwhen FDA initial warnings were published

Increased suicide rateIncreased suicide rate ? Due to decrease in antidepressant use? Due to decrease in antidepressant use Gibbons et al., Am J Gibbons et al., Am J

Psychiatry 164:1356-1363, September 2007Psychiatry 164:1356-1363, September 2007

Antidepressant treatment study Antidepressant treatment study antidepressant use in juveniles significantly associated antidepressant use in juveniles significantly associated

with suicide attempts/deathswith suicide attempts/deaths Olfson et al., Olfson et al., Arch Gen Arch Gen Psychiatry.Psychiatry. 2006;63:865-872  2006;63:865-872

Treatment of Juvenile Depression with Antidepressants: Rationale for Continued Use

American College of Neuropsychopharmacolgy Task American College of Neuropsychopharmacolgy Task Force ReportForce Report ( January 2004)( January 2004)

Suicide occurs most often in untreated depressionSuicide occurs most often in untreated depression Confirmed by autopsy studiesConfirmed by autopsy studies

Several SSRI trials showed efficacy in treating Several SSRI trials showed efficacy in treating depressiondepression

SSRI did not increase risk of suicide or suicidal SSRI did not increase risk of suicide or suicidal thinking in youths based upon strong evidence from thinking in youths based upon strong evidence from clinical trials, epidemiology, and autopsy studiesclinical trials, epidemiology, and autopsy studies

Increase use of SSRI worldwide led to decline in 33% Increase use of SSRI worldwide led to decline in 33% decline in youth suicide in the last 15 yearsdecline in youth suicide in the last 15 years

SSRIs: Side Effects

ABCs of SSRIs ABCs of SSRIs AActivation / ctivation / AAkathisiakathisia BBipolar switchingipolar switching CCytochrome P450-based interactions. Common:ytochrome P450-based interactions. Common:

FLUOX / PAR: CYP 2D6 (FLUOX / PAR: CYP 2D6 (TCAs)TCAs) FLUV: CYP 2C9 (FLUV: CYP 2C9 (Phenytoin)Phenytoin) FLUV: CYP 1A1/2 (FLUV: CYP 1A1/2 (Theophylin)Theophylin)

DDiscontinuation syndromeiscontinuation syndrome EEvolving Psychopathologyvolving Psychopathology

Long Term Management in Treatment of Major Depression Continuation therapy recommended for all Continuation therapy recommended for all

patients for at least 6 to 12 monthspatients for at least 6 to 12 months Maintenance treatment may be indicated for Maintenance treatment may be indicated for

some patients with > 2 or 3 discrete some patients with > 2 or 3 discrete episodes of depressionepisodes of depression

Combined meds +psychotherapy therapy Combined meds +psychotherapy therapy likely will lead to best outcomeslikely will lead to best outcomes

Always be vigilant for emergence of mania!! Can occur any time from few hours to many Can occur any time from few hours to many

weeks later weeks later Initial agitation sometimes difficult to Initial agitation sometimes difficult to

distinguish from manic symptomsdistinguish from manic symptoms

What happens if a “switch occurs” Refer to psychiatrist if possibleRefer to psychiatrist if possible Monitor patient very closelyMonitor patient very closely Educate caregiversEducate caregivers Re-evaluate diagnosisRe-evaluate diagnosis Taper and discontinue SSRITaper and discontinue SSRI Consider mood stabilizerConsider mood stabilizer Consider more intensive level of careConsider more intensive level of care

Summary

Mood disorders are common in children and adolescentsMood disorders are common in children and adolescents Differentiating between unipolar depression and bipolar Differentiating between unipolar depression and bipolar

disorder is vital prior to initiating treatment with antidepressantsdisorder is vital prior to initiating treatment with antidepressants Effective treatments of mood disorders are emerging but Effective treatments of mood disorders are emerging but

controversies remaincontroversies remain Close monitoring of patients is imperative when antidepressants are usedClose monitoring of patients is imperative when antidepressants are used Important for MD and allied mental health clinicians to optimally Important for MD and allied mental health clinicians to optimally

communicate with each other on shared patientscommunicate with each other on shared patients

Primary care physicians and other mental health clinicians are Primary care physicians and other mental health clinicians are having to manage these complex children and adolescents with having to manage these complex children and adolescents with little training or supportlittle training or support