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 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 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 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 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 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 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 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 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) sdsdfsadfaefa

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 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

Cycles of Affective Disorder Stahl, 2000

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

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

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 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 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 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 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 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 Major Depression SSRIs Cognitive Behavior Therapy and Interpersonal Psychotherapy Bipolar Disorders Mood stabilizers Atypical antipsychotics Interpersonal Social Rhythms Therapy

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

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

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 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 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 Adolescents with Depression Study 2004

The Treatment for Adolescents With Depression Study 2004

FDA Regulations for Antidepressant Use in Children and Adolescents

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

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 http://www.fda.gov/cder/drug/antidepressants/default.htm

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

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 164:1356-1363, September 2007 Antidepressant treatment study antidepressant use in juveniles significantly associated with suicide attempts/deaths Olfson et al., Arch Gen Psychiatry. 2006;63:865-872

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 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 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!! 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” 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 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