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Treatment of Mood Disorders in Children and Adolescents. Terrence Clark MD January 23, 2007. Treatment. GOOD TREATMENT BEGINS WITH GOOD ASSESSMENT. Objectives. Aware of the occurrence of mood disorders in children and adolescents

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  • Aware of the occurrence of mood disorders in children and adolescents
  • Share with you some of the literature that influences my treatment of mood disorders in children and adolescents
  • Aware of the phenotypes of Bipolar Disorder in children and adol
  • Treatment most often is multimodal
  • Pre-pubertal Bipolar Disorder may or may manifest as BP in adults
  • Adolescent BP phenotype is more similar to adult presentation
  • Aware of treatment guidelines
four cases 1
Four Cases#1
  • 20 year old man with depression
  • Hospitalized twice at ages 15 and 16
  • Some marijuana and alcohol use
  • Age 18 relapses and takes 6 months to gain full remission
  • Paroxetine and mirtazepine and low dose clonazepam
case 2
Case #2
  • !6 year old girl with depression
  • “excellent” response to an SSRI
  • Clinician feels good about the excellent treatment outcome
  • Truth
case 3
Case # 3
  • 16 year old boy Bipolar Disorder
  • Hospitalized 4 times at ages 9, 10 (2), and 16
  • Mood stabilized plus an atypical
  • Expelled from school at age 16- fighting
case 4
Case # 4
  • 10 year old boy
  • Anger, rage, aggression
  • Chronically impaired for 3 years
  • Family history of Bipolar
  • Responds well to a mood stabilizer plus an atypical antipsychotic

Identification of Mood Disorders in kids is based upon Adult based DSM-IV Criteria with some modifications

  • DSM III and DSM IV created as a guide to improve reliability of DX
  • Yet, once created, the diagnostic criteria become the disorder rather than a guide and the illness by definition equals a specified # of criteria
  • McClellan, J. JPL AACAP, 44:3, March 2005Commmentary on Treatment Guidelines
normal children
Normal Children
  • Active
  • Imaginative
  • Boastful
  • Sensitive to the environment
  • “Act out” periodically
  • Interview of parents
  • Interview of child
  • Review of prior mental health records
  • Review of medical/PCP records
  • Psychological Inventories
interview of parents
Interview of Parents
  • Birth and developmental history
  • Family history
  • Social
  • School
  • Medical
  • Marital
interview of child
Interview of Child
  • Kids will tell you what is going on if you follow their leads in the interview
  • Rapport
  • Let them know why you are interviewing them “doctor that helps kids with….”
  • Social distance
interview with kids
Interview with kids
  • Listen to the patients story, following leads with open ended questions
  • Don’t squeeze the patient into a medical model shoe
  • Save medical model, closed-ended questions to the later part of the interview
major depression
Major Depression
  • Epidemiology
    • Prevalence increases as age increases
      • less than 0.3-0.5% of preschoolers
      • 1-2% of prepubertal children
      • 5% of adolescents
      • 10-25% of women
      • 5-12% of men
    • Sex ratio
      • Prepubertal onset: male approximately equal female
      • Adolescence same as adult sex ratios (female > male: ~2:1) until 50 Years old
depressive disorders in children cont
Depressive Disorders in Children (cont)
  • Greater genetic loading then adult depression
  • High co-morbidity with other psychiatric disorders
  • Co-morbidity is the rule rather than the exception with childhood disorders
depressive disorders in children cont19
Depressive Disorders in Children (cont)
  • Mortality – Risk of suicide

- Estimated 8-10% of adolescents attempt suicide

- Approximately 1% of preadolescents attempt suicide

- Firearms account for a large percent of suicides in youth

major depression20
Major Depression
  • Criteria for Major Depressive Episode
    • 1. Depressed mood most of the day,
    • IN children and adolescent can be irritable mood.
adolescent depression
Adolescent Depression
  • Increased moodiness, irritability, argumentativeness
  • Poor concentration
  • Sleep and appetite changes
  • Increased self-criticism
  • Despair, sadness, emptiness
  • Loss of energy
  • Lack of interest in usual activities and friends
  • Increased talk of death and dying
  • Threats of suicide
course of major depression in children and adolescents
Course of Major Depression in Children and Adolescents
  • 7- 9 months average duration of episode
  • 90% recovered in 18 mos
  • 50% relapse
  • 40% another episode within 2 years
  • 70% another episode within 5 years
  • 6-10% have a chronic course
  • Psychotherapy first
  • CBT
  • Interpersonal
  • Family
  • Psycho education
treatment for youth with major depression
Treatment for Youth with Major Depression
  • Psychoeducation of pt and family
  • Multimodal treatment
  • Medication rarely is the sole treatment
  • Psychosocial interventions 1st in preschool
  • Address safety
  • Treat co-morbid conditions
  • FDA warnings – share with pt and family
  • Manualized therapy
  • Children’s group CBT
  • Multi-parent group CBT
cbt research
CBT Research
  • Comparison across studies is difficult due to variability in outcome assessment methodology
  • CBT studies rarely report on remission rates
  • Remission and Residual Symptoms after Short-term treatment of adolescents with Depression study (TADS) Jl. AACAP, 45:12, Dec. 2006
pharmacotherapy of major depression in children and adol
Pharmacotherapy of Major Depression in Children and Adol
  • Fluoxetine- only FDA approved treatment
  • 2003- approved for treatment of Major Depression and OCD in children ages 7 thru 17
selecting an antidepressant for pediatric depression
Selecting an Antidepressant for Pediatric Depression
  • Fluoxetine efficacy supported by 3 independent multisite clinical trials (Emslie, TADS)
  • Fluoxetine is the only antidepressant whose efficacy has been compared with CBT, alone and in combination with fluoxetine
  • Emslie et al., 1997; 2002; TADS Team, 2004)
selecting antidepressant
Selecting Antidepressant
  • Fluoxetine – consider first, not necessarily prescribe first
  • Family response history toantidepressants
  • Indiv patient context, expectations and preferences
  • 20-40% of depressed youth do not adequately respond to fluoxetine
selecting antidepressant30
Selecting antidepressant
  • Sertraline and citalopram- there is some literature supporting clinical efficacy
  • Citalopram, escitalopram – much lower potential for drug interactions
  • At least 8 adult studies, a person may respond poorly to one SSRI, then well to another
  • Sertraline – FDA approved for treatment of OCD, ages 6
  • Selecting an antidepressant for the Treatment of Ped Depression Jl AACAP; 45:3; March 2006
pharmacotherapy of maj dep in children and adolescents
Pharmacotherapy of Maj Dep in Children and Adolescents
  • Emslie et al. 96 children, ages 7-17, mean age 12.35, dbl bl, placebo controlled

8 weeks

  • Fluoxetine significantly better than placebo
treatment of depression in children pharmacotherapy
Treatment of Depression in Children - Pharmacotherapy
  • SSRI’S – all SSRI’s effective
  • Recent concern regarding risk of increased suicidal thinking in children taking antidepressants
  • Tricyclic antidepressants – no proven efficacy, more side effects, fatal in overdose
bipolar disorder
Bipolar Disorder
  • Epidemiology:
    • Occurs in 1% of adults
    • About 20% bipolar patients have first episode in adolescence
    • Clear mania in children as young as 6 years old
    • Gender ratio males = females
    • 10-15% of adolescents with recurrent major depression develop bipolar disorder
bipolar disorder35
Bipolar Disorder
  • Clinical Description
      • First symptoms usually depressive
      • Psychotic symptoms commons
        • therefore misdiagnosed as schizophrenia
      • Hyperactivity, pressured speech, distractibility
nimh research roundtable on pre pubertal bipolar disorder
NIMH Research Roundtable on Pre-Pubertal Bipolar Disorder
  • Significant number of children do not meet full diagnostic criteria for bipolar disorder
  • Recommended use of “Bipolar disorder not otherwise specified”, BP-NOS
    • For children with manic symptoms, i.e. irritability and aggression
    • Journal of ACAP, 40:8 August, 2001
comorbidity in adolescent inpatients with bipolar disorder
Comorbidity in Adolescent Inpatients with Bipolar Disorder


West et al, Biol Psych 1996;39:458-460

pediatric bipolar disorder two phenotypes
Pediatric Bipolar DisorderTwo Phenotypes
  • Pre-pubertal and early adolescent onset bipolar disorder (PEA-BD) – a broad phenotype
  • Adolescent onset bipolar disorder (AO-BD) a Narrow phenotype: classical mood cycling, adolescent onset
prepubertal and early adolescent bipolar disorder pea bd
Prepubertal and early adolescent Bipolar Disorder (PEA-BD)
  • Irritability, rapid cycling, little inter-episode recovery
  • Emotional dysregulation, rage , meltdowns
  • Early sudden onset of depression and psychomotor retardation
  • Pharmacologically induced mania
  • Family history of Bipolar Disorder
  • Strober M, Carlson GA.Arch Gen Psy. 1982;39:549-555
adolescent onset bipolar disorder ao bd
Adolescent onset Bipolar Disorder (AO-BD)
  • Episodic course in at least 25% of patients
  • High rates of substance abuse
  • High rates of anxiety symptoms
  • Often presents with classic symptoms of adult mania including psychosis
  • May be confused with schizophrenia
differential pea bd vs adhd
Differential PEA-BD vs. ADHD
  • Five DSM-IV criteria do not overlap:
  • Elation
  • Grandiosity
  • Racing thoughts/flight of ideas
  • Decreased need for sleep
  • Hypersexuality
similarities pea bd and ao bd
Similarities: PEA-BD and AO-BD
  • Elated mood
  • Mixed episodes, long duration episodes
  • low inter-episode recovery
is bipolar disorder common in children pro con
Is Bipolar Disorder common in Children? (pro/con)
  • Pro:
  • Unstable, labile mood
  • Hyperactivity, Sleep dis., racing thoughts aggression
  • Mixed presentation
  • Chronic, leading to severe disability
  • Bipolar Disorder is Common in Children (Pro/Con), Gianni Faedda vs Gabrielle Carlson, The JL of BP Disorders, Vol 3
con carlson
Con (Carlson)
  • Prepubertal Bipolar kids rarely become classic BP adults
  • This is a new concept to define the prepubescent presentation as BP
  • Yet, 64% of BP adults in Suffolk Co study had childhood psych problems
  • DSM IV gentrified ADHD removing mood symptoms…. Thus new home “BPD NOS”
dsm and the increased diagnosis of childhood bipolar disorder
DSM and the Increased Diagnosis of Childhood Bipolar Disorder
  • ADHD prior to DSM III, 1981, called “Minimal Brain Damage” (MBD”)
  • Affective symptoms: depression, mania, anger, tantrums and rage
  • MBD included affective symptoms and mood liability
  • DSM III eliminated affective symptoms from ADHD
is this the same disorder as in adults
Is this the same disorder as in adults?
  • Limited data
    • Do not suggest that pre-pubertal bipolar disorder evolves into the classic adult illness (McClellan, 2005)
    • Adolescent bipolar disorder predicts an increase in psychopathology and adverse outcomes, antisocial and borderline personality symptoms (Lewinsohn, et al.,2000)
    • Classical BPD, adol, likely leads to adult BPD
two year outcome of bipolar children geller
Two Year Outcome of Bipolar Children (Geller)
  • 89 outpt subjects with presence of mania
  • Mean age 10.9 years
  • Eval at 6,12,18, and 24 months
  • Naturalistic study, outpt sites
  • Required elation or grandiosity
  • Mean age of onset 7.3 years (SD =3.5)
  • Mean duration baseline episode 3.6 years

Geller et al, AmJ Psychiatry, 159:927-933

two year study continued
Two Year Study (continued)
  • Poor outcome:
  • 65% recovered from mania
  • Yet 55% relapsed
  • 36 weeks mean time to recovery
  • Relapse after a mean of 28 weeks

Geller et al

bipolar disorder in adolescence
Bipolar Disorder in Adolescence
  • Rapid cycling in 80%
  • Mixed mania in 58%
  • Frequent psychotic mania
  • Co-morbid ADHD and conduct disorders
  • Suicidality in 46%
  • Marked impairment
  • Prepubertal depression

Geller, et al. Am J Psychiatry. 2001;158:125-127.

differentiating bipolar from other disorders
Differentiating Bipolar from other Disorders
  • Requires detailed history from multiple sources (“100% different story”)
  • Qualitative changes from baseline
  • Persistence, severity-in multiple contexts
  • Typical clustering of symptoms
bipolar disorder vs adhd
Bipolar Disorder vs. ADHD
  • Strong family history
  • Discrete episodes of extremely disruptive behavior
  • Severe behavior may be seasonal
  • Early sexual themes
  • Greater capacity for eliciting emotional responses from others
  • Intensity of anger
  • Poor response to stimulants
  • Poor or too quick response to antidepressants
  • Being a dare-devil or risk taker
  • Extremes of emotional lability and irritability
treatment of bp in children and adolescents
Treatment of BP in Children and Adolescents
  • Guidelines similar to adults
  • Medications are effective
  • Combination pharmacotherapy often necessary to gain remission
treatment guidelines for children and adol with bipolar disorder
Treatment Guidelines for Children and Adol with Bipolar Disorder
  • Expert consensus and review of the literature
  • Three family considerations:

1.) Information from family is essential to diagnose

2.) Refer family with mod disorders for Rx.

3.) Educate family re BPD, web resources

Kowatch et al jl. AACAP, 44:3Mar. 2005

treatment guidelines of bipolar in children and adolescents
Treatment Guidelines of Bipolar in Children and Adolescents
  • Very similar to treatment of adults
  • Bipolar I, manic or mixed, without psychosis, start with monotherapy of a mood stabilizer or atypical antipsychotic
  • Bipolar I, manic or mixed with psychosis, start with a mood stabilizer and an atypical

Kowatch et alJl AACAP, 44:3, Mar, 2005

bipolar disorder55
Bipolar Disorder
  • Psychopharmacology
    • Mania symptoms must be stabilized before treatment of co-occurring disorders will be effective
    • Mood-stabilizing medications and some of the novel antipsychotic medications lead to significant improvement in symptoms
bipolar disorder56
Bipolar Disorder
  • Psychopharmacology
    • Taper and discontinue stimulants and antidepressants
    • Youth are highly resistant to monotherapy with a mood stabilizer
    • Long-term follow-up is necessary
mood stabilizers
Mood Stabilizers
  • Lithium
    • Tried & tested
    • Narrow therapeutic index
    • 30-50% non-compliance
    • Onset 7-10 days
    • 18 days for response
    • Avoid in dysfunctional families – suicide risk
common lithium side effects
Common Lithium Side Effects
  • Nausea
  • Diarrhea
  • Polyuria
  • tremor
  • Weight gain
  • Cognitive dulling
major concerns with lithium
Major Concerns with Lithium
  • Lithium toxicity
  • Lethal in overdose
  • Fetal malformations (cardiovascular)
  • Lithium: cognitive dulling, Lithium toxicity, tremor, renal function, thyroid
  • Topiramate: cognitive impairment
  • Carbamazepam , Oxcarbamazepam: interference with birth control pills
common depakote side effects
Common DepakoteSide Effects
  • tremor
  • fatigue
  • Weight gain
valproate depakote adverse side effects
Valproate (Depakote) Adverse Side Effects
  • Fetal abnormalities (neural tube defects)
  • Polycystic Ovarian Syndrome
  • Pancreatitis
  • Elevated Ammonia
  • Lowered platelets
concerns re divalproex
Concerns re. Divalproex
  • Polycystic Ovary Syndrome
  • Case: 15 yo girl with PCOS on DVPX
  • Polycystic ovaries hyperandrogenism, chronic anovulation
  • Hirsutism, alopecia, acne, menstrual abnormalities
  • Elevated testosterone, inc LH, inc pit sensitivity to GRH, dec. FSH
  • # of reports, high rates of PCOS in women with epilepsy treated with DVPX
  • Few studies of PCOS in women with PBD treated with DVPX

McIntyre et al. Valproate, bipolar disorder and PCOS. Bipolar Disord 5:28-35

newer antiepileptic drugs
Newer Antiepileptic Drugs
  • No treatment studies for bipolar disorder in children and adolescents
    • Lamotrogine (Lamictal) – effective in Bipolar Depression, risk of Stevens – Johnson Syndrome
    • Topirimate (Topomax) – Decreases weight, risk of cognitive impairment, metabolic alkalosis
    • Gabapentin (Neurontin) – NO proven efficacy, has anti-anxiety effect, weight gain risk
atypical antipsychotics
Current agents






Often necessary

Limit use because of...

Metabolic syndrome


Weight gain

Atypical Antipsychotics
metabolic syndrome due to atypical antipsychotic meds
Metabolic Syndrome due to Atypical Antipsychotic Meds
  • Atypicals may have a direct effect on hypothalamic appetite centers, alter satiety signals emanating from adipose tissue or gut, or create hormonal resistance to satiety control
  • Not necessarily due just to weight gain
  • Long term atypical can cause insulin resistance and decreased glucose effectiveness (even in lean schizophrenics)
  • Metformin.. Atypicals.. Children and Adol. Am Jl Psychiatry, 2006, 163:2072-2079
  • Pediatric Bipolar Disorder is a serious illness
  • Treatment works but is difficult, often needs periodic readjustment
  • Team approach is necessary
  • Treatment guidelines for Ped BP largely based on adult literature which justifiably promotes aggressive pharmacotherapy
  • Co-morbidity is the rule rather then the exception
  • Incorrect diagnosis is common, especially as depression or ADHD
  • Treat actively to achieve remission early in the disease
  • Educate patient and family
  • All effective medicines have potential side effects
  • Continue medications that are effective, unless side effects are problematic
  • Children with what is now conceptualized as PB-BD are common in psychiatric clinics
  • Mood stabilizers and atypicals are reasonable agents to consider based on (limited) evidence for effectiveness with aggression
  • Despite community treatment most youth with BP remain chronically impaired
  • MCClellan JlAACAP:, March 2005
  • Avoid circular reasoning such as: a mood stabilizer helps greatly thus the patient must have a mood disorder
  • 1.) We find what we look for
  • 2.) # 1 does not apply to me
  • 3.) Although it is far easier to conceptualize complex sets of behavioral/emotional responses and interactions as emanating from a unique specific illness, DSM “Disorders”
  • It is unlikely that nature simply divided these phenomena into normal and categorically impaired
  • See on handout
bipolar disorder76
Bipolar Disorder
  • Psychopharmacology
    • Use meds approved for adults
      • Mood stabilizers
      • Atypicals
    • Proceed systematically
    • Avoid undue polypharmacy
valproate vs lithium
Valproate vs. Lithium
  • Prospective, 8 week, open label outpt.
  • BP I or II,Ages 5-17, mean age 10years
  • Remission with Li/DVPA combo
  • Relapsed on LI or DVPX monotherapy
  • Findling et al JAAP,45:2, Feb. 2006
dvpx vs lithium
DVPX vs Lithium
  • 276 children screened
  • 161 children enrolled
  • 139 dosed with Li/DVPX
  • 60 randomized to Li or DVPX
li vs dvpx
Li vs DVPX
  • Mean age of onset 6.4 (3.9) years old
  • Mean length of illness: 185.1 (131.5) days

Findling et al

lithium vs dvpx
Lithium vs DVPX
  • 60 responders to combination of Li/DVPX
  • Randomized to Li or DVPX alone
  • 38 of the relapse subjects re-initiated to Li/DVPX combined
  • 34 (89.5%) responded well to combination