Treatment of Mood Disorders in Children and Adolescents

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Treatment of Mood Disorders in Children and
Adolescents

• Terrence Clark MD
• January 23, 2007

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(No Transcript)
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Treatment

• GOOD TREATMENT BEGINS WITH GOOD ASSESSMENT

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Objectives

• 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

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Objectives

• 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

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Four Cases1

• 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

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Case 2

• !6 year old girl with depression
• excellent response to an SSRI
• Clinician feels good about the excellent
  treatment outcome
• Truth

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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

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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

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

• 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, 443, March
  2005Commmentary on Treatment Guidelines

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Normal Children

• Active
• Imaginative
• Boastful
• Sensitive to the environment
• Act out periodically

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Assessment

• Interview of parents
• Interview of child
• Review of prior mental health records
• Review of medical/PCP records
• Psychological Inventories

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Interview of Parents

• Birth and developmental history
• Family history
• Social
• School
• Medical
• Marital

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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

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Interview with kids

• Listen to the patients story, following leads
  with open ended questions
• Dont squeeze the patient into a medical model
  shoe
• Save medical model, closed-ended questions to
  the later part of the interview

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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 gt
  male 21) until 50 Years old

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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

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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

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Major Depression

• Criteria for Major Depressive Episode
• 1. Depressed mood most of the day,
• IN children and adolescent can be irritable
  mood.

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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

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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

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Depression

• Psychotherapy first
• CBT
• Interpersonal
• Family
• Psycho education

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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

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CBT

• Manualized therapy
• Childrens group CBT
• Multi-parent group CBT

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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, 4512, Dec. 2006

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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

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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)

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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

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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 453 March 2006

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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

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Treatment of Depression in Children -
Pharmacotherapy

• SSRIS all SSRIs effective
• Recent concern regarding risk of increased
  suicidal thinking in children taking
  antidepressants
• Tricyclic antidepressants no proven efficacy,
  more side effects, fatal in overdose

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• BIPOLAR DISORDER

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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

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Bipolar Disorder

• Clinical Description
• First symptoms usually depressive
• Psychotic symptoms commons
• therefore misdiagnosed as schizophrenia
• Hyperactivity, pressured speech, distractibility

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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, 408 August, 2001

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Comorbidity in Adolescent Inpatients with Bipolar
Disorder
(N34)
West et al, Biol Psych 199639458-460
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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

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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.
  198239549-555

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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

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Differential PEA-BD vs. ADHD

• Five DSM-IV criteria do not overlap
• Elation
• Grandiosity
• Racing thoughts/flight of ideas
• Decreased need for sleep
• Hypersexuality

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Similarities PEA-BD and AO-BD

• Elated mood
• Mixed episodes, long duration episodes
• low inter-episode recovery

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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

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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

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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

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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

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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, 159927-933

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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

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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. 2001158125-127.
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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

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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

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Treatment of BP in Children and Adolescents

• Guidelines similar to adults
• Medications are effective
• Combination pharmacotherapy often necessary to
  gain remission

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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,
  443Mar. 2005

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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, 443, Mar,
  2005

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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

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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

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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

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Common Lithium Side Effects

• Nausea
• Diarrhea
• Polyuria
• tremor
• Weight gain
• Cognitive dulling

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Major Concerns with Lithium

• Lithium toxicity
• Lethal in overdose
• Fetal malformations (cardiovascular)

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Concerns

• Lithium cognitive dulling, Lithium toxicity,
  tremor, renal function, thyroid
• Topiramate cognitive impairment
• Carbamazepam , Oxcarbamazepam interference with
  birth control pills

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Common DepakoteSide Effects

• tremor
• fatigue
• Weight gain

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Valproate (Depakote) Adverse Side Effects

• Fetal abnormalities (neural tube defects)
• Polycystic Ovarian Syndrome
• Pancreatitis
• Elevated Ammonia
• Lowered platelets

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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

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PCOS

• 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 528-35

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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

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Atypical Antipsychotics

• Current agents
• Risperidone
• Olanzapine
• Quetiapine
• Ziprazidone
• Aripiprazole

• Often necessary
• Limit use because of...
• Metabolic syndrome
• Sedation
• Weight gain

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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, 1632072-2079

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Conclusion

• Pediatric Bipolar Disorder is a serious illness
• Treatment works but is difficult, often needs
  periodic readjustment
• Team approach is necessary

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Conclusions

• Treatment guidelines for Ped BP largely based on
  adult literature which justifiably promotes
  aggressive pharmacotherapy

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Conclusion

• Co-morbidity is the rule rather then the
  exception
• Incorrect diagnosis is common, especially as
  depression or ADHD

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Conclusions

• 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

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Conclusions

• 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

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Caveats

• Avoid circular reasoning such as a mood
  stabilizer helps greatly thus the patient must
  have a mood disorder

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Caveats

• 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

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Resources

• See on handout

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Bipolar Disorder

• Psychopharmacology
• Use meds approved for adults
• Mood stabilizers
• Atypicals
• Proceed systematically
• Avoid undue polypharmacy

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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,452, Feb. 2006

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DVPX vs Lithium

• 276 children screened
• 161 children enrolled
• 139 dosed with Li/DVPX
• 60 randomized to Li or DVPX

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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

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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