Mood Disorders Children and Adolescents

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Mood DisordersChildren and Adolescents

• Waqar Waheed, MD FRCPC, DABPN
• Department of Psychiatry
• University of Calgary

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Impact

• Impaired relationships
• Poor school performance
• Substance use
• Legal problems
• Suicide

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Mood Disorders Depressive

• Major Depressive Disorder
• Dysthymic Disorder
• Depressive Disorder Not Otherwise Specified

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Statistics

• 1 in 250 pre-schoolers,
• 1 in 40 children,
• 1 in 12 adolescents
• suffers from depression
• (Birmaher et al 1996a)

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Etiology

• The single most predictive factor associated with
  risk of developing MDD is

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• High family loading, heritability for MDD is 40
• Craddock et al 2005

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Etiology

• Biological Factors
• Genetic Factors
• Psychological Factors
• Social Factors

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Biological Factors

• Subnormal Growth Hormone Secretion (Ryan et al
  1994)
• Subnormal Thyroid Hormone Secretion (Dorn et al
  1996)
• Dysregulation of the Hypothalamic-Pituitary-Adrena
  l axis-Conflicting data
• (Birmaher et al 1996, Pfeiffer et al 1991)

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• Neurotransmitters
• Norepinephrine/Serotonin Dysregulation (Ryan et
  al 1990)
• MRI Findings-Decreased frontal lobe volume and
  increased ventricular volume (Steingard et al
  1996)

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Genetic Factors

• Concordance rates for depression are at least
  double in monozygotic twins (McGuffin and Katz
  1989) than in dizygotic twins (Carlson and Abbott
  1995)

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• Lifetime risk for Major Depression in children
  of depressed patients ranges from 15 (Orvaschel
  et al 1988) to 45 (Hammen et al 1990)

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Neuronal serotonin presynaptic reuptake site

• People who have homozygosity or heterozygosity
  for the less functional allele for this site are
  most likely to develop MDD when exposed to
  recurrent negative life events
• Caspi et al 2003, Kendler et al 2005

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Psychological Factors

• Cognitive Behavioral Model
• Research in children and adolescents supports the
  validity and clinical utility of this model
  (Brent et al 1997)

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Social Factors

• Less Than 100 Twin Concordance
• Positive correlation of life events with the
  onset of depression in children

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Major Depressive Disorder

• Either
• 1. Depressed or Irritable
• Mood
• or
• 2. Anhedonia
• Failure to make expected weight gains

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Dysthymic Disorder

• Depressed or Irritable Mood for at least one year

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Double Depression

• Dysthymia has been theorized to be a gateway to
  recurrent mood disorders
• Children usually have their first episode of
  Major Depressive Disorder 2-3 years after the
  onset of Dysthymia
• (Kovacs et al 1994)

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Clinical Presentation

• The expression of depressive symptoms varies
  according to age

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Pre-School Children

• appear sad and slowed
• limited verbal communication (Kashani and
  Carlson, 1987)

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mood congruent auditory
hallucinationssomatic complaints(E.B. Weller
et al 2004a)
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Adolescents

• Delusions
• Pervasive anhedonia

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Co-Morbidities

• Up to 50 have two or more comorbidities
• Anxiety Disorders
• Disruptive Behavior Disorders
• ADHD
• Substance Use Disorders
• (Presenting symptom in 20 of depressed
  adolescents, Weller and Weller 2004)

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Mood Disorders Bipolar

• Bipolar I Disorder
• Bipolar II Disorder
• Cyclothymic Disorder
• Bipolar Disorder Not Otherwise Specified

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Mood Disorders Bipolar

• Diagnostic (DSM-IV TR) Criteria are identical to
  those for adults
• Less common than Depressive Disorders in this age
  group (Lifetime Prevalence 1)
• (Levinsohn et al 1995)
• 2 out of every 3 patients with Bipolar Disorder
  initially present with a Major Depressive
  Disorder

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Diagnostic Controversy

• Use of the A/I phenotype
• Wash U cardinal symptoms
• Biederman group approach
• CBCL phenotype

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A/I Phenotype

• Also present in
• ODD/CD
• Autistic Disorder
• ADHD
• MDD

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Wash U Phenptype

• Requires elation and/or grandiosity as cardinal
  symptoms

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Biederman group phenotype

• Broad, there is no construct of cardinal
  symptom(s)

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CBCL Bipolar Phenotype

• Includes hyperactivity and suicidal
  ideation/behaviors

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Proposed definitions of episodes and cycling
phenomena
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Episode

• Onset to offset of manic episode using DSM-IV TR
  criteria

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Ultra-rapid cycling

• Mood switches every few days during an episode

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Ultradian Cycling

• Mood switches multiple times daily during an
  episode
• In 78-99 of children with Bipolar I (in 20 of
  adult patient)

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Clinical Presentation

• The expression of manic symptoms varies in
  children according to their age

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Pre-School Children

• Explosive/unmanageable temper tantrums
• Sexualized behaviors
• Nightmares with violent themes
• (Popper 1984)

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School Age Children

• Atypical" manic episodes among prepubertal
  children
• Chronic, non-episodic, rapid cycling pattern
• (Geller and Luby 1997)

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Adolescents

• Irritable/labile mood is MORE common than
  elevated/expansive mood
• Psychotic features are MORE common than in
  adults
• (Ballenger et al 1992, McElroy et al 1997)

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Differential Diagnosis of Bipolar Disorder
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Differential Diagnosis of Bipolar Disorder

• ADHD
• Disruptive Behavior Disorders (ODD/CD)

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Suspect the presence of Bipolar Disorder in a
child vs. ADHD if

• The ADHD symptoms appeared later in life (e.g.,
  at age 10 years old or older)
• The symptoms of ADHD appeared abruptly in an
  otherwise healthy child
• The ADHD symptoms were responding to stimulants
  and now are not
• The ADHD symptoms come and go and tend to occur
  with mood changes

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Bipolar Disorder vs. ADHD

• A child with ADHD has recurrent severe mood
  swings, temper outbursts, or rages.
• A child with ADHD has hallucinations and/or
  delusions.
• A child with ADHD has a strong family history of
  bipolar disorder in his or her family,

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BIPOLAR DISORDER VS. DISRUPTIVE BEHAVIOR
DISORDER

• If a child has off and on oppositional or
  conduct symptoms or these symptoms only appear
  when the child has mood problems,
• If a child has severe behavior problems that are
  not responding to treatment,

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BIPOLAR DISORDER VS. DISRUPTIVE BEHAVIOR
DISORDER

• If a child has behavior problems and a family
  history of BP disorder,
• If a child has behavior problems and is having
  hallucinations and delusions.

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Cyclothymia

• In children and adolescents, the minimum
  duration of symptoms is 1 year

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Co-Morbidities

• Occurrence of co-morbid disorders with bipolar
  disorders is close to 100 (Kessler et al 2001)
• ADHD
• Disruptive Behavior Disorders
• Anxiety Disorders
• Substance use Disorders

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Assessment

• Clinical interviews of identified patient, family
  and school teacher

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Rating Scales

• Children's Depression Inventory (CDI)
• Children's Depression Rating Scale (CDRS)

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• Hamilton Depression Rating Scale (HAM-D)
• Young Mania Rating Scale-Parent Version (P-YMRS)

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Lab Tests

• Thyroid Function Tests
• Urine Drug Screen
• Pregnancy Test

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Dexamethasone Suppression Test

• Positive initial DST status in major depression
  does not add significantly to the likelihood of
  antidepressant response
• Negative test (Cortisol suppressed in response to
  Dex) is not an indication for withholding
  antidepressant treatment
• No relationship to suicidality

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Other Investigations

• MRI Head
• Not indicated in the absence of focal
  neurological signs.

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EEG/Sleep Study

• To assess for seizure disorder if there is
  clinical suspicion

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Prognosis
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• Greater symptom severity and the presence of
  co-morbidity are predictors of a poorer prognosis

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• The mean duration of a untreated Major Depressive
  Episode is 9 months

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• For untreated Dysthymic Disorder, the mean
  duration is 4 years

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• 18 month rate of recurrence for patients
  noncompliant with successful medication treatment
  is 90 (38 in med-comlian

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Treatment Modalities

• Setting
• Psychotherapy
• Medications

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Other Modalities

• ECT
• Light Therapy
• Transcranial Deep Brain Stimulation
• Vagal Nerve Stimulation

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Psychotherapy

• Supportive Therapy
• Cognitive-Behavioral Therapy
• Interpersonal Psychotherapy

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Cognitive-Behavioral Therapy

• CBT is based on the cognitive triad negative
  thoughts about the self, the world, and the future

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Supportive Psychotherapy

• Maintain/improve self-esteem
• Minimize/prevent symptom recurrence
• Maximize patients adaptive capacities
• The most widely practiced form of individual

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Interpersonal Psychotherapy

• IPT aims to intervene specifically in social
  functioning with consequent benefits in symptom
  experience. (for 12 and older)

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IPT-A

• Patient's social functioning problems are
  conceptualized as one or more of four areas

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• Interpersonal Disputes (relationship conflict)
• Role Transitions (puberty, new school, new
  family)
• Grief (death of a loved one)
• Interpersonal Deficits (social/communication
  skills)

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Other Forms of Therapy

• Group Therapy
• Family Therapy
• Play Therapy

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MEDICATION MANAGEMENT OFDEPRESSIVE DISORDERS
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SSRI treatment

• Fluoxetine - FDA approved for depression in
  children and adolescents
• Escitalopram - FDA approved for depression in
  adolescents
• Recent meta-analysis indicates a NNT of 6 for
  fluoxetine, 10 for other SSRIs in adolescent
  depression (Bridge et al 2007)

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Other treatments

• There is evidence for the use of venlafaxine
  (Emslie et al 2007) and bupropion in the
  treatment of adolescent depression (Daviss 2008).
• TCAs have been shown to be of benefit in child
  and adolescent depression (Hazell et al 2006) but
  their use continues to be limited by the a/e,
  toxicity profiles.

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SSRIs and Suicidality

• Two meta-analyses (Bridge et al 2007, Hammad et
  al 2006) found an increase of 1 to 3
  spontaneously reported suicidal adverse events
  per 100 youth treated with SSRIs
• The adverse event included increases in suicidal
  ideation (majority) and attempts at suicide (less
  commonly) with no completed suicides

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SSRIs and Suicidality

• The NNH was 112
• Given the NNT of 10, nearly 11 times the number
  of adolescents would respond favorably than might
  spontaneously report suicidality
• Suicide rates went up following a decline in the
  use of SSRIs due to the black box warning
  (Gibbons et al 2006, 2007 Libby et al 2007)

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Other adverse effects

• GI
• Headache
• Insomnia/hypersomnia
• Jitteriness/tremulousness
• Decreased sexual drive
• Behavioral activation (8) usually within 7-10
  days, mgmt is to switch med
• Onset of mania (2-3) usually in 2-3 weeks,
  switch med, consider mood stabilizer

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Side Effects
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Indications

• Mild depressive illness? supportive psychotherapy
• For moderate to severe depressive illnesses
  (having more than the minimal number of
  diagnostic criteria) or non-responders to brief
  supportive therapy ? consider SSRI, CBT/IPT or a
  combination.

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Dosing

• Prozac usually 10 mg x 1 week then 20 mg,
  re-evaluate in 4-6 weeks, if no response, change
  to 30-40 mg
• Escitalopram, similar except at half the dosages

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Psychotic Depression

• Augment SSRI with an antipsychotic until
  psychosis stable, then taper and discontinue the
  antipsychotic while maintaining antidepressant med

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• Should be continued for at least 6 months after
  complete symptom remission

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Treatment-resistant depression

• Treatment-resistant depression is defined as
  failure of at least two adequate antidepressant
  drug trials of at least 810 weeks' duration,
  each at a therapeutic dose and serum level (if
  available) without even mild improvement
• (American Academy of Child and Adolescent
  Psychiatry 2004 Ghaziuddin et al. 1996 Kutcher
  and Robertson 1995 Walter and Rey 1997).

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TRD

• Optimization (extending the initial medication
  trial and/or adjusting the dose adding CBT or
  IPT)-usually used if there has been partial
  response
• Switching to another agent in the same or a
  different class of medications, augmentation, or
  a combination (e.g., lithium, triidothyronine)
  (Hughes et al. 2007) usually used if no
  response or unable to tolerate
• No studies have validated these practices in
  children.

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TRD

• Finally, the use of somatic therapies that have
  not been well studied in children, such as
  transcranial magnetic stimulation, or more
  intensive somatic therapies for depressed teens,
  such as ECT, should be considered

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Light Therapy

• Typically used for the treatment of Seasonal
  Affective Disorder
• and of delayed sleep phase disorder (DSPD)

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• 20-30 minutes each morning during the fall,
  winter and early spring months
• Symptom relief within one to two weeks of regular
  use

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Electro-Convulsive Therapy

• May be used for adolescents

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• The principal adverse effect of ECT is
  anterograde and retrograde memory impairment
• Used for refractory depression/mania or psychotic
  depression

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Transcranial Magnetic Stimulation

• TMS is a procedure in which electrical activity
  in the brain is influenced by a pulsed magnetic
  field

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Types of TMS

• Single-pulse TMS (diagnostic and research
  applications)
• Paired-pulse TMS (used to evaluate cortical
  excitability)
• Repetitive TMS (rTMS) has been used in
  therapeutic applications because it is capable of
  producing rapid bursts of pulses lasting
  approximately 60 seconds
• An advantage of the rTMS procedure in the
  clinical setting is that no anesthesia is needed.
• (Curra et al. 2002 Quintana 2005)

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rTMS Research in adolescent depression

• Adjunctive rTMS treatment in a prospective open
  label study in 8 adolescents demonstrated benefit
  (Wall et al 2011)
• Two small case series (totaling nine subjects)
  have reported on the use of rTMS in adolescent
  depression (Loo et al. 2006 Walter et al. 2001).
  

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rTMS Adverse Effects

• Tension headaches reported in one patient were
  the only adverse effects noted from the rTMS
  procedure
• (Walter et al. 2001)
• Neuropsychological testing revealed no cognitive
  side effects after the course of rTMS was
  completed
• (Loo et al. 2006).

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Deep Brain Stimulation

• Deep brain stimulation (DBS) is a neurosurgical
  procedure
• Stimulation electrodes are chronically implanted
  into specific areas of the brain
• An implanted, externally programmable pacemaker
  delivers high-frequency electrical pulses.
• The site of electrode placement differs depending
  on the disorder to be treated.

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DBS

• DBS is currently approved for generalized
  dystonia in children 7 years and older. Its place
  in psychiatry is presently unclear.
• DBS is considered an experimental procedure in
  children and adolescents with psychiatric
  disorders.

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Vagal Nerve Stimulation

• In July 2005, the VNS Therapy System was
  approved by the FDA for depression patients who
  have run out of treatment options
• No studies to date in use for children/adolescents
  with mood disorders

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MEDICATION MANAGEMENT OFBIPOLAR DISORDERS
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Medications Bipolar Disorders

• Lithium Carbonate (2 RCTs)
• Valproic Acid (2 RCTs)
• Carbamazepine (open label)
• Atypical Antipsychotic Medications (1 RCT for R,
  O, S, A and Z)

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General Considerations

• FDA approved medications
• Risperidone/Aripiprazole (10 yo)
• Lithium Co3 (12 yo)
• Olanzapine (13 yo)

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• Blood levels are monitored for Lithium, Valproic
  acid and Carbamazepine

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• Onset of action usually within the first week of
  treatment
• (most RCTs were 3 weeks in duration)

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Pharmacogenetics of CBZ

• CBZ places individuals with HLA B1502 allele at
  high risk of SJ Syndrome
• These patients may continue if identified 1-2
  months after initiation of treatment.
• Absence of allele does not preclude risk of SJ
  Syndrome

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Side Effects
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Monitoring

• In addition to clinical evaluation, lab tests are
  usually recommended periodically to assess for
• Blood Levels of Medication
• Bone Marrow Function
• Liver/Pancreas Function
• Thyroid Function
• Kidney Function/Electrolyte levels
• ECG

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Types of Antipsychotic Medications
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Mechanism of Action

• Both types of antipsychotics block Dopamine
  receptors
• The defining feature of the atypical
  antipsychotics is that they also block Serotonin
  receptors.

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Common Side Effects

• Sedation
• Weight Gain
• EPS (parkinsonism, akathisia, dystonia)-managed
  with anticholinergic meds
• Metabolic Syndrome
• Dyslipidemia
• Impaired glucose tolerance
• BP elevation/ Central adiposity

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Uncommon Side Effects

• Neuroleptic Malignant Syndrome
• Heat Stroke
• Tardive dyskinesia
• Seizures
• Heart Rhythm disturbance

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Monitoring

• In addition to clinical evaluation (including
  weight and blood pressure assessment), lab tests
  used for monitoring including
• Fasting blood sugar
• Cholesterol levels
• Liver functions
• Electrocardiogram

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Abuse Potential

• Although not as common as with medications such
  as Ritalin, Dexedrine or benzodiazepines, the
  antipsychotic medication Seroquel (street name
  Qwell, Susie Q) has been increasingly
  identified as a substance of abuse
• (Pinta et al 2007, Waheed et al 2005, Wirshing
  et al 2004)

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Treatment Resistant Bipolar Disorder

• For bipolar disorder, failure of at least one
  antipsychoticmood stabilizer/antidepressant
  combination treatment trial of at least 6 weeks'
  duration without even mild improvement is
  considered evidence for treatment refractoriness
• (American Academy of Child and Adolescent
  Psychiatry 2004 Kutcher and Robertson 1995
  Walter et al. 1999).

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Treatment for Bipolar Depression

• Lithium CO3
• Lamotrigine
• They have both demonstrated benefit either as
  monotherapy or as adjunctive treatment in open
  label studies

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Questions/Comments?

• Waqar.Waheed_at_albertahealthservices.ca