Download The Mind Child and Adolescent Psychiatry

Mood Disorders
Children and
Adolescents
Waqar Waheed, MD FRCPC, DABPN
Department of Psychiatry
University of Calgary
Impact
• Impaired relationships
• Poor school performance
• Substance use
• Legal problems
• Suicide
Mood Disorders: Depressive
• Major Depressive
Disorder
• Dysthymic Disorder
• Depressive Disorder Not
Otherwise Specified
Statistics
1 in 250 pre-schoolers,
1 in 40 children,
1 in 12 adolescents
suffers from depression
(Birmaher et al 1996a)
Etiology
• The single most predictive factor
associated with risk of developing MDD
is…
• High family loading,
heritability for MDD is 40 %
• Craddock et al 2005
Etiology
•
•
•
•
Biological Factors
Genetic Factors
Psychological Factors
Social Factors
Biological Factors
• Subnormal Growth Hormone
Secretion (Ryan et al 1994)
• Subnormal Thyroid Hormone
Secretion (Dorn et al 1996)
• Dysregulation of the HypothalamicPituitary-Adrenal axis-Conflicting data
(Birmaher et al 1996, Pfeiffer et al 1991)
• Neurotransmitters
– Norepinephrine/Serotonin Dysregulation
(Ryan et al 1990)
• MRI Findings-Decreased frontal lobe
volume and increased ventricular
volume (Steingard et al 1996)
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)
Lifetime risk for Major
Depression in children of
depressed patients ranges
from 15% (Orvaschel et al 1988) to 45%
(Hammen et al 1990)
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
Psychological Factors
• Cognitive Behavioral Model
–Research in children and
adolescents supports the
validity and clinical utility
of this model (Brent et al 1997)
Social Factors
• Less Than 100% Twin
Concordance
• Positive correlation of life
events with the onset of
depression in children
Major Depressive Disorder
• Either
1. Depressed or Irritable
Mood
or
2. Anhedonia
• Failure to make expected
weight gains
Dysthymic Disorder
Depressed or Irritable
Mood for at least one
year
“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)
Clinical Presentation
The expression of
depressive symptoms varies
according to age
Pre-School Children
• appear sad and slowed
• limited verbal
communication (Kashani and
Carlson, 1987)
mood congruent
auditory hallucinations
somatic complaints
(E.B. Weller et al 2004a)
Adolescents
• Delusions
• Pervasive anhedonia
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)
Mood Disorders: Bipolar
• Bipolar I Disorder
• Bipolar II Disorder
• Cyclothymic Disorder
• Bipolar Disorder Not
Otherwise Specified
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
Diagnostic Controversy
• Use of the A/I phenotype
• Wash U cardinal symptoms
• Biederman group approach
• CBCL phenotype
A/I Phenotype
• Also present in
– ODD/CD
– Autistic Disorder
– ADHD
– MDD
Wash U Phenptype
• Requires elation and/or grandiosity as
cardinal symptoms
Biederman group phenotype
• Broad, there is no construct
of cardinal symptom(s)
CBCL Bipolar Phenotype
• Includes hyperactivity and suicidal
ideation/behaviors
Proposed definitions of
episodes and cycling
phenomena
Episode
• Onset to offset of manic
episode using DSM-IV
TR criteria
Ultra-rapid cycling
• Mood “switches” every few
days during an episode
Ultradian Cycling
• Mood “switches” multiple
times daily during an
episode
• In 78-99% of children with
Bipolar I (in 20 % of adult
patient)
Clinical Presentation
The expression of manic
symptoms varies in
children according to
their age
Pre-School Children
• Explosive/unmanageable
temper tantrums
• Sexualized behaviors
• Nightmares with violent
themes
School Age Children
• “Atypical" manic
episodes among
prepubertal children
• Chronic, non-episodic,
rapid cycling pattern
(Geller and Luby 1997)
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)
Differential Diagnosis of
Bipolar Disorder
Differential Diagnosis of Bipolar
Disorder
• ADHD
• Disruptive Behavior Disorders (ODD/CD)
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
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,
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,
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.
Cyclothymia
In children and
adolescents, the
minimum duration of
symptoms is 1 year
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
Assessment
• Clinical interviews of identified
patient, family and school teacher
Rating Scales
•Children's Depression
Inventory (CDI)
•Children's Depression
Rating Scale (CDRS)
•Hamilton Depression
Rating Scale (HAM-D)
•Young Mania Rating
Scale-Parent Version
(P-YMRS)
Lab Tests
• Thyroid Function Tests
• Urine Drug Screen
• Pregnancy Test
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
Other Investigations
•MRI Head
Not indicated in the absence of
focal neurological signs.
EEG/Sleep Study
• To assess for seizure disorder if there is
clinical suspicion
Prognosis
• Greater symptom
severity and the
presence of co-morbidity
are predictors of a poorer
prognosis
•The mean duration of
a untreated Major
Depressive Episode is
9 months
•For untreated
Dysthymic Disorder,
the mean duration is 4
years
• 18 month rate of recurrence
for patients noncompliant with
successful medication
treatment is 90 (38% in medcomlian%
Treatment Modalities
•Setting
•Psychotherapy
•Medications
Other Modalities
• ECT
• Light Therapy
• Transcranial Deep Brain
Stimulation
• Vagal Nerve Stimulation
Psychotherapy
• Supportive Therapy
• Cognitive-Behavioral
Therapy
• Interpersonal
Psychotherapy
Cognitive-Behavioral Therapy
• CBT is based on the
cognitive triad; negative
thoughts about the self, the
world, and the future
Supportive
Psychotherapy
• Maintain/improve self-esteem
• Minimize/prevent symptom
recurrence
• Maximize patient’s adaptive
capacities
• The most widely practiced
form of individual
Interpersonal Psychotherapy
IPT aims to intervene
specifically in social
functioning with consequent
benefits in symptom
experience. (for 12 and older)
IPT-A
• Patient's social functioning
problems are conceptualized
as one or more of four areas
• Interpersonal Disputes
(relationship conflict)
• Role Transitions (puberty,
new school, new family)
• Grief (death of a loved one)
• Interpersonal Deficits
(social/communication
skills)
Other Forms of Therapy
•Group Therapy
•Family Therapy
•Play Therapy
MEDICATION MANAGEMENT OF
DEPRESSIVE DISORDERS
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 SSRI’s in adolescent
depression (Bridge et al 2007)
Other treatments
• There is evidence for the use of venlafaxine
(Emslie et al 2007) and bupropion in the
treatment of adolescent depression (Daviss
2008).
• TCA’s 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.
SSRI’s 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
SSRI’s 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)
Other adverse effects
•
•
•
•
•
•
GI
Headache
Insomnia/hypersomnia
Jitteriness/tremulousness
Decreased sexual drive
“Behavioral activation” (8%) usually within 710 days, mgmt is to switch med
• Onset of mania (2-3%) usually in 2-3 weeks,
switch med, consider mood stabilizer
Side Effects
Effexor
Wellbutrin
• Mild Hypertension
• Dry Mouth
• Decreased Appetite
• Insomnia
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.
Dosing
• Prozac usually 10 mg x 1 week then 20 mg, reevaluate in 4-6 weeks, if no response, change
to 30-40 mg
• Escitalopram, similar except at half the
dosages
Psychotic Depression
• Augment SSRI with an antipsychotic until
psychosis stable, then taper and discontinue
the antipsychotic while maintaining
antidepressant med
•Should be continued
for at least 6 months
after complete
symptom remission
Treatment-resistant depression
• Treatment-resistant depression is defined
as failure of at least two adequate
antidepressant drug trials of at least 8–10
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).
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.
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
Light Therapy
Typically used for the treatment of
Seasonal Affective Disorder
and of delayed sleep phase
disorder (DSPD)
• 20-30 minutes each
morning during the fall,
winter and early spring
months
• Symptom relief within one to
two weeks of regular use
Electro-Convulsive Therapy
• May be used for adolescents
• The principal adverse effect of
ECT is anterograde and
retrograde memory
impairment
• Used for refractory
depression/mania or psychotic
depression
Transcranial Magnetic
Stimulation
• TMS is a procedure in
which electrical activity in
the brain is influenced by
a pulsed magnetic field
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)
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).
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).
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.
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.
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
MEDICATION MANAGEMENT OF
BIPOLAR DISORDERS
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)
General Considerations
• FDA approved medications
–Risperidone/Aripiprazole
(10+ yo)
–Lithium Co3 (12+ yo)
–Olanzapine (13+ yo)
• Blood levels are monitored
for Lithium, Valproic acid
and Carbamazepine
• Onset of action usually
within the first week of
treatment
(most RCTs were 3 weeks in duration)
Pharmacogenetics of CBZ
• CBZ places individuals with HLA
B*1502 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
Side Effects
Tegretol
Lithium
Epival
• Agranulocytosis
• Aplastic Anemia
• Thyroid Problems
• Kidney Damage
• Heart Rhythm problems
• Liver/Pancreas Damage
• Alopecia
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
Types of Antipsychotic
Medications
First-Generation “Typical”
• Narrow Spectrum of action
• Haldol, Prolixin
Second Generation “Atypical”
• Broader Spectrum of action
• Risperdal, Zyprexa/Zydis, Seroquel
Mechanism of Action
•
Both types of antipsychotics block
Dopamine receptors
• The defining feature of the
“atypical” antipsychotics is that they
also block Serotonin receptors.
Common Side Effects
• Sedation
• Weight Gain
• EPS (parkinsonism, akathisia,
dystonia)-managed with
anticholinergic meds
• Metabolic Syndrome
–Dyslipidemia
–Impaired glucose tolerance
Uncommon Side Effects
• Neuroleptic Malignant
Syndrome
• Heat Stroke
• Tardive dyskinesia
• Seizures
• Heart Rhythm disturbance
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
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)
Treatment Resistant Bipolar
Disorder
• For bipolar disorder, failure of at least one
antipsychotic–mood
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).
Treatment for Bipolar Depression
• Lithium CO3
• Lamotrigine
• They have both demonstrated benefit
either as monotherapy or as adjunctive
treatment in open label studies
Questions/Comments?
Waqar.Waheed@albertahealth
services.ca