Title: Mood Disorders Children and Adolescents
1Mood DisordersChildren and Adolescents
- Waqar Waheed, MD FRCPC, DABPN
- Department of Psychiatry
- University of Calgary
2Impact
- Impaired relationships
- Poor school performance
- Substance use
- Legal problems
- Suicide
3Mood Disorders Depressive
- Major Depressive Disorder
- Dysthymic Disorder
- Depressive Disorder Not Otherwise Specified
4 Statistics
-
- 1 in 250 pre-schoolers,
- 1 in 40Â children,
- 1 in 12 adolescents
- suffers from depression
- (Birmaher et al 1996a)
5Etiology
- The single most predictive factor associated with
risk of developing MDD is
6- High family loading, heritability for MDD is 40
- Craddock et al 2005
7Etiology
- Biological Factors
- Genetic Factors
- Psychological Factors
- Social Factors
8 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)
9- Neurotransmitters
- Norepinephrine/Serotonin Dysregulation (Ryan et
al 1990) - MRI Findings-Decreased frontal lobe volume and
increased ventricular volume (Steingard et al
1996) -
10Genetic Factors
- Concordance rates for depression are at least
double in monozygotic twins (McGuffin and Katz
1989) than in dizygotic twins (Carlson and Abbott
1995)
11- Lifetime risk for Major Depression in children
of depressed patients ranges from 15 (Orvaschel
et al 1988) to 45 (Hammen et al 1990)
12Neuronal 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
13Psychological Factors
- Cognitive Behavioral Model
- Research in children and adolescents supports the
validity and clinical utility of this model
(Brent et al 1997) -
14Social Factors
- Less Than 100 Twin Concordance
- Positive correlation of life events with the
onset of depression in children
15Major Depressive Disorder
- Either
- 1. Depressed or Irritable
- Mood
- or
- 2. Anhedonia
- Failure to make expected weight gains
16Dysthymic Disorder
- Depressed or Irritable Mood for at least one year
17Double 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)
18Clinical Presentation
- The expression of depressive symptoms varies
according to age
19Pre-School Children
- appear sad and slowed
- limited verbal communication (Kashani and
Carlson, 1987)
20mood congruent auditory
hallucinationssomatic complaints(E.B. Weller
et al 2004a)
21Adolescents
- Delusions
- Pervasive anhedonia
22Co-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)
23Mood Disorders Bipolar
- Bipolar I Disorder
- Bipolar II Disorder
- Cyclothymic Disorder
- Bipolar Disorder Not Otherwise Specified
24Mood 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
25Diagnostic Controversy
- Use of the A/I phenotype
- Wash U cardinal symptoms
- Biederman group approach
- CBCL phenotype
26A/I Phenotype
- Also present in
- ODD/CD
- Autistic Disorder
- ADHD
- MDD
27Wash U Phenptype
- Requires elation and/or grandiosity as cardinal
symptoms
28Biederman group phenotype
- Broad, there is no construct of cardinal
symptom(s)
29CBCL Bipolar Phenotype
- Includes hyperactivity and suicidal
ideation/behaviors
30Proposed definitions of episodes and cycling
phenomena
31Episode
- Onset to offset of manic episode using DSM-IV TR
criteria
32Ultra-rapid cycling
- Mood switches every few days during an episode
33Ultradian Cycling
- Mood switches multiple times daily during an
episode - In 78-99 of children with Bipolar I (in 20 of
adult patient)
34Clinical Presentation
- The expression of manic symptoms varies in
children according to their age
35Pre-School Children
- Explosive/unmanageable temper tantrums
- Sexualized behaviors
- Nightmares with violent themes
- (Popper 1984)
36School Age Children
- Atypical" manic episodes among prepubertal
children - Chronic, non-episodic, rapid cycling pattern
- (Geller and Luby 1997)
37Adolescents
- 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)
38Differential Diagnosis of Bipolar Disorder
39Differential Diagnosis of Bipolar Disorder
- ADHD
- Disruptive Behavior Disorders (ODD/CD)
40Suspect 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
41Bipolar 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,
42BIPOLAR 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,
43BIPOLAR 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.
44Cyclothymia
- In children and adolescents, the minimum
duration of symptoms is 1 year
45Co-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
46Assessment
- Clinical interviews of identified patient, family
and school teacher
47Rating Scales
- Children's Depression Inventory (CDI)
- Children's Depression Rating Scale (CDRS)
48- Hamilton Depression Rating Scale (HAM-D)
- Young Mania Rating Scale-Parent Version (P-YMRS)
49Lab Tests
- Thyroid Function Tests
- Urine Drug Screen
- Pregnancy Test
50Dexamethasone 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
51Other Investigations
- MRI Head
- Not indicated in the absence of focal
neurological signs.
52EEG/Sleep Study
- To assess for seizure disorder if there is
clinical suspicion
53Prognosis
54- Greater symptom severity and the presence of
co-morbidity are predictors of a poorer prognosis
55- The mean duration of a untreated Major Depressive
Episode is 9 months
56- For untreated Dysthymic Disorder, the mean
duration is 4 years
57- 18 month rate of recurrence for patients
noncompliant with successful medication treatment
is 90 (38 in med-comlian
58Treatment Modalities
- Setting
- Psychotherapy
- Medications
59Other Modalities
- ECT
- Light Therapy
- Transcranial Deep Brain Stimulation
- Vagal Nerve Stimulation
60Psychotherapy
- Supportive Therapy
- Cognitive-Behavioral Therapy
- Interpersonal Psychotherapy
61Cognitive-Behavioral Therapy
- CBT is based on the cognitive triad negative
thoughts about the self, the world, and the future
62Supportive Psychotherapy
- Maintain/improve self-esteem
- Minimize/prevent symptom recurrence
- Maximize patients adaptive capacities
- The most widely practiced form of individual
63Interpersonal Psychotherapy
- IPT aims to intervene specifically in social
functioning with consequent benefits in symptom
experience. (for 12 and older)
64IPT-A
- Patient's social functioning problems are
conceptualized as one or more of four areas
65- Interpersonal Disputes (relationship conflict)
- Role Transitions (puberty, new school, new
family) - Grief (death of a loved one)
- Interpersonal Deficits (social/communication
skills)
66Other Forms of Therapy
- Group Therapy
- Family Therapy
- Play Therapy
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68MEDICATION MANAGEMENT OFDEPRESSIVE DISORDERS
69SSRI 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)
70Other 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.
71SSRIs 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
72SSRIs 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)
73Other 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
74Side Effects
75Indications
- 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.
76Dosing
- 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
77Psychotic Depression
- Augment SSRI with an antipsychotic until
psychosis stable, then taper and discontinue the
antipsychotic while maintaining antidepressant med
78- Should be continued for at least 6 months after
complete symptom remission
79Treatment-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).
80TRD
- 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.
81TRD
- 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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83Light Therapy
- Typically used for the treatment of Seasonal
Affective Disorder - and of delayed sleep phase disorder (DSPD)
84- 20-30 minutes each morning during the fall,
winter and early spring months - Symptom relief within one to two weeks of regular
use
85Electro-Convulsive Therapy
- May be used for adolescents
86- The principal adverse effect of ECT is
anterograde and retrograde memory impairment - Used for refractory depression/mania or psychotic
depression
87Transcranial Magnetic Stimulation
- TMS is a procedure in which electrical activity
in the brain is influenced by a pulsed magnetic
field
88Types 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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90rTMS 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).
91rTMS 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).
92Deep 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.
93DBS
- 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.
94Vagal 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
95MEDICATION MANAGEMENT OFBIPOLAR DISORDERS
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97Medications 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)
98General Considerations
- FDA approved medications
- Risperidone/Aripiprazole (10 yo)
- Lithium Co3 (12 yo)
- Olanzapine (13 yo)
99- Blood levels are monitored for Lithium, Valproic
acid and Carbamazepine
100- Onset of action usually within the first week of
treatment - (most RCTs were 3 weeks in duration)
101Pharmacogenetics 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
102Side Effects
103Monitoring
- 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
104Types of Antipsychotic Medications
105Mechanism of Action
- Both types of antipsychotics block Dopamine
receptors - The defining feature of the atypical
antipsychotics is that they also block Serotonin
receptors.
106Common Side Effects
- Sedation
- Weight Gain
- EPS (parkinsonism, akathisia, dystonia)-managed
with anticholinergic meds - Metabolic Syndrome
- Dyslipidemia
- Impaired glucose tolerance
- BP elevation/ Central adiposity
107Uncommon Side Effects
- Neuroleptic Malignant Syndrome
- Heat Stroke
- Tardive dyskinesia
- Seizures
- Heart Rhythm disturbance
108Monitoring
- 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
109Abuse 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)
110Treatment 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).
111Treatment for Bipolar Depression
- Lithium CO3
- Lamotrigine
- They have both demonstrated benefit either as
monotherapy or as adjunctive treatment in open
label studies
112Questions/Comments?
- Waqar.Waheed_at_albertahealthservices.ca