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Children and Adolescents with Bipolar Disorder

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Title: Children and Adolescents with Bipolar Disorder


1
Children and Adolescents with Bipolar Disorder
Boris Birmaher MD Department of Child
Psychiatry Western Psychiatric Institute and
Clinic University of Pittsburgh Medical Center
2
Do children and adolescents have Bipolar
Disorder (BP)? What are the manifestations of
BP disorder in children and adolescents? What
happens to these children over time? What is the
treatment for children with BP?
3
Bipolar Disorder in Youth
  • To validate a disorder
  • Reliable diagnosis
  • Continuous over time (follow-up studies)
  • Runs in Families
  • Biological correlates
  • Response to treatment

Robins and Guze, 1980
4
Clinical Manifestations
5
Bipolar Disorder Classical Clinical
Manifestations
  • DSM-IV Manic episode
  • Persistent elevated, expansive, or irritable mood
    for at least one week and
  • Inflated self-esteem decreased need for sleep
    talkativeness racing thoughts distractibility
    increased activity and daring behaviors
  • Impairment in psychosocial functioning
  • Not only due to other psychiatric and medical
    conditions
  • DSM-IV Hypomanic episode less intensity than
    mania, at least 4 days

6
Bipolar Disorder Clinical Manifestations
  • DSM-IV Major depression episode
  • Persistent depressed mood or irritability for at
    least 2 weeks and
  • Motivation, sleep, appetite, concentration, and
    energy disturbances
  • Guilt, suicidal thoughts or behaviors
  • Impairment in psychosocial functioning
  • Not only due to other psychiatric and medical
    conditions

7
Subtypes of Bipolar Disorder
  • Bipolar I disorder
  • Manic
  • Depressed
  • Mixed
  • Rapid cycling
  • Psychotic
  • Bipolar II disorder (hypomania and MDD episodes)
  • Cyclothymic disorder (hypomania and mild
    depressions)
  • Bipolar Not Otherwise Specified (NOS)

8
Bipolar NOS
Bipolar II
Bipolar I
Not Bipolar
9
Difficulties Diagnosing Pediatric Bipolar
Disorder
  • Variability in clinical presentation
  • Severity, phase of the illness (depressed, manic,
    mixed, rapid cycling) and subtype of BP disorder
  • Highly comorbid with other psychiatric disorders
  • Effects of development in symptom expression
  • Childs problems expressing her/his symptoms
  • Effects of medications
  • Context where the BP disorder is developing

10
Developmental Manifestations of Manic Symptoms in
Children
  • Elation/euphoria
  • giggling uncontrollably in class while peers are
    calm laughing hysterically when talking about
    killing others
  • Dancing and laughing at home while telling
    parents they are suspended
  • Finds everything funny they dont know why
  • Decreased need for sleep
  • Up at 2 AM rearranging furniture, cleaning, then
    awake at 6 AM dressed and ready for school
  • Child awake at 4 AM during summer vacation

Geller et al., 2002
11
Developmental Manifestations of Manic Symptoms in
Children (cont)
  • Grandiosity
  • Telling principal to shut up and listen because
    the principal is the childs slave demanding
    that teacher be fired for stupidity
  • child stealing go-kart because he felt rules did
    not apply to him (acute onset of conduct d/o)
  • child believing he/she is a superhero tries to
    fly
  • child spends evenings practicing when they
    become president, despite failing in school
  • Hypersexuality drawing or preoccupied with
    pictures of naked people inappropriate kissing,
    touching of others breasts/buttocks 1-900-sex
    lines sexually vulgar language sending notes
    propositioning peers

12
  • To clarify the diagnosis
  • Retrospective studies of bipolar adults
  • Prospective studies of bipolar children
  • Studies of children of bipolar parents

13
Retrospective Studies of Adults with BP-I
  • Survey of 500 adults with Bipolar-I/II Disorders
  • 60 had symptoms before age 20 y.o
  • Prodromal symptoms
  • Depressed mood/hopeless (33)
  • Mania/hyperactivity (32)
  • Sleep problems (24)
  • Mood swings (13)
  • Anger/irritability (9)

Lish et al., 1994
14
Retrospective Studies of Adults with BP- I
(Cont)
  • 58 adults with Bipolar-I
  • Prodromal symptoms appeared 9-12 years before the
    formal diagnosis of BP-I
  • Depressed Mood (53)
  • Increased Energy (47)
  • Decreased energy/tiredenss(38)
  • Anger dysregulation and /or quick temper (38)
  • Irritable mood (33)
  • Bold/Intrusive behavior, excessive behavior
    conduct problems(28)
  • Decreased need to sleep (26
  • Cried (26)
  • Overly sensitive(24)

Egeland et al., 2000
Highly Episodic
15
Frequent Prodromal Features Before Onset of BP-I
Ages 0-6 (n13) Ages 7-10 (n24) 11-12 (n10)
Symptoms/Behaviors () Symptoms/Behaviors () Symptoms/Behaviors ()
Cried -23 Increased energy-23 Bold/Demanding-23 Quick temper-15 Anxious-15 Irritable mood-29 Overly sensitive-25 Cried-21 Bold /Demanding-21 Quick Temper-21 Energy-17 Depressive mood-50 Low energy/tired-30 Increased energy-30 Labile/mood changes-30 Anxious-30 Cried-30
Egeland et al., 2000
16
Studies in BP Adults (Cont)
  • Early onset BP occurs in families with high
    loading for affective disorders
  • The earlier the onset of BP the higher chance of
    more mixed, rapid cycling, other non-bipolar
    psychopathology, and poor psychosocial
    functioning
  • Age onset in adults with BP plus ADHD
    significantly lower than the age of onset for BP
    adults without ADHD
  • Attentional and behavior problems during
    childhood predict mood disorders during young
    adulthood
  • Many adults with BP disorder have persistent
    attentional deficits during remission

Carlson and Weintrub, 1993Cavanaugh et al.,
2002 Mendlewicz et al., 1972Lych et al., 1994
Puls et al., 1992Rice et al., 1987Sachs et al.,
2000)
17
WPIC Child Mood Anxiety Disorder Outpatient
Clinic
  • Kiddie Schedule for Affective Disorders and
    Schizophrenia, present episode (KSADS-P)
  • 1,926 subjects ages 5 to 17.11 y.o ( mean 14.1
    2.8 years) were assessed using the KSADS from
    April 1986 until April 1995
  • 58 female SES 37 ? 14 (Social Class III) 79
    Caucasian 18 African-American and 3 other

18
WPIC Child Mood Anxiety Disorder Outpatient
Clinic (Cont)
  • 120 (6.2) had BP disorder
  • 918 MDD
  • 1008 non-mood psychiatric disorders
  • The manic and hypomanic episodes in this
    population were generally shorter (median 1-2
    days) than the DSM-IV duration criteria
  • Only 19 of BP patients had episodes of mania
    that lasted one week or longer

19
WPIC Child Mood Anxiety Disorder Outpatient
Clinic (Cont)
  • Distinct episodes of elated mood and unusual
    energy differentiated BP patients from non-BP
    psychiatric disorders
  • There were no between group differences in
    irritability levels

20
WPIC Child Mood Anxiety Disorder Outpatient
Clinic (Cont)
  • 40 of the BP patients had current MDD
  • 80 3 criteria for MDD
  • Depression is a common feature of pediatric BP,
    and mixed state is just one end of a continuum of
    depressive symptoms that are associated with
    manic episodes

21
Hamilton Depression Scores (Cont)
22
WPIC Child Mood Anxiety Disorder Outpatients
(Cont)
BP gt Other (p .01)
BP gt Other (plt.001)
BP gt MDD (p.003)
BP gt MDD (plt.001)
23
Child Adolescent Bipolar Services (CABS)
  • Referred outpatient clinic
  • 335 patient intakes over past 4 years
  • Research clinicians do Mania Depression Items
    from KSADS-P
  • KSADS-P/L for other diagnoses
  • Child Psychiatrist confirmatory interview
  • BP-NOS clinically significant manic symptoms
  • At least 4 days but 1 symptom short
  • Full symptom criteria but brief duration (need
    multiple episodes)
  • Significant change in functioning

24
CABS Intake Diagnoses (Cont)
21
45
9
25
25
BP NOS, BP I gt BP II (p lt .01)
26
Course and Outcome of Bipolar Youth (COBY)
  • Multicenter study (UPMC, UCLA, Brown University)
  • 210 children and 210 adolescents with Bipolar
    disorder - I, II and NOS
  • Evaluations of mood, behavior, life events, and
    school and family functioning (interviews with
    youth and parents)
  • Follow-up every 6 months for 5 years

27
BP-NOS Defined for COBY (Cont)
  • Goal was to be broad at intake
  • Elated Mood plus 2 symptoms or Irritable Mood
    plus 3 symptoms
  • Change in functioning
  • At least 4 hours of symptoms in a 24-hour period
    to count as one day
  • Lifetime of 4 days total of symptoms (e.g. 4 one
    day episodes 2 two day episodes, etc.)

28
COBY subjects at Intake (Cont)
42
46
12
29
Demographics (COBY) (Cont)
30
COBY Subjects at Intake (Cont)
BP I BP II BP NOS
KSADS-MRS (Mania Rating Scale) 18.5 12.1 19.3 12.1 20.9 11.5
CGI-S (Depression) 2.9 1.3 2.8 1.4 3.1 1.2
CGAS (Current) 59 12 65 15 60 13
CGAS (Most Severe Past) 31 12 39 9 40 11
BP I lt BP NOS (p .001)
31
COBY Subjects Lifetime Presence of Psychiatric
Diagnoses (Cont)
BP I BP II BP NOS
ADHD 63 39 61
ODD 57 31 42
Conduct D/O 8 8 23
Anxiety D/O (SAD, GAD, Social Phobia) 47 54 51
Psychosis 38 23 25
Major Depressive Episode 67 100 67
32
COBY BPNOS Subjects (Cont)
  • Median of 107 days of BP-NOS level of symptoms
    lifetime
  • Only 4 subjects had lt 10 days lifetime
  • 20th Percentile 17 days
  • Duration of Continuous Symptoms are brief (most
    often 4 24 hours)

33
Prepubertal Bipolar Disorder
Geller et al., 1998
Mean age 10.9 2.6 y.o
34
Bipolar Disorder in High School Students
Suicide Attempts
Global Assessment of Function
90
50
87.5
44.4
88
45
86
40
83.6
84
35
82
30
Percentage of Subjects
80
22.2
25
78
20
74.9
76
15
74
10
72
5
1.2
70
0
68
Bipolar
MDD
Never Mentally Ill
BP
MDD
NMI
Lewinsohn et al., 1995
35
In General, BP in youth can presented as
  • Typical phenotype (DSM Bipolar I and II)
  • Many have frequent episodes and mixed bipolar
    episodes
  • Typical phenotype but for a short time (DSM-IV BP
    NOS or rapid cycling)
  • Many have frequent episodes and mixed episodes
  • Broad phenotype (DSM-IV BP NOS or rapid cycling)

Nottelmann et al., 2001
36
Bipolar- Broader Phenotype (Cont)
  • Many children referred to the clinics present
    with a broader phenotype
  • Mood lability, mood swings, affective storms
  • Irritability, anger, aggressiveness
  • Periodic agitation, explosiveness, severe temper
    tantrums
  • ADHD-like symptoms

Nottelmann et al., 2001
37
Clinical Manifestations - Questions?
  • Are the very short presentations and the broader
    phenotypes ?
  • Symptoms of other mood and non-mood disorders
    (e.g., recurrent unipolar agitated MDD ADHD)?
  • Prodromal symptoms of bipolar disorder?
  • The symptoms by which bipolar disorder manifests
    in early childhood?
  • The manifestations of a tendency for mood
    lability?

38
In addition to different subtypes of BP disorder,
severity of symptoms, and rapid changes in
symptomatology it is difficult to diagnose BP in
children because 1) Coexisting disorders 2)
Overlap in symptoms with other disorders
39
Bipolar Disorder - Comorbidity
  • The rule more than the exception
  • Approximately 50-90
  • Disruptive Disorders
  • Anxiety Disorders
  • Substance Abuse (adolescents)

40
Bipolar Disorder - Differential Diagnoses
  • Normal moodiness and behaviors
  • Recurrent explosive, aggressive, and irritable
    behaviors Bipolar vs. unipolar recurrent
    agitated MDD vs. ADHD ODD
  • Asperger Disorder
  • ADHD vs Bipolar
  • Abrupt onset of ADHD
  • Late onset ADHD
  • Intermittent ADHD
  • Intermittent worsening of the ADHD symptoms
  • ( tolerance to the stimulants)
  • In adolescents Borderline Personality Disorder

41
Diagnostic Overlap between Mania ADHD
DSM-IV Mania ADHD
Elevated, expansive mood No
Irritability Commonly associated
Inflated self-esteem / grandiosity No
Decreased need for sleep Can be present
More talkative / pressured speech DSM-IV Criteria
Flight of Ideas or racing thoughts No
Hyperactivity / goal-directed activity DSM-IV Criteria
Pleasurable activities with high risk for painful consequences Commonly associated
Distractibility DSM-IV Criteria
42
BP children with elation/grandiosity (n93) vs
ADHD (n81)
Elated
Energy
Irritable
Grandiose
Distractible
Sleep Need
Judgment
Speech
Racing/Flight
Geller et al., 2002
43
Epidemiology
44
Bipolar Disorder -Epidemiology
  • Clinical samples 0.6 - 15
  • Community sample (adolescents) 1.0 (mostly
    BP-II and cyclothymia)
  • Subthreshold symptoms in community adolescents
    5.6
  • Reported in children as young as 4 y.o
  • Adults studies 20-40 started before age 20 y.o

45
Natural Course
46
BP-I Natural Course Multicenter Pilot Study
  • 3 Centers (WPIC, UCLA, Brown)
  • 73 adolescents outpatients with BP-I, mean age
    17.1 ? 1.8, 75 females, 84 Caucasian
  • KSADS, LIFE
  • At intake, 64 (47/73) were in an acute episode
    (11 mania, 18 MDD, and 18 mixed) and 36 (26/73)
    were euthymic
  • Follow-up every 4 months for 4 to 224 weeks
    (mean 76.6 ?? 61.6 weeks)

47
BPD-I Natural CourseMulticenter Pilot Study
(Cont)
  • 68 (32 / 47) recovered (Psychiatric Status
    Rating -PSR1-2 for 8 weeks)
  • Mania gt depression gt mixed
  • Time to recover Mixed gt Manic gt Depressed
  • 59 (19 / 32) recurrence
  • Patients with mixed presentations had more
    recurrences

48
BP I Natural Course Multicenter Pilot Study
(Cont)
  • 96 of the follow-up time patients received
    medications
  • 26 of the time patients received 3 medications
    (e.g., mood stabilizers, antidepressants,
    stimulants)
  • 12 of the time 5-6 medications

49
BP I Natural Course Multicenter Pilot Study
(Cont)
  • Increased services utilization (70
    hospitalizations 50 outpatient 20 day
    hospital)
  • Increased family problems induced by the illness
    (e.g., 40 negative effect on marital
    relationships 40 conflict in the family and
    less time with other siblings)
  • Increased economical burden and family problems
    induced by the illness (e.g. 40 increased
    expenses 70 used their savings 94 incurred in
    debts

50
Course and Outcome of Bipolar Youth (COBY)
  • Multicenter study (UPMC, UCLA, Brown University)
  • 210 children and 210 adolescents with Bipolar
    disorder - I, II and NOS
  • Evaluations of mood, behavior, life events, and
    school and family functioning (interviews with
    youth and parents)
  • Follow-up every 6 months for 5 years

51
COBY subjects at Intake (Cont)
42
46
12
52
COBY follow-up (Cont)
  • Occurs every 6 months parent subject
    interviewed, records reviewed
  • Intake Diagnoses BP I (n26) BP II (n11)
    BP NOS (n23)
  • 8.8 4.4 months duration (6 18 months)
  • Follow-up using the Longitudinal Interval
    Follow-Up Evaluation (A-LIFE)
  • Weekly ratings of depression and mania intensity
  • Ratings anchored on DSM-IV thresholds
  • Subthreshold manic/depression symptoms rated

53
COBY 6 Month follow up (Cont)
Diagnosis at Intake
54
Longitudinal Course COBY vs BP-Adults (Judd et
al., 2002
SubthresholdDepressive Symptoms
No Significant Mood Symptoms
55
COBY follow-up (Cont)
  • 2/11 BP II subjects converted to BP I
  • 2/23 BP NOS subjects converted to BP I

BP I BP II BP NOS
CGI-S Overall 3.3 1.1 2.6 1.1 3.3 1.0
CGI-S Mania 2.7 1.2 2.0 1.2 2.5 1.1
CGAS (current) 66 13 64 16 58 15
CGAS (most severe) 39 18 45 13 41 12
56
BP- II at Intake Convert to BP-I
Mania
Hypomania
Euthymia
Major Depression
57
BP-NOS at Intake Convert to BP-I
Mania
Hypomania
Euthymia
Major Depression
58
Bipolar Disorder - Natural Course
  • OTHER STUDIES
  • Strober at al., 1995 (n 54 adolescents,
    clinical sample, inpatients, BP-I)
  • Lewinsohn et al., 1995 (n 18 adolescents,
    community sample, mostly BP-II)97 subthreshold
    BP
  • Geller et al., 2001 (Clinical sample, n 93
    children and adolescents, outpatients, subjects
    needed to have grandiose thoughts and/or elation

59
Natural Course General Conclusions
  • Approximately 40 - 70 will recover
  • Approximately 60 - 70 will recur
  • Those with mixed and rapid cycling episodes will
    do worse
  • Bipolar patients had worse course that unipolar
    depressed and normal controls
  • Bipolar patients had more functional impairment,
    suicidal attempts, comorbid anxiety and
    disruptive disorders, and mental health services
    utilization than the depressed and normal
    controls

60
Natural Course General Conclusions (Cont)
  • Patients usually take multiple medications (e.g.,
    mood stabilizers, antidepressants, stimulants)
    and have increased mental health services
    utilization
  • Bipolar disorder produces family conflicts (e.g.,
    marital, siblings) and economical problems
  • Adolescents with subthreshold bipolar symptoms
    (distinct period of abnormally and persistently
    elevated, expansive or irritable mood) have
    levels of impairment and comorbidity comparable
    with the BP group

61
Sequela
62
Bipolar Disorder - Sequela
  • Poor academic functioning
  • Interpersonal and family difficulties
  • Increased risk for suicide
  • Increased use of tobacco, alcohol, and other
    substances
  • Behavior problems
  • Legal difficulties
  • Increased health services utilization (e.g.,
    hospitalizations)

63
Pediatric Bipolar Disorder - WPIC Mood Anxiety
D/O Outpatients
40
30
26.1
19.1
Percentage of Patients
20
15.7
10
3.7
0
plt.001
Suicide Attempt
Psychosis
plt.05
BP
All other diagnoses
64
Pediatric Bipolar Disorder Oregon Study
Suicide Attempts
Global Assessment of Function
90
50
87.5
44.4
88
45
86
40
83.6
84
35
82
30
Percentage of Subjects
80
22.2
25
78
20
74.9
76
15
74
10
72
5
1.2
70
0
68
Bipolar
MDD
Never Mentally Ill
BP
MDD
NMI
Lewinsohn et al., 1995
65
Predictors of Bipolar Disorder
66
Predictors of Bipolar Disorder
  • MDD with
  • Psychosis
  • Psychomotor retardation
  • Pharmacological induced mania/hypomania
  • Family history of bipolar disorder

67
Bipolar Disorder- Family Studies
  • Runs in Families
  • Top- down studies
  • Bottom-up studies

68
Children of Parents with BP
  • Children of BP parents have 4 times greater risk
    to develop BP when compared with controls
  • Children of parents with BP are also at risk to
    develop MDD, anxiety, ADHD, and disruptive
    behavior disorders
  • Methodological problems (small sample sizes,
    instruments, no- controls, no blindness to
    parental diagnosis, no direct evaluation of
    children).
  • Very few follow up studies ( a total of 20
    children for a period of 1-3 years).

Chang et al., 2001 DelBello and Geller, 2000
LaPalme et al 1994
69
Children of Parents with BP
  • 60 children (mean age 11 years old) of 37
    families with at least one parent with BP-I or
    II.
  • No controls, no blind to parental diagnosis
  • 55 Axis I (BP15 MDD15, ADHD 28 ODD10)
  • Children with BP had more severity of mood
    symptoms and problems with mood regulation
  • Parents of children with BP had earlier onset
    mood disorder and history of ADHD

Chang et al., 2000
70
NIMH-Bipolar Offspring Study (BIOS)
  • Children (ages 6-18 y.o) of bipolar parents
  • Children of community control parents
  • Other non-bipolar psychiatric disorders
  • Healthy controls
  • Evaluations at intake and yearly for 5 years
    blind to parental diagnosis
  • Interviews are performed by research assistants
    trained to good reliability (Ksgt.8)
  • All assessments are staffed by a child
    psychiatrist (DA, DB and BB)

71
Bipolar Offspring Study (BIOS) Instruments
  • Psychopathology (dimensional and categorical)
  • Parents SCID I and II Aggression questionnaire
    BDI, Young adult self report history of abuse and
    suicide
  • Children and parents about their children
  • Categorical KSADS,
  • Dimensional CBCL,MFQ, SCARED, DBD, CADSCHI,YSR
  • Pubertal stage and medical history
  • Teacher Report Form

72
Bipolar Offspring Study (BIOS) Instruments
  • Psychosocial Functioning GAS,CBCL,TRF
  • Family psychiatric history first and second
    degree relatives, CBQ, FACES-II
  • Life Events SLES
  • Children 2-5 years old KSADS (parents about the
    child), EAS, ECI, TRF, CBCLPDD

73
BIOS - SAMPLE
  • This presentation includes cases recruited until
    March 1, 2003
  • Bipolar parents 58
  • Controls parents 41
  • Parents with non-BP psychopathology 26
  • Parents without any psychopathology 15
  • Offspring of bipolar parents 103
  • Offspring of control parents 75
  • Offspring of parents with non-BP psychopathology
    46
  • Offspring of healthy controls 29

74
BIOS - Demographics OffspringPreliminary
Analyses
Offspring of Bipolar Parents (n103) Offspring of Control Parents (n75) STAT p-value
Mean Age SD 11.7 3.4 11.4 3.5 t-.01 n.s.
Sex (Female) 46.6 60.0 ?23.12 .08
Race ( White) 84.5 72.0 ?24.10 .04
Siblings () 78.6 77.3 ?2 n.s.
75
BIOS- ProbandsLifetime Disorders
Disorder () Bipolar Parents (n58) Controls (n41) STAT P-value
BP-I 44.8 0 ?224.93 lt.001
BP-II 36.2 0 ?218.84 lt.001
Other BP 10.3 0 FET .04
MDD 12.1 24.4 ?22.56 n.s.
Dysthymic Disoder 5.2 9.8 FET n.s
Any Mood 98.3 36.6 ?246.09 lt.001
76
BIOS- ProbandsLifetime Disorders
Disorder () Bipolar Parents (n58) Controls (n41) STAT P-value
Any Anxiety 72.4 41.5 ?29.56 .002
Panic Disorder 29.3 7.3 ?27.2 .007
Any Disruptive 20.7 2.4 ?27.01 .008
ODD/CD 12.1 2.4 FET n.s.
ADHD 12.1 0 FET .04
Any Substance/alcohol (ETOH, marihuana, cocaine) 50 24.4 ?26.60 .01
77
BIOS- Offspring of BP parents-Lifetime Disorders-
Definite/Probable
Disorder () Offspring of BP Parents (n103) Offspring of Controls (n75) STAT P-value
BP-I 1.0 0 FET n.s
BP-II 1.9 1.3 FET n.s.
Other BP 2.9 0 FET n.s.
All BP disorders 5.8 1.3 FET n.s.
MDD/Dysthymia 10.7 4.0 ?22.67 n.s.
Any Mood (including NOS) 20.4 8.0 ?25.18 .02
78
BIOS- OffspringLifetime Disorders (Cont)
Disorder () Offspring of BP parents (n103) Offspring of Controls (n75) STAT P-value
SAD, GAD, or SP 16.5 6.7 ?23.88 .04
Any Disruptive 38.8 17.3 ?29.60 .002
ODD 23.3 6.7 ?28.81 .003
ADHD 24.3 13.3 ?23.29 .07
Any Substance/alcohol 1.9 2.7 FET n.s.
79
Offspring of BP vs. Controls-CBCL Scores
CBCL-T scores Offspring of BP (n87) Offspring of Controls (n63) STAT P-value
Total Problem 51.2 13.7 47.1 12.2 T-1.88 .06
Externalizing 50.7 12.4 48.3 12.1 T n.s.
Internalizing 51.5 12.2 47.6 11.7 T-1.99 .05
Somatic Complaints 57.0 9.4 54.4 7.5 T-1.83 .07
Anxious/ depressed 55.3 7.5 53.4 5.6 T-1.76 .08
80
Treatment
81
TREATMENT
  • Acute
  • Maintenance (prevention of relapses and
    recurrences)
  • Treatment of Mania, Depression, Rapid Cycling,
    Mixed episodes, and sometimes Psychosis
  • Tools
  • Medications
  • Psychotherapy

82
Bipolar Disorder - Psychoeducation
  • Symptomatology
  • Etiology ( e.g., genetics)
  • Treatment
  • Prognosis
  • Prevention (early signs of relapse/recurrence)
  • Psychosocial Scars
  • Stigma
  • Mood Hygiene
  • Importance of compliance

83
Pharmacological Treatment
  • Mood Stabilizers
  • Lithium
  • Anticonvulsants
  • Valproate (Depakote) carbamazepine (Tegretol)
    oxcarbamazepine (Tryleptal) lamotrigine
    (Lamictal) etc.
  • New antipsychotics
  • Riperidol (Risperdal), olanzapine (Zyprexa)
    quetiapine (Seroquel), ziprasedone (Geodon),
    aripripazol (Abilify) etc.
  • Antidepressants
  • Selective Serotonin Reuptake Inhibitors
  • Venlafaxine (Effexor), bupropion (Wellbutrim)
    etc.
  • Others benzodiazepines etc.

84
Bipolar Disorder Pharmacological Treatment
(Cont)
  • Very few studies in youth - mostly open
  • Response to acute treatment with mood stabilizers
    (lithium, VPA, CBZ) approx. 40-80
  • Small study showed that valproate quetiapine
    was better than valproate placebo for children
    with mania
  • Open studies suggest that the atypicals alone or
    in combination may be efficacious
  • Need treatment with multiple medications

85
Bipolar Disorder Pharmacological Treatment
(Cont)
  • Presence of psychosis predicts poor response to
    treatment
  • Conflicting reports on the effects of comorbid
    ADHD and substance abuse
  • Poor compliance
  • Approximately 70 relapse in those who
    discontinue treatment with lithium
  • Ongoing studies

86
Lithium vs. Valproate vs. CBZ
  • 42 outpatients (mean11.4 y.o.) with BP-I and
    BP-II disorder
  • Randomly assigned to 6 weeks open treatment with
    lithium, valproate, or carbamazepine
  • Primary outcome measures
  • Young Mania Rating Scale (? 50)
  • Clinical Global Impression Scale - Improvement
    subscale (1 or 2)

Kowatch et al., 2000
87
Lithium vs. Valproate vs. CBZ Intent-to-treat
Analysis (Y-MRS) (Cont)
  • Lithium (? 0.8 mEq/L) Response 38
  • Valproate (? 80 ?g/L) Response 53
  • Carbamazepine (? 7.0 ?g/L) Response 38
  • Poor Compliance 30
  • gt 50 needed other medications (atypical
    neuroleptics and/or stimulants)

Kowacht et al., 2000
88
Lithium Vs. Valproate Vs. CBZ (Cont)
89
Lithium vs. Valproate vs. CBZ (Cont)
90
Divalproex Treatment for Bipolar Disorder
  • Multicenter (5 sites)
  • 40 children and adolescents (7-17 y.o.)
  • 69 (16) had comorbid diagnosis
  • First open-label study (2-8 weeks)
  • Responders randomized to continue divalproex or
    placebo

Wagner et al., 2000
91
Divalproex Treatment for Bipolar Disorder (Cont)
  • Open phase
  • 61 improved (? 50 on the YMRS)
  • 58 (23) discontinued the study (no response,
    side effects)

Wagner et al., 2000
92
Lithium for Adolescents with Acute Mania
  • 85 adolescents (12-18 y.o.) with mania or mixed
    mania
  • Most were inpatients who completed the study as
    outpatients
  • At least 4 weeks open lithium treatment
  • Psychotic subjects initially received 4 weeks of
    antipsychotics

Kanfataris et al., 2000
93
Lithium for Adolescents with Acute Mania (Cont)
  • Response rate 59.2 (45/85)
  • With psychosis 28.6 (8/28)
  • Without psychosis 64.9 (37/57)
  • No effect on response
  • Depressive symptoms
  • Comorbid ADHD
  • Substance Abuse

Kanfataris et al., 2000
94
Side Effects/Laboratory Tests Prior and During
Psychopharmacological Treatment
  • Lithium
  • GI, weight gain, tiredness, polydipsia, polyuria,
    cognition, tremor, and dermatological problems
  • Signs of toxicity drunkenness
  • Renal and Thyroid Function Tests, electrolytes,
    CBC differential, U/A, glucose?, EKG?
  • Valproate
  • GI, weight gain, tiredness, sedation, tremor,
    hair loss, hepatitis, pancreatitis, cognition?,
    polycystic ovary?
  • Liver Function Tests, CBC differential
  • Carbamazepine
  • Ataxia, dizziness, tiredness, sedation,
    nystagmus, liver, hematological, and
    dermatological side effects
  • CBC differential electrolytes, LFTs
  • Oxacarbamazepine, topiramate, lamotrigine,
    gabapentin etc.

Check for presence of side effects prior to
starting treatment
95
Side Effects/Laboratory Tests Prior and During
Psychopharmacological Treatment
  • Typical Antipsychotics
  • Drowsiness, EPS, tardive dyskinesia,
    hyperprolactinemia Low potency weight gain,
    cardiovascular
  • CBC diff low potency EKG (QTc)
  • Atypical Antipsychotics
  • Neurological disturbances, hypotension,
    dizziness, weight gain, ,drowsiness, liver
    problems, diabetes, hyperlipidemia, and
    hyperprolactinemia
  • Liver Function Tests Glucose lipid profile CBC
    diff ziprasedone EKG (QTc) clozapine EEG
    EKG.
  • Clozapine agranulocytosis, eosinophilia,
    seizures, myocarditis, orthostatic hypotension,
    and salivation

Check for presence of side effects prior to
starting treatment
96
Bipolar Depression- Treatment
BP II/NOS Hypomania (? SSRI)
Pure Unipolar
Pure Bipolar
too little Hypomania (Use SSRI)
BP-I depressed or BP-II with Too Much
Hypomania (Use Mood Stabilizer, if no response
add an antidepressant)
97
Bipolar Depression - Treatment
  • Mood stabilizers
  • Consider adding antidepressants (SSRIs,
    bupropion, venlafaxine, MAOIs )
  • For BP-II, if hypomania is not severe and not
    frequent An antidepressant alone ?
  • Psychosocial interventions (CBT, IPT) alone or in
    conjunction with medications

98
Psychosocial Treatments
  • Family Focus Therapy (FFT)
  • Cognitive Behavior Therapy (CBT)
  • Interpersonal Psychotherapy (IPT)
  • Interpersonal and Social Rhythms Therapy (IPSRT)

99
Why Treat Adolescent Bipolar Patients with
Adjunctive Family Psychoeducation?
  • Family psychoeducation is a powerful adjunct to
    pharmacotherapy for adult bipolar I patients
  • Family factors are correlated with the course of
    recurrent mood disorders in adults and children
  • Early-onset mood and behavioral disturbances are
    associated with a high familial loading for major
    affective disorder
  • Mood stabilizers can be difficult to dispense
    safely to adolescents living in chaotic family
    environments

100
Family Expressed Emotion Status as a Predictor of
9-Month Clinical Outcome
c2(1) 3.82, p.05
Miklowitz DJ , et al. Arch Gen Psychiatry,
198845(3)225-231
101
Family-Focused Treatmentof Bipolar Disorder
  • 21 outpatient sessions over 9 months
  • Assessment of family
  • Psychoeducation about bipolar disorder
  • Communication skills training
  • Problem solving skills training

Miklowitz DJ and Goldstein MJ. Bipolar Disorder
A Family-Focused Treatment Approach. NY Guilford
Press, 1997
102
Bipolar Disorder- Family Focused Treatment (FFT)
  • Education about bipolar disorder
  • Strategies for preventing relapses and
    re-hospitalizations
  • Enhance adherence to treatment
  • Effective communication strategies
  • Training in problem solving for illness related
    family conflicts

David J. Miklowitz, Ph.D.
103
1-Year Survival Rates Among Bipolar Patients in
Family-Focused Treatment versus Case Management
FFT, N31
CM, N70
Wilcoxon Test, c2 (1)3.99, P .046
Miklowitz DJ, et al. Biol Psychiatry,
200048(6)582-592
104
Positive Verbal and Nonverbal Interactional (KPI)
Behavior Among Families of Bipolar
PatientsEffects of Treatment During 1 Year (n44)
FFT, n22
CM, n22
1 year
Baseline
Analysis of covariance baseline positive
behavior F(1,41)10.08, Plt0.01 Treatment
F(1,41)5.15, Plt0.03
Frequency of positive behaviors
(patient/relative) during two 10-minute
interactions.
Simoneau TL, et al. J Abnorm Psychol,
1999108(4)58-597
105
Family-Focused Treatment of Bipolar Disorder
Effect on Depression and Mania
3
CM (N44)
Mean SADS-C Item Score
2
FFT (N23)
1
3
6
9
12
0
18
24
Months of follow-up
Repeated measures ANOVA (linear time effects)
Treatment F(1,65)0.66, ns Time F(1,65)13.49,
Plt0.01 Treatment / Time F(1,65)4.91, P 0.03.
106
Family-Focused Treatment for Adolescent Bipolar
Patients
  • Focus on day-to-day mood fluctuations and changes
    in functioning rather than discrete episodes
  • Help adolescent and parents distinguish
    age-appropriate moodiness from bipolar disorder
  • Use developmentally appropriate terminology
  • Empathize with the adolescents discomfort with
    diagnosis
  • Use visually stimulating handouts and homework
    sheets

107
Family-Focused Treatment for Adolescent
Bipolar Patients (Cont)
  • Support parents behavioral management efforts
  • Address the adolescents medication-taking habits
  • Emphasize sleep/wake regularity, avoiding
    overstimulation
  • Address mood disturbances in other family members
  • From Miklowitz, D. George, E. (2000).
    Clinicians Manual for Family-Focused Treatment
    of Bipolar Adolescents.

108
Adolescents functioning at baseline
Parental distress and mood instability
FFT vs. TAU
Adolescent outcomes at one year
109
Interpersonal and Social Rhythms Therapy (IPSRT)
  • Principles of Interpersonal Psychotherapy (IPT)
  • Circadian Rhythms (Sleep)
  • Intensive Clinical Management
  • Education about bipolar disorder
  • Education about medications used to treat bipolar
    disorder
  • Education about basic sleep hygiene
  • Careful review of side effects
  • Medical and behavior management of side effects
  • Nonspecific support
  • Education regarding early warning signs of
    impending episodes and use of rescue medications
  • 24-hout on call-service

110
Bipolar Disorder TreatmentOther Considerations
  • Treat comorbid disorders
  • Manage psychosocial factors (e.g., family
    conflicts, peer problems)
  • Recommend mood hygiene (circadian rhythms)
  • Remediation of academic problems

111
Bipolar Disorder-TreatmentOther Considerations
  • Need for Inclusion of Parents
  • Children depend on parents
  • Usually family has psychiatric disorder or
    conflicts
  • Family conflicts increase the risk of onset,
    relapses, and depressive recurrences


112
Bipolar DisorderNo Response to Treatment
  • Misdiagnosis
  • Compliance
  • Adequate treatment (type, doses, duration)
  • Comorbidity ( e.g., substance abuse)
  • Exposure to Stressful Life Events (e.g., abuse)
  • Psychosocial Factors

113
Bipolar Disorder Prevention of Further Episodes
  • Who
  • Those with 2 ( 3 ?) or more episodes of
    mania/depression
  • Those with 1 (2 ?) episode
  • difficult to treat
  • severe (suicide, poor functioning)
  • psychosis
  • family loading for bipolar disorder or MDD with
    psychosis

114
Bipolar Disorder Prevention of Further Episodes
  • How Long?
  • Depends on severity, frequency, type, motivation,
    compliance, treatment response and side effects
  • One year (?) to lifelong treatment

115
Conclusions
116
Conclusions
  • Bipolar disorder in children and adolescents
    exist
  • Reliable diagnoses
  • Prevalent (in adolescents 1)
  • Runs in families
  • Continuous overtime
  • Pending- biological studies
  • Response to Treatment

117
BP Conclusions (Cont)
  • BP disorder in youth is a chronic and difficult
    to treat illness that conveys high morbidity
    (e.g., behavior problems, substance abuse), poor
    psychosocial functioning, psychosis, and risk for
    suicide
  • Youth with BP usually have mixed and rapid
    cycling which are the types of bipolar disorder
    that have worst prognosis and are more difficult
    to treat
  • BP is highly comorbid with other psychiatric
    disorders. These disorders require identification
    and treatment
  • The differential diagnosis of BP may be difficult
    and requires longitudinal follow-up

118
Bipolar Disorder Conclusions (Cont)
  • Despite that a substantial number may recover
    (30-70), most patients experience recurrences
    (up to 70)
  • BP has severe adverse impact on family
    relationships and economics
  • Most patients do not seek treatment
  • Patients require multiple medications and
    psychosocial interventions
  • The mood stabilizers and the atypicals seem
    useful but there is an urgent need for acute
    treatment and preventative studies

119
Bipolar Disorder - Conclusions (Cont)
  • Patients and their families require education and
    intensive support and follow-up systems
  • In adults, psychotherapy, particularly FFT, CBT
    and IPSRT increase adherence to treatment,
    diminish the relapses and recurrences, and FFT
    improves family communication
  • Psychotherapies seems more efficacious to manage
    periods of depression than mania

120
Bipolar Disorder - Conclusions (Cont)
  • Offspring of parents with bipolar disorder seem
    to be at high risk to develop bipolar, depression
    and other psychiatric disorders
  • Youth with MDD and psychosis, psychomotor
    retardation, pharmacological-induced mania,
    and/or family history of BPD are at risk to
    develop BPD
  • Youth with subthreshold bipolar symptoms have as
    much problems as those with the full syndrome

121
Bipolar Disorder- Conclusions (Cont)
  • Bipolar Disorder is associated with high risk for
    suicide
  • Need prompt identification and treatment of BPD
    because at least in adults, the highest rate of
    suicide happens during the first years of illness
  • Continuous reappraisal of suicidal risk
  • Persons with early onset, previous attempts,
    severe depression, mixed episodes, rapid cycling,
    psychosis, comorbid disorders (substance,
    disruptive, anxiety?), family history of suicidal
    attempts availability of methods, and exposure
    to stressful events are at higher risk
  • In adults, lithium seems beneficial to prevent
    suicide independent of its antimanic/antidepressiv
    e effects

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