Title: Children and Adolescents with Bipolar Disorder
1Children 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?
3Bipolar 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
4Clinical Manifestations
5Bipolar 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
6Bipolar 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
7Subtypes 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)
8Bipolar NOS
Bipolar II
Bipolar I
Not Bipolar
9Difficulties 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
10Developmental 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
11Developmental 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
13Retrospective 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
14Retrospective 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
15Frequent 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
16Studies 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)
17WPIC 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
18WPIC 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 -
19WPIC 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 -
20WPIC 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
21Hamilton 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)
23Child 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
24CABS Intake Diagnoses (Cont)
21
45
9
25
25 BP NOS, BP I gt BP II (p lt .01)
26Course 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
27BP-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.)
28COBY subjects at Intake (Cont)
42
46
12
29Demographics (COBY) (Cont)
30COBY 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)
31COBY 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
32COBY 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)
33Prepubertal Bipolar Disorder
Geller et al., 1998
Mean age 10.9 2.6 y.o
34Bipolar 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
35In 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
36Bipolar- 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
37Clinical 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?
38In 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
39Bipolar Disorder - Comorbidity
- The rule more than the exception
- Approximately 50-90
- Disruptive Disorders
- Anxiety Disorders
- Substance Abuse (adolescents)
40Bipolar 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
41Diagnostic 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
42BP children with elation/grandiosity (n93) vs
ADHD (n81)
Elated
Energy
Irritable
Grandiose
Distractible
Sleep Need
Judgment
Speech
Racing/Flight
Geller et al., 2002
43Epidemiology
44Bipolar 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
45Natural Course
46BP-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)
47BPD-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
48BP 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
49BP 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
50Course 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
51COBY subjects at Intake (Cont)
42
46
12
52COBY 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
53COBY 6 Month follow up (Cont)
Diagnosis at Intake
54Longitudinal Course COBY vs BP-Adults (Judd et
al., 2002
SubthresholdDepressive Symptoms
No Significant Mood Symptoms
55COBY 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
56BP- II at Intake Convert to BP-I
Mania
Hypomania
Euthymia
Major Depression
57BP-NOS at Intake Convert to BP-I
Mania
Hypomania
Euthymia
Major Depression
58Bipolar 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
59Natural 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
60Natural 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
61Sequela
62Bipolar 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)
63Pediatric 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
64Pediatric 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
65Predictors of Bipolar Disorder
66Predictors of Bipolar Disorder
- MDD with
- Psychosis
- Psychomotor retardation
- Pharmacological induced mania/hypomania
- Family history of bipolar disorder
67Bipolar Disorder- Family Studies
- Runs in Families
- Top- down studies
- Bottom-up studies
68Children 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
69Children 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
70NIMH-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)
71Bipolar 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
72Bipolar 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
73BIOS - 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
74BIOS - 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.
75BIOS- 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
76BIOS- 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
77BIOS- 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
78BIOS- 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.
79Offspring 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
80Treatment
81TREATMENT
- Acute
- Maintenance (prevention of relapses and
recurrences) - Treatment of Mania, Depression, Rapid Cycling,
Mixed episodes, and sometimes Psychosis - Tools
- Medications
- Psychotherapy
82Bipolar Disorder - Psychoeducation
- Symptomatology
- Etiology ( e.g., genetics)
- Treatment
- Prognosis
- Prevention (early signs of relapse/recurrence)
- Psychosocial Scars
- Stigma
- Mood Hygiene
- Importance of compliance
83Pharmacological 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.
84Bipolar 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
85Bipolar 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
86Lithium 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
87Lithium 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
88Lithium Vs. Valproate Vs. CBZ (Cont)
89Lithium vs. Valproate vs. CBZ (Cont)
90Divalproex 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
91Divalproex 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
92Lithium 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
93Lithium 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
94Side 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
95Side 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
96Bipolar 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)
97Bipolar 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
98Psychosocial Treatments
- Family Focus Therapy (FFT)
- Cognitive Behavior Therapy (CBT)
- Interpersonal Psychotherapy (IPT)
- Interpersonal and Social Rhythms Therapy (IPSRT)
99Why 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
100Family 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
101Family-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
102Bipolar 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.
1031-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
104Positive 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
105Family-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.
106Family-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
107Family-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.
108Adolescents functioning at baseline
Parental distress and mood instability
FFT vs. TAU
Adolescent outcomes at one year
109Interpersonal 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
110Bipolar Disorder TreatmentOther Considerations
- Treat comorbid disorders
- Manage psychosocial factors (e.g., family
conflicts, peer problems) - Recommend mood hygiene (circadian rhythms)
- Remediation of academic problems
111Bipolar 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
112Bipolar 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
113Bipolar 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
114Bipolar Disorder Prevention of Further Episodes
- How Long?
- Depends on severity, frequency, type, motivation,
compliance, treatment response and side effects - One year (?) to lifelong treatment
115Conclusions
116Conclusions
- Bipolar disorder in children and adolescents
exist - Reliable diagnoses
- Prevalent (in adolescents 1)
- Runs in families
- Continuous overtime
- Pending- biological studies
- Response to Treatment
117BP 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
118Bipolar 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
119Bipolar 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
120Bipolar 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
121Bipolar 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