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 I Bipolar II Bipolar NOS 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 • Child’s 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 don’t 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 child’s “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 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, 1993;Cavanaugh et al., 2002; Mendlewicz et al., 1972;Lych et al., 1994; Puls et al., 1992;Rice et al., 1987;Sachs 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 > Other (p = .01) BP > Other (p<.001) BP > MDD (p=.003) BP > MDD (p<.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 > BP II (p < .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 NOS (p = .001)

31. COBY Subjects – Lifetime Presence of Psychiatric Diagnoses (Cont’)

32. COBY BPNOS Subjects (Cont’) • Median of 107 days of BP-NOS level of symptoms lifetime • Only 4 subjects had < 10 days lifetime • 20thPercentile = 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

42. BP children with elation/grandiosity(n=93) vs ADHD (n=81) Elated Energy Irritable Distractible Grandiose 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 -PSR:1-2 for 8 weeks) • Mania > depression > mixed • Time to recover: Mixed > Manic > 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