EARLY AGE MANIAAnything New ?

Paramjit T. Joshi, M.D.PJOSHI@cnmc.org

Childrens National Medical Center George Washington University School of Medicine

EPIDEMIOLOGY PEDIATRIC BIPOLAR DISORDERSNo prevalence studies in pre-pubertal BPD1% lifetime prevalence rate in adolescents5.7% lifetime prevalence of sub-syndromal BPDIrritability the rule rather than the exceptionGrandiosity, poor judgementImpaired concentrationDO NOT MEET DURATION CRITERIAAdolescents with BPD and sub-syndromal BPD had significant psychosocial impairment by age 24 yearsLewinshon et al., 2000

As Adults !Childhood onset subjects were MOST likely to:Have non-remitting BPDProlonged episodesAntisocial PDChildhood & adolescent onset subjects had increased prevalence of Drug Use DisordersPrevalence of mixed episodes or irritability did not differ significantly between groups

Goldstein & Levitt, AJP 163:1633-1636, 2006

MANIC EPISODEDSM - IV: Lasting at least one week with A and three of B persistent symptoms:A. Expansive mood / irritabilityB. 1. Inflated self-esteem / grandiosity 2. Decreased need for sleep 3. More talkative / pressured speech than normal 4. Racing thoughts / flight of ideas 5. Easily distracted 6. Increase in goal-directed activity 7. Poor judgement or excessively involved in pleasurable but risky activities, hypersexuality

Core Symptoms of Bipolar Disorder

Extremely elevated mood Racing thoughts / flight of ideas Decreased need for sleep Grandiosity Poor judgement: hypersexualitydaredevil actssilliness, laughing uninhibited people seeking

BPD vs ADHDGeller et al., 2002

MANIA ITEMS

BPD(%)

ADHD(%)

Irritability

97

72

Grandiosity **

85

7

Elated mood **

87

5

Dare devil acts *

70

13

Uninhibited people

seeking

68

21

Silliness / laughing

65

21

Flight of ideas *

66

10

Accelerated speech

97

78

Hypersexuality **

45

8

Robert Post et al., Presented at the 3rd Annual NIMH P-BPD Conference, 2005

Rx of Early Age Mania (TEAM STUDY)Funded by the NIMH (2003-2009)AIM: To investigate the effectiveness of medications for C&A who have DSM-IV BP-1 (manic or mixed phase) mania540 subjects aged 6-15 years of ageNarrow BP phenotype based on WASH-U K-SADS interviews video-taped and reviewed by the coordinating site for consensus diagnosis

RESEARCH PLANInvestigate the effectiveness of Lithium (Li), Valproate (Val) and Risperidone (Rsp) as monotherapy and as add-on agents for childhood BP-1 (manic or mixed phase) mania

Explore the effects of psychosocial factors (e.g. parental warmth, parental BPD, family tension), discontinuation, compliance and outcome

TREATMENT OF EARLY AGE MANIA (TEAM) FLOW CHARTStratum OneDrug free strategy

Baseline: Antimanic drug freeRandomize: Li, Val, RspStratum TwoAdd-on strategyBaseline: On one drug withpartial responseRandomize: To add-on oneof two other drugsStratum ThreeCross-taper strategyBaseline: On one drug withpoor responseRandomize: To Cross-taper one of two other drugsScreening for EligibilityBaseline AssessmentsIneligible GivenClinical ReferralsBaseline AssessmentsIf eligible, assigned to one of Three Strata8 Week ProtocolIneligible GivenClinical ReferralsPartial RespondersRe-randomize: Within stratum two for another 8 weeksPoor RespondersRe-randomize: Within stratum three for another 8 weeks

Subjects Randomized: (All sites 315)AT CNMC:Total number of baseline subjects = 101Males 74%C: 46%AA: 44% H: 5% Other: 5%Number of randomized subjects = 67Strata 1 = 48Strata 2 = 5Strata 3 =14(Lost 34 due to either lack of diagnostic consensusagreement between sites or not meeting diagnostic criteriaat the completion of the baseline interviews)