Bipolar Disorder:

Complex, chronic, life-longspectrum of disorders

that are inheritedbut are also

strongly influenced by environmental factors

Stanley Foundation Study

• Prospective study• 2/3 rds have symptoms all of the time• Chronic, fluctuating symptoms• Inter-episode: chronic low grade mixed states…dysphoric hypomania

2

An episodic conditionthat often, ultimately

deteriorates into a chronic,

treatment-resistantdepression

3

Complex:spectrum of

disorders and95% have

co-morbidity

Psychiatric Co-Morbidity

• 50-93% Anxiety Disorder50-93% Anxiety Disorder• 71% Substance Use/abuse71% Substance Use/abuse• 30% Binge Eating Disorder30% Binge Eating Disorder

Frequently Mis-diagnosed

Nat’l. Depression and BipolarSupport Alliance Survey

(2000)

• 69% Misdiagnosed 69% Misdiagnosed as Unipolar MDDas Unipolar MDD• 35% Symptomatic 10+ years35% Symptomatic 10+ years before correct Dx and Txbefore correct Dx and Tx

Frequently Frequently Mis-diagnosedMis-diagnosed

Only 20%:Only 20%:correct Diagnosis in correct Diagnosis in

first yearfirst yearand why it mattersand why it matters

8

First Episodes: Major Depression

• Childhood onset: 70%• Adolescent / adult onset: 60%

9

Treating Bipolar With Antidepressants

• Ineffective• Cause cycle acceleration• Provoke mania (switching)

10

Chronicity: Bipolar IJudd et al. 2003; Frey, 2004

• 13 year follow-up study13 year follow-up study• 47% of weeks: Symptomatic47% of weeks: Symptomatic• 32% weeks: Depressed32% weeks: Depressed• 9%: Manic9%: Manic• 6%: Mixed states6%: Mixed states

Chronicity: Bipolar IIJudd et al. 2003

• 13 year follow-up study13 year follow-up study• 54% of weeks: Symptomatic54% of weeks: Symptomatic• 53% weeks: Depressed53% weeks: Depressed• 1.3%: hypomanic1.3%: hypomanic

DiagnosticDiagnosticIssuesIssues

13

High Index ofHigh Index ofSuspicionSuspicion

With Major With Major DepressionsDepressions

Unipolar vs. BipolarUnipolar vs. Bipolar14

Family History• 11stst. Degree relatives. Degree relatives• Blood relatives with:Blood relatives with: > Substance Abuse> Substance Abuse > Psych Hospitalizations> Psych Hospitalizations > 3+ Marriages> 3+ Marriages > Suicides> Suicides > 4+ jobs before age 40> 4+ jobs before age 40 > Hyperthymia> Hyperthymia

Hyper-thymia• EnergeticEnergetic• TalkativeTalkative• OutgoingOutgoing• Sleeps < 6 hours/nightSleeps < 6 hours/night• ImpulsiveImpulsive• Risk-takingRisk-taking• ““Natural Grandiosity”Natural Grandiosity”

Think Bipolar When…

• Family Hx of BipolarFamily Hx of Bipolar• Hx of childhood onsetHx of childhood onset• Post-partum onsetPost-partum onset• Post-hysterectomyPost-hysterectomy (total hysterectomy)(total hysterectomy)

Think Bipolar When…• Treatment resistant to Treatment resistant to antidepressantsantidepressants• Antidepressants cause Antidepressants cause agitation,irritabilityagitation,irritability

Think Bipolar When…• History of + response toHistory of + response to antidepressants, butantidepressants, but loss of efficacy afterloss of efficacy after a month or twoa month or two

Think Bipolar When…• Clear Seasonal PatternClear Seasonal Pattern• MDD with racing thoughtsMDD with racing thoughts

Think Bipolar When…• Psychotic SymptomsPsychotic Symptoms• Frequent recurrenceFrequent recurrence more than one a yearmore than one a year … ….almost 100%.almost 100%• Atypical Symptoms…Atypical Symptoms…

Atypical Depression

• Hyper-somniaHyper-somnia• Extreme FatigueExtreme Fatigue• Increased AppetiteIncreased Appetite > Carbo Craving> Carbo Craving > Weight Gain> Weight Gain

Atypical DepressionPerugi, Toni, et al., 2003

• 78% ultimately meet78% ultimately meet criteria for bipolarcriteria for bipolar• Especially BP IIEspecially BP II

Life Charting

National Institute of Mental Health

BIPOLAR SPECTRUM DISORDERSBIPOLAR SPECTRUM DISORDERS

BIPOLAR I Bipolar II (most common)

Bipolar IIICyclothymia

Substance induced maniaSchizoaffective disorderChildhood-Onset Bipolar

25

26

27

Bipolar IIBipolar IINew Diagnostic criterionNew Diagnostic criterion

hypomania: 2+ dayshypomania: 2+ days

Most commonly misdiagnosed:Most commonly misdiagnosed:as recurrent or chronicas recurrent or chronic

major depressionmajor depression 28

Screening for a History of Screening for a History of Mania orMania or

HypomaniaHypomania

> Mood Disorder ?aire> Mood Disorder ?aire

29

BIPOLAR SPECTRUM DISORDERS

BIPOLAR IIIBIPOLAR III (Pseudo-unipolar depression)(Pseudo-unipolar depression)

(highly recurrent major depression)(highly recurrent major depression)

Substance InducedMania

95% have bipolar95% have bipolar

Adverse MedicationEffects:

Activation,Switching,and

Cycle Acceleration

Warning Signs of Switching:

Racing thoughtsRacing thoughtsthat prevent that prevent sleep onsetsleep onset

CycleAcceleration

AntidepressantsThe most commonlyThe most commonlyPrescribed drugs in Prescribed drugs in

the USA for the USA for Bipolar DisordersBipolar Disorders

(Hirshfield, et al., 2003)

23%judged to have had

antidepressants causecycle acceleration

MANIA SUBTYPES• ““CLASSIC MANIA” CLASSIC MANIA” 60%60%• MIXED / DYSPHORIC MIXED / DYSPHORIC 40% 40%

Mixed State• Unrelenting dysphoriaUnrelenting dysphoria• Marked Irritability Marked Irritability • Severe Agitation / anxietySevere Agitation / anxiety• Intractable InsomniaIntractable Insomnia• High Suicide RiskHigh Suicide Risk

Rapid Cycling

• 4 or more episodes4 or more episodes per yearper year• Ultra-Rapid Cycling:Ultra-Rapid Cycling: 4 per month4 per month• Ultradian: DailyUltradian: Daily

Rapid Cycling(Arch. Gen Psych.)

(Gitlin, 2002)

• N= 919 patients: followed: 7 yearsN= 919 patients: followed: 7 years• 19% were Rapid Cyclers19% were Rapid Cyclers• Of these only 18% had more Of these only 18% had more than two years of RCthan two years of RC• Only 2% had continuous RCOnly 2% had continuous RC• ““Flair up” not continuousFlair up” not continuous

Rapid CyclingAssociated With:

• Delayed treatment Delayed treatment (11 vs 7 years)(11 vs 7 years)

• History of child abuseHistory of child abuse• Thyroid diseaseThyroid disease• Substance AbuseSubstance Abuse * *

Bipolar Disorder:Age of OnsetNIMH: STEP-BD (2004)

• Pre-pubertal: 27%Pre-pubertal: 27%• Adolescent Adolescent (13-18)(13-18) 38% 38%• After age 18 35% After age 18 35%

By age 15-16

Bipolar PresentationBipolar PresentationIs “Adult Onset”Is “Adult Onset”

VersionVersion

Bipolar in Children(Anthony, 2001)

• 70% first episode is MDD70% first episode is MDD• 1% “Classic mania”1% “Classic mania”• 29% Mixed mania29% Mixed mania

MANIA in CHILDREN

• NOT EPISODICNOT EPISODIC• CHRONIC DYSPHORIACHRONIC DYSPHORIA• EXTREME IRRITABILITYEXTREME IRRITABILITY• INTENSE EPISODICINTENSE EPISODIC RAGES…RAGES…

Discriminating Symptoms

• Decreased Need for Sleep Decreased Need for Sleep (40% vs 6%)(40% vs 6%)

• Hypersexuality Hypersexuality (43% vs 6%)(43% vs 6%)

• Intense, prolonged Rage Attacks Intense, prolonged Rage Attacks (92% vs 0%) (92% vs 0%)

• Morbid DreamsMorbid Dreams• Predictable am activity: ADHDPredictable am activity: ADHD

Realistic MedicalRealistic MedicalProphylaxisProphylaxis

• Chronic treatment after first Chronic treatment after first episodeepisode• What is realisticWhat is realistic

““I’m doing a lot better nowI’m doing a lot better nowthat I am back in denial”that I am back in denial”

Realistic MedicalRealistic MedicalProphylaxisProphylaxis

• 30% true cessation of episodes• Realistic Good Outcome: > 75% reduction in episode frequencies > Reduce severity and hospitalizations

Medication AdherenceMedication AdherenceScott and Pope, (2002)Scott and Pope, (2002)

• 18 month study• Required repeated hospitalizations: > Partial Adherence: 81% > Adherent: 9%• Overall: 50% are compliant• Main problem: Long-term tolerability

Instability Model• Goodwin and JamisonGoodwin and Jamison• Marked CircadianMarked Circadian

VulnerabilityVulnerability

Circadian IntegrityThe Most Critical Features

• Regular Times:Regular Times: To Bed & AwakeningTo Bed & Awakening• Early Morning Bright LightEarly Morning Bright Light• Adequate SleepAdequate Sleep

Circadian IntegrityThe Most Critical Features

• Maintain Social RhythmsMaintain Social Rhythms• EatingEating• ExerciseExercise• Bright light exposureBright light exposure

for Bipolar

• Shift workShift work• Time Zone ChangesTime Zone Changes• Substance AbuseSubstance Abuse• Disrupted SleepDisrupted Sleep

Empirically ValidatedPsychotherapies

• Psycho-educational family TxPsycho-educational family Tx• Interpersonal and SocialInterpersonal and Social Rhythm Therapy (IPSRT)Rhythm Therapy (IPSRT)

Family focusedPsycho-education

Miklowitz, et al. 2003

• N: 101N: 101• Fewer hospitalizations: 12% vs 60%Fewer hospitalizations: 12% vs 60% (two year follow-up)(two year follow-up)• Relapses (one year follow-up):Relapses (one year follow-up): > Tx as usual: 53%> Tx as usual: 53% > Family Tx Psy. Ed. 29%> Family Tx Psy. Ed. 29%• Better Med Compliance: p < 0.04Better Med Compliance: p < 0.04

IPSRTInterpersonal and Social Rhythm Therapy

(Frank and Ehlers)

• Support medication adherenceSupport medication adherence• Stabilize environmental factorsStabilize environmental factors• Develop and maintain “socialDevelop and maintain “social rhythms”rhythms”• Manage provocative social Manage provocative social interactions andinteractions and Interpersonal problemsInterpersonal problems

Outcomes: IPSRT(Kupfer, et al., 2000)

• Time to stabilization; N= 151• Treatment as usual: 40 weeks• IPSRT: 22 weeks• Significantly different: 0.05 level

STEP-BD

• Systematic Treatment Enhancement Program for Bipolar Disorder• N: 5000…currently: 1000• NIMH supported study

Systematic Trials

Aggressive Treatmentvs.

Compliance Considerations

Episode resolutionvs

Functional Recovery

Average Time toFull Resolution

NIMH Collaborative Study Data

• Mania: 11 weeksMania: 11 weeks• Depression: 19 weeksDepression: 19 weeks• Mixed State: 36 weeks*Mixed State: 36 weeks* * * up toup to

Full Resolution of Mania

Time Adults ChildrenTime Adults Children6 months 85% 14%6 months 85% 14%1 year 92% 36%1 year 92% 36%2 years 98% 65%2 years 98% 65%

Poly-PharmacologySTEP-BP program:

only 11%: monotherapy

TREATMENT and PHASES of BIPOLAR DISORDER

Ideal Mood Stabilizer • Prevents relapse andPrevents relapse and cycle accelerationcycle acceleration “ “do no harm”do no harm”

Lithium30% started on:

prevented relapse*

Seroquel

* (Swann, et al., 2002)

FDA ApprovedMedications for Bipolar Disorder

FDA:FDA: Acute Mania Acute Mania * 1970: Lithium* 1970: Lithium * 1973: Thorazine * 1973: Thorazine * 1995: Depakote* 1995: Depakote * 2000: Zyprexa * 2000: Zyprexa * 2003: Risperdal * 2003: Risperdal * 2004: Seroquel* 2004: Seroquel * 2004: Abilify* 2004: Abilify * 2005: Geodon* 2005: Geodon * 2005: Equetro (Tegretol)* 2005: Equetro (Tegretol)

FDA: Acute FDA: Acute Bipolar DepressionBipolar Depression

* 2004: Symbyax* 2004: Symbyax (Prozac and Zyprexa)(Prozac and Zyprexa) * 2007: Seroquel* 2007: Seroquel

FDA:FDA: Maintenance Maintenance

* 1974: Lithium: both* 1974: Lithium: both * 2003: Lamictal:* 2003: Lamictal: depressiondepression * 2004: Zyprexa: both * 2004: Zyprexa: both * 2005: Abilify: both* 2005: Abilify: both

Off-LabelOff-LabelUseUse

Acute Mania and Prophylaxis

• Lithium• Depakote *• Tegretol (Equatro) *• Trileptal *• Antipsychotics (all)

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Dysphoric ManiaDysphoric Mania

Rapid CyclingRapid Cycling

DepakoteDepakote, Lithium, Lithiumor antipsychoticsor antipsychotics

LamictalLamictal77

Black Box Warnings• Depakote: liver failure, birth defects, pancreatitis• Tegretol: aplastic anemia, agranulocytosis• Lithium: birth defects, toxicity associated with increased serum level • Atypical Antipsychotic: increased mortality in elderly / demented patients

78

Medications for Bipolar Mania: Efficacy

not Established

• TrileptalTrileptal• TopamaxTopamax

Medications for Bipolar Mania:

Not Effective

•NeurontinNeurontin• GabitrilGabitril

(seizures)(seizures)

Treating AcuteManic Episodes

Severe Agitation

• Benzodiazepines Benzodiazepines (e.g. Ativan, Klonopin)(e.g. Ativan, Klonopin)

• AntipsychoticsAntipsychotics• ECTECT

Xanaxmay provoke mania

Caution !Caution !

Efficacy: Treatment of Mania

• Lithium (pooled): 58%Lithium (pooled): 58%• Depakote (pooled): 54%Depakote (pooled): 54%• Tegretol (pooled): 52%Tegretol (pooled): 52%• Other agents: open studiesOther agents: open studies

Side Effects

Side Effect Management

• Sustained release (Sustained release ( peaks) peaks) or twice a day dosing or twice a day dosing • dose with maintenancedose with maintenance• Drug combos !!!!!!!…..Drug combos !!!!!!!…..

Once a day dosing

Two drugs

Compliance:Mono vs Combo Treatments

(Goodwin, 2004; P. Keck, 2002)

• N= 140 Bipolar IN= 140 Bipolar I• Lithium or Depakote monotherapyLithium or Depakote monotherapy compliance rates: 50-60%compliance rates: 50-60%• CombinedCombined (lower doses)(lower doses)

Compliance rates: 40% betterCompliance rates: 40% better compliancecompliance

Compliance:Mono vs Combo Treatments

(Goodwin, 2004; P. Keck, 2002)

SometimesSometimes2+2=52+2=5

Lithium

Lithium Side Effects• Weight GainWeight Gain (50%) (50%)• SedationSedation• Cognitive BluntingCognitive Blunting creativity; drivecreativity; drive• TremorTremor (65%) (65%)• Weakness (transient)• Nausea (50%)• Diarrhea, vomiting

Lithium Side Effects

•Weight Gain Weight Gain (60%)(60%)

•Weakness Weakness (tr ansient(tr ansient))

•SedationSedation

•Cognitive Cognitive BluntingBlunting

creativit y; dr ivecreativit y; dr ive•

Tremor Tremor (65%)(65%)

•Nausea Nausea (50%)(50%)

•Diar rhea, Diar rhea, vomitingvomiting

•Metallic Metallic TasteTaste

• FatigueFatigue• Sexual Dys.Sexual Dys. (10%) (10%)• Thirst, polydipsia (40%)• Polyuria (40%)• Dermatological• Hypothyroid• Renal (Kidney) Effects (?)

Average Length ofLithium Continuation

Johnson, 1996Johnson, 1996

Average Length ofLithium Continuation

Johnson, 1996Johnson, 1996

Lithium Levels

0.8-1.20.8-1.2

Lithium Toxicity• 1.5-2.01.5-2.0: ataxia, coarse tremor, : ataxia, coarse tremor, confusion, drowsinessconfusion, drowsiness slurred speechslurred speech• 2.0+:2.0+: coma, seizures, coma, seizures, stupor, kidney failurestupor, kidney failure• 4.0:4.0: death death• No antidoteNo antidote, but can treat with , but can treat with hemo-dialysis orhemo-dialysis or peritoneal dialysis peritoneal dialysis

Maintenance Doses(maybe)

• Levels: 0.6: Bipolar IILevels: 0.6: Bipolar II 0.8: Bipolar I0.8: Bipolar I

Lithium trivia question:

If you discontinue yourlithium how can you

still use your medication?

Anti-ConvulsantAnti-ConvulsantBipolar MedicationsBipolar Medications

Anti-convulsantsAnti-convulsants

• Depakote• Tegretol (Equetro)• Trileptal• Topamax• Neurontin• Lamictal (not for mania)

Side Effects Common toMost Anticonvulsant

Mood Stabilizers

• Lethargy/SedationLethargy/Sedation• TremorTremor• Weight GainWeight Gain• Nausea• Rash

Depakote

PREDICTORS OF GOODDEPAKOTE RESPONSE

• ““CLASSIC” MANIA = LITHIUMCLASSIC” MANIA = LITHIUM• RAPID CYCLINGRAPID CYCLING• DYSPHORIC / MIXED MANIADYSPHORIC / MIXED MANIA• USE FOR RAPID ONSETRAPID ONSET OF ACTIONS

Depakote Levels

• Levels: 50-125Levels: 50-125

Poly-cystic Ovaries• Women under 20: 80%Women under 20: 80%• Often associated with:Often associated with: weight gain weight gain • Pre-treatment sonogramPre-treatment sonogram• Watch for: weight gainWatch for: weight gain and irregular menses and irregular menses

Tegretol

Trileptal

Targeting Co-morbidity:

TopamaxTopamax > Bulimia> Bulimia > Binge eating> Binge eating > Obesity> Obesity > Neuropathic pain> Neuropathic pain > Migraine prophylaxis> Migraine prophylaxis > Alcohol dependence> Alcohol dependence

Targeting Co-morbidity:

NeurontinNeurontin

> Social anxiety> Social anxiety > Panic disorder> Panic disorder (not OCD)(not OCD) > Neuropathic pain> Neuropathic pain > Substance withdrawal > Substance withdrawal

Atypical Antipsychotics

Not just for Not just for Psychotic SymptomsPsychotic Symptoms

AntipsychoticsAntipsychotics

Anti-psychoticAnti-manic

Anti-aggression111

Atypical AntipsychoticsAtypical Antipsychotics

SEROQUELRISPERDALZYPREXAGEODONABILIFYINVEGAFANAPTSAPHRIS 112

Atypical Antipsychotics:Side Effect Issues

• Weight gainWeight gain• Increased CholesterolIncreased Cholesterol and triglyceridesand triglycerides• HyperglycemiaHyperglycemia• Type II Diabetes …….Type II Diabetes …….

Metabolic Side Effects

• Most common:Most common: > Clozaril> Clozaril > Zyprexa (Symbyax)> Zyprexa (Symbyax)• Moderate: Moderate: > Seroquel, Risperdal. Invega> Seroquel, Risperdal. Invega• Least Likely:Least Likely: > Abilify, Geodon> Abilify, Geodon

The Real ChallengeIn Treating

Bipolar Disorder:

Bipolar Depression

The greatest morbidity

Bipolar Depression(Not necessarily the same as Unipolar)

BIPOLAR DEPRESSION

• ““Do No Harm”Do No Harm”• IneffectiveIneffective• SwitchingSwitching• Cycle Acceleration Cycle Acceleration

BIPOLAR DEPRESSION

APA GuidelinesAPA GuidelinesDo Do notnot recommend recommendantidepressants forantidepressants forfirst line treatmentfirst line treatment

Switch Rates

• STEP-BD programSTEP-BD program• 37% report hx of switching37% report hx of switching

Bipolar Meds withAntidepressant Actions

• LamictalLamictal• SymbyaxSymbyax• SeroquelSeroquel• LithiumLithium if above 0.8if above 0.8

Bipolar Meds withBipolar Meds withAntidepressant ActionsAntidepressant Actions

• Lamictal• Symbyax *• Seroquel *• Lithium *

Stevens-Johnson SyndromeStevens-Johnson Syndrome

Lamictal: DosingLamictal: Dosing• Dosing: 25 mg week one and twoDosing: 25 mg week one and two 50 mg week three…50 mg week three… 100 mg bid100 mg bid (see PDR…)(see PDR…)

• Target Dosing: 75-225 mg per dayTarget Dosing: 75-225 mg per day• Onset of Actions: 3-4 weeksOnset of Actions: 3-4 weeks

Lamictal: RashLamictal: Rash• Prevalence:Prevalence: * benign: 12%* benign: 12% * Stevens Johnson: 1/1000* Stevens Johnson: 1/1000 adults and teensadults and teens * 2% in Children* 2% in Children

How Risky is Lamictal ?How Risky is Lamictal ?German Rash RegistryGerman Rash Registry

• Since slow titration startedSince slow titration started• Benign: 9% drug, 8% placeboBenign: 9% drug, 8% placebo• Serious rash: placebo: 0.06% Serious rash: placebo: 0.06% drug; 0.09%drug; 0.09%• No cases of Stevens-JohnsonNo cases of Stevens-Johnson adults and teensadults and teens• Children: 3/10,000Children: 3/10,000

SymbyaxSymbyax

SeroquelSeroquel

• Zyprexa-Prozac ComboZyprexa-Prozac Combo• Quick onset of actionQuick onset of action

Bipolar Depression AlgorithmsBipolar Depression Algorithms

If Bipolar IIf Bipolar I::recent mania or history ofrecent mania or history of

switching, stronglyswitching, stronglyrecommend an antimanic agent: recommend an antimanic agent:

first line first line

Algorithm: BP IAlgorithm: BP I

> Lamictal and Anti-manic> Lamictal and Anti-manic > Symbyax or Seroquel> Symbyax or Seroquel > Add lithium> Add lithium > ECT> ECT

Algorithm: BP IIAlgorithm: BP II

> Lamictal > Lamictal > Symbyax or Seroquel> Symbyax or Seroquel > Add lithium> Add lithium > ECT> ECT

Maintenance

Tolerability, Safety and Efficacy

• Seroquel and Lamictal combination: long-term maintenance• Lithium: for suicide prevention

Time to Next Manic Episode

(Keck and McElroy, 2002; Bowden, et al., 2004)

• Combo TherapyCombo Therapy (Li and Depakote): (Li and Depakote):

6 x longer vs. monotherapy6 x longer vs. monotherapy

Childhood-Onset Bipolar DisorderChildhood-Onset Bipolar Disorder

Childhood Onset Bipolar

•Diagnostic confusion !!!!!•Guarded prognosis

134

Narrow phenotype Bipolar

•Meet DSM-IV criteria for bipolar •Most have a bipolar parent• Versus broad phenotype

135

Chronic Rapid CyclingChronic Rapid Cycling (J. Walkup, 2002)(J. Walkup, 2002)

• Chronic lability due to any mixture of: ADHD, anxiety, depression, poor self-control, adverse life circumstances, fetal drug/alcohol exposure, substance abuse, lack of supervision, family dysfunction….

136

137

138

Temper Dysregulation Disorderwith Dysphoria: DSM-V

• Severe temper outbursts• Grossly out of proportion in intensity and duration• In response to common stressors• 3 or more times per week

Temper Dysregulation Disorderwith Dysphoria: DSM-V

• Onset: after 6 and before 10• Mood between temper outbursts: > Nearly every day: angry, irritable and/or sad• Continuous symptoms: for at least 12 months

Temper Dysregulation Disorderwith Dysphoria: DSM-V

• Present in at least 2 settings (e.g. home and school)• Never a period of time with abnormally elevated or expansive mood

Temper Dysregulation Disorderwith Dysphoria: DSM-V

• No history of > decreased need for sleep > grandiosity > pressured speech

Temper Dysregulation Disorderwith Dysphoria: DSM-V

• Can co-exist with ADHD, conduct disorder, oppositional-defiant disorder and substance abuse disorder

Target symptomapproach

144

Bipolar Meds with Kids:Monotherapy

• Two studies: ages 10-17…bipolar I• Trileptal: Am. J. Psychiatry (2006)

• Depakote: J. Am. Acad. Child and Adol. Psychiatry (2009)

• Neither different than placebo

145

Medication Combinations• Children and adolescents• Lithium and atypical antipsychotic only slightly better than lithium and placebo• Very high rates of relapse: monotherapy• Lithium and Depakote: effective in 40% BNN, V. 13, 2009

BNN, V.12, 2008

146

Experimental Lithium treatment

• Teens and adults: Li blood level: 1.0…..brain level: 1.0 • Children: Li blood level: 1.0…..brain level: 0.5• May require dosing up to 2.0 Li level to achieve adequate levels in the brain BNN, V. 12, 2008

147

Full Resolution of ManiaFull Resolution of Mania

Time Adults Children6 months 85% 14%1 year 92% 36%2 years 98% 65%

148

Two Year Outcome:Children with Bipolar

(Geller and Craney, 2002)(Geller and Craney, 2002)

• Average age: 10.9…N=89• 55% relapsed after recovery > Mean time to relapse: 28 weeks

149

Seroquel• Childhood onset bipolar• Broad efficacy and tolerability• Bipolar Network News (2008)

Am. College of neuropsychopharmacology

• Open label studies• De Bello, et al. (2008)

150

Trivia QuestionWhat is the favorite flavorWhat is the favorite flavor

of snow cone syrupof snow cone syrupused to flavor liquidused to flavor liquid

Antipsychotic medications?Antipsychotic medications?

Raspberry

V