Download Pediatric Bipolar Disorder

Pediatric Bipolar Disorder
David Camenisch, MD/MPH
PAL Conference
Jackson, WY
May 5, 2012
PAL Conference
May 5, 2012
Cody (RR 2.5) - History
 6 year old mixed-race (NA/AA) boy new to your practice
 ADHD diagnosis at age 4.
 On and off stimulants for 2 years.
 Has been tried on both methylphenidate and amphetamine
preparations.
 They tend to work for a while but then things “go back to normal.”
 He has always been “moody.”
 Struggling at school socially but “really smart.” Per mom, “He
reads real history books and remembers everything.”
PAL Conference
May 5, 2012
Cody – Presentation
 Mom thinks he is bipolar. She just got diagnosed and
medications have really helped her.
 Mom says she can’t control him at home. A little better
with mom’s boyfriend of who has been in and out of the
picture for 2 years.
 Actually, mom just stopped stimulants because she heard
they can make things worse if your kid has bipolar. She
thinks he is doing better.
 She asks you to prescribe “something” to treat his bipolar
mood swings……
PAL Conference
May 5, 2012
What To Do?
 What role should a primary care provider take regarding
the question of child bipolar disorder?
 Psychoeducation?
 Referral?
 Treatment?
 How do you assess for childhood bipolar disorder?
 When does it make sense to…
 Wait
 Prescribe a mood stabilizer?
 Refer to a therapist?
 Refer to a (child and adolescent) psychiatrist?
PAL Conference
May 5, 2012
Bipolar Is A Hot Topic
 Bipolar disorder in kids is much talked about
 “Child Anxiety Disorder” on Google
 26,600,000 hits (3,120,000)
 “Child Bipolar Disorder” on Google
 33,100,000 hits (4,370,000)
(Camenisch 2012, Camenisch 2011)
 Child anxiety disorders are actually about 10 times more common
than child bipolar disorder
 40 fold increase in office visits for child bipolar disorder
from 1994 to 2003 (Also 40-fold increase in diagnosis.)
National Center for Health Statistics
PAL Conference
May 5, 2012
Frequency of Childhood Bipolar
 Very controversial
 Some assert a high frequency of all children have bipolar
disorder
 “The Bipolar Child” by Papolos and Papolos
 Assert 1/3 of all children with ADHD
 States about 6% of all children are bipolar
 “Is Your Child Bipolar” by McDonnell and Wozniak
 States more than 3 million US kids have it
 Based on their estimates, incidence is 4%.
PAL Conference
May 5, 2012
Quoted Child Rates Don’t Match Our Adult
Knowledge
 Adult Lifetime prevalence rates of bipolar disorder 1 to 2%
 Greater diagnostic certainty with adults
 Bipolar disorder is a lifelong diagnosis – need plausible
explanation if pediatric bipolar is 3-6X > adult bipolar
 Lessons from Great Smoky Mountain data set
 child bipolar NOS ≠ bipolar adult
 Kids with bad mood swings cannot all have “true”
bipolar disorder
PAL Conference
May 5, 2012
Why is diagnosis so challenging?
 Symptom overlap + high rates of co-morbidity
 Confounding developmental issues
 Environmental influences
 Limited ability of (many) children to verbalize emotions
 Many different “expert” opinions
 Influence of popular media/pharmaceutical industry
 Requires extensive history – assessment of both current
symptoms and past episodes (subject to recall bias.)
PAL Conference
May 5, 2012
DSM-IV TR (Hypo)Manic Episode
 Manic Episode – 7 days + impairment, or hospitalization or
psychosis
 Distinct period of abnormal and persistently elevated*, expansive or
irritable mood
 Plus 3 (4 if “irritable-only” mood) of the following:
 Distractible
 Grandiose/inflated self-esteem*
 Decrease need for sleep (< 3 hrs)
 More talkative/pressured speech
 Indiscretions/risk taking
 Flight of ideas/racing thoughts
 Increased goal directed activities/PMA
 Hypomanic Episode – 4 days. No hospitalizations. No
impairment.
PAL Conference
May 5, 2012
Depressive Episode
 5 or more of following in same 2 week period +
depressed/irritable mood OR lost of interest/anhedonia
 Sleep
 Interest
 Guilt
 Energy (fatigue)
 Concentration
 Attention
 PMA/PMR (observable)
 Suicidal thoughts/feelings/behaviors
 Functional Impairment
 No Mixed Episode, R/O Substance, R/O GMC, R/O
Bereavement
PAL Conference
May 5, 2012
Diagnosis of Mood Disorders
Current
None
MDE
Hypo
Manic
Mixed
No Dx
MDD
No Dx
BP1
BP1
MDD
MDD
BP2
BP1
BP1
No Dx
BP2
BP, NOS
BP1
BP1
BP1
BP1
BP1
BP1
BP1
BP1
BP1
BP1
BP1
BP1
Past
None
MDE
Hypo
Manic
Mixed
Remember to ask about past mood symptoms, otherwise bipolar will be
misdiagnosed as depression.
PAL Conference
May 5, 2012
Bipolar, NOS DSM-IV TR
 Rapid alternation between manic and depressive
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
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symtpoms that do not meet duration criteria
Recurrent hypomanic episodes w/o depressive symptoms
Manic or mixed episode in context of thought disorder
Hypomanic episodes w/ chronic depressive symptoms
Hypomanic/manic symptoms but haven’t yet been able to
rule out influence of substance use or general medical
condition.
PAL Conference
May 5, 2012
Bipolar Disorder, NOS
 Contributes to the current bipolar “epidemic”
 Label often given to impulsive, aggressive kids
 Prognosis could be normal, MDD, or (rarely) true
bipolar
 Diagnosis confused with:



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


ADHD
Depression
Abuse (current and PTSD)
Anxiety Disorders
Disruptive Behaviors Disorders
Reactive Attachment Disorder
Intermittent Explosive Disorder
PAL Conference
May 5, 2012
Why is Bipolar, NOS so common?
 Broad Category/catch-all
 Not (yet) another more suitable diagnosis that captures
complex behavioral picture (SMD, TDDD)
 Sounds better to us than “I don’t know”
 Justifies the limited(medication) treatment options.
 If we give a child medicine as if bipolar, parents often report
improvement
 Bipolar medicines have many non-specific effects
 All decrease impulsivity and aggression
PAL Conference
May 5, 2012
If not bipolar, then what?
 Depression
 Ongoing abuse/neglect
 Post-trauma symptoms or syndrome
 Environmental Instability (frequent change in living





arrangement/primary care giver; parental mental illness)
Disordered Attachment (RAD)
Temperament Mismatch (Parent-Child Relational Problem)
Anxiety (especially brief, episodic, reactive “mood swings” )
Disruptive Behavior Disorders (ADHD,ODD)
Affective lability in context of autism spectrum disorder (comorbidity versus core disorder attribution)
PAL Conference
May 5, 2012
Severe Mood Dysregulation (SMD)
 Clinical syndrome not a diagnosis (3.3% lifetime prevalence
ages 9-19)
 “chronically irritable children whose diagnosis is in doubt.”
(Often the “Bipolar, NOS crew)
 IS real and confers risk of psychopathology down the line,
but is NOT bipolar disorder (also not Axis II)
 Presence of SMD increases risk of depressive disorder and
GAD at 20 year follow-up.
Stringaris et al, 2010
PAL Conference
May 5, 2012
Bipolar Disorder Frequency Depends On Where
You Look
 Prevalence of “true” adolescent bipolar
 0.6% of high school students
 1% in general outpatient practice
 6 % of child psychiatry outpatients (CMHC)
 22% incarcerated adolescents
 26-34% of child psychiatry inpatients manic symptoms
(1996-2004 CDC survey of discharge diagnosis)
Youngstrom et al, CAPC Vol 18
PAL Conference
May 5, 2012
Cody – The Questions
 Test out whether un/under-treated ADHD (haven’t found
right medication, right dose; hasn’t had behavioral help,
parenting support) or do you need to consider mood
disorder?
 Or co-morbidity (depression, anxiety, ODD)
 Ask for more detail than just “labile moods” (hyperarousal)and “won’t listen” (distractibility)
 How is his mood most of the day?
 What causes (if anything) his mood to change?
 When not upset, what does he look like?
 Can he “pull out of it”
 Does he “listen” when he is asked to do something he wants to do?
PAL Conference
May 5, 2012
Cody – The Answers
 Mom says he “never listens to me” especially when asked to
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
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
do chore/homework/go to bed.
Goes into rages when doesn’t get his way
Throws things at mom, hits her. Says “I hate you.”
Tried “everything,” even spanking, taking away the Xbox.
With dad or other adults he behaves better. Some talking
back, but manageable. Knows he needs to cool it or he going
to get in trouble.
PAL Conference
May 5, 2012
Cody – At School
 In 2nd grade, teacher said he was not listening well in




beginning of year, is better now
In kindergarten he didn’t follow rules well
Performing at grade level
Not having rages at school
Generally more of a problem at home more than at school
PAL Conference
May 5, 2012
Cody – Social History and
Development
 Mom is primary caregiver.
 1 younger brother, mom thinks she might be pregnant.
 No contact with dad. Left before Cody was born.
 Mom has few supports. Mom’s family and tribe
“disowned” her and Cody because his father is AA.
 Developmental milestones were OK
 “Read early. Very verbal. Reads “anything about history”
and “remembers everything.”
 No in utero drug exposure identified.
PAL Conference
May 5, 2012
How to answer Mom’s Question if
this is Bipolar Disorder?
 Difficult diagnosis (no “tests”)
 Diagnosis best made “over time” ; usually not point-in-time
diagnosis --especially with chronic presentation
 Many different opinions, even among specialists
 Down side of labeling too early
 If you think NOT bipolar, continue with…
 Psycho-education. (Non-specific nature of “mood swings”
and “irritability” e.g. cough analogy)
 Reasonable to consider treatment depending on potential
consequences. (Sx-driven versus dx-driven treatment*)
PAL Conference
May 5, 2012
Consider the large differential for each of these Mania
symptoms in kids:
 Distractible
 Indiscretions/risk taking
 Grandiose
 Flight of ideas/racing thoughts
 Activity (goal directed) increase
 Sleep need decreased
 Talkative (pressured speech)
Which can mimic ADHD symptoms?
PAL Conference
May 5, 2012
Manic symptoms versus ADHD
(Kowatch et al, 2005)
Symptom
Irritability
Accelerated Speech
Distractibility
Unusual Energy
ADHD
72%
82%
96%
95%
PBD*
98%
97%
94%
100%
* Pediatric Bipolar Disorder
PAL Conference
May 5, 2012
Diagnostic Perspective
 Experience with adult mania helps, but can be challenging
to translate to kids. (Different patterns of diagnosis
between Adult and C&A psychiatrists?)
 Compare child to a prototypic “manic” patient
 Pressured speech -- not just talkative
 Having no doubt about their grandiose ideas -- impaired reality
testing/lack of insight)
 Thought process is fast and jumping around
 Episodes that most commonly last days not minutes or hours
 Little need for sleep (versus poor sleep.)
PAL Conference
May 5, 2012
Look for Episodes and Patterns
 Individual episodes represent a clear departure from baseline with
some hallmark symptoms
 Hopefully, the presence of hallmark symptoms will help
distinguish irritable mania from irritable depression
 The correct mood diagnosis (and treatment) requires
establishing the pattern of mood episodes, not just presenting
(current) episode.
PAL Conference
May 5, 2012
Rapid Cycling Controversy
 Typical adult pattern is episodic. Rapid cycling is rare in adult
bipolar populations.
 Kids are more reactive and more common to get story of “rapid
cycling.”
 Consider “rapid cycling” in kids if there is no trigger identifiable
for the mood changes
 Where many “episodes” become static, chronic mood state is
controversial.
 ADHD plus irritability should not generate a bipolar diagnosis
 Youth with BP do spend more time cycling and have more changes in
mood polarity that adult populations. (Birmaher et al, 2006)
PAL Conference
May 5, 2012
Chronic versus Episodic Irritability
Objective: Test validity of distinction between chronic and episodic
irritability. (Central debate in pediatric bipolar)
Method: Community sample of 776 children and adolescents
interviewed at 3 points in time (T0, T2y, T7y). Irritability rating
scales used to tease out chronic versus episodic irritability.
Association with age, gender and diagnosis were examined.
(Liebenluft et al, 2006)
PAL Conference
May 5, 2012
Chronic vs Episodic Irritability
Those with episodic irritability were more likely than those with
chronic irritability to have:
 A parent diagnosed with Bipolar Disorder
 Experienced elation and/or grandiosity
 More symptoms of mania
 Psychotic symptoms
 Had a depressive episode
 Made a suicide attempt
PAL Conference
(Liebenluft et al, 2006)
May 5, 2012
Irritability and Later Psychopathology
Chronic irritability at TI - associated with ADHD at T2 and
depression at T3
Episodic Irritability – associate with simple phobia at T2 and mania at
T3
Conclusions:
- Episodic and chronic irritability are distinct constructs.
- Episodic irritability is associated with bipolar disorder and
confers higher risk of future manic episodes than chronic
irritability.
PAL Conference
May 5, 2012
Irritability Controversy
 Geller: Irritability is not diagnostic of PBD; it is very
common and shows high sensitivity, but poor
specificity for PBD
 Wozniak: irritability may be primary mood symptom;
episodicity not relevant.
 Leibenluft: In diagnosing PBD, episodic irritability is
more suggestive of PBD than is chronic irritability
 Hunt/Birmaher – episodic irritability alone can
represent manic phase of illness; “irritable-only”
mania exists but is rare; more common in younger
children. (COBY).
PAL Conference
May 5, 2012
Look for “Hallmark” Symptoms
 Increased specificity
 More likely bipolar…
 Elation
 Hyperactivity
 Grandiosity
 Hypersexuality
 Decreased need for sleep
PAL Conference
May 5, 2012
Bipolar Diagnostic Aides
 Rating Scales
 Young Mania Rating Scale
 Useful for monitoring symptoms over time
 Not a diagnostic tool (very low specificity)
 DISC or KSADS
 Used in research, have flaws
 Impractical for your office practice
 Rating scales are too misleading to recommend for
diagnostic use and are intentionally excluded from the
PAL guide.
PAL Conference
May 5, 2012
Cody
 Rage episodes seem directed mostly at mom, and
mom’s attempts to set limits at home
 Mood changes occur mostly in response to
frustrations
 There are not any hallmark symptoms of
grandiosity, euphoria, hypersexuality
 No history of days-long episodes
 He is very young to diagnose as bipolar
PAL Conference
May 5, 2012
What about Family History?
 Mom says she has been diagnosed with bipolar and his uncle is
bipolar, “just like him”
 Avoid overcalling a positive family history
 many adults who call themselves bipolar may not have that illness
 first degree relative bipolar disorder, increases OR by 5
 second degree relative bipolar, increase OR by 2.5
 given a generous prevalence of 2% bipolar in the population, most children
of a bipolar parent (~90%) will not have bipolar disorder
PAL Conference
Youngstrom E & Duax J, JAACAP 44:7,May
20055, 2012
Looking back at adult bipolar….
 Several studies have asked adults with bipolar about onset of
their symptoms retrospectively
 Bipolar adults look back and note symptoms became bipolarlike in their teen years (50-66%)
 Many bipolar adults had major depression episodes as
children
 The younger the child’s first major depression, the more
likely bipolar disorder is in the future
PAL Conference
May 5, 2012
What if a “Bipolar” Child Really is Bipolar?
 Though rare in a PCP practice, becomes more
likely the older the child.
 Typical pattern is early onset depression, and
during teenage years getting first symptoms of
mania.
 Expect mood “episodes”. COBY study established
validity of episodic course.
 Assemble a team. Real deal bipolar disorder is a
big problem.
PAL Conference
May 5, 2012
Course Of True Bipolar Disorder
 Suicidalilty
 up to 15% eventually complete suicide
 Substance Abuse in up to 60%
 Anxiety disorders in up to 50%
 Psychotic features in up to 50%
 Relationship Disruptions
 Work Disruptions
 Hospitalizations
PAL Conference
2012
Stern TA and HermanMay
JB, 5,2004
Bipolar Treatment
 If clear manic episodes, strongly recommend get
them to child psychiatrist
 Management difficult because:
 High rate of substance abuse
 High rate of medication non-compliance
 Even with medication, recurrences happen
 High rates of family disruption from the illness
 Suicidal behavior is common
PAL Conference
5, 2012
Brent et al, 1988,May
1993
If No Child Psychiatrist Can Assume Care, Then
What?
 Get collateral evaluations to help establish correct
diagnosis
 Strongly advise against rushing to offer diagnosis of bipolar disorder.
 Seek consultant advice on medication (when they are
appropriate to consider)
 Preferred model of care:
 MH specialist is primary prescriber
 PCP is a partner in the treatment team
 Call the Provider Access Line. Sometimes PCP is left
holding the bag
PAL Conference
May 5, 2012
Bipolar Treatments
(for when you are left holding the bag)
 Atypical antipsychotics
 Mood Stabilizers
 Combination therapy
 Antidepressants if used cautiously
 Family therapy (support/education/adherence)
 Sleep hygeine
 Psychotherapy for:
 depression treatment
 coping skills
 supporting medication treatment adherence
PAL Conference
May 5, 2012
Bipolar Medications
PAL Conference
May 5, 2012
What Is A Mood Stabilizer?
 Includes both atypical anti-psychotics and anti-epileptic drugs
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(AEDs)
Generic term – clarify what they mean when taking history
and what you mean when proposing treatment.
FDA does not recognize this term
As relates to treatment of bipolar disorder, ideally treats both
depressive and manic episodes as well as prevents recurrence
of mood episodes.
Since no one compound does this well, multiple meds are
often used together (but little evidence base to support it.)
PAL Conference
May 5, 2012
Mood Stabilizers are Non-Specific to PBD
 Maladaptive aggression
 Mental retardation (lithium, risperidone)
 Autism (risperidone, aripiprazole)
 Conduct Disorder (risperidone, valproic acid, lithium)
 Seizure Disorders – kindling hypothesis; neuroprotective
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effects in mood disorders (lithium)
Depression (risperidone, aripiprazole, quetiapine,
lamotrigine)
Psychosis (primary, mood disorder, delirium)
OCD (refractory)
PTSD (intrusive thoughts)
PAL Conference
May 5, 2012
Pharmacotherapy of Pediatric Bipolar
(Liu et al, JAACAP 2011)
PAL Conference
May 5, 2012
Positive Randomized Trials
 Blinded RCT knowledge base in kids is low
 Aytpical anti-psychotics
 Olanzapine
 Aripiprazole (2)
 Quetiapine (3)
 Risperidone (1)
 AEDs
 Divalproex sodium (Depakote)
 Li (maintenance)
PAL Conference
May 5, 2012
Atypical Antipsychotics
 risperidone, quetiapine, olanzapine, aripiprazole, ziprasidone
 11 OTs with 53% response rate
 8 DBRCTs with 66% response rate
 N = 1474
That DBRCTs showed greater efficacy than placebo is
encouraging and noteworthy
Better tolerated than AEDs as a group.
PAL Conference
May 5, 2012
Risks common to all Atypical
Antipsychotics (Correll, JAACAP. 2008)
 Sedation (olanzapine, quetiapine)
 Tardive Dyskinesia (0.4% annual incidence)
 Increased Cholesterol/ Triglycerides (olanzapine)
 Akathesia (aripiprazole) (youth<adults)
 Increase glucose (olanzapine, quetiapine)
 EPS (risperidone)
 Lower seizure threshold (mildly)
 QT interval change (~20ms for ziprasidone)
 Weight gain (olanzapine > quetiapine, risperidone >the rest)
 Neuroleptic Malignant Syndrome
PAL Conference
May 5, 2012
Atypical Heterogeneity
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May 5, 2012
Adverse and Therapeutic Effects of Occupancy and Withdrawal
(Correll, JAACAP. 2008)
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May 5, 2012
Risperidone (Risperdal)
PROS
 QD-BID dosing (T½ = 20 hours)
 FDA for mania > 10 years old, irritability/aggression in ASD
 Multiple dosage forms (liquid, dissolving tab, tabs, depot)
 Low doses (<2 mg) adequate for non-specific aggression
 TD incidence reported less than 0.5%
CONS
 Weight gain and sedation common
 Hyperprolactinemia risk
 Relatively high rates of dystonic reactions/EPS
PAL Conference
May 5, 2012
Aripiprazole (Abilify)
PROS
 QD-BID dosing ( T½=75 hrs) But kids may do better BID
 FDA for mania (>10 yrs) and limited RCT support
 Mixed agonist/antagonist (less dystonia/EPS)
 Often less sedation
CONS
 Limited dosage forms
 Misperception of less weight gain/metabolic SE
 Agitation/activation not uncommon
 Higher rates of akithesia
 Long T ½ -may take longer to see impact of changes
PAL Conference
May 5, 2012
Quetiapine (Seroquel)
PROS
 Lower potency - may be experienced as “milder”
 FDA approval (>10 years old)/limited RCT evidence
 Effective anxiolytic
 Cross indication for bipolar and unipolar depression
CONS
 Short half-life (T½ = 6 hours); multiple daily dose; mixed
results w/ XR preparation
 Large tablets - may be hard to swallow
 Effective sleep aide (high risk, high cost sleep aide)
 Cataract risk
PAL Conference
May 5, 2012
Olanzapine (Zyprexa)
PROS
 QD-BID dosing (T½ = 30 hours)
 FDA approval (> 13 years) and limited RCT evidence
 Multiple dosage forms (tablets, oral disintegrating, IM)
 Very effective for acute stabilization of mania and psychosis
CONS
 Weight gain (dose related, less of plateau than others)
 High rates of metabolic side effects
 Sedation common
PAL Conference
May 5, 2012
Ziprasidone (Geodon)
PROS
 Often less sedating
 Most weight neutral
 Fewer metabolic side effects
 Unique receptor profile
CONS
 BID-QID dosing (T ½ = 7 hrs)
 No FDA approval for pediatric mania
 No pediatric RCT support
 Concern for EKG changes has lowered its usage
PAL Conference
May 5, 2012
Monitoring for all atypical antipsychotics: AIMS exam at baseline and Q6months due to risk of tardive
PAL Conference
May 5, 2012
dyskinesia.
Warn of dystonia risk. Weight checks, fasting glucose/lipid panel Q6months at minimum.
Anti-convulsants
 Lithium (Li), divalproex sodiumm(VPA), carbamazepine
(CBZ)
 14 OTs (41% response rate)
 6 RCTs (40 % response rate)
 n = 915
 Only RCTs for divalproex sodium
 No RCTs for Li or CBZ
 Lamotrigine, oxcarbazepine, topiramate
 3 OTs (43% response rate)
 2 RCTs (39%)
 n = 244
PAL Conference
May 5, 2012
Lithium
PROS
 FDA approved for mania >12 years
 Some evidence in refractory depression
 Anti-suicide properties
 Some EB dosing guidelines (adjust for age/GFR)
CONS
 Narrow therapeutic index (close monitoring for toxicity w/
illness/dehydration; no NSAIDs)
 Usually best in combination, so committing to polypharmacy if
you start here (best w/ atypical or VPA)
 SE in therapeutic range similar to early toxicity (tremor, diarrhea)
 SE often limit use (weight gain, acne, GI); HS dosing can minimize
 Hard to predict who will respond
May 5, 2012
 PAL
NoConference
evidence for maintenance treatment /slow anti-manic effects
Early
Signs
PAL Conference
May 5, 2012
Valproic Acid (Depakote)
PROS
 Single daily dosing can be effective (Depakote ER)
 Can be useful for maladaptive/non-specific aggression
 Studies suggest helpful, usually in combination
CONS
 Requires blood draws (levels, LFTs, amylase, CBC)
 Risk of hepatotoxicity (highest in first 6 months)
 High side-effect burden (weight gain, GI, tremor, sedation,
rash)
 Less ideal for females (risk of birth defects (NTD), PCOS)
PAL Conference
May 5, 2012
Depakote
 How well does it work?
 Fair, usually works best in adolescents in combination with an
antipsychotic (better than either one alone)
 Some RCT’s have suggested that it works better than lithium on
acute manic symptoms
 Broad effects: also used for externalizing behavior disorders,
conduct disorder
 Lost in head-to-head trial with quetiapine
 Similar long-term stabilizing effect to Lithium after stabilization
with both divalproex and lithium
DelBello MP et al, 2002, 2006
Bowden C et al, 2004
Rana M et al, 2005
Findling, R et al 2005
PAL Conference
May 5, 2012
Carbamazepine (Tegretol)
PROS
 Some empirical supports for aggression
 2 OTs
 Similar response rates as Li and VPA (38%) (Kowatch et al, 2005)
CONS
 Drug/drug interactions (OCPs, Lithium)
 Blood draws to check levels (auto-induced metabolism)
 Weak evidence of benefit in bipolar (McClellan and Werry, 1997)
 Risk of aplasia and liver failure
PAL Conference
May 5, 2012
Hard to Compare Effectiveness
42 child outpatients with Bipolar 1 or 2, randomized to one of
three open label treatments
R Kowatch et al, 2000
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May 5, 2012
Lamotrigine (Lamictal)
PROS
 Bipolar depression treatment
 Less sedation and lower side effect profile in general
CONS
 Not helpful for manic phase
 Requires monitoring of CBC and liver function
 Significant rash risk
 Slow titration (age >12)
PAL Conference
May 5, 2012
Oxcarbazepine (Trileptal)
PROS
 FDA approval for adults bipolar disorder
 Weight neutral
 Less risks/side effects than carbamazepine
 Monitoring of levels not required
CONS
 Levels do not correlate well with efficacy or toxicity
 Negative adolescent bipolar trial (Cochrane Review. Vasudev et al. 2008)
 Hyponatremia not uncommon
PAL Conference
May 5, 2012
Anticonvulsants Shown Not To Help
In Adult Bipolar Disorder
 topiramate (Topamax) (1 negative pediatric trial)
 gabapentin (Neurontin)
 levetiracetam (Keppra) - can cause psychiatric
symptoms
 zonisamide (Zonegran)
 pregabalin (Lyrica)
 felbamate (Felbatol) - can cause psychiatric
symptoms
PAL Conference
May 5, 2012
Bipolar Take-Home Message
 Diagnosis of bipolar disorder made with relative confidence in the
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presence of manic (Bipolar I) or hypomanic (Bipolar II) episodes.
It gets tricky after that.
Mood episodes (all) involve distinct change from baseline with
alternations in behavior and evidence of impairment.
Bipolar diagnosis is a serious diagnosis that has a life-long course
and many management challenges.
True bipolar has high rates of morbidity and mortality.
If suspected, strongly recommend involving a child and adolescent
psychiatrist .
If you, as PCP, are playing central role in management, check-in
frequently to monitor side effects of medication(s) and
surveillance of mood symptoms.
PAL Conference
May 5, 2012
“Not-Bipolar” Take-Home Message
 Currently, there is no single diagnosis for chronically dysregulated
or irritable kids. Evidence is more suggestive of current and/or
future depressive disorder.
 Kids with severe, non-episodic irritability differ from those with
bipolar in course, family history and performance in many
cognitive tasks linked to more severe psychopathology.
 Still a major role for parent support/training and mental health
support. These kids can be draining and are high risk.
 There can be a role for medications to decrease maladaptive
aggression and affective instability.
PAL Conference
May 5, 2012
At PCP level, recommend….
 …keeping in mind many possible causes of mood swings
and irritability.
 …resisting temptation to label impulsive, difficult kids as
“bipolar.”
 …reminding yourself and parents who are struggling
that most disruptive, irritable children do not have
bipolar disorder but can still benefit from help.
 …getting help with diagnostic and treatment questions
as often as necessary.
PAL Conference
May 5, 2012
Selected Bibliography
 Pharmacologic Treatments for Pediatric Bipolar Disorder: A Review
and Meta-Analysis. Liu et al. JAACAP. August 2011.
 Practitioner Review:The Assessment of Bipolar Disorder in Children
and Adolescents. Baroni et al. JCPP. 2009.
 Antipsychotic Use in Children and Adolescents:Minimizing Adverse
Effects to Maximize Outcomes. Correll. JAACAP. January 2008.
PAL Conference
May 5, 2012