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Pediatric Bipolar Disorder

Pediatric Bipolar Disorder. David Camenisch , MD/MPH PAL Conference Jackson, WY 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.

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Pediatric Bipolar Disorder

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  1. Pediatric Bipolar Disorder David Camenisch, MD/MPH PAL Conference Jackson, WY May 5, 2012 PAL Conference

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. Diagnosis of Mood Disorders Current None MDE Hypo Manic Mixed Past None No Dx MDD No Dx BP1 BP1 MDE MDD MDD BP2 BP1 BP1 Hypo No Dx BP2 BP, NOS BP1 BP1 Manic BP1 BP1 BP1 BP1 BP1 Mixed BP1 BP1 BP1 BP1 BP1 Remember to ask about past mood symptoms, otherwise bipolar will be misdiagnosed as depression. PAL Conference

  12. Bipolar, NOS DSM-IV TR • Rapid alternation between manic and depressive 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

  13. 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: • ADHD • Depression • Abuse (current and PTSD) • Anxiety Disorders • Disruptive Behaviors Disorders • Reactive Attachment Disorder • Intermittent Explosive Disorder PAL Conference

  14. 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

  15. 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 (co-morbidity versus core disorder attribution) PAL Conference

  16. 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

  17. 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

  18. 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” (hyper-arousal)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

  19. Cody – The Answers • Mom says he “never listens to me” especially when asked to 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

  20. 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

  21. 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

  22. 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

  23. 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

  24. Manic symptoms versus ADHD (Kowatch et al, 2005) SymptomADHDPBD* Irritability 72% 98% Accelerated Speech 82% 97% Distractibility 96% 94% Unusual Energy 95% 100% * Pediatric Bipolar Disorder PAL Conference

  25. 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

  26. 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

  27. 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

  28. 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

  29. Chronic vs Episodic Irritability Those with episodicirritability were more likely than those with chronicirritability 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 (Liebenluft et al, 2006) PAL Conference

  30. 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. (Liebenluft et al, 2006) PAL Conference

  31. 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

  32. Look for “Hallmark” Symptoms • Increased specificity • More likely bipolar… • Elation • Hyperactivity • Grandiosity • Hypersexuality • Decreased need for sleep PAL Conference

  33. 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

  34. 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

  35. 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, 2005

  36. 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 bipolar-like 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

  37. 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

  38. 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 Stern TA and Herman JB, 2004

  39. 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 Brent et al, 1988, 1993

  40. 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

  41. 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

  42. Bipolar Medications PAL Conference

  43. What Is A Mood Stabilizer? • Includes both atypical anti-psychotics and anti-epileptic drugs (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

  44. 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 effects in mood disorders (lithium) • Depression (risperidone, aripiprazole, quetiapine, lamotrigine) • Psychosis (primary, mood disorder, delirium) • OCD (refractory) • PTSD (intrusive thoughts) PAL Conference

  45. Pharmacotherapy of Pediatric Bipolar (Liu et al, JAACAP 2011) PAL Conference

  46. 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

  47. 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

  48. 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

  49. Atypical Heterogeneity PAL Conference

  50. Adverse and Therapeutic Effects of Occupancy and Withdrawal (Correll, JAACAP. 2008) PAL Conference

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