Help for the Primary Care Physician Gregory P. Barclay, M.D. November 19, 2008 Pediatric and Adolescent Bipolar Disorder
Goals of Today’s Presentation <ul><li>Discuss the current controversy surrounding pediatric bipolar disorder </li></ul><ul...
What we aren’t going to discuss <ul><li>The Diagnostic and Statistical Manual of Mental Disorders IV (DSM IV) specific cri...
The Pediatric Bipolar Debate <ul><li>Why has the diagnosis of Pediatric Bipolar Disorder (PBD)increased 40-fold from 1994-...
Clinical Quiz! Case #1 <ul><li>16 year old male, several year history of social anxiety with recent situational depression...
Clinical Quiz! Case #2 <ul><li>6 year old male, history of hyperactivity, impulsivity, and chronic behavior problems inclu...
Clinical Quiz! Case #3 <ul><li>14 year old female referred by therapist with note saying “needs medications for Bipolar Di...
Will the Real Bipolar Patient Please Stand Up? <ul><li>Each case marked by mood fluctuations </li></ul><ul><li>Each has a ...
<ul><li>Historically under-diagnosed or currently over-diagnosed? </li></ul><ul><li>Managed Care and Reimbursement Factors...
Softening of Diagnostic Criteria  <ul><li>The DSM IV criteria were established pre-1994 and applied only to the adult form...
Other Contributing Factors <ul><li>Genetic Anticipation </li></ul><ul><ul><li>Known clustering of certain disorders in fam...
The role of stimulating medications <ul><li>Children who progress to develop PBD often present with depressive, anxious, o...
The Sad Truth <ul><li>Children identified as having mood and behavior disturbances are increasingly common in American soc...
The Experts  (and everyone else) agree on these points <ul><li>PBD is a chronic disturbance manifested by rapid, continuou...
Comorbidity Issues <ul><li>Comorbidity is the rule, not the exception </li></ul><ul><li>95% have comorbid ADHD </li></ul><...
Points of Disagreement  that Muddy the Waters <ul><li>The role of “Cardinal Symptoms” that best differentiate PBD from ADH...
What, then are the “Cardinal Symptoms”? <ul><li>5 symptoms most significantly differentiate PBD for ADHD & Controls (p<.00...
Cardinal Symptom Specifics  <ul><li>Elated  children laugh hysterically & act infectiously happy out of context </li></ul>...
Clinical Features of Mania in PBD <ul><li>Children experiencing mania or mixed states may be alternatively: </li></ul><ul>...
Common but non-distinguishing symptoms <ul><li>Poor judgment </li></ul><ul><li>Irritable mood </li></ul><ul><ul><li>A dist...
ADHD and PBD - Key Differences Not seen Present Flight of Ideas/Racing Thoughts ADHD/ADD Bipolar/Depression Common Family ...
NIMH Roundtable  Classification (2002)  <ul><li>“Narrow” </li></ul><ul><ul><li>Full DSM IV Criteria for Mania </li></ul></...
The  8-year outcome study results <ul><li>“ Narrow” phenotypes are similar to the sickest 20% of adult Bipolar Patients an...
Evaluation Recommendations <ul><li>Do a good assessment, including: </li></ul><ul><ul><li>Establish a positive family hist...
Medication issues <ul><li>Very limited studies to date, most open label </li></ul><ul><li>As of 2005, only 5 published pla...
Medication  Issues II <ul><li>Response rates 33% to 50% at best! </li></ul><ul><li>Those that respond generally relapse qu...
The dilemma with medications <ul><li>They all have side effects: </li></ul><ul><ul><li>Weight gain - Atypicals, Some Mood ...
Other important interventions <ul><li>Psychotherapy, especially Dialectical Behavior Therapy & Child/Family Focused Cognit...
Prevention Tips <ul><li>Factors that predict the development of mania include: </li></ul><ul><ul><li>Depression with rapid...
Additional Pearls to remember <ul><li>Diagnosis of PBD  cannot be made  if patient is taking SSRI’s or Stimulants, due to ...
Support for Families <ul><li>The Child and Adolescent Bipolar Foundation (CABF) </li></ul><ul><ul><li>www.bpkids.org </li>...
Summing it up <ul><li>There is ample evidence to support the presence of PBD but the diagnostic criteria are still uncerta...
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Barclay Gr 11 19 08 Pediatric Bipolar Disorder Revised111708

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This is a grand rounds presentation I gave in November, 2008 relating to the current Pediatric Bipolar Conundrum

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  • Medline search: 5 publications relating to PBD before 1980 27 from 1980-1989 50 from 1990-1999 227 from 2000-2005
  • Most recent epidemiologic data suggest that PBD may not be rare at all, but that it is difficult to diagnose and rather than identify bipolar disorder clinicians instead diagnose one of its multiple comorbidities Direct to consumer advertising has been shown to have profound influences on physician prescribing patterns that promote overuse. Biederman (Harvard) has received $15 million from pharmaceutical companies Melissa Del Bello (Cincinnati) received $180K in fees from Seroquel’s manufacturer, not including her research funding. “ Just as a child with a hammer discovers new things that “need” to be hammered, when psychiatry finds new drugs it discovers new people who “need” to be treated with them.
  • DSM IV - “A hypomanic episode requires a distinct period of persistently elevated, expansive, or irritable mood lasting throughout at least 4 days” However, the vast majority (&gt;70%) of PBD patients have mood/energy shifts several times per day. Reports of very early onset bipolar disorder raise questions about the appropriateness of applying adult criteria to toddlers The validity of diagnosing bipolar disorder in preschool children has NOT been established and therefore caution should be taken before making the diagnosis. One must ascertain the context of emotional and behavioral dysregulation.
  • Trinucleotide Repeat Amplification (Adenine, Cytosine, Guanine)
  • 35-40% of parents whose children took stimulants said their child “gets wild” when the medication wears off Stimulant rebound doesn’t appear to portend mania or even bipolar spectrum disorder (but it needs to be ruled out before a diagnosis is made) 61% of treatment emergent mania cases were related to SSRI use. 9% were triggered by atypical antidepressants and 6% tricyclics. -TEM much more common in girls vs........ boys Treatment with mood elevating agents in children diagnosed with BPD led to new manic, often psychotic or aggressive behavioral changes in half of cases exposed and almost half of those given antidepressants. Risk of such responses was nearly as high in girls as in boys and was predicted by exposure to a mood elevating agent and by early onset anxiety symptoms. “Megamania” (per Geller, 2007) Agitation and manic symptoms affect 1:10 children treated with SSRI’s. TEM is recognized in DSM IV as a substance-induced mood disorder distinct from PBD.
  • More than 60% of Adult Bipolar Patients retrospectively report the onset of symptoms before age 20, 30% noted the onset before age 13 While longitudinal studies show that 75-80% eventually recover from their first episode, recovery takes many months and &gt;70% relapse. Life time mortality for Bipolar Disorder = 18%
  • Continuous, rapid cycling was the most prevalent pattern 60% prevalence of psychosis 55% had mixed mania 50% grandiose delusions Chronic picture of long current episode duration (mean = 309.8 days to 4 years) and daily (ultradian) cycling
  • High rates of “mania” are described in clinical samples of ADHD Follow-up studies did not show increase bipolar disorder as adults “Burgeoning administration of stimulants and antidepressants to the general pediatric population - the potential for adverse effects in children are high” Geller+DelBello, 2006 Conduct Disorder is highly comorbid. The main differentiating feature is the lengthy prodrome in conduct disorder manifested by progressively more severe rule breaking, whereas mania mostly presents with an abrupt onset of impulsive behavior (Singh, 2006)
  • Manic grandiosity and irritability present as marked changes in the individual’s mental and emotional state rather than reactions to situations, temperamental traits, negotiation strategies, or anger outbursts. Adolescents with BD are reported to have a high rate of suicide attempts and clearly are at risk for completed suicide Less than 1% of the hypersexual group had a history of sexual abuse.
  • Pathological Elation = elated mood is out of context and impairing Grandiosity = out of context and impairing Children developmentally cannot present with many of the manifestations of mania observed in late teenage &amp; adult onset mania.
  • Prepubertal Mania is non-classic: Dysphoric Mania Irritability Aggressiveness Absence of clear cut episodes that follow good premorbid adjustment Chronically impaired Ill for 3+ years w/multiple daily episodes Post-Pubertal mania follows a more classic pattern
  • ADHD: Often talks Excessively PBD: Pressure to keep talking ADHD: Often runs about or climbs excessively Hypomania: Agitation GAD: Restlessness ADHD: Is often easily distracted by extraneous stimuli Hypomania: Distractibility GAD/Depression: Difficulty Concentrating Conduct Disorders, Substance Abuse, Cluster B Personality Disorders can be characterized by mood and behavioral problems similar to those seen in hypomania and mania. Pressured speech is rapid and difficult to interrupt. Racing thoughts correlate with pressured speech and discriminate PBD from ADHD There are no definitive studies outlining a developmentally valid method for assessing manic symptoms in very young children.
  • NIMH Roundtable on prepubertal Bipolar Disorder in 2001 reached an agreement that the disorder could present in different phenotypes Broad phenotype represents the most referrals There is no evidence that intermediate and broad phenotypes go on to “adult” or classic bipolar disorder; however narrow phenotype shows most continuity with adult disorder.
  • Subsyndromalcases of bipolar disorder showed increased psychopathology and an increase in adverse outcomes, but not an increase in classic bipolar I/II diagnoses Compared with a group of full syndrome bipolar youth, both groups had an increased risk of antisocial and borderline personality disorder at follow-up. Are the Broad Phenotypes more representative of a form of ADHD + the unexpected effects of stimulant medications? Relatively poor outcomes in those with phenotypic resemblance to severely ill adults with bipolar disorder + mixed mania, psychosis, rapid cycling, or treatment resistance. Recovered cases had ADHD (33%), ODD (24%), MDD (30%)
  • No lab work or imaging tests are diagnostic Baseline labs for most meds include CBC, UA + Lytes, BUN, Creat., LFT’s, TFT’s, lead levels (if child under age 7). Child self-report includes the symptoms that best differentiate ADHD from Bipolar Disorder FIND: Frequency, Intensity, Number of symptoms, Duration of symptoms (Number = 3/4 per day, duration = 4 or more times per day)
  • Randomized Controlled Trial without placebo As of 2005, only 5 placebo controlled studies; many open label Many needed “rescue” medications for aggression, psychosis, and sleep disturbance, which affects the validity of the studies Majority of patients received stimulants before the trial - no placebo used in this study Marginal efforts and poor compliance plague efforts to treat PBD with monotherapy. Need to try for 6-8 weeks @ therapeutic doses before trying another medication. Combinations, based on symptoms profile, seem to yield a much higher response rate. Lithium to date most used in PBD, but results are modest at best. Most recent studies suggest it is best utilized in combination with an atypical antipsychotic. There is no agreement on what “mood stabilizer” means - anticonvulsants have never been shown to stabilize moods; their use is based on an analogy to seizures - not science. Repackaging of drugs for newer more profitable indications. (flora et al) Quetiapine, Aripiprazole, Valproate, Olanzapine, risperidone &amp; Ziprasidone approved for acute mania in adults Both Lamotrogine and Olanzapine are approved for maintenance therapy in adults with BPD Combination of Olanzapine and Fluoxetine approved for Bipolar Depression in adults, as is Quetiapine and Aripiprazole. The short and long term safety of mood stabilizers and atypical antipsychotics in young children has not been established.
  • Controlled studies have found Gabapentin or Topiramate useful No evidence that tiagabine, oxcarbazepine, or zonisamide are effective for PBD Stimulants possibly useful once mood symptoms are controlled on mood stabilizers High relapse rates suggest that once remission occurs, should stick with initial regimen for 12-24 months If meds are tapered, need to monitor closely and restart meds if any signs of relapse evident. LiCO3 - cognitive problems Valproate - increased testosterone, PCOS Lamotrogine - Stevens Johnson Syndrome Risperidone - Hyperprolactinemia, pituitary tumors - “perhaps the best supported by evidence, given targeted symptoms of explosive outbursts, mood stabilization, and psychotic like symptoms” (McClellan) Olanzapine - weight gain Quetiapine - Sedataion, wide dose range Ziprasidone - EKG - prolonged QT Aripiprazole - Dyskinesias Olanzapine - one open trial (mean dose 9.8 mg./d) - effective in PBD Topiramate - inhibits glutamate activity, augments the effect of GABA Carbamazepine - best for acute mania and mixed states
  • Maternal Warmth = “The quality of involvement, understanding, acceptance, and love that parents communicate on different levels and in ever-evolving ways as their children grow” (Levine) Youths with significant emotional and behavioral problems likely need intensive behavioral and parenting interventions in addition to medication therapy “Rainbow Program” (univ chicago) highly effective in pre/post studies. Parent therapy - addresses guilt, ineffective expectations, recognizing limits, not personalizing, &amp; not using dx as an excuse. Depressed mothers express the most affectively charged negative statements which in turn are highly associated with low self worth and high child psychopathology rates Sibling therapy - help them understand issues relating to getting lost in the shuffle and feeling embarrassed. Group therapy programs are empirically supported but not yet validated - focus is on self management skills DBT - combination of compassion, warmth, and validation are critical to success
  • Screen those with family history There is evidence that youths will often have depressive episodes before having their first hypomanic or manic episode Factors that predict development of mania noted in slide. “A child with symptoms of ADHD and mood lability who has a parent with bipolar disorder may actually be in the prodromal state of PBD. Treatment with stimulants has been reported to trigger manic episodes in children.
  • Barclay Gr 11 19 08 Pediatric Bipolar Disorder Revised111708

    1. 1. Help for the Primary Care Physician Gregory P. Barclay, M.D. November 19, 2008 Pediatric and Adolescent Bipolar Disorder
    2. 2. Goals of Today’s Presentation <ul><li>Discuss the current controversy surrounding pediatric bipolar disorder </li></ul><ul><li>Review the various clinical presentations of pediatric mood and behavior disorders </li></ul><ul><li>Discuss evaluation and treatment recommendations </li></ul>
    3. 3. What we aren’t going to discuss <ul><li>The Diagnostic and Statistical Manual of Mental Disorders IV (DSM IV) specific criteria for Adult Bipolar Disorder </li></ul><ul><li>Neurobiological pathways, circuits, and brain structures thought to be related to mood dysregulation </li></ul><ul><li>Complex Psychopharmacological algorithms </li></ul><ul><li>If these interest you, email me and I will be happy to supply details: [email_address] </li></ul>
    4. 4. The Pediatric Bipolar Debate <ul><li>Why has the diagnosis of Pediatric Bipolar Disorder (PBD)increased 40-fold from 1994-2003, e.g. 80,000 newly diagnosed patients in 2003 alone? </li></ul><ul><li>What truly constitutes PBD? Is there any consensus among the experts? </li></ul><ul><li>When there is a very poor concordance rate between parents and between parent+patient on pediatric manic symptoms, how valid is the diagnosis? </li></ul><ul><li>Does “My Kid’s Bipolar” become a way for parents or youths to excuse problematic/criminal behavior or avoid changing ineffective parental discipline? </li></ul><ul><li>What are the implications of diagnosing & aggressively medicating PBD, especially given the high rates of sub-threshold symptoms (5-15%) reported in general population studies? </li></ul><ul><ul><ul><ul><ul><li> Moreno et al., 2007 </li></ul></ul></ul></ul></ul>
    5. 5. Clinical Quiz! Case #1 <ul><li>16 year old male, several year history of social anxiety with recent situational depression, started on Fluoxetine, 20 mg. daily 14 days ago, now with 7 day history of: </li></ul><ul><ul><li>Decreased Need for Sleep </li></ul></ul><ul><ul><li>Grandiose Ideas - “Inventions I used dream about are now reality!” </li></ul></ul><ul><ul><li>Pressured Speech </li></ul></ul><ul><ul><li>Feels “super great” but now quick to anger, which is a distinct change from past demeanor </li></ul></ul><ul><ul><li>Positive Family History of Depression </li></ul></ul>
    6. 6. Clinical Quiz! Case #2 <ul><li>6 year old male, history of hyperactivity, impulsivity, and chronic behavior problems including defiance and aggressive behavior, directed mainly at mother who is a single parent with 2 younger sons, ages 4 and 2, both with behavior problems. </li></ul><ul><li>Mother states he “can be loving one minute and hateful the next”. Moods are highly unpredictable and more labile since institution of Methylphenidate 8 months ago at urging of kindergarten teacher. </li></ul><ul><li>Trouble going to sleep at night, has trouble getting going in the morning. Awakens during the night to forage for food. </li></ul><ul><li>Biological father described as violent, abusive, and prone to methamphetamine addiction. Currently incarcerated for armed robbery. </li></ul>
    7. 7. Clinical Quiz! Case #3 <ul><li>14 year old female referred by therapist with note saying “needs medications for Bipolar Disorder” </li></ul><ul><li>Mother describes daughter as chronically unhappy and irritable, self-centered, impulsive, and drifting to a negative peer group. Smokes cigarettes and has used marijuana, drinks alcohol with peers. Seems chronically angry at her mother. Tends to isolate and self-mutilate when upset. Sexually promiscuous. </li></ul><ul><li>History of sexual abuse by stepfather, who is now incarcerated. Biological father’s whereabouts and history unknown. Mother abuses alcohol. </li></ul><ul><li>Describes her mood as angry unless she is with her boyfriend. </li></ul>
    8. 8. Will the Real Bipolar Patient Please Stand Up? <ul><li>Each case marked by mood fluctuations </li></ul><ul><li>Each has a family history that raises some concerns </li></ul><ul><li>Each has psychosocial issues </li></ul><ul><li>Each has comorbid additional psychiatric disorders </li></ul><ul><li>Clinical Case #1 </li></ul><ul><ul><li>SSRI-induced hypomania </li></ul></ul><ul><li>Clinical Case #2 </li></ul><ul><ul><li>Stimulant-induced mood disorder with stimulant rebound </li></ul></ul><ul><li>Clinical Case #3 </li></ul><ul><ul><li>Possible PTSD vs. Personality Disorder, with substance abuse </li></ul></ul>
    9. 9. <ul><li>Historically under-diagnosed or currently over-diagnosed? </li></ul><ul><li>Managed Care and Reimbursement Factors </li></ul><ul><ul><li>PBD Diagnosis Significantly increased among African American Male and Caucasian Female Adolescents from 10% in 1996 to 36% in 2004 </li></ul></ul><ul><ul><li>Coincides with decline in diagnoses of Conduct Disorder & various personality disorders (Borderline, Antisocial) Blader, et al., 2007 </li></ul></ul><ul><li>Popular press and marketing </li></ul><ul><ul><li>“ Direct to Consumer” advertising </li></ul></ul><ul><ul><li>Direct Compensation paid to PBD researchers </li></ul></ul><ul><ul><li>“ Rebranding” of old drugs by pharmaceutical companies </li></ul></ul><ul><li>“ Softening” of Diagnostic Criteria </li></ul>The PBD Epidemic - Contributing Factors
    10. 10. Softening of Diagnostic Criteria <ul><li>The DSM IV criteria were established pre-1994 and applied only to the adult forms of the illness (Bipolar I, Bipolar II and “Bipolar Disorder NOS”) </li></ul><ul><li>Post-1994 there has been a two-fold increase in reported prevalence of Bipolar II and Bipolar NOS diagnoses among the adult population, while prevalence of Bipolar I remains ca. 1%. </li></ul><ul><li>Now in 2008 there is consensus that the PBD is distinctly different from the adult presentations, but little agreement on proper diagnostic criteria. The great majority of children referred and treated do not fulfill current DSM IV criteria for Bipolar Disorder </li></ul>
    11. 11. Other Contributing Factors <ul><li>Genetic Anticipation </li></ul><ul><ul><li>Known clustering of certain disorders in families </li></ul></ul><ul><ul><li>Assortative Mating </li></ul></ul><ul><ul><li>Progressively earlier age of onset and increasing severity of illness in successive generations </li></ul></ul><ul><ul><li>“ Unstable DNA” &”Kindling” </li></ul></ul><ul><ul><ul><ul><ul><li>Petronis, et al., 1995, Geller et al., 2006 </li></ul></ul></ul></ul></ul><ul><li>Twin and Family Prevalence Rates support this theory </li></ul><ul><ul><li>One Bipolar Parent, risk increases to 15-30% </li></ul></ul><ul><ul><li>Two Bipolar Parents, risk increases to 50-75% </li></ul></ul><ul><ul><li>Fraternal Twins 15-25% </li></ul></ul><ul><ul><li>Identical Twins 70% </li></ul></ul><ul><ul><li>Singh, 2008 </li></ul></ul>
    12. 12. The role of stimulating medications <ul><li>Children who progress to develop PBD often present with depressive, anxious, or ADHD symptoms </li></ul><ul><li>These presentations encourage trials of antidepressant and stimulant medications </li></ul><ul><li>61% of cases of Treatment Emergent Mania (TEM) emerged after exposure to SSRI’s </li></ul><ul><ul><li>Risk twice as high in girls vs. boys </li></ul></ul><ul><ul><li>Anxiety Symptoms significantly predicted TEM </li></ul></ul><ul><ul><li>1:10 children treated with SSRI’s display agitation and manic symptoms </li></ul></ul><ul><li>36% TEM emerged after exposure to stimulant drugs </li></ul><ul><li>Faedda et al, 2004, Vitello, 2004 </li></ul><ul><li>“ Stimulant Rebound” manifested by irritability, euphoria, sadness, crying, and insomnia occurred in 21% of children exposed to stimulant drugs Carlson et al., 2003 </li></ul>
    13. 13. The Sad Truth <ul><li>Children identified as having mood and behavior disturbances are increasingly common in American society. </li></ul><ul><li>These patients often will present to their primary care physician requesting treatment. </li></ul><ul><li>There is increased public awareness, information availability via the Internet, and expectation that complex, multi-factorial behavior and mood problems require medical treatment </li></ul><ul><li>There are growing numbers of non-physician mental health professionals who share this perspective and who will refer expecting medication </li></ul><ul><li>Patients with severe mood and behavior disorders in childhood DO go on to display significant impairment as adults </li></ul><ul><li>The shortage of child/adolescent psychiatric services in most areas will worsen for the foreseeable future, putting increased pressure on primary care physicians to evaluate and medicate </li></ul>
    14. 14. The Experts (and everyone else) agree on these points <ul><li>PBD is a chronic disturbance manifested by rapid, continuous cycling of the mood </li></ul><ul><ul><li>Majority of PBD children symptomatic for over 3 years at time of diagnosis </li></ul></ul><ul><ul><li>Most display daily cycling (“Ultradian cycling”, >365 cycles/yr) </li></ul></ul><ul><ul><li>Smaller percentage display “Ultrarapid cycling” (5-364 cycles/yr) </li></ul></ul><ul><ul><li>High rates of comorbidity with other conditions </li></ul></ul><ul><ul><li>Absence of clear cut episodes that follow good premorbid adjustment </li></ul></ul><ul><li>These youth are chronically impaired in most measures of daily functioning </li></ul><ul><ul><li>The more impaired children tend to have severe symptoms from earlier on, and tend to have a strong family history of mood disorders. </li></ul></ul>
    15. 15. Comorbidity Issues <ul><li>Comorbidity is the rule, not the exception </li></ul><ul><li>95% have comorbid ADHD </li></ul><ul><li>91% have comorbid Oppositional Defiant Disorder (ODD) </li></ul><ul><li>80% of preschoolers recently diagnosed with PBD have comorbid ADHD+ODD </li></ul><ul><li>69-74% have comorbid conduct disorder </li></ul><ul><li>Lesser but significant comorbidity with Pervasive Developmental Disorders and Tourette’s Disorder </li></ul><ul><li>Patients with very early onset of depression are at extremely high risk for PBD -- 48-61% switch from depression to PBD </li></ul><ul><li>Numerous reports of increased cycling or induction of mania when children or adolescents were exposed to antidepressants </li></ul>
    16. 16. Points of Disagreement that Muddy the Waters <ul><li>The role of “Cardinal Symptoms” that best differentiate PBD from ADHD and other psychiatric disorders (Geller, et al.) </li></ul><ul><li>The value placed on accompanying symptoms that poorly differentiate BPD from other psychiatric disorders but seem to be highly prevalent in BPD nonetheless (Biederman, et al.) </li></ul><ul><ul><li>Irritability </li></ul></ul><ul><ul><li>Rages (“Affective Storms”) </li></ul></ul><ul><ul><li>Hyperactivity </li></ul></ul><ul><li>“ Irritability is as diagnostic of PBD as a sore throat is diagnostic of streptococcal pharyngitis” (e.g. 5%) </li></ul><ul><li>Geller, 2007 </li></ul>
    17. 17. What, then are the “Cardinal Symptoms”? <ul><li>5 symptoms most significantly differentiate PBD for ADHD & Controls (p<.0001) </li></ul><ul><ul><li>Elated Mood </li></ul></ul><ul><ul><li>Grandiosity </li></ul></ul><ul><ul><ul><li>Commonly see mood congruent, grandiose delusions </li></ul></ul></ul><ul><ul><ul><li>Most common hallucinations are auditory hallucinations </li></ul></ul></ul><ul><ul><li>Decreased Need for Sleep </li></ul></ul><ul><ul><li>Flight of Ideas/Racing Thoughts </li></ul></ul><ul><ul><li>Hypersexuality </li></ul></ul><ul><ul><li>Geller et al., 2002 </li></ul></ul>
    18. 18. Cardinal Symptom Specifics <ul><li>Elated children laugh hysterically & act infectiously happy out of context </li></ul><ul><li>Grandiose children will act as if the rules to not pertain to them; they are so smart they can tell teachers what to teach, etc. Delusions frequently involve special powers and beliefs </li></ul><ul><li>Flight of ideas : Ask whether topics of discussion change rapidly in an manner quite confusing to anyone listening </li></ul><ul><li>Racing thoughts : “It’s hard to do anything because my thoughts are distracting me” </li></ul><ul><li>Decreased need for sleep : Sleep 3-5 hrs & not tired the next day; up arranging furniture, talking on phone, etc. night after night </li></ul><ul><li>Hypersexuality has an erotic, pleasure-seeking quality to it, unlike the behavior of sexually abused children, which has an anxious/compulsive quality. </li></ul><ul><li>Singh, 2008 </li></ul>
    19. 19. Clinical Features of Mania in PBD <ul><li>Children experiencing mania or mixed states may be alternatively: </li></ul><ul><ul><li>Demanding yet hilariously funny </li></ul></ul><ul><ul><li>Hostile and in despair at various times during any given day </li></ul></ul><ul><ul><li>Prone to intensive, seemingly uncontrollable rages during which time they may: </li></ul></ul><ul><ul><ul><li>Damage property </li></ul></ul></ul><ul><ul><ul><li>Run away </li></ul></ul></ul><ul><ul><ul><li>Dash into a street without any thought of the consequences </li></ul></ul></ul><ul><li>Dysphoric Mania is most common prepubertally, while post-pubertal mania tends to follow a more adult-type pattern </li></ul>
    20. 20. Common but non-distinguishing symptoms <ul><li>Poor judgment </li></ul><ul><li>Irritable mood </li></ul><ul><ul><li>A distinct feature of irritability in PBD patients is extremely aggressive and/or self-injurious behavior </li></ul></ul><ul><li>Accelerated Speech </li></ul><ul><li>Distractibility </li></ul><ul><li>Increased Energy </li></ul><ul><li>> 44% of ADHD children without PBD display these symptoms! </li></ul><ul><li>Geller and DelBello, 2006 </li></ul>
    21. 21. ADHD and PBD - Key Differences Not seen Present Flight of Ideas/Racing Thoughts ADHD/ADD Bipolar/Depression Common Family History Rare Common Aggressive or suicidal behavior Less prominent Very prominent Irritable mood Not seen Common Psychotic Symptoms Not seen Common Hypersexuality Much less common Common Elevated Mood ADHD PBD Symptom
    22. 22. NIMH Roundtable Classification (2002) <ul><li>“Narrow” </li></ul><ul><ul><li>Full DSM IV Criteria for Mania </li></ul></ul><ul><ul><li>No debate as to diagnosis </li></ul></ul><ul><li>“Intermediate” </li></ul><ul><ul><li>Category I - Hallmark symptoms of short duration (1-3 days) </li></ul></ul><ul><ul><li>Category II - Episodic Irritable Mania without elation </li></ul></ul><ul><li>“Broad” </li></ul><ul><ul><li>Nonepisodic and chronic symptoms of severe irritability and hyperarousal </li></ul></ul><ul><ul><li>“ Affective Storms” </li></ul></ul><ul><ul><li>Severe Temper Outbursts </li></ul></ul><ul><ul><li>No elation, grandiosity, or hypersexuality </li></ul></ul><ul><ul><li>Leibenluft, 2002 </li></ul></ul>
    23. 23. The 8-year outcome study results <ul><li>“ Narrow” phenotypes are similar to the sickest 20% of adult Bipolar Patients and tend to be severely and chronically impaired through childhood </li></ul><ul><li>Children with the “Broad” Phenotype represent the bulk of new referrals, yet there is now unequivocal evidence that they display a different clinical course with less impairment </li></ul><ul><li>In essence, this is the conclusion: Children with narrow phenotype grow into adults with severe Bipolar Disorder, while children with broader phenotypes grow into adults with impulse control and personality disorders </li></ul><ul><ul><ul><li>Geller et al, 2008 </li></ul></ul></ul>
    24. 24. Evaluation Recommendations <ul><li>Do a good assessment, including: </li></ul><ul><ul><li>Establish a positive family history </li></ul></ul><ul><ul><li>Interview parents and child separately due to very poor concordance between parties </li></ul></ul><ul><ul><li>Use a rating scale such as the parent version of the Young Mania Rating Scale (YMRS); >13 = possible, >21=likely </li></ul></ul><ul><ul><li>2 week mood chart </li></ul></ul><ul><li>Discontinue any psychiatric medication </li></ul><ul><ul><li>Especially SSRI’s and Stimulants </li></ul></ul><ul><ul><li>Explain rationale to parents and prepare them </li></ul></ul><ul><ul><li>Wait 3-4 weeks before re-evaluating </li></ul></ul><ul><li>Obtain a psychiatric consultation if at all possible </li></ul>
    25. 25. Medication issues <ul><li>Very limited studies to date, most open label </li></ul><ul><li>As of 2005, only 5 published placebo controlled studies, but much research currently underway </li></ul><ul><li>Until 2007, only LiC03 was FDA approved for use in PBD (down to age 12) </li></ul><ul><li>Traditional mood stabilizers have not shown promising results - this is different from adults </li></ul><ul><li>Atypical Antipsychotics alone or in combination with mood stabilizers seem helpful </li></ul><ul><ul><li>Risperidone and Aripiprazole recently FDA-approved for PBD </li></ul></ul>
    26. 26. Medication Issues II <ul><li>Response rates 33% to 50% at best! </li></ul><ul><li>Those that respond generally relapse quickly (>70%) </li></ul><ul><li>Most effective mood stabilizers = Valproate, LiC03, Carbamazepine </li></ul><ul><li>Most effective Atypical Antipsychotics = risperidone, aripiprazole, quetiapine, olanzapine, ziprasidone Pavuluri et al, 2004 </li></ul><ul><li>Most studies have focused on treatment of manic or mixed symptoms; treatment of bipolar depression in children less effective </li></ul><ul><ul><li>Lamotrogine, possibly Olanzapine+Fluoxetine </li></ul></ul>
    27. 27. The dilemma with medications <ul><li>They all have side effects: </li></ul><ul><ul><li>Weight gain - Atypicals, Some Mood Stabilizers </li></ul></ul><ul><ul><li>Metabolic Syndrome - Atypicals </li></ul></ul><ul><ul><li>Prolactinomas - Atypicals </li></ul></ul><ul><ul><li>Polycystic Ovarian Syndrome - Depakote </li></ul></ul><ul><ul><li>Dyskinesias - Aripiprazole </li></ul></ul><ul><ul><li>Diminished Testosterone - Atypicals </li></ul></ul><ul><ul><li>Arrhythmias - Ziprasidone </li></ul></ul><ul><li>Compliance often poor </li></ul><ul><ul><li>Frequent dosing </li></ul></ul><ul><ul><li>Serum Monitoring </li></ul></ul>
    28. 28. Other important interventions <ul><li>Psychotherapy, especially Dialectical Behavior Therapy & Child/Family Focused Cognitive Behavior Therapy, has been shown to be highly effective (Pavuluri, et al.) </li></ul><ul><ul><li>Immediate focus is on affect regulation and conjoint problem solving </li></ul></ul><ul><ul><li>Diminish parental criticism and rejection and increase maternal warmth </li></ul></ul><ul><ul><li>Maternal warmth single greatest predictor in maintaining remission (Geller, 2008) </li></ul></ul><ul><ul><li>Problem is: Finding a local therapist who even knows what Dialectical Behavior Therapy is, much less having had the training. </li></ul></ul><ul><li>ECT for the most severe, non-responsive cases </li></ul>
    29. 29. Prevention Tips <ul><li>Factors that predict the development of mania include: </li></ul><ul><ul><li>Depression with rapid onset, psychomotor retardation, and psychosis </li></ul></ul><ul><ul><li>Family history of mood disorder, especially bipolar disorder </li></ul></ul><ul><ul><li>History of hypomania or mania with antidepressant treatment </li></ul></ul><ul><li>Therefore, with any acutely depressed child or teen, it is critically important to obtain a detailed family history </li></ul><ul><li>If family history is positive, avoid antidepressants and refer! </li></ul>
    30. 30. Additional Pearls to remember <ul><li>Diagnosis of PBD cannot be made if patient is taking SSRI’s or Stimulants, due to evidence that those agents trigger non-specific and possibly cardinal symptoms of PBD </li></ul><ul><li>Even a combination of mood stabilizers and atypical antipsychotics are effective in 50% of cases, at best </li></ul><ul><li>So, take your time, refer if you can, and make sure to stress the need for multi-modal intervention! </li></ul>
    31. 31. Support for Families <ul><li>The Child and Adolescent Bipolar Foundation (CABF) </li></ul><ul><ul><li>www.bpkids.org </li></ul></ul><ul><ul><li>Information and education </li></ul></ul><ul><li>Depression and Bipolar Support Alliance (DBSA) </li></ul><ul><ul><li>www.dbsalliance.org </li></ul></ul><ul><li>National Alliance for the Mentally Ill (NAMI) </li></ul><ul><ul><li>www.nami.org </li></ul></ul><ul><li>National Institute of Mental Health (NIMH) </li></ul><ul><ul><li>www.nimh.nih.gov </li></ul></ul>
    32. 32. Summing it up <ul><li>There is ample evidence to support the presence of PBD but the diagnostic criteria are still uncertain </li></ul><ul><li>The extensive use of antidepressant and stimulant drugs in children and teens has clearly contributed to the explosion of referrals with the “Broad” phenotype classification </li></ul><ul><li>Most recent outcome studies suggest that the “Broad” sub-type of PBD is currently over-diagnosed, raising questions about the appropriateness of utilizing antipsychotic medications in this group </li></ul><ul><li>There is a desperate need for rigorous controlled studies to establish clear diagnostic and treatment criteria </li></ul>
    33. 33. Questions & Comments

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