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Treatment Of  Pediatric  Bipolar  Disorder 82010
 

Treatment Of Pediatric Bipolar Disorder 82010

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Dr. Grcevich\'s Grand Rounds Lecture delivered at Akron Children\'s Hospital, August 20, 2010

Dr. Grcevich\'s Grand Rounds Lecture delivered at Akron Children\'s Hospital, August 20, 2010

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    Treatment Of  Pediatric  Bipolar  Disorder 82010 Treatment Of Pediatric Bipolar Disorder 82010 Presentation Transcript

    • Bipolar: To Be or Not To Be… Pediatric Bipolar Update
      • Stephen Grcevich, MD
      • President and Founder, Family Center by the Falls Chagrin Falls, OH
      • Department of Psychiatry Northeastern Ohio Universities College of Medicine
      • Presented at: Children’s Hospital Medical Center of Akron August 20, 2010
      E-mail: drgrcevich@fcbtf.com Phone: (440) 543-3400 Twitter: @drgrcevich
    • Educational objectives:
      • Familiarize health care professionals with current information regarding the diagnosis of Bipolar Disorder in Children Review recent evidence-based literature regarding Bipolar Spectrum Disorders Identify treatment options, including medication management, of mood disorders in children
    • Stephen Grcevich, MD: disclosures: Pharmaceutical Industry Consulting: Shire US (100% of compensation donated to charity since 1/1/08) Grant/Research Support Child and Adolescent Psychiatry Trials (CAPTN) Network-ASK, PARCA, NOTA studies funded through NIMH Speakers’ Bureaus None since 2006 Other Financial/Material Support Web MD/Medscape Leerink-Swann Major Shareholder None
    • The greatest controversy in our field?
      • 40X increase in outpatient visits for pediatric bipolar disorder between 1994-95 and 2002-03 (6X increase in prevalence of bipolar diagnosis)
      • The majority of kids receiving the diagnosis don’t meet traditional DSM-IV criteria for the disorder
      • Average number of psychotropic medications: 3.4
      • Average number of medication trials: 6.3 (+/- 3.7)
      • Medications approved for pediatric bipolar disorder associated with rapid, large increases in weight, lipid, cholesterol elevation, Type 2 diabetes
      Moreno C, Laje G, Blanco C, et al. Arch. Gen. Psychiatry 64, 1032–1039 (2007).
    • Weight gain in antipsychotic naïve pediatric patients: Correll, CU et al., JAMA. 2009;302:1765–1773.
    • Metabolic effects of second-generation antipsychotics in pediatric patients: Correll, CU et al., JAMA. 2009;302:1765–1773. Agent: Metabolic Effects: Olanzapine  fasting glucose  insulin  insulin resistance Quetiapine  total cholesterol  triglycerides  HDL cholesterol  triglyceride:HDL ratio Risperidone  triglycerides Aripiprazole No significant metabolic effects
    • Diagnostic criteria for Bipolar Disorder:
      • A distinct period of elevated, expansive or irritable mood lasting at least one week in which three or more of the following are present (four if mood is only irritable):
      • Inflated self-esteem, grandiosity
      • Decreased need for sleep
      • Pressured speech
      • Flight of ideas, racing thoughts
      • Increased distractibility
      • Increased goal-directed activity (psychomotor agitation)
      • Involvement in pleasurable behaviors with potential for painful consequences
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition - Text Revision (DSM IV-TR)
    • Diagnostic criteria for Bipolar Disorder:
      • Mixed episodes: symptoms of mania and depression last at least seven days
      • Bipolar II: major depression and hypomania last at least four days
      • Rapid Cycling: four or more full episodes in a calendar year
      • Bipolar NOS: cases that don’t meet criteria for other bipolar conditions…the majority of pediatric cases
      • *Ultrarapid Cycling: brief, frequent episodes lasting from a few hours to less than four days
      • *Ultradian Cycling: cycles last minutes to hours, >365 cycles/year
      • *Condition not listed in DSM-IV
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition - Text Revision (DSM IV-TR)
    • Comorbidity and pediatric bipolar disorder:
      • ADHD: 90% in children with bipolar disorder, 60% in teens with bipolar disorder, 13% in adults with bipolar disorder
      • Prevalence of anxiety disorders: 56-76%
      • Increased substance abuse risk-greater risk in adolescent-onset vs. childhood onset BPD
      • 4X greater risk of post-traumatic stress disorder
      Joshi G, Wilens T. Child Adolesc Psychiatric Clin N Am 18 (2009) 291–319
    • Differentiating between ADHD and BPD in early adolescence: Geller et al. J Affect Disord. 1998;51:81. Geller B, Luby J. J Am Acad Child Adolesc Psychiatry (1998): 37(10) 1005 Symptom BPD (n=60) % ADHD (n=60) % P Value Elated mood 86.7 5 0.001 Grandiosity 85 6.7 0.001 Hypersexuality 45 8.3 0.001 Decreased need for sleep 43.3 5 0.001 Racing thoughts 48.3 0 0.001 Hyperenergetic 96.7 91.7 0.44 Distractibility 91.7 95 0.72
    • Differential diagnosis of pediatric bipolar disorder :
      • Medical/neurologic concerns (iatrogenic)
      • ADHD/Conduct Disorder
      • Anxiety disorders
      • Psychotic disorders
      • Substance use disorders
      • Borderline Personality Disorder (and other Cluster B conditions)
      • Environmental, psychosocial, parenting factors
    • The center of the controversy:
      • There’s a large group of kids who demonstrate:
      • Irritability as their predominant mood state
      • Problems with emotional self-regulation often resulting in aggression
      • Problems with attention, concentration, academic performance
      • “At-risk” behaviors…self-injury, substance use, suicidal threats
    • Temper Dysregulation Disorder (TDD) with Dysphoria (proposed in DSM-V):
      • Characterized by severe recurrent temper outbursts in response to common stressors
      • Temper outbursts are manifest verbally and/or behaviorally, such as in the form of verbal rages, or physical aggression towards people or property
      • The reaction is grossly out of proportion in intensity or duration to the situation or provocation
      • Responses inconsistent with developmental level
      • Temper outbursts occur, on average, three or more times per week.
      • Mood between temper outbursts is persistently negative (irritable, angry, and/or sad).
      • Negative mood is observable by others (e.g., parents, teachers, peers).
      DSM-V Task Force, American Psychiatric Association, 2010
    • AACAP concerns about “TDD”
      • Diagnosis Is imprecise
      • Syndrome based on work in patients described as “SMD”
      • Invites criticism for “pathologizing” temper tantrums
      • Proposed criteria are almost certainly premature
      • Research hasn’t clarified boundaries between “TDD”, ADHD, Oppositional Defiant Disorder and developmentally acceptable behavior
      • More information needed on how the phenotype changes over the lifespan
      American Academy of Child and Adolescent Psychiatry, March 30, 2010
    • What will kids with SMD/TDD look like in your clinic?
      • They have ADHD
      • They have difficulty with transitions
      • They tend to “ruminate”…indecisive, think too much about things, perseverate
      • They may experience some improvement in some settings from ADHD medication, but become more irritable, have more meltdowns at home
      • They have a higher than expected prevalence of anxiety disorders, but are probably subsyndromal for OCD
      • They’re prone to behavioral activation on SSRIs, often mistaken for mania, hypomania
    • AACAP Practice Parameters for Assessment and Treatment of Bipolar Disorder (2007)
      • Pharmacotherapy is the primary treatment in well-defined DSM-IV Bipolar I disorder
      • A comprehensive treatment plan, combining medications with psychotherapeutic interventions is needed to address the symptomatology and confounding psychosocial factors found in children and adolescents with bipolar disorder
      J . Am. Acad. Child Adolesc. Psychiatry, 46:1, January 2007
    • FDA-approved medications for youth with Bipolar Disorder
      • Risperidone: Bipolar mania (10-17)
      • Aripiprazole: Bipolar mania (10-17)
      • Quetiapine: Bipolar mania (10-17)
      • Olanzapine: (labeling-consider other drugs first) Bipolar mania (13-17)
      • Lithium Carbonate: Bipolar mania (12-17)
      http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/PediatricAdvisoryCommittee/UCM193200.pdf
    • Second generation antipsychotics in pediatric bipolar disorder:
      • As of July, 2010: 26 studies published, including 5 RCTs (but several others completed)-all RCTs published in 2007 or later
      • Response rates in acute RCTs 45-89%, remission achieved in 25-72%
      • Treatment-refractory nature of patients enrolled at academic medical centers attenuated magnitude of AEs
      • Little data examining long-term course on SGAs, efficacy in preventing relapse
      Hamrin V, Ienacco J. Expert Rev Neurother. 2010;10(7):1053-1088.
    • Lithium in pediatric bipolar disorder:
      • One acute RCT: Li>PBO (46% response rate vs. 8%)
      • Didn’t appear to prevent relapse
      • Negative RCT in SMD
      • Narrow therapeutic window, toxicity in overdose concerns in adolescents
      Hamrin V, Ienacco J. Expert Rev Neurother. 2010;10(7):1053-1088
    • Anticonvulsants in pediatric bipolar disorder:
      • Divalproex sodium: open-label studies have demonstrated response rates of 56-92%, but two RCTs have failed to demonstrate efficacy
      • Lamotrigine: Three open-label studies suggest 50-60% remission rates, helpful with bipolar depression results confounded by adjunct meds
      • Topiramate, oxcarbazepine: Negative RCTs
      Hamrin V, Ienacco J. Expert Rev Neurother. 2010;10(7):1053-1088
    • Strategies for treating ADHD with comorbid Bipolar Disorder:
      • Effective mood stabilization may be necessary before patients will respond to stimulants
      • Stimulants will be used in combination with mood stabilizers/antipsychotics
      • Many patients have histories of failed stimulant trials, or use of high doses of stimulant before bipolar disorder identified
      • RCT: Mixed amphetamine salts highly effective for ADHD in patients who had achieved mood stabilization on divalproex
      Scheffer R et al. Am J Psychiatry (2005) 162:58-64
    • Psychotherapy/psychosocial treatment:
      • Multi-family psychoeducational groups: 1 RCT (N=35), families did better, no effect on severity of child’s mood symptoms
      • IFP (Individual/family psychoeducation) 1 RCT (N=20) improved children’s mood symptoms
      • FFT (Family focused therapy) psychoeducation, communication enhancement training, and problem solving skills training-two year RCT indicated improvement in depressive sx. With bipolar disorder
      • DBT: One open label trial (N=10)
      • CFF-CBT: Open-label trial (N=34) with three year follow-up showed benefits of treatment were maintained
      West A, Pavuluri M. Child Adolesc Psychiatric Clin N Am 18 (2009) 471–482
    • Take-home points:
      • Use of the term “Bipolar Disorder” in pediatric population should be reserved for mood episodes lasting four days or longer
      • A large subset of patients exists with chronic irritability, explosive outbursts, chronic negativism, long-term risk of ADHD, depression, differences in neural circuitry and cognitive flexibility. Little research is available to inform our treatment of them.
      • Careful evaluation and a comprehensive treatment plan developed by a fully trained child and adolescent psychiatrist, combining medications with psychotherapeutic interventions, are essential
    • Resources for pediatricians:
      • AACAP Bipolar Disorder Resource Center http://www.aacap.org/cs/BipolarDisorder.ResourceCenter
      • Child and Adolescent Bipolar Foundation http://www.bpkids.org/
      • Psychopharmacology of Pediatric Bipolar Disorder Expert Review of Neurotherapeutics http://www.medscape.com/viewarticle/724852 (Medscape membership required-membership, article free. Click on print version for summary tables of all studies)
    • Questions?