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Treatment Of  Pediatric  Bipolar  Disorder 82010

Treatment Of Pediatric Bipolar Disorder 82010



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)
    • 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?