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Bipolar: To Be or Not To Be…  Pediatric Bipolar Update  <ul><li>Stephen Grcevich, MD </li></ul><ul><li>President and Found...
Educational objectives: <ul><li>Familiarize health care professionals with current information regarding the diagnosis of ...
Stephen Grcevich, MD: disclosures: Pharmaceutical Industry Consulting: Shire US (100% of compensation donated to charity s...
The greatest controversy in our field? <ul><li>40X increase in outpatient visits for pediatric bipolar disorder between 19...
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....
Diagnostic criteria for Bipolar Disorder: <ul><li>A distinct period of elevated, expansive or irritable mood lasting  at l...
Diagnostic criteria for Bipolar Disorder: <ul><li>Mixed episodes: symptoms of mania  and  depression last at least seven d...
Comorbidity and pediatric bipolar disorder: <ul><li>ADHD: 90% in children with bipolar disorder, 60% in teens with bipolar...
Differentiating between ADHD and BPD in early adolescence: Geller et al.  J Affect Disord.  1998;51:81. Geller B, Luby J. ...
Differential diagnosis of pediatric bipolar disorder : <ul><li>Medical/neurologic concerns (iatrogenic) </li></ul><ul><li>...
The center of the controversy: <ul><li>There’s a large group of kids who demonstrate:  </li></ul><ul><li>Irritability as t...
Temper Dysregulation Disorder (TDD) with Dysphoria (proposed in DSM-V):  <ul><li>Characterized by severe recurrent  temper...
AACAP concerns about “TDD”  <ul><li>Diagnosis Is imprecise </li></ul><ul><li>Syndrome based on work in patients described ...
What will kids with SMD/TDD look like in your clinic? <ul><li>They have ADHD </li></ul><ul><li>They have difficulty with t...
AACAP Practice Parameters for Assessment and Treatment of Bipolar Disorder (2007) <ul><li>Pharmacotherapy is the primary t...
FDA-approved medications for youth with Bipolar Disorder <ul><li>Risperidone: Bipolar mania (10-17) </li></ul><ul><li>Arip...
Second generation antipsychotics in pediatric bipolar disorder: <ul><li>As of July, 2010: 26 studies published, including ...
Lithium in pediatric bipolar disorder: <ul><li>One acute RCT: Li>PBO (46% response rate vs. 8%) </li></ul><ul><li>Didn’t a...
Anticonvulsants in pediatric bipolar disorder: <ul><li>Divalproex sodium: open-label studies have demonstrated response ra...
Strategies for treating ADHD with comorbid Bipolar Disorder: <ul><li>Effective mood stabilization may be necessary before ...
Psychotherapy/psychosocial treatment:  <ul><li>Multi-family psychoeducational groups: 1 RCT (N=35), families did better, n...
Take-home points: <ul><li>Use of the term “Bipolar Disorder” in pediatric population should be reserved for mood episodes ...
Resources for pediatricians: <ul><li>AACAP Bipolar Disorder Resource Center   http://www.aacap.org/cs/BipolarDisorder.Reso...
Questions?
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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

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Treatment Of Pediatric Bipolar Disorder 82010

  1. 1. Bipolar: To Be or Not To Be… Pediatric Bipolar Update <ul><li>Stephen Grcevich, MD </li></ul><ul><li>President and Founder, Family Center by the Falls Chagrin Falls, OH </li></ul><ul><li>Department of Psychiatry Northeastern Ohio Universities College of Medicine </li></ul><ul><li>Presented at: Children’s Hospital Medical Center of Akron August 20, 2010 </li></ul>E-mail: drgrcevich@fcbtf.com Phone: (440) 543-3400 Twitter: @drgrcevich
  2. 2. Educational objectives: <ul><li>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 </li></ul>
  3. 3. 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
  4. 4. The greatest controversy in our field? <ul><li>40X increase in outpatient visits for pediatric bipolar disorder between 1994-95 and 2002-03 (6X increase in prevalence of bipolar diagnosis) </li></ul><ul><li>The majority of kids receiving the diagnosis don’t meet traditional DSM-IV criteria for the disorder </li></ul><ul><li>Average number of psychotropic medications: 3.4 </li></ul><ul><li>Average number of medication trials: 6.3 (+/- 3.7) </li></ul><ul><li>Medications approved for pediatric bipolar disorder associated with rapid, large increases in weight, lipid, cholesterol elevation, Type 2 diabetes </li></ul>Moreno C, Laje G, Blanco C, et al. Arch. Gen. Psychiatry 64, 1032–1039 (2007).
  5. 5. Weight gain in antipsychotic naïve pediatric patients: Correll, CU et al., JAMA. 2009;302:1765–1773.
  6. 6. 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
  7. 7. Diagnostic criteria for Bipolar Disorder: <ul><li>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): </li></ul><ul><li>Inflated self-esteem, grandiosity </li></ul><ul><li>Decreased need for sleep </li></ul><ul><li>Pressured speech </li></ul><ul><li>Flight of ideas, racing thoughts </li></ul><ul><li>Increased distractibility </li></ul><ul><li>Increased goal-directed activity (psychomotor agitation) </li></ul><ul><li>Involvement in pleasurable behaviors with potential for painful consequences </li></ul>Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition - Text Revision (DSM IV-TR)
  8. 8. Diagnostic criteria for Bipolar Disorder: <ul><li>Mixed episodes: symptoms of mania and depression last at least seven days </li></ul><ul><li>Bipolar II: major depression and hypomania last at least four days </li></ul><ul><li>Rapid Cycling: four or more full episodes in a calendar year </li></ul><ul><li>Bipolar NOS: cases that don’t meet criteria for other bipolar conditions…the majority of pediatric cases </li></ul><ul><li>*Ultrarapid Cycling: brief, frequent episodes lasting from a few hours to less than four days </li></ul><ul><li>*Ultradian Cycling: cycles last minutes to hours, >365 cycles/year </li></ul><ul><li>*Condition not listed in DSM-IV </li></ul>Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition - Text Revision (DSM IV-TR)
  9. 9. Comorbidity and pediatric bipolar disorder: <ul><li>ADHD: 90% in children with bipolar disorder, 60% in teens with bipolar disorder, 13% in adults with bipolar disorder </li></ul><ul><li>Prevalence of anxiety disorders: 56-76% </li></ul><ul><li>Increased substance abuse risk-greater risk in adolescent-onset vs. childhood onset BPD </li></ul><ul><li>4X greater risk of post-traumatic stress disorder </li></ul>Joshi G, Wilens T. Child Adolesc Psychiatric Clin N Am 18 (2009) 291–319
  10. 10. 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
  11. 11. Differential diagnosis of pediatric bipolar disorder : <ul><li>Medical/neurologic concerns (iatrogenic) </li></ul><ul><li>ADHD/Conduct Disorder </li></ul><ul><li>Anxiety disorders </li></ul><ul><li>Psychotic disorders </li></ul><ul><li>Substance use disorders </li></ul><ul><li>Borderline Personality Disorder (and other Cluster B conditions) </li></ul><ul><li>Environmental, psychosocial, parenting factors </li></ul>
  12. 12. The center of the controversy: <ul><li>There’s a large group of kids who demonstrate: </li></ul><ul><li>Irritability as their predominant mood state </li></ul><ul><li>Problems with emotional self-regulation often resulting in aggression </li></ul><ul><li>Problems with attention, concentration, academic performance </li></ul><ul><li>“At-risk” behaviors…self-injury, substance use, suicidal threats </li></ul>
  13. 13. Temper Dysregulation Disorder (TDD) with Dysphoria (proposed in DSM-V): <ul><li>Characterized by severe recurrent temper outbursts in response to common stressors </li></ul><ul><li>Temper outbursts are manifest verbally and/or behaviorally, such as in the form of verbal rages, or physical aggression towards people or property </li></ul><ul><li>The reaction is grossly out of proportion in intensity or duration to the situation or provocation </li></ul><ul><li>Responses inconsistent with developmental level </li></ul><ul><li>Temper outbursts occur, on average, three or more times per week. </li></ul><ul><li>Mood between temper outbursts is persistently negative (irritable, angry, and/or sad). </li></ul><ul><li>Negative mood is observable by others (e.g., parents, teachers, peers). </li></ul>DSM-V Task Force, American Psychiatric Association, 2010
  14. 14. AACAP concerns about “TDD” <ul><li>Diagnosis Is imprecise </li></ul><ul><li>Syndrome based on work in patients described as “SMD” </li></ul><ul><li>Invites criticism for “pathologizing” temper tantrums </li></ul><ul><li>Proposed criteria are almost certainly premature </li></ul><ul><li>Research hasn’t clarified boundaries between “TDD”, ADHD, Oppositional Defiant Disorder and developmentally acceptable behavior </li></ul><ul><li>More information needed on how the phenotype changes over the lifespan </li></ul>American Academy of Child and Adolescent Psychiatry, March 30, 2010
  15. 15. What will kids with SMD/TDD look like in your clinic? <ul><li>They have ADHD </li></ul><ul><li>They have difficulty with transitions </li></ul><ul><li>They tend to “ruminate”…indecisive, think too much about things, perseverate </li></ul><ul><li>They may experience some improvement in some settings from ADHD medication, but become more irritable, have more meltdowns at home </li></ul><ul><li>They have a higher than expected prevalence of anxiety disorders, but are probably subsyndromal for OCD </li></ul><ul><li>They’re prone to behavioral activation on SSRIs, often mistaken for mania, hypomania </li></ul>
  16. 16. AACAP Practice Parameters for Assessment and Treatment of Bipolar Disorder (2007) <ul><li>Pharmacotherapy is the primary treatment in well-defined DSM-IV Bipolar I disorder </li></ul><ul><li>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 </li></ul>J . Am. Acad. Child Adolesc. Psychiatry, 46:1, January 2007
  17. 17. FDA-approved medications for youth with Bipolar Disorder <ul><li>Risperidone: Bipolar mania (10-17) </li></ul><ul><li>Aripiprazole: Bipolar mania (10-17) </li></ul><ul><li>Quetiapine: Bipolar mania (10-17) </li></ul><ul><li>Olanzapine: (labeling-consider other drugs first) Bipolar mania (13-17) </li></ul><ul><li>Lithium Carbonate: Bipolar mania (12-17) </li></ul>http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/PediatricAdvisoryCommittee/UCM193200.pdf
  18. 18. Second generation antipsychotics in pediatric bipolar disorder: <ul><li>As of July, 2010: 26 studies published, including 5 RCTs (but several others completed)-all RCTs published in 2007 or later </li></ul><ul><li>Response rates in acute RCTs 45-89%, remission achieved in 25-72% </li></ul><ul><li>Treatment-refractory nature of patients enrolled at academic medical centers attenuated magnitude of AEs </li></ul><ul><li>Little data examining long-term course on SGAs, efficacy in preventing relapse </li></ul>Hamrin V, Ienacco J. Expert Rev Neurother. 2010;10(7):1053-1088.
  19. 19. Lithium in pediatric bipolar disorder: <ul><li>One acute RCT: Li>PBO (46% response rate vs. 8%) </li></ul><ul><li>Didn’t appear to prevent relapse </li></ul><ul><li>Negative RCT in SMD </li></ul><ul><li>Narrow therapeutic window, toxicity in overdose concerns in adolescents </li></ul>Hamrin V, Ienacco J. Expert Rev Neurother. 2010;10(7):1053-1088
  20. 20. Anticonvulsants in pediatric bipolar disorder: <ul><li>Divalproex sodium: open-label studies have demonstrated response rates of 56-92%, but two RCTs have failed to demonstrate efficacy </li></ul><ul><li>Lamotrigine: Three open-label studies suggest 50-60% remission rates, helpful with bipolar depression results confounded by adjunct meds </li></ul><ul><li>Topiramate, oxcarbazepine: Negative RCTs </li></ul>Hamrin V, Ienacco J. Expert Rev Neurother. 2010;10(7):1053-1088
  21. 21. Strategies for treating ADHD with comorbid Bipolar Disorder: <ul><li>Effective mood stabilization may be necessary before patients will respond to stimulants </li></ul><ul><li>Stimulants will be used in combination with mood stabilizers/antipsychotics </li></ul><ul><li>Many patients have histories of failed stimulant trials, or use of high doses of stimulant before bipolar disorder identified </li></ul><ul><li>RCT: Mixed amphetamine salts highly effective for ADHD in patients who had achieved mood stabilization on divalproex </li></ul>Scheffer R et al. Am J Psychiatry (2005) 162:58-64
  22. 22. Psychotherapy/psychosocial treatment: <ul><li>Multi-family psychoeducational groups: 1 RCT (N=35), families did better, no effect on severity of child’s mood symptoms </li></ul><ul><li>IFP (Individual/family psychoeducation) 1 RCT (N=20) improved children’s mood symptoms </li></ul><ul><li>FFT (Family focused therapy) psychoeducation, communication enhancement training, and problem solving skills training-two year RCT indicated improvement in depressive sx. With bipolar disorder </li></ul><ul><li>DBT: One open label trial (N=10) </li></ul><ul><li>CFF-CBT: Open-label trial (N=34) with three year follow-up showed benefits of treatment were maintained </li></ul>West A, Pavuluri M. Child Adolesc Psychiatric Clin N Am 18 (2009) 471–482
  23. 23. Take-home points: <ul><li>Use of the term “Bipolar Disorder” in pediatric population should be reserved for mood episodes lasting four days or longer </li></ul><ul><li>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. </li></ul><ul><li>Careful evaluation and a comprehensive treatment plan developed by a fully trained child and adolescent psychiatrist, combining medications with psychotherapeutic interventions, are essential </li></ul>
  24. 24. Resources for pediatricians: <ul><li>AACAP Bipolar Disorder Resource Center http://www.aacap.org/cs/BipolarDisorder.ResourceCenter </li></ul><ul><li>Child and Adolescent Bipolar Foundation http://www.bpkids.org/ </li></ul><ul><li>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) </li></ul>
  25. 25. Questions?

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