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Step #1: Start with the Base Rate

Step #1: Start with the Base Rate. ‘Base Rate’ is the prevalence rate of PBD in a specific context Base rates are often our best guess Best guess from overall prevalence in the population = 2% Use the Base Rate for your Pre-Test Probability.

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Step #1: Start with the Base Rate

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  1. Step #1: Start with the Base Rate • ‘Base Rate’ is the prevalence rate of PBD in a specific context • Base rates are often our best guess • Best guess from overall prevalence in the population = 2% • Use the Base Rate for your Pre-Test Probability ** Unpublished Diagnostic Likelihood Ratios (Youngstrom, 2008); Use with Caution!

  2. Initial Selection Pool Initial Base Rate Likelihood

  3. Base Rates of PBD • Best estimates from available research: • High School = 0.6% • Community Mental Health = 2.75% • 11%? • General Outpatient = 6-8% • DCFS = 11% • Specialty Outpatient = 15-17% • Incarcerated Adolescents = 2% • Inpatient = 30-40% with symptoms, • only 2% with strict diagnosis Youngstrom et al, 2005

  4. What the Base Rate does at: 2% Chance General Population                                                                                                  

  5.                                                                         What the Base Rate does at: 18% Chance Specialty Outpatient          

  6.                                                                       What the Base Rate does at: 30% Chance Inpatient?

  7. Pre-test Prob. Base Rate Column Find the Base Rate .1% 99% 1000 1% 18% base rate 100 10 50% 25% 1 .1 .01 2% .001 99% .1% Likelihood Ratio Post-test Prob. Youngstrom et al, 2007

  8. Step #2: Add the DLR for Family History • Find the DLR for Family History: • Weak or none = 1.0 • Possible/Fuzzy = 2.0 • Strong in extended/ 2nd degree = 2.5 • Strong in immediate/ 1st degree = 5.0 • Find the DLR for Family History • Obtain the Post-Test Probability ** Unpublished Diagnostic Likelihood Ratios (Youngstrom, 2008); Use with Caution!

  9. Selection Pool Shrinks Initial Base Rate Strong Family History Likelihood

  10. Pre-test Prob. Find the DLR for Family History .1% 99% 1000 DLR Column 5.00 DLR 1% 100 10 50% 25% 1 .1 .01 2% .001 99% .1% Likelihood Ratio Post-test Prob. Youngstrom et al, 2007

  11. Step #3: Obtain the Posttest Probability for Family History • Using the Base Rate and the DLR score, line up the numbers to find the post-test probability • Post-test probability is the chance that the person has PBD based on the available data ** Unpublished Diagnostic Likelihood Ratios (Youngstrom, 2008); Use with Caution!

  12. Pre-test Prob. Obtain the Post-Test Probability 18% base rate 5.00 DLR .1% 99% 1000 Post-Test Probability Column 1% 100 10 50% 25% 1 .1 .01 2% .001 99% .1% Likelihood Ratio Post-test Prob. Youngstrom et al, 2007

  13. Step #4: Add the DLR for the CMRS • DLR’s associated with CMRS scores** • 0-2 = 0.05 • 3-6 = 0.33 • 7-10 = 1.47 • 11-30 = 4.90 • Use the Post-Test Probability from the Family History for the new Pre-Test Probability • Obtain the new Post-Test Probability ** Unpublished Diagnostic Likelihood Ratios (Youngstrom, 2008); Use with Caution!

  14. Selection Pool Shrinks Even More Initial Base Rate Strong Family History Likelihood High Mania

  15. Pre-test Prob. Obtain the New Post-Test Probability Family HX Post-Test Probability 4.9 DLR for CMRS .1% 99% 1000 1% 100 10 50% 25% 1 .1 .01 New Post-Test Probability 2% .001 99% .1% Likelihood Ratio Post-test Prob. Youngstrom et al, 2007

  16. Is the Nomogram Worth Using? Most tend to overdiagnose 55% Probability Still extreme range of opinion (Adding Test Result) N = 427 clinicians, 10 sites

  17. Is the Nomogram Worth Using? Reduces overdiagnosis Much more accurate 55% Probability (Adding Test Result) Much less range of opinion N = 427 clinicians, 10 sites

  18. Treatment of PBD

  19. Multi-Modal Treatment • Medication • Stabilize mood & treat comorbid conditions • Psychoeducation • Psychosocial Interventions • Treat acute depression, reduce stress, regulate emotion, prevent recurrence, improve functioning, increase medication adherence • Sleep and mood hygiene • Family therapy to treat conflict, expressed emotion

  20. Medications • Lithium • Anticonvulsants • Divalproex • Carbamazepine • Lamotrigine • Topiramate • Oxcarbazepine • Gabapentin • Atypical/2nd Generation Antipsychotics: • Clozapine • Risperidone • Olanzapine • Quetiapine • Ziprasidone • Aripiprazole Bourin et al., 2005; Pavuluri et al., 2004; McClellan & Werry, 1997; Smarty & Findling, 2007

  21. Randomized Controlled Trials for Pediatric Bipolar Disorder • Lithium = 1 study • 25 adolescents • vs. placebo • Anticonvulsants = NONE! • Atypical Antipsychotics = NONE!

  22. Pharmacologic Patterns • Anticonvulsants & Atypical Antipsychotics most common • Limited response to monotherapy is typical • Combination therapy is common • 14% on 5 or more medications! Hellander et al., 2002; Smarty & Findling, 2007

  23. Pharmacologic Complexities • Medications that may complicate treatment: • Antidepressants • Psychostimulants • Little research on treating depression • Attention-deficit hyperactivity disorder must be re-evaluated after mood stabilized Biederman et al., 1998; Smarty & Findling, 2007

  24. Treating Children with Bipolar Disorder

  25. Multi-Modal Treatment • Medication • Stabilize mood & treat comorbid conditions • Psychoeducation • Psychosocial Interventions • Treat acute depression, reduce stress, regulate emotion, prevent recurrence, improve functioning, increase medication adherence • Sleep and mood hygiene • Family therapy to treat conflict, expressed emotion

  26. Common Medications • Lithium • Anticonvulsants • Valproate (Depakote) • Carbamazepine (Tegretol) • Lamotrigine (Lamictal) • Topiramate (Topamax) • Oxcarbazepine (Trileptal) • Gabapentin (Neurontin) • Atypical/2nd Generation Antipsychotics: • Clozapine (Clozaril) • Risperidone (Risperdal) • Olanzapine (Zyprexa) • Quetiapine (Seroquel) • Ziprasidone (Geodon) • Aripiprazole (Abilify) Bourin et al., 2005; Pavuluri et al., 2004; McClellan & Werry, 1997; Smarty & Findling, 2007

  27. Evidence • Limited Research • Strongest Evidence = Lithium • Yet, only 1 Randomized Controlled Trial! • Good evidence = Valproate (Depakote) • Atypical Antipsychotics • Likely effective: • Olanzapine (Zyprexa) • Aripiprazole (Abilify) • Quetiapine (Seroquel) • Ongoing Studies: • Rilutek, (Riluzole) • Amyptrophic Lateral Sclerosis (ALS) • Lamotrigine (Lamictal) • Fluoxetine & olanzapine (Symbya) DelBello, et al.Bipolar Disorders.2009;11:483-493;

  28. Why not Lithium all the time? • Lithium • Moderate effect • Takes 6-8 weeks for full response • Side Effects: Weight gain, enuresis, acne, possible long-term renal problems • Valproate • Faster than lithium, better tolerated • Concerns with polycystic ovary syndrome, weight gain, and abnormal menses Kowatch, 2009

  29. Bipolar Mania

  30. Bipolar Depression

  31. On-Line Survey (N = 854)Percentage on Medications Youngstrom et al, 2007; CABF, 2002

  32. Pharmacologic Patterns • Limited response to monotherapy is typical • Combination therapy is common Hellander et al., 2002; Smarty & Findling, 2007

  33. Number of Current Medications 85% on 2+ meds Youngstrom et al, 2007; CABF, 2002

  34. Lifetime Medication Exposure 85% exposed to 4+ meds Youngstrom et al, 2007; CABF, 2002

  35. Pharmacologic Complexities • Medications that may complicate treatment: • Antidepressants • Psychostimulants • Little research on treating depression • Attention-deficit hyperactivity disorder must be re-evaluated after mood stabilized Biederman et al., 1998; Smarty & Findling, 2007

  36. Side-Effects • Lithium • Dangerous drug interactions, excessive thirst, overdose potential, tremors, acne, psoriasis, weight gain, hypothyroidism, and increased white blood cell count • Anticonvulsants • Dangerous drug interactions, liver toxicity, hair loss, irritability, abnormal platelets counts, pancreatitis, and polycystic ovary disease • Atypical Antipsychotics • Weight gain, somnolence, slowed thinking, extrapyramidal side effects, and tardive dyskinesia

  37. How do we know if Rx is working? • Provide feedback to parents and clinicians • Be specific (who, what, how often, how much) • Be behavioral • Put it in writing • Use a checklist or questionnaire • Day-to-day 3-5 symptom target list • Standardized questionnaires • Report any side-effects to parent or clinician

  38. Psychosocial Treatment: Targets • Medication Adherence • Address symptoms not treated by medication • Improve long-term functioning (social, occupational, relational) • Monitor progress

  39. Psychosocial Approaches • Parent/Family Psychoeducation • Cognitive Behavioral Therapy • Interpersonal Therapy • Interpersonal and Social Rhythm Therapy • Family Focused Therapy • Multi-Family Therapy • Community Support Programs • Dialectical Behavior Therapy

  40. Family-Focused Treatment • Components: • Psychoeducation • Relapse prevention • Improve adherence to treatment • Motivate adolescent to address disorder • Communication Skills Training • Problem Solving Skills Training • Behavioral Management Training • Focus on Wake/Sleep schedule • Address mood disturbances in the family Miklowitz DJ et al. Family-focused treatment for adolescents with bipolar disorder. J Affect Disord. 2004;82(suppl 1):S113-S128.

  41. Child- and Family-Focused Cognitive Behavioral Therapy • Integrates psychoeducation, CBT, and interpersonal techniques with pharmacotherapy • Targets: psychosocial and interpersonal stress in children and families • Treatment Components: • Routine • affect regulation • self-efficacy and coping • coping with depressive cognitions, • social skill building, • interpersonal problem solving • social support Pavuluri et al., 2004; West et al., 2006

  42. Multifamily Psychoeducational Psychotherapy • Eight, 90-minute adjunctive treatment • Combines: • Pschoeducation • Family Systems therapy • Cognitive Behavioral Techniques • Goals: • Learn about bipolar and treatment • Gain support from other families & professionals • Develop skills in mood management, affect regulation, problem solving, and communication. • RCTs indicate promising efficacy Fristad, et al. Impact of multifamily psychoeducational psychotherapy in treating children aged 8 to 12 Years with mood disorders. Arch Gen Psychiatry. 2009;66(9):1013-1021

  43. Dialectical Behavior Therapy • Individual and Family sessions • Telephone skills coaching • Treatment Components: • Psychoeducation • Mood charting • Mood regulation • Skills training Goldstein et al., 2007

  44. Future Therapeutic Approaches? • Transcranial Magnetic Stimulation • Deep Brain Stimulation • Electroconvulsive Therapy Stein et al., 2006

  45. Summary • PBD exits • But still confusion in the community about what it exactly is... • Diagnosis is complicated • But screening is possible! • Nomogram approach improves validity/ reliability of screening • Treatment is complicated, but options are available

  46. Thank you!Questions? Comments? Jason J. Washburn, Ph.D., ABPP Center for Evidence-Based Practice Alexian Brothers Behavioral Health Hospital jason.washburn@abbhh.net 847-755-8579

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