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Ricardo J. Fermo, MD Diplomate of the American Board of Psychiatry and Neurology            

Ricardo J. Fermo, MD Diplomate of the American Board of Psychiatry and Neurology             Diplomate of American Board of Child and Adolescent Psychiatry East Cooper Psychiatric Solutions, LLC 887 Johnnie Dodds Blvd. , Suite 100 Mount Pleasant, South Carolina 29464 ECPSLLC.COM

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Ricardo J. Fermo, MD Diplomate of the American Board of Psychiatry and Neurology            

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  1. Ricardo J. Fermo, MD • Diplomate of the American Board of Psychiatry and Neurology             • Diplomate of American Board of Child and Adolescent Psychiatry • East Cooper Psychiatric Solutions, LLC • 887 Johnnie Dodds Blvd. , Suite 100 • Mount Pleasant, South Carolina 29464 • ECPSLLC.COM • O (843) 856 6998 • F (843) 856 6997

  2. Disclosures • Abbott Laboratories • AstraZeneca • Bristol Myer-Squibb • Cephalon • Eli Lilly & Co. • Forest Laboratories, Inc. • GalaxoSmithKline • Janssen Research • Jazz Pharmaceuticals • Lundbeck • Mallinckrodt • Merck • Novartis • Otsuka America Pharmaceuticals Inc. • Palmlabs • Pfizer, Inc. • Sanofi Aventis • Sepacor Inc. • Shire Pharmaceuticals • Somaxon Pharmaceuticals • Sunovion Pharmaceuticals Inc. • Takeda • Teva • UCB Pharma Inc. • Vaya Pharmaceuticals • Wyeth Pharmaceuticals

  3. EPIDEMIOLOGY

  4. Affects ~5.7 million American adults -NIMH • 2.6 % of the U.S. pop. age 18 and older in a given year • Mean age of onset 25 y/o (correct dx >10 yr.) • Equal Distribution between men and women • 5th leading cause of disability

  5. Total cost estimated to exceed $ 45 Billion per year • 1st-degree relatives of individuals with Bipolar Disorder has an increased risk ranging from 4% to 24%. • Long term illness that must be managed throughout a persons life (90% relapse rate)

  6. HERITABILITY (GENETICS) – RELATIVE WITH BIPOLAR DISORDER AND CHILD ODDS • One parent 25 % • Two parents 50-75% • One MZ twin 30-90% • One DZ twin 5-25 % • American Journal of Medical Genetics Part C (Semin. Med. Genet.) 123C:48–58 (2003)

  7. ETIOLOGY

  8. No single cause • Hereditary factors • The most prominent theory centers around changes in monoamine neurotransmitters within the CNS i.e. excessive NE and DA in mania and deficits in NE, 5-HT, and DA • Psychodynamic “A defense against depression”. • Stress Diathesis Theory

  9. DIAGNOSIS

  10. DSM V CHANGES TO BIPOLAR DISORDER • Criteria for mania/hypomania – includes emphasis on changes in activity and energy –not just mood • Mixed episode – now – is a new specifier – “with mixed features” • Anxious distress specifier • No more Bipolar NOS - “Other Specified Bipolar and Related Disorder” diagnosis

  11. Diagnostic Problems • Time-consuming and difficult to differentiate • Subtle Symptoms • Moody ADHD/Disruptive Disorders • Non-Bipolar Depression • Pervasive Developmental Disorders (High Functioning autistic Spectrum • Substance Use Disorders

  12. Cues that “Unipolar” Depression may be Bipolar Disorder: • Early onset of depression • Highly recurrent depression (4 or more episodes) • Psychotic Depression • Postpartum onset of depression • History of mixed mood states • Family History of Bipolar Disorder • >3 failed antidepressant trials • Marked agitation with an antidepressant • Manning JS Family Practice 300; 2 Supp S 6-9

  13. Qualities that differ between Bipolar D/O vs. Unipolar D/O • Total Sleep Time BP>UP • Hypersomnia BP>UP • Psychomotor Retardation BP>UP • Postpartum Depression BP>UP • Weight Loss UP>BP

  14. Comorbidity of Psychiatric Disorders in Pediatric Bipolar Disorder Bipolar Disorder ADHD ODD/CD Tic Disorders Learning Disorders Depression/Anxiety Disorders • The rule more than the exception • Approximately 50%-90% • Disruptive Disorders • Anxiety Disorders • Substance Abuse (adolescents) ADHD = attention deficit hyperactivity disorder CD = conduct disorders ODD = oppositional defiant disorder Pliszka SR. Pediatr Drugs. 2003;5:741-750.

  15. Clinical Presentation of Pediatric Bipolar I Disorder • Adolescent patients with Bipolar I Disorder are diagnosed using the same DSM-IV-TR criteria as adults • Pediatric patients with Bipolar Disorder are more likely to present with: • Predominantly mixed episode • Rapid Cycling • Prominent irritability that may lead to violence and explosiveness • Frequently associated with psychotic symptoms and markedly labile mood • Often suffer from a more chronic form of the illness characterized by longer symptomatic episodes that are often refractor to treatment APA DSM IV AACAP Pavuluri MN et al. J Am Acad Chld and Adolecnet Psychiatry 1005: 44:849-871

  16. Characteristics Common to Pediatric Mania • Severe, prolonged irritability • Affective storms • Prolonged and aggressive temper outbursts • Mixed mania or rapid cycling (> 70% of cases) • High comorbidity with ADHD • Chronic and unremitting course Biederman J et al. Biol Psychiatry. 2000;48:458-466. State RC et al. Am J Psychiatry. 2002;159;918-925.

  17. DEFINITIONS • BIPOLAR DISORDER NOT OTHERWISE SPECIFIED (NOS): - recommendedto describe the large number of youths who receive a diagnosis of bipolar disorder who do not have the classic adult presentation 1 • Definitions currently used in the juvenile bipolar literature, but not provided in DSM-IV-TR, include the following: • ULTRARAPID CYCLING: refers to brief, frequent manic episodes lasting hours to days, but less than the 4-day prerequisite for hypomania. Having 5 to 364 cycles per year 2 • ULTRADIAN CYCLING: refers to repeated brief (minutes to hours) cycles that occur daily. Having greater than 365 cycles per year 2 • NIMH, 2001 • Geller et al. (2000)

  18. Clinical course of recurrent mood disorders

  19. MEDICAL CONDITIONS THAT MAYMIMIC PEDIATRIC BIPOLAR DISORDER • Hypothyroidism • Closed or open head injury • Temporal lobe epilepsy • Multiple Sclerosis • Systemic lupus erythematosus • Fetal alcohol spectrum disorder/ alcohol related neurodevelopmental disorder • Wilson’ s disease Kowatch et al. JCAAP. 2006; 15:73108

  20. Factors Suggestive of Pediatric Bipolar Disorder • Depression • Family history of mood disorders • Disruptive behavior & prominent mood symptoms • Psychosis • Attention-deficit / hyperactivity disorder • Poor stimulant response • History of medication-induced manic symptoms

  21. PEARLS TO HELP WITH DIAGNOSIS • Family history (BP is highly heritable; Identical twin concordance – 70% vs. Fraternal – 20%) –Best Predictor • Presence of elation/euphoria or grandiosity • Look at timeline of symptoms – not just current mental status • Episodic worsening within chronic symptoms • MDD + Psychosis, psychomotor retardation, childhood onset • History of medication-induced manic symptoms

  22. PEDIATRIC BP VS. ADHD Geller et al. J Affect Disord 1998

  23. NON-SPECIFIC SYMPTOMS Irritability (98% vs. 72%) Accelerated Speech (97% vs. 82%) Distractability (94% vs. 96%) Unusual Energy (100% vs. 95%) Geller et al. J Child and Adol Psychophar m.2002

  24. Clinical Pearls • Difficult to diagnosis/Be sure diagnosed is correct • Select a evidence based medication regiment • Use the right doses of medication/Ensure the medication trial continues for an adequate periods of time. • Be aware of any psychiatric comorbitities • Carfully Assess for adverse reactions/Remove agents that may be exacerbating situations • Combination interventions most often used

  25. Predictors of Bipolar Disorder • MDD with • Psychosis • Psychomotor retardation • Pharmacological induced mania/hypomania • Family history of bipolar disorder

  26. Mood Disorder Questionnaire Has there ever been a period of time when you were not your usual self and… … you felt so good or so hyper that other people thought you were not your normal self or you were so hyper that you got into trouble? … you were so irritable that you shouted at people or started fights or arguments? … you felt much more self-confident than usual? … you got much less sleep than usual and found you didn’t really miss it? … you were much more talkative or spoke much faster than usual? … thoughts raced through your head or you couldn’t slowyour mind down? Hirschfeld. Prim Care Companion J Clin Psychiatry. 2002;4:9-11.

  27. DISEASE STATE

  28. Depression Is the PredominantMood in Bipolar I Disorder 12.8-year prospective NIMH natural history study (N = 146) • Patients with bipolar I disorder spent nearly half of the time symptomatically ill • Time spent depressed was  3 times more than time spent manic • Time spent manic accounted for only 9.3% of the time • Depression (but not mania) predicted greater future illness burden Judd LL et al. Arch Gen Psychiatry. 2002;59:530–537.

  29. Mania 57% Mania 29% Depression 43% Depression 71% Patients currentlyor recently manic/hypomanic Patients currentlyor recently depressed Maintenance Treatment to Help Maintain Stability Against Depressive Episodes Is Particularly Important Depression: A Dominant Next Episode Among Patients Receiving Placebo During Two 18-Month Maintenance Trials Mood Polarity of Events in Bipolar I Disorder Bowden C et al. Arch Gen Psychiatry. 2003;60:392–400. Data on file, GlaxoSmithKline.

  30. TREATMENT

  31. Treatment Objectives for Bipolar Disorder • Bipolar disorder is a lifelong illness; therefore, maintenance treatment is the core of management1 • Treatment choice should be made by collaborative effort between patient and physician2 • The goal of acute therapy is to stabilize acute episodes with the goal of remission2 • The goal of maintenance therapy is to optimize protection against recurrence of episodes2 • Concurrently, attention needs to be devoted to maximizing patient functioning and minimizing subthreshold symptoms and adverse effects of treatment2 1. Calabrese et al. J Clin Psychiatry. 2002;63(suppl 10):18-22. 2. Hirschfeld et al. Am J Psychiatry. 2002;159(4 suppl):1-50.

  32. SOMATIC TREATMENTS • Recommendation 6. For Mania in Well-Defined DSM-IV-TR Bipolar I Disorder, Pharmacotherapy Is the Primary Treatment

  33. THE CHOICE OF MEDICATION(S) SHOULD BE MADE BASED ON: • (1) Evidence of efficacy • (2) Phase of illness • (3) Presence of confounding presentations (e.g., rapid cycling mood swings, psychotic symptoms) • (4) Agent`s side effect spectrum and safety • (5) Patient`s history of medication response • (6) Preferences of the patient and his or her family. A history of treatment response in parents may predict response in offspring Duffy et al., 2002

  34. Psychosocial Treatments as an adjunct to • Medications • Parent/Family Psychoeducation • Relapse Prevention • CBT or IPT for Depression • Interpersonal and Social Rhythm Therapy • Family Focused Therapy • Community Support Programs

  35. AACAP Treatment goals for pedicatric Patients with Bipolar Disorder • The general goals of treatment are: • Manage Symptoms and maintain response • Provide education about the illness • Promote Adherence to treatment • AACAP Guidelines suggest using a comprehensive treatment plan, combining pharmacotherapy with behavioral/psychosocial interventions AACAP 2007

  36. FDA APPROVED MEDICATIONS FOR PED BPD I, MIXED OR MANIC • Airpiprazole 10-17 • Olanzapine 13-17 • Quetiapine 10 - 17 • Risperidone 10-17 • Lithium 12-10

  37. SCREENING • Recommendation 1. Psychiatric Assessments for Children and Adolescents Should Include Screening Questions for Bipolar Disorder • Distinct mood changes associate sleep distrubances and psychomotor activation • Family history of mood disorders • Symptoms of irritability, reckless behaviors or increased energy • Perspective by family, school, peer, and other psychosocial factors rather than simply using checklist

  38. ASSESSMENT • Recommendation 2. The DSM-IV-TR Criteria, Including the Duration Criteria, Should Be Followed When Making a Diagnosis of Mania or Hypomania in Children and Adolescents • Recommendation 3. Bipolar Disorder NOS Should Be Used to Describe Youths With Manic Symptoms Lasting Hours to Less Than 4 Days or for Those With Chronic Manic-Like Symptoms Representing Their Baseline Level of Functioning

  39. ASSESSMENT (CONTINUED) • Recommendation 4. Youths With Suspected Bipolar Disorder Must Also Be Carefully Evaluated for Other Associated Problems, Including Suicidality, Comorbid Disorders (Including Substance Abuse), Psychosocial Stressors, and Medical Problems • Recommendation 5. The Diagnostic Validity of Bipolar Disorder in Young Children Has Yet to Be Established. Caution Must Be Taken Before Applying This Diagnosis in Preschoolchildren • Exposes them to aggressive pharmacotherapy

  40. Pharmacologic Treatment Goals in Bipolar Disorder Achieve rapid control of manic symptoms Acute phase Achieve remission of depressive symptoms Return to normal levels of psychosocial functioning Maintenancephase Delay or prevent recurrence of manic or depressive episodes Minimize subthreshold symptoms Hirschfeld RM et al. Am J Psychiatry. 2002;159(Suppl):1–50.

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