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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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slide1

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
disclosures
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
slide4

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
slide5

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)
heritability genetics relative with bipolar disorder and child odds
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)
slide11
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
dsm v changes to bipolar disorder
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
diagnostic problems
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
cues that unipolar depression may be bipolar disorder
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
qualities that differ between bipolar d o vs unipolar d o
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
comorbidity of psychiatric disorders in pediatric bipolar disorder
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.

clinical presentation of pediatric bipolar i disorder
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

characteristics common to pediatric mania
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.

definitions
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)
medical conditions that may mimic pediatric bipolar disorder
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

factors suggestive of pediatric bipolar disorder
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
pearls to help with diagnosis
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
pediatric bp vs adhd
PEDIATRIC BP VS. ADHD

Geller et al. J Affect Disord 1998

non specific symptoms
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

clinical pearls
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
predictors of bipolar disorder
Predictors of Bipolar Disorder
  • MDD with
    • Psychosis
    • Psychomotor retardation
    • Pharmacological induced mania/hypomania
    • Family history of bipolar disorder
mood disorder questionnaire
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.

depression is the predominant mood in bipolar i disorder
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.

slide38

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.

treatment objectives for bipolar disorder
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.

somatic treatments
SOMATIC TREATMENTS
  • Recommendation 6. For Mania in Well-Defined DSM-IV-TR Bipolar I Disorder, Pharmacotherapy Is the Primary Treatment
the choice of medication s should be made based on
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

slide44

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
aacap treatment goals for pedicatric patients with bipolar disorder
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

fda approved medications for ped bpd i mixed or manic
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
screening
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
assessment
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
assessment continued
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
pharmacologic treatment goals in bipolar disorder
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.

the goal of therapy
THE GOAL OF THERAPY
  • Ameliorate distressing symptoms
  • Provide education about the illness
  • Promote adherence to treatment - prevent relapse
  • Improve functioning
  • Reverse illness Course
  • Prevent full expression of condition
    • – “they just don’t grow out of it”
    • – Neuroprotection
  • Multi-modal treatment is a must
  • Reduce long-term morbidity, and promote normal growth and developmental pathways
recommendations
RECOMMENDATIONS:
  • Assure Safety
  • Stabilize mood, ADHD, and disruptive behavior
  • Labs/Physical
  • Clarification Diagnosis
    • Collateral information from Pediatrician, School, other caretakers, DSS/Legal involvement?
    • Psychological testing
    • Psychotherapy

Individual/Family/School diagnostic evaluation, intervention, education

  • Psychopharmacological intervention
  • Informed Consent
comprehensive treatment approach for children and adolescents with bipolar disorder
Comprehensive Treatment Approach for Children and Adolescents with Bipolar Disorder

Medication Therapy

Educational

Interventions

Psychotherapy

bipolar disorder psychoeducation
Bipolar Disorder - Psychoeducation
  • Symptomatology
  • Etiology ( e.g., genetics)
  • Treatment
  • Prognosis
  • Prevention (early signs of relapse/recurrence)
  • Psychosocial Scars
  • Stigma
  • Mood Hygiene
  • Importance of compliance
psychosocial interventions
PSYCHOSOCIAL INTERVENTIONS
  • Family Therapy
    • Psychoeducation (Diagnosis, Treatment)
    • Emphasize Compliance
    • Mood monitoring
    • Social skills training
    • Strategies aimed at increasing life style regularity (Adhering to regular schedule, normal sleep/wake cycle)
    • Parent training in behavioral interventions to deal with problematic behavior
    • Therapist helps family see family dynamics that may be contributing to patient’s illness.
bipolar disorder no response to treatment
Bipolar Disorder No Response to Treatment
  • Misdiagnosis
  • Compliance
  • Adequate treatment (type, doses, duration)
  • Comorbidity ( e.g., substance abuse)
  • Exposure to Stressful Life Events (e.g., abuse)
  • Psychosocial Factors
risk factors
RISK FACTORS

Strong genetic component in Adults –four- to six fold increase risk of disorder in first degree relatives of affected individuals 1

Degree of familiality appears even higher in early onset, highly comorbid cases 2

Premorbid psychiatric problems are common in early-onset bipolar disorder, especially difficulties with disruptive behavior disorders, irritability, and behavioral dyscontrol 3

Most childhood cases are associated with Attention Deficit Hyperactivity Disorder 4

In those whose first mood episode is a depressive disorder. Approximately 20% of youths withmajor depression go on to experience manic episodes by adulthood 5

  • Nurnberg and Foroud, 2000
  • Faraone et al., 2003
  • Carlson, 1990; Fergus et al., 2003; Geller et al., 2002a; McClellan et al., 2003; Werry et al., 1991; Wozniak et al., 1995)
  • 4. Findling et al. 2001; Geller et al., 2002a; Wozniak et al., 1995).
  • 5. Geller et al., 1994, 2001; Kovacs, 1996; Rao et al., 1995; Strober and Carlson, 1982).
slide60

Depression is the Predominant Moodin Bipolar I Disorder

Based on the 12.8-year NIMH natural history study (n = 146), of the 47% of time spent symptomatically ill, patients experienced depressive symptoms 3 times more than manic symptoms1

67%

Time spent symptomatically ill (%)

Depressed

13%

20%

Cycling/

mixed

Manic

  • In another naturalistic study, patients treated for bipolar disorder experienced 121 days of depression, versus 40 of mania, in a single year2*

*76% of patient cohort were patients with bipolar I disorder.

1. Judd LL et al. Arch Gen Psychiatry. 2002;59:530–537.

2. Post RM et al. Clin Neurosci Res. 2002;2:142–157.

prognositic indicators
PROGNOSITIC INDICATORS:
  • Good
  • Short Duration of manic episodes
  • Advanced age of onset
  • Few suicidal thoughts
  • Few coexisting psychiatric disorder
  • Few medical problems
  • Poor
  • Poor premorbid occupational status
  • Alcohol Dependence
  • Psychotic features
  • Depressive features
  • Interepisode depressive features
  • Male gender
  • coexisting psychiatric disorder
bipolar disorder sequela
Bipolar Disorder - Sequela
  • Poor academic functioning
  • Interpersonal and family difficulties
  • Increased risk for suicide
  • Increased use of tobacco, alcohol, and other substances
  • Behavior problems
  • Legal difficulties
  • Increased health services utilization (e.g., hospitalizations)

Emslie GJ, Mayes TL. Biol Psychiatry. 2001;49:1082-1090.

estimated total lifetime cost per case by prognosis group
Estimated Total Lifetime Cost per Case by Prognosis Group

Thousands of dollars, 1998

Begleyet al. Pharmacoeconomics. 2001;19(5 pt 1):483-495.

headache in teens with bipolar disorder
HEADACHE IN TEENS WITH BIPOLAR DISORDER
  • Unpublished, presented at AACAP
  • Canadian teens, bipolar d/o
  • 55 outpts., 13 y/o-19 y/o BP I, II, NOS
  • 60% F, 60% with HA – Sig. > severity on depressive, manic and CGI
  • Teens with BP with HA Sig. rates of identity confusion, anger/depression, and disinhibition /persistence
  • Results BP teen w/ HA more prone to > severity than BP teens w/o
  • Psy. Hosp. and psychosis > BP teen without headaches-results counterintuitive
headache in teens with bipolar disorder cont
HEADACHE IN TEENS WITH BIPOLAR DISORDER (Cont.)
  • Rational:
    • 1) BP teens with HA a different subtype? –unique course, characterisics and perhaps treatment?
    • 2) under dx or tx in adult BP and headaches is well doc. Potential treating in youth is important.
summary
Summary
  • Difficult to diagnosis
  • Comorbidity
  • Comprehensive treatments
  • Goals and re-evaluation
  • Prognosis?
unmet needs in pediatric bipolar disorder
Unmet Needs in Pediatric Bipolar Disorder
  • Diagnostic Criteria
  • Faster improvement
  • Fewer side effects and better tolerability
  • Greater efficacy
  • Long term efficacy

Source: Datamonitor, Stakeholder Insight: MDD, Q1.2; Adult population figures from www.census.gov and MDD prevalence rates applied.

resources
RESOURCES

WEBSITES:

  • The Child and Adolescent Bipolar Foundation
    • www.bpkids.org
  • Depression and Bipolar Support Alliance
    • www.dbsalliance.org
  • The Bipolar Child
    • www.bipolarchild.com
  • Parents of Bipolar Children
    • www.bpparent.org
  • The Gray Center for Social Learning and Understanding
    • www.thegraycenter.org/Social_Stories.htm
  • National Institute of Mental Health (NIMH)
    • www.nimh.org