CE on SUNDAY Newark, NJ October 18, 2009

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1 CE on SUNDAY Newark, NJ October 18, 2009 Date: Sunday, October 18, 2009 Time: 12:15 PM 1:30 PM Location: Sheraton Newark Airport Hotel Title: Speaker(s): Confronting Adolescent Bipolar Disorder ACPE # L01-P CEU ACPE # L01-T CEU Financially supported by Bristol-Myers Squibb Elizabeth Montagnese, M.D. Learning Objectives: Upon completion of this activity, participants will be able to: 1. Identify the a-typically implications of bipolar illness in adolescents as well as the controversies associated with this diagnosis currently in the field. 2. Describe the treatment implications of bipolar illness in adolescents and the need for diagnostic clarity. Disclosures: Elizabeth Montagnese, M.D. declares no conflicts of interest or financial interests in any product or service mentioned in this program, including grants, employment, gifts, stock holdings, or honoraria. Speaker(s) Biography: Dr. Montagnese received her medical degree at Wayne State University in Detroit, Michigan. She completed her general psychiatry and child psychiatry training at the Penn State University Milton S. Hershey Medical Center. Dr. Montagnese has been in private practice in the Central Pennsylvania area since She has also served as medical director for six years at a nonprofit community mental health center. She has worked in inner city schools, juvenile justice facilities and outpatient community mental health settings in the Central Pennsylvania region. She currently provides consultation to several schools and also to an adolescent drug and alcohol treatment facility. Dr. Montagnese sits on the board of the Central Pennsylvania Institute for Mental Health. This agency serves to meet the needs for training and education of mental health providers as well as the lay public. Dr. Montagnese also consults with CERMUSA, a subsidiary of St. Francis University in Loretto, Pennsylvania. This relationship serves to meet the needs of various medical professionals through web-based seminars for continuing medical education credits.

2 Confronting Child and Adolescent Bipolar Disorder Elizabeth Montagnese, M.D. Adult, Child and Adolescent Psychiatrist Quittie Qutte Ge Glen Center for Mental Health eat Annville, Pennsylvania This program has been financially supported by an educational grant from Bristol-Myers Squibb Company.

3 Confusion and Controversy in Pediatric Bipolar Disorder Spectrum disorder or categorical? Atypical presentation Diverse manifestations with development Comorbidity clouds the picture Diagnosis in children markedly increased in last decade in U.S.

4 The Case of Nikki 8 years old Adopted Biological mother: bipolar, substance abuse Hyperactive, impulsive, very attentive Aggressive, irritable, assaultive, periods of grandiosity Episodes of psychosis

5 Epidemiology Bipolar I: %, M=F (All forms: 2.6%) Bipolar II: 0.5%, F>M May be as high as 1% in youths Early onset M>F Across cultures, races Age of onset: 21 years Males manic first Females depressed first

6 Epidemiology 2/3 affected have close family member affected One parent: risk is 15-30% Two parents: risk is 50-75% Sibling: risk is 15-25% Identical twin: risk is 70%

7 Cost of Bipolar Disorders $45 billion annually: direct and indirect costs Bipolar pt/yr: $3415 Diabetes pt/yr: $2570 General medical outpatient/yr: $1462 Unemployment rate: up to 60% 6 th th leading cause of disability in world Delay in diagnosis increases costs

8 What is Classic Bipolar? Manic Depression Bipolar is both ends of the spectrum Severe mood swings Classic form: periods of extreme e e depression ess to periods of exaggerated happiness or euphoria or irritability Many shades of the illness in between the extremes Episodic nature, chronic, variable course

9 What are the forms of bipolar disorder? Bipolar I Disorder Bipolar II Disorder Bipolar Disorder NOS Cyclothymic Disorder Mood Disorder Due to General Medical Condition Substance-Induced Mood Disorder Multiple Specifiers For Most Types

10 DSM Criteria for Bipolar I D.O. Must have or had at least one episode of mania Some patients have had or will have a major depression Episodes can be depressive, manic or mixed

11 What is Bipolar II D.O.? Must have or had one or more episodes of MDD Must have or had at least one episode of hypomania Never had a manic episode

12 What is Cyclothymic y Disorder? 2 years minimum (1 year in children) Numerous periods of hypomania Numerous periods of depression but not MDD

13 What is Mania? Period of abnormally elevated, expansive or irritable mood Lasts at least one week or less if hospitalized Inflated self esteem, grandiosity Decreased need for sleep More talkative, pressured speech Flight of ideas, racing thoughts Distractibility Increased goal-directed activity or psychomotor agitation Increased pleasure seeking with high potential for negative consequences

14 What is Hypomania? Like mania, just less severe Period of elevated, expansive or irritable mood At least 4 days Not severe enough to cause marked impairment i or require hospitalization, ti no psychotic features

15 What is a Major Depressive Event? Depressed mood (irritable in children) and SIG-E-CAPS criteria S: suicidal iidlid ideation I: decreased interests G: excessive guilt (worthlessness, hopelessness) E: decreased energy C: decreased concentration A: appetite P: psychomotor retardation or agitation S: sleep disturbance

16 Bipolar Depression Earlier onset < 25 y. o. 5 or more spells of MDD Family hx of bipolar Atypical depressive symptoms Psychotic features Brief, frequent episodes of depression Complex comorbidity Mixed episodes History of antidepressant induced mania/hypomania

17 Bipolar Disorder and Psychosis Psychosis may be part of mania or depression Catatonia Mania in adolescents: psychosis common, grandiose delusions

18 Task Force Recommendations International team of experts Expanding diagnostic criteria for several subtypes Add pediatric category Bipolar II: not soft bipolar Add ultra-rapid rapid cycling specifier Not over diagnosed d A spectrum disorder Use of diagnostic tools increase accuracy of diagnosis

19 Pediatric Variant of Bipolar Disorder Broad phenotype Most often don t display classic mania Broad or narrow application of criteria??? No pathognomonic clincher for diagnosis i Is there another dx: Severe Mood Dysregulation?

20 Pediatric Bipolar = Bipolar N.O.S.? Predominant mood is highly irritable Aggressive Mood swings Rapid cycling of mood (ultradian) Recurrent & chronic (low inter-episodic episodic recovery) Mixed mood symptoms Comorbid psychiatric disorders Family history of bipolar disorder

21 What does mania look like in children? Poor sleep but energetic during day Goal-directed activities: coloring, drawing with bright colors, building, writing, i making big plans Hypersexuality: pleasure-seeking, seeking, not anxious, compulsive Melt-downs over trivial items Poor boundaries, taking charge, little regard for authority

22 Diagnostic Conundrum Many youth with explosive, dysregulated moods and emotional lability Are they all bipolar? Is this the same bipolar as seen in adults?

23 Controversy Continues NIMH round-table: children can be diagnosed with bipolar disorder Bipolar disorder Not Otherwise Specified best working diagnosis Current treatment is based on adult literature. Need more research in children Serious treatment implications

24 Controversy Continues Later adolescence dx = bipolar dx age 24 Bipolar NOS dx in younger children=psychopathology, adverse outcomes in young adults Bipolar NOS dx younger children = bipolar dx in young adults

25 Controversy Continues 28% 35% >18 yr <13 yr 65% of those with BPD report symptoms during childhood & adolescence yr 37% Kowatch, R. et al, J.Am.Acad.Child.Adol.Psychiatri 44-3, March, 2005

26 Course of Disease in Adults First episode may be mania, hypomania, depressive or mixed. First episode may be followed by symptom- free years Associated with substance abuse, recklessness, impulsivity, i i antisocial i behavior Variability is hallmark of illness Chronic illness No cure Very treatable Suicide completion rate is high: 10-15% 15% (M>F)

27 Course of Disease in Children and Adolescents Not one episode Symptoms ever present, fluctuating Limited periods of euthymia No clear pattern of cycling Diagnosis often changes in adult Severe comorbidity

28 Differential Diagnosis: Medical Conditions Neoplasms Epilepsy p Multiple Sclerosis Trauma a Endocrine: thyroid, pheochromocytoma Substance-induced Lupus Medication-induced: induced: steroids Infection: HIV Wilson s Disease

29 Comorbid Conditions ADHD Anxiety disorders: OCD and Panic Disorder Conduct DO/ODD Substance abuse

30 Bipolar Disorder : 1 ADHD: up to 90% Anxiety Disorders: 51% Conduct Disorder: 41-74% Substance Abuse: 60%

31 Other Disorders 1 ADHD: 23% had bipolar Panic Disorder: 12-23% 23% had bipolar Conduct Disorder: 40% had bipolar Substance Abuse: 40% had bipolar

32 Diagnostic Work-up Clinical diagnosis: history and interview Screening rating scales: Young Mania Rating Scale, CBCL Labs: CMP, TSH, LFTs, U/A, toxicology screen, lead (<7yo) Neuroimaging if abnl neuro exam

33 Neuroimaging Findings Nonspecific and variable Some studies: increased gray matter in left temporal, decrease gray matter in anterior cingulate gyrus bilaterally Ventricular enlargement Not diagnostic More research needed

34 Suicide Risk with Bipolar Disorder 25-50% 50% attempt suicide 10-15% 15% complete suicide

35 Suicide Risk with Bipolar Disorder Higher with: Mixed episode Psychosis History of hospitalization ti History of self-injurious behavior Comorbid panic disorder Comorbid substance abuse

36 Treatment Approaches Acute phase: Hospitalization: secure patient Day treatment Medication a must Education: patient and family Psychotherapy & family therapy Mood charting Sleep hygiene

37 Treatment Approaches Preventative/maintenance phase: Noncompliance is common Two or more episodes mania/depression=life long medication Maintain regular sleep and daily patterns Do not use drugs/alcohol Reduce stress Recognize early warning signs Don t abruptly stop meds-talk to your doctor Enlist support of family/friends

38 Treatment Goals Assess and treat acute exacerbations Decrease distress Improve functioning between episodes Prevent recurrences Provide support and insight to patient and family HOPE!

39 Specific Therapies FFT: Functional Family Therapy Triggers and day to day changes Understanding diagnosis & need for med compliance Preventative Measures Sleep/waking cycle importance Address mood issues in family members

40 Now, let s get to the meds Lithium: antimanic effects discovered in 1949, used extensively since 1960 s Anticonvulsants: effects discovered in 1970 s Antipsychotics: atypicals and typicals

41 Lithium (Eskalith, Lithobid) Generic available mg/day QD or BID Check serum levels: mEq/L Check serum levels: Day 3-4, 1 mos, 3-6 mos, dose change Labs: CBC, renal, lytes, U/A, TSH, pregnancy test, ECG

42 Lithium (Eskalith, Lithobid) Side effects: Acne Renal dysfunction Cognition Diarrhea, GI distress Hypothyroidism Polyuria, polydipsia Tremor Weight gain Sedation Drug interactions: ACE inhibitors Diuretics NSAIDs Theophylline Caffeine

43 Valproate (Depakote) mg/day Q hs or BID Labs: LFTs, CBC, Cr, BUN, pregnancy test Check serum levels: mcg/ml Check serum levels: 1-2 weeks, then 3-6 months, dosage change

44 Valproate (Depakote) Side effects: Alopecia Ataxia, tremor Cognitive impairment Dizziness GI upset Liver and platelet dysfunction PCOS Weight gain Sedation Rash Drug interactions: Antipsychotics Benzodiazepines Carbamazepine Lamotrigine Lithium MAOIs Phenytoin TCAs Warfarin

45 Carbamazepine (Tegretol) Generic available mg/day BID or TID Labs: CBC, LFTs, pregnancy test, lytes Check serum levels: 4-12 mcg/ml Check serum levels: day 5-7, weekly til stable, 3-6 6months

46 Carbamazepine (Tegretol) Side effects: Ataxia Diplopia, nystagmus Dizziness Dysarthria GI upset Hyponatremia Leukopenia Rash Sedation Drug interactions: Induces own metabolism Antipsychotics Benzodiazepines Cimetidine Corticosteroids Valproate Erythromycin Lamotrigine OCP TCA Warfarin

47 Lamotrigine Generic available 200mg/day Titrate slowly QD or BID Labs: renal, LFTs, pregnancy test

48 Lamotrigine Side effects: Ataxia Dizziness Headache e Nausea Serious rash- Stevens Johnson Syndrome Sedation Drug interactions: Carbamazepine Valproate

49 Recent Advisory for Mood Stabilizers All current antiepileptics pose increase risk of suicidality Patients/parents should be warned No black box advisory Included carbamazepine, oxcarbazepine, valproate among others

50 Risperidone (Risperdal) mg daily Only depot form of atypical Depot form q 2 weeks Weight gain, sedation and high prolactin most common Above 6 mg daily- EPS

51 Olanzapine (Zyprexa) 5-20mg daily Very sedating Excessive weight gain Metabolic syndrome

52 Quetiapine (Seroquel) mg daily Moderate for weight gain Slit lamp eye exam recommended- cataracts, not often done Very sedating

53 Ziprasidone (Geodon) mg daily 2001 Short acting injectable available Can be used for acute agitation ti More weight neutral than other atypicals Lower incidence of metabolic syndrome

54 Aripiprazole (Abilify) 10-30mg daily Dopamine stabilizer Agonist in areas of low activity More weight neutral Low incidence of metabolic syndrome

55 Clozapine (Clozaril) mg daily 1989 Weight gain Agranulocytosis- serious, fatal Weekly WBC count Specific protocol-complex complex to manage Used in refractory cases Seizures Excessive salivation

56 FDA Approved Medications for Pediatric Bipolar Disorder Lithium: ages yo Risperidone, Aripiprazole: ages yo Panel recommended approval of Quetiapine, Ziprasidone, Olanzapine

57 Treatment Algorithm Pediatric Mania/Mixed Psychosis No response Li, VPA or CBZ Or SGA no Some response yes Li or VPA or CBZ + SGA Switch (monotherapy) Li+VPA or Li+ SGA or VPA+ SGA Some response Li+VPA+SGA Or Li+CBZ+SGA Some response Li+VPA+SGA or Li+CBZ+SGA Kowatch, RA, et al, J.Am.Acad.Child.Adol.Psych, 44(3): , 2005 SGA: Olanzapine, Risperidone, id Quetiapine i VPA: Valproic Acid CBZ: Carbamazepine Li: Lithium

58 Treatment Algorithm: Depressive Symptoms Add lithium, buproprion or SSRI to mood stabilizer Consider lamotrigine

59 Treating Comorbidity Stabilize mood (manic, mixed symptoms) first Treat ADHD symptoms ( watch stimulants closely,??atomoxetine) Treat anxiety Watch for activation

60 Long term Maintenance Use what works 1-2 years stable, then consider careful taper Don t let children cycle without intervention

61 Bipolar Knows No Boundaries Kurt Cobain Jane Pauley Patty Duke Ted Turner Sinead O Connor Winston Churchill Handel Keats Dickens

62 References Diagnostic and Statistical Manual of Mental Disorders, fourth edition, Text Revision, American Psychiatric Association, 2000 Physicians Desk Reference, 2008 Konstantinos N et al; Treatment of Bipolar Disorder: A Complex Treatment for a Multi- Faceted Disorder; Annals of General Psychiatry, y, 2007, 6:27 Ghaemi, SN, Bauer M, Cassidy F, et al; ISBD Diagnostic Guidelines Task Force. Diagnostic Guidelines for Bipolar Disorder: A Summary of the International Society for Bipolar Disorders Diagnostic Guidelines Task Force Report. Bipolar Disord ;10(1, pt 2): NIMH, Questions and Answers about the NIMH Clinical Antipsychotic Trials of Intervention ti Effectiveness Study (CATIE), Practice Guidelines for the Treatment of Patients with Bipolar Disorder, Second Edition, 2002, American Psychiatric Association Pandey, G. et al, Brain-derived Neutrophic Factor Gene Expression in Pediatric Bipolar Disorder: Effects of Treatment and Clinical Response, J.Am.Acad.Child.Adolesc.Psychiatry,, 47:9, , 1085, Sept Weller, E. et al, Bipolar Disorder in Children and Adolescents: Diagnosis and Treatment, Current Opinion in Psychiatry,, 16(4), West, S., Adolescent Mania and Bipolar Disorder, Medscape Psychiatry and Mental Health ejournal, 2(5), 1997

63 References Kahn, D., Ross, R., Printz, D., Sachs G., Treatment of Bipolar Disorder: A Guide for Patients and Families; Medication Treatment of Bipolar Disorder 2000, Expert Consensus Guideline Series Ghaemi, S. N., Defining the Boundaries of Childhood Bipolar Disorder, Am.J.Psychiatry, 164: k 188k Feb 2007 Levin, A., Researchers Refine Criteria for Childhood Bipolar Disorder, Psychiatric News, Vol 44, Number 1,p. 17, Jan. 2,2009 Schapiro, N., Bipolar Disorders in Children and Adolescents, J. of Pediatric Health Care, 19 (3): , 141, 2005 Weller, E. et al, Bipolar Disorder in Children: Misdiagnosis, Underdiagnosis, and Future Directions, J.Am.Acad.Child.Adolesc.Psychiatry,, 34:6, , 714, June, 1995 Karantaris, V., Treatment of Bipolar Disorder in Children and Adolescents, J.Am.Acad.Child.Adolesc.Psychiatry, Acad Adolesc, 34:6, , 741, June, Akiskal, H., Developmental Pathways to Bipolarity: Are Juvenile-Onset Depressions Pre- Bipolar, J.Am.Acad.Child.Adolesc.Psychiatry,, 34:6, , 763, June, Biederman, J., Developmental Subtypes of Juvenile Bipolar Disorder, Harvard Rev. Psychiatry,, 3: , 1995 American Academy of Adolescent and Child Psychiatry, Practice Parameter for the Assessment and Treatment of Children and Adolescents with Bipolar Disorder, J.Am.Acad.Child.Adolesc.Psychiatry,, 46:1, , 125, January, 2007.