Page 1 Confronting Adolescent Bipolar Disorder Confronting Adolescent Bipolar Disorder Elizabeth Montagnese, M.D. Adult, Child and Adolescent Psychiatrist Quittie Glen Center for Mental Health Annville, Pennsylvania This program has been supported by an education grant from Bristol- Myers Squibb PharmCon is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education Copyright 2009 PharmCon Accreditation: Pharmacists: 0798-0007-09-081-L01-P-P Pharmacy Technicians: 0798-0000-09-081-L01-T Nurses: N-110209-474-L01 Target Audience: Pharmacists, Technicians & Nurses CE Credits: 1.25 Credit hour or 0.125 CEU for pharmacists/technicians Expiration Date: 10/18/2012 Program Overview: This program reviews the phenomenology and clinical characteristics of pediatric bipolar disorder and current approaches to pharmacotherapy. It is becoming apparent that bipolar disorder is often a chronic disorder in children and adolescents and is best managed with a combination of medications and psychosocial therapy. Objectives: Identify the a-typicality of bipolar illness in adolescents as well as the controversies associated with this diagnosis currently in the field. Describe the treatment implications of bipolar illness in adolescents and the need for diagnostic clarity. Review the therapies used in treating bipolar disorder in adolescents to include pharmacotherapy, behavioral, individual and various psychosocial therapies. Review the FDA approved pharmacotherapy options to include the modes of action, efficacy, and advantages and disadvantages. Copyright 2009 PharmCon Confronting Adolescent Bipolar Disorder Speaker: Dr. Montagnese is board certified in adult, child, and adolescent psychiatry by the American Board of Psychiatry and Neurology. Dr. Montagnese provides comprehensive psychiatric evaluation and treatment for individuals, couples and families. Her primary area of focus is working with children and adolescents but she also treats adults.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 is the medical director at Family and Children Services of Central Pennsylvania. This is a United Way funded nonprofit agency that serves the greater Harrisburg, York and Lancaster areas. To contact her at this agency please call 717-238-8118. Speaker Disclosure: Dr. Montagnese has no actual or potential conflicts of interest in relation to this program PharmCon is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education 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. Legal Disclaimer: The material presented here does not necessarily reflect the views of Pharmaceutical Education Consultants (PharmCon) or the companies that support educational programming. A qualified healthcare professional should always be consulted before using any therapeutic product discussed. Participants should verify all information and data before treating patients or employing any therapies described in this educational activity. Copyright 2009 PharmCon
Page 2 The Case of Nikki Epidemiology 8 years old Adopted Biological mother: bipolar, substance abuse Hyperactive, impulsive, very attentive Aggressive, irritable, assaultive, periods of grandiosity Episodes of psychosis Bipolar I: 0.4-1.6%, 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 Epidemiology Cost of Bipolar Disorders 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% $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 leading cause of disability in world Delay in diagnosis increases costs
Page 3 What is Classic Bipolar? Manic Depression Bipolar is both ends of the spectrum Severe mood swings Classic form: periods of extreme depression to periods of exaggerated happiness or euphoria or irritability Many shades of the illness in between the extremes Episodic nature, chronic, variable course 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 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 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
Page 4 What is Cyclothymic Disorder? 2 years minimum (1 year in children) Numerous periods of hypomania Numerous periods of depression but not MDD 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 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 or require hospitalization, no psychotic features What is a Major Depressive Event? Depressed mood (irritable in children) and SIG-E-CAPS criteria S: suicidal 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
Page 5 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 Bipolar Disorder and Psychosis Psychosis may be part of mania or depression Catatonia Mania in adolescents: psychosis common, grandiose delusions Task Force Recommendations International team of experts Expanding diagnostic criteria for several subtypes Add pediatric category Bipolar II: not soft bipolar Add ultra-rapid cycling specifier Not over diagnosed A spectrum disorder Use of diagnostic tools increase accuracy of diagnosis 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 Is there another dx: Severe Mood Dysregulation?
Page 6 Pediatric Bipolar = Bipolar N.O.S.? Predominant mood is highly irritable Aggressive Mood swings Rapid cycling of mood (ultradian) Recurrent & chronic (low inter-episodic recovery) Mixed mood symptoms Comorbid psychiatric disorders Family history of bipolar disorder What does mania look like in children? Poor sleep but energetic during day Goal-directed activities: coloring, drawing with bright colors, building, writing, making big plans Hypersexuality: pleasure-seeking, not anxious, compulsive Melt-downs over trivial items Poor boundaries, taking charge, little regard for authority Diagnostic Conundrum Controversy Continues Many youth with explosive, dysregulated moods and emotional lability Are they all bipolar? Is this the same bipolar as seen in adults? 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 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
Page 7 Controversy Continues 35% 65% of those with BPD report symptoms during childhood & adolescence. >18 yr 13-18yr Kowatch, R. et al, J.Am.Acad.Child.Adol.Psychiatri 44-3, March, 2005 <13 yr 37% 28% Course of Disease in Adults First episode may be mania, hypomania, depressive or mixed. First episode may be followed by symptomfree years Associated with substance abuse, recklessness, impulsivity, antisocial behavior Variability is hallmark of illness Chronic illness No cure Very treatable Suicide completion rate is high: 10-15% (M>F) Course of Disease in Children and Adolescents Differential Diagnosis: Medical Conditions Not one episode Symptoms ever present, fluctuating Limited periods of euthymia No clear pattern of cycling Diagnosis often changes in adult Severe comorbidity Neoplasms Epilepsy Multiple Sclerosis Trauma Endocrine: thyroid, pheochromocytoma Substance-induced Lupus Medication-induced: steroids Infection: HIV Wilson s Disease
Page 8 Comorbid Conditions Bipolar Disorder : 1 ADHD Anxiety disorders: OCD and Panic Disorder Conduct DO/ODD Substance abuse ADHD: up to 90% Anxiety Disorders: 51% Conduct Disorder: 41-74% Substance Abuse: 60% Other Disorders 1 Diagnostic Work-up ADHD: 23% had bipolar Panic Disorder: 12-23% had bipolar Conduct Disorder: 40% had bipolar Substance Abuse: 40% had bipolar 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
Page 9 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 Suicide Risk with Bipolar Disorder 25-50% attempt suicide 10-15% complete suicide Higher with: Mixed episode Psychosis History of hospitalization History of self-injurious behavior Comorbid panic disorder Comorbid substance abuse Treatment Approaches Treatment Approaches Acute phase: Hospitalization: secure patient Day treatment Medication a must Education: patient and family Psychotherapy & family therapy Mood charting Sleep hygiene 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
Page 10 Treatment Goals Specific Therapies Assess and treat acute exacerbations Decrease distress Improve functioning between episodes Prevent recurrences Provide support and insight to patient and family HOPE! 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 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 Lithium (Eskalith, Lithobid) Generic available 900-2400 mg/day QD or BID Check serum levels: 0.6-1.5 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
Page 11 Lithium (Eskalith, Lithobid) Valproate (Depakote) Side effects: Acne Renal dysfunction Cognition Diarrhea, GI distress Hypothyroidism Polyuria, polydipsia Tremor Weight gain Sedation Drug interactions: ACE inhibitors Diuretics NSAIDs Theophylline Caffeine 750-2000mg/day Q hs or BID Labs: LFTs, CBC, Cr, BUN, pregnancy test Check serum levels: 50-150mcg/ml Check serum levels: 1-2 weeks, then 3-6 months, dosage change Valproate (Depakote) Carbamazepine (Tegretol) 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 Generic available 400-1600mg/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 months
Page 12 Carbamazepine (Tegretol) Lamotrigine 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 Generic available 200mg/day Titrate slowly QD or BID Labs: renal, LFTs, pregnancy test Lamotrigine Side effects: Ataxia Dizziness Headache Nausea Serious rash- Stevens Johnson Syndrome Sedation Drug interactions: Carbamazepine Valproate 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
Page 13 Risperidone (Risperdal) Olanzapine (Zyprexa) 1993 1-8mg daily Only depot form of atypical Depot form q 2 weeks Weight gain, sedation and high prolactin most common Above 6 mg daily- EPS 5-20mg daily Very sedating Excessive weight gain Metabolic syndrome Quetiapine (Seroquel) Ziprasidone (Geodon) 300-800 mg daily Moderate for weight gain Slit lamp eye exam recommendedcataracts, not often done Very sedating 40-160mg daily 2001 Short acting injectable available Can be used for acute agitation More weight neutral than other atypicals Lower incidence of metabolic syndrome
Page 14 Aripiprazole (Abilify) 10-30mg daily Dopamine stabilizer Agonist in areas of low activity More weight neutral Low incidence of metabolic syndrome Clozapine (Clozaril) 25-900mg daily 1989 Weight gain Agranulocytosis- serious, fatal Weekly WBC count Specific protocol-complex to manage Used in refractory cases Seizures Excessive salivation FDA Approved Medications for Pediatric Bipolar Disorder Lithium: ages 12-17 yo Risperidone, Aripiprazole: ages 10-17 yo Panel recommended approval of Quetiapine, Ziprasidone, Olanzapine No response Switch (monotherapy) Treatment Algorithm Li, VPA or CBZ Or SGA no Some response Li+VPA or Li+ SGA or VPA+ SGA Some response Pediatric Mania/Mixed Psychosis yes Li or VPA or CBZ + SGA Some response Li+VPA+SGA Or Li+CBZ+SGA Li+VPA+SGA or Li+CBZ+SGA Kowatch, RA, et al, J.Am.Acad.Child.Adol.Psych, 44(3):213-223, 2005 SGA: Olanzapine, Risperidone, Quetiapine VPA: Valproic Acid CBZ: Carbamazepine Li: Lithium
Page 15 Treatment Algorithm: Depressive Symptoms Add lithium, buproprion or SSRI to mood stabilizer Consider lamotrigine Treating Comorbidity Stabilize mood (manic, mixed symptoms) first Treat ADHD symptoms ( watch stimulants closely,??atomoxetine) Treat anxiety Watch for activation Long term Maintenance Use what works 1-2 years stable, then consider careful taper Don t let children cycle without intervention Bipolar Knows No Boundaries Kurt Cobain Jane Pauley Patty Duke Ted Turner Sinead O Connor Winston Churchill Handel Keats Dickens
Page 16 References 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, 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. 2008;10(1, pt 2):117-128. NIMH, Questions and Answers about the NIMH Clinical Antipsychotic Trials of Intervention Effectiveness Study (CATIE), http://www.nimh.gov/healthinformation.catieqa.cfm 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, 1077-1085, Sept. 2008 Weller, E. et al, Bipolar Disorder in Children and Adolescents: Diagnosis and Treatment, Current Opinion in Psychiatry, 16(4), 2003. West, S., Adolescent Mania and Bipolar Disorder, Medscape Psychiatry and Mental Health ejournal, 2(5), 1997 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, 164:185-188k 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): 131-141, 2005 Weller, E. et al, Bipolar Disorder in Children: Misdiagnosis, Underdiagnosis, and Future Directions, J.Am.Acad.Child.Adolesc.Psychiatry, 34:6, 709-714, June, 1995 Karantaris, V., Treatment of Bipolar Disorder in Children and Adolescents, J.Am.Acad.Child.Adolesc.Psychiatry, 34:6, 732-741, June, 1995. Akiskal, H., Developmental Pathways to Bipolarity: Are Juvenile-Onset Depressions Pre- Bipolar, J.Am.Acad.Child.Adolesc.Psychiatry, 34:6, 754-763, June, 1995. Biederman, J., Developmental Subtypes of Juvenile Bipolar Disorder, Harvard Rev. Psychiatry, 3: 227-230, 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, 46:1,107-125, January, 2007. Notes Notes