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Pediatric Bipolar Disorder Copyright © The REACH Institute. All rights reserved. Learning Objectives In order to effectively use medications for pediatric behavioral health problems, participants will learn to: 1) Identify and differentiate among pediatric behavioral health problems, especially bipolar disorder, depression, ADHD and oppositional defiant disorder 2) Describe treatment algorithms and evidence-based medications used to treat bipolar disorder Copyright © The REACH Institute. All rights reserved. Agenda • We will review different presentations and diagnostic dilemmas associated with pediatric bipolar disorder • We will discuss a treatment algorithm for pediatric bipolar disorder Copyright © The REACH Institute. All rights reserved. RESOURCE SLIDE: Collaborative Role of the Pediatrician in the Diagnosis and Management of Bipolar Disorder in Adolescents. Shain BN, et al. Pediatrics 2012;130:e1725–e1742 Despite the complexity of diagnosis and management, pediatricians have an important collaborative role in referring and partnering in the management of adolescents with bipolar disorder. This report presents the classification of bipolar disorder as well as interviewing and diagnostic guidelines. Treatment options are described, particularly focusing on medication management and rationale for the common practice of multiple, simultaneous medications. Medication adverse effects may be problematic and better managed with collaboration between mental health professionals and pediatricians. Case examples illustrate a number of common diagnostic and management issues. Copyright © The REACH Institute. All rights reserved. The Assessment of Bipolar Disorder in Children and Adolescents Copyright © The REACH Institute. All rights reserved. What is Johnny’s Diagnosis? (see workbook page I 1.1) Pick one best answer: A. ADHD B. Bipolar Disorder C. Oppositional Defiant Disorder D. ADHD and Oppositional Defiant Disorder E. Generalized Anxiety Disorder F. Major Depressive Disorder G. All of the above Copyright © The REACH Institute. All rights reserved. Lifetime Prevalence of Bipolar Disorder in the USA • Adults (NCS Replication Study, Merikangas et al. 2007) – Bipolar I Disorder: 1.0% – Bipolar II Disorder: 1.1% – Bipolar Subthreshold: 2.4% • Adolescents – Bipolar Disorder: 1.0-1.4% (e.g., see Shaffer D et al. 1996 [MECA]; Kessler RC et al., 2011) • Children – ??? Copyright © The REACH Institute. All rights reserved. DSM-5 Manic Episode • A DISTINCT PERIOD of abnormally and persistently elevated, expansive, or irritable mood; accompanied by increased energy/activity, lasting at least 1 week or resulting in hospitalization – (or any duration if hospitalization because of mania is necessary) • At Least Three: – – – – – – – Inflated self esteem or grandiosity Decreased need for sleep More talkative than usual Flight of ideas or racing thoughts Distractibility Increase in goal-directed activity or psychomotor agitation Excessive involvement in pleasurable activities potential for painful consequences • Causes a marked impairment in occupational or social functioning Copyright © The REACH Institute. All rights reserved. Developmental Issues • Similarities between adults and children with Bipolar Disorder – elated mood, grandiosity, hypersexuality, decreased need for sleep, flight of ideas, racing thoughts, social intrusiveness (Geller et al. J Child and Adolescent Psychopharmacology 10:157-164, 2000) • Importance of developmental differences in presentation Copyright © The REACH Institute. All rights reserved. Developmental Differences Between Bipolar Children and Adolescents Children • BP-NOS Adolescents • BP-I-II • More Severe Depressions • Irritability • Melancholic • Mood Lability • Atypical • Suicidality • Hallucinations • Worse course • ADHD • ODD • More typical and severe mania • Elation • Grandiosity • Substance abuse Copyright © The REACH Institute. All rights reserved. Developmental Differences in the Expression of Manic and Depressive Symptoms SYMPTOM ADULT CHILD Grandiosity I’m the world’s greatest lover, The president will be calling me for advice I’m smarter than my teacher; I am the best writer in my whole school Decreased need for sleep Several nights in a row without needing any sleep and no sense of fatigue Needing only a few hours of sleep and engaging in activity in the middle of the night Hypersexuality Unprotected sex with multiple partners Child propositions adult, self stimulates in public Weckerly J., Developmental Behav. Ped.,Vol 23, No. 1, 42-56. Copyright © The REACH Institute. All rights reserved. Developmental Differences in the Expression of Manic and Depressive Symptoms SYMPTOM ADULT CHILD Racing thoughts Jumping from one Describes mind is thought to another in like a video on fast an illogical manner forward Pressured speech Hard to interrupt and Child talks not phased when you continuously and do difficult to redirect Weckerly J., Developmental Behav. Ped.,Vol 23, No. 1, 42-56. Copyright © The REACH Institute. All rights reserved. The Broad Phenotype • There may be a large group of children who show manic symptoms – Especially the affective storms & rages – Don’t clearly cycle between mood states – May not have bipolar in family pedigree – Severe Mood Dysregulation (Leibenluft et al 2003) • Are these bipolar cases? – Will they grow up to look more classic? – Safety screen of neglect/abuse – Possible medical conditions like temporary lobe epilepsy, hyperthyroidism, alcohol-related neurodevelopment, Wilson’s Disease Copyright © The REACH Institute. All rights reserved. Need For Better Diagnostic Criteria For Pediatric Bipolar Disorder • DSM-4 & 5: no model is perfect, but even imperfect models can help • DSM criteria based primarily on adult research • Changes with the Adult Diagnostic “Spectrum” of Bipolar disorder – “Classic” Type I Bipolar Disorder (less than 50% of adults) – Type II Bipolar Disorder, also mixed, rapid cycling • DSM 5 Disruptive Mood Dysregulation Disorder Copyright © The REACH Institute. All rights reserved. Disruptive Mood Dysregulation Disorder, DSM-5 A. Severe recurrent temper outbursts Verbal and/or behavioral, grossly out of proportion in intensity or duration, inconsistent with developmental level B. Frequency >=3/week C. Mood between temper outbursts: Persistently negative (irritable, angry, and/or sad) Negative mood is observable by others D. Duration; Criteria A-C >= 12 months E. >= 2 settings F. Chronological age >= 6 years (or equivalent developmental level). G. .Onset before 10 years. H. No history of (elevated) manic mood with associated B criteria for >= 1day I. Not occur exclusively during the course of a Psychotic or Mood Disorder; not better accounted for by another mental disorder (e.g., PDD, PTSD). Can co-occur with ODD, ADHD, CD Copyright © The REACH Institute. All rights reserved. Bipolar Symptoms Shared with Other Childhood Disorders Mania MDD ADHD ODD Anxiety Elated mood Irritability 67% Low frustration tolerance Touchy/ Easily annoyed Irritability Hyperactivity agitation Agitation Hyperactivity Restlessness agitation Distractibility Poor conc. Distractibility Difficulty in concentration Communication disorders Flight of ideas Grandiosity Impulsivity Poor judgment Reduced sleep Insomnia Trouble settling wakes early Copyright © The REACH Institute. All rights reserved. Initial insomnia ADHD vs. Bipolar • Irritability is non-specific: – Irritability does not = Bipolar – Geller et al 2002 found irritability in 72% of Children with ADHD and 97.9% of Children with Bipolar Disorder • Elation, grandiosity, flight of ideas/racing thoughts, decreased need for sleep and hypersexuality provide the best discrimination between ADHD and BD in children and adolescents (Geller et al 2002) Copyright © The REACH Institute. All rights reserved. The Unipolar Depression vs. Bipolar Distinction • First mood episode of Juvenile Bipolar Disorder is often a depressive episode • MDD in children often associated with high rates of irritability…i.e., children with depression can present with irritable mood, not depressed mood • Children and Adolescents with major depressive disorder can have very labile mood • What do you mean by “mood swings?” – euthymia to depressed vs. depressed to manic or hypomanic Copyright © The REACH Institute. All rights reserved. Substance Abuse vs. Pediatric Bipolar Disorder • The substance abuse may mimic a bipolar presentation – Check urine drug screens, educate patients and families • There are high rates of co-morbid substance abuse in adolescents with bipolar disorder – The substance abuse must be addressed Copyright © The REACH Institute. All rights reserved. Conduct Disorder vs. Pediatric Bipolar Disorder • Conduct Disorder – The negative behaviors are often calculating and predatory • Pediatric Bipolar – The negative behaviors are secondary to grandiosity and risky, poor judgment Copyright © The REACH Institute. All rights reserved. Bipolar or Psychosis? Copyright © The REACH Institute. All rights reserved. Bipolar or Trauma? Copyright © The REACH Institute. All rights reserved. With Pediatric Bipolar Disorder There Are High Rates of Co-occurring Psychiatric Conditions • ADHD • ODD • Conduct Disorder • Learning Disabilities • Substance Abuse • Anxiety Disorders Copyright © The REACH Institute. All rights reserved. Individually or in combination A Family History of Bipolar Disorder • Take a careful family psychiatric history – Bipolar disorder in one parent = 5x odds of bipolar disorder in child (but still only ~5% prevalence; LaPalme et al., 1997), still less than likelihood of ADHD – Bipolar disorder in parents, grandparents, and siblings is clinically meaningful but doesn’t rule out “bad” ADHD – The presence of bipolar disorder in more distant relatives may not confer greater genetic risk – No clear family history doesn’t rule out pediatric bipolar disorder Copyright © The REACH Institute. All rights reserved. Pediatric Bipolar Rating Scales • Young Mania Rating Scale for Parents P-YMRS (Gracious et al. JAACAP,2002) – the scale can be found at www.healthyplace.com/bipolar/p-ymrs.asp • General Behavioral Inventory, GBI (Findling et al. Bipolar Disorder, 2002) – Self and parent report ages 5-17 – Very long tool 73 mood items • Life Mood Charts – Asking about mood symptoms throughout the patient’s life – Can be found at www.dballiance.org • These rating scales do a better job of ruling out pediatric bipolar disorder then ruling it in • Still very helpful to follow symptoms to assist with diagnosis and to follow symptoms Copyright © The REACH Institute. All rights reserved. Summary • In evaluating pediatric bipolar disorder look for classic criteria, i.e., a DISTINCT EPISODE, different from the child’s normal state, characterized by: – elevated mood, grandiosity, decreased need for sleep, racing thoughts • High rates of psychiatric co-morbidity – Especially ADHD, ODD, Conduct Disorder and Learning disabilities • Careful family history – Focus on first and second degree relatives • Rating scales do a better job of ruling out pediatric bipolar disorder then ruling it in • If significantly concerned get a child psychiatry consultation Copyright © The REACH Institute. All rights reserved. Bipolar Disorder Treatment Options Copyright © The REACH Institute. All rights reserved. Bipolar Management • • • • • • If neglect/abuse, crisis intervention Mental Health Specialist for diagnostic assessment and sometimes concurrent treatment: CBT, social skills, problem solving, psych education. If bipolar, psychiatric assessment and treatment with on-going therapy, lab testing and medication treatment. Lab testing Medications review/ monitoring for side effects Inquire about concerns/safety Copyright © The REACH Institute. All rights reserved. FDA Pediatric Labeling for BD Brand name Cibalith-S Generic Name Lithium citrate Indicated Age 12 and older 12 and older Eskalith Lithium CO3 Lithobid Lithium CO3 12 and older Risperdal Risperidone 10 and older Abilify Aripiprazole 10 and older Zyprexa Olanzapine 10 and older Seroquel Quetiapine 10 and older Copyright © The REACH Institute. All rights reserved. Atypical Antipsychotic Use for Pediatric Mania • Refer for hospitalization • Risperidone, target dose 2-4 mg/day, divided doses • Start 0.5 mg qhs, add 0.5-1mg q. 3-4 days if welltolerated • Onset of action: 7 days; full efficacy in 4-6 weeks • Side effects: weight gain, sedation, elevated prolactin • At baseline: fasting glucose, lipids, BMI, girth, dietary consultation • Taper at 6 months Copyright © The REACH Institute. All rights reserved. Treatment Algorithm for Mania/ Hypomania in Children and Adolescents Stage 1 Monotherapy 1A: Mixed/Manic Quetiapine/ Aripiprazole/Risperidone 1B: Lithium/Valproate/ Olanzapine/Ziprasidone Negative response Evaluate Positive response Continue Positive response Continue Partial response Stage 2 Augmentation 2: Add mood stabilizer to atypical or vice versa Evaluate Stage 3 2 drug combinations Partial response or nonresponse 3: 2 mood stabilizers + 1 atypical or 2 atypicals + mood stabilizer Kowatch RA et al. Clinical Manual for the Management of Bipolar Disorder in Children and Adolescents. Arlington, VA: American Psychiatric Publishing, Inc; 2008. Copyright © The REACH Institute. All rights reserved. Lithium Use • Target dose of 30 mg/kg/day – Start outpatients 25 mg/kg/day – Serum level of 0.9 -1.1 mEq/L • Onset of action: 7-14 days – Full efficacy in 6-8 Weeks • Side effects – Weight gain/Exacerbation of Acne/Enuresis/Hypothyroidism • Baseline labs: – CBC/diif, pregnancy, EKG, renal & thyroid function, calcium • Q 6 Months – Lithium Level, TSH, BUN, serum creatinine Copyright © The REACH Institute. All rights reserved. Management of Common Lithium Side Effects Copyright © The REACH Institute. All rights reserved. Divalproex Sodium Use in Children • Target dose of 20 mg/kg/day – Start outpatients at 15 mg/kg/day – Serum level of 80-120 mg/mL • Onset of action: 7-14 days – Full efficacy in 4-6 weeks • Labs: pregnancy, CBC, platelets, LFTs • Monitor for PCOS Copyright © The REACH Institute. All rights reserved. Divalproex/Valproate Side Effects • Nausea, vomiting, diarrhea • Tremor/Myoclonus • Sedation, mental dulling • Weight gain • Hair loss, decreased platelets • Liver toxicity, pancreatitis, hyperinsulinism, polycystic ovary syndrome (PCOS) • FDA Warning Box – Hepatotoxicity: Hepatic failure resulting in fatalities has occurred in patients receiving valproic acid and its derivatives. Experience has indicated that children under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity, especially those on multiple anticonvulsants… – Pancreatitis: Cases of life-threatening pancreatitis have been reported in both children and adults receiving valproate. Copyright © The REACH Institute. All rights reserved. Depression Switching to Bipolar Disorder • Prepubertal depression BD – Limited outcome studies – 24/72 (33%) MDD children BD-I at age 20, 11/72 (11%) BD-II or hypomania (Geller et al., 2001) • Adolescent depression BD – Limited studies – 58 MDD inpatients followed up in 24 months Overall: 5/58 (8.6%) BD; 0/40 without psychotic symptoms, 5/18 (28%) with psychotic symptoms (Strober et al., 1992) – Epidemiological sample; 275 teens with MDD, < 1% BD by age 24 (Lewinsohn et al., 2000) – 5/26 (19%) of MDD adolescents had BD after ~7 year follow-up (compared to 0% of controls) (Rao et al.,1995) Copyright © The REACH Institute. All rights reserved. Switching to Bipolar Disorder with Antidepressants: • Antidepressants may induce mania in children with a bipolar diathesis – In a survey of child and adolescent psychiatrists: 10/228 (4.4%) of children under 13 y/o treated by psychiatrists switched to BD (Reichart & Nolen, 2004) – Treatment for Adolescent Depression Study (TADS), of 439 12-17 year olds: 0 switches to BD after 12-week follow-up (2004) – large private insurance database, 5.4% switch rates, increased risk for youth on antidepressants and risk greatest for age group of 10-14 y/o (San Martin et al., 2004) Copyright © The REACH Institute. All rights reserved. Switching to Bipolar Disorder with Stimulants: • Concerns that stimulants may precipitate mania or destabilize children with bipolar who are not stabilized on other medications – In the Multimodal Treatment Study of Children with ADHD (MTA), children with ADHD and some manic symptoms responded well to stimulants with decrease in ADHD symptoms and without increased rates of developing bipolar disorder (Galanter et al 2003, 2005) – “Follow-back” study of children originally diagnosed and treated for “minimal brain dysfunction.” Those diagnosed with bipolar spectrum disorders as young adults had responded well to stimulants as children Those children with more comorbidities did not develop higher rates of bipolar as compared to those with uncomplicated ADHD (Carlson et al 2000) However…some medications (including stimulants) can increase mood instability and irritability Copyright © The REACH Institute. All rights reserved. Expert Panel Question & Answer • Treat or Refer? • ADHD versus BD? • When to add medications vs. switch medications? • Other questions? Copyright © The REACH Institute. All rights reserved. REMINDER: Please fill out Unit I evaluation Copyright © The REACH Institute. All rights reserved. Getting it Paid For: Self-Study Do you know how to code these cases so you will get paid? Do you know when to use these coding variations? Copyright © The REACH Institute. All rights reserved. Johnny’s Visit: Diagnosis At this visit, with information available to us, the following are all plausible as primary diagnosis: – – – – – – 799.2 Signs and sxs. Involving emotional state 799.21 Nervousness 799.24 Irritability 312.9 Disruptive behavior disorder, NOS 313.81 Oppositional defiant disorder 314.9 Unspecified hyperkinetic syndrome Copyright © The REACH Institute. All rights reserved. Johnny’s Diagnosis: Primary Without more information, cannot make formal dx. Of ADHD, bipolar disorder, generalized or specific anxiety disorder, major depressive disorder All the above certainly are possible Copyright © The REACH Institute. All rights reserved. Johnny’s Diagnosis: Secondary V40.0 Problems w/ learning V40.3 Mental and behavioral problems, other behavioral problems V61.29 Parent-child problems, other 780.50 Sleep disturbance, unspecified Copyright © The REACH Institute. All rights reserved. Johnny: Secondary Diagnosis 313.83 Academic underachievement disorder 799.51 Attention or concentration deficit, not associated with attention deficit disorder 300.20 Other isolated or simple phobia Copyright © The REACH Institute. All rights reserved. Johnny’s Visit: E/M E/M only –no report of rating scales or developmental testing Complex Medical Decision Making: – Medical Diagnosis: Extensive – Data: Extensive – Risk: High History: – HPI: 4+ – ROS: 10+ – PFSH: 2 Copyright © The REACH Institute. All rights reserved. Johnny’s Visit: 99215 I would certainly advise home care plan oversight as this child could require a lot of non-face-to-face care! Standardized rating scales could be extremely useful in obtaining information from multiple informants in a format allowing valid comparison of observations Copyright © The REACH Institute. All rights reserved. Mood Stabilizer Toolbox Mood Stabilizer Start at Target Serum Level Monitor Lithium 25-30 mg/kg/day 0.8-1.2 Meq/L Renal/Thyroid Function Valproate 15-20 mg/kg/day 85-110 μg/mL Liver/Pancreas/ PCOS Plats. Hyperammonemia Carbamazepin e 15-20 mg/kg/day 7-10 μg/mL WBC/Plats. Copyright © The REACH Institute. All rights reserved. Watch Out For Dehydration toxicity CYP450 Interactions Atypical Toolbox Atypical Antipsychotic Start at (mg/day) Target Dose (mg/day) Risperidone 0.25-0.50 1-3 Weight/Height/BMI EPS/TD Aripiprazole 2.5-5 5-20 Weight/Height/BMI EPS Quetiapine 50-100 300-600 Weight/Height/BMI Take with food, Weight/Height/BMI Assess cardiac ECG risk factors Ziprasidone 20-40 80-160 Olanzapine 5 5-20 Monitor Watch Out For Weight/Height/BMI Choles/FAs Copyright © The REACH Institute. All rights reserved. RESOURCE SLIDE FDA-Approved Bipolar Disorder Treatments in Adults Agents Manic Mixed Maintenance Depression + + + + + + + – + + + + – – – – – + – – + + + – + – + – + – – – – – – + + – – – – – – + ATYPICALS Aripiprazole (Abilify) Olanzapine (Zyprexa) Quetiapine (SEROQUEL) Risperidone (Risperdal) Ziprasidone (Geodon) OTHER Carbamazepine ER (EquetroTM) Divalproex DR (Depakote) Divalproex ER (Depakote ER) Lamotrigine (Lamictal) Lithium (Lithobid, Eskalith) Olanzapine/fluoxetine (Symbyax) Slide courtesy of Robert Kowatch M.D. Copyright © The REACH Institute. All rights reserved. RESOURCE SLIDE DBPRCTs for Pediatric Bipolar and Related Disorders: Mood Stabilizers Authors Treatment Sample Diagnosis Results Geller et al. (1998) Lithium N=25; 16.3 ± 1.2 y/o (12-18); Outpatient Bipolar I or II, substance dependency Li > PC (measures of psychopathology and urine tests) Kafantaris et al. (2001) Lithium (Discontinuation) N=40; 15.2 ± 1.7 y.o. (12-18); Inpatient BD-I manic episode, responders to Li Li = PC in preventing exacerbation (although trend in favor of Li 52.6% vs. 61.9%) Findling et al. (2005) Lithium vs. Divalproex (Maintenance; stable after Li/DVP combo) N=60; 10.8 ± 3.5 y.o. (5-17); Outpatient BD-I or II Li = DVP (time to relapse, time to discontinuation) DelBello et al. (2006) Divalproex vs. Quetiapine N=50; 15 ± 1.5 y.o. (12-18); Inpatient Bipolar-I, manic or mixed episode Quet = DVP (diff in YMRS scores); Quet > DVP (time to improvement and response/remission) Donovan et al. (2000) Divalproex (Crossover) N=20; 13.8 ± 2.4 y.o. (10-18); Outpatient *CD or ODD with explosive temper & mood lability Phase 1: DVP > PC Phase 2: DVP > PC DineenWagner et al., (2006) Oxcarbazepine N=116; 7-18 y.o.; Outpatient Bipolar-I, manic or mixed episode Oxcarbazepine = PC (change in YMRS) DelBello et al. (2005) Topiramate N=56; 6-17 y.o.; Inpatient/outpatie nt Bipolar-I, manic or mixed episode Discontinued early when adult studies failed to show efficacy; trend toward improvement BD Divalproex ER = Placebo; 4 week study only; >50% dec YMRS; DVP = 24%; Placebo = 28% ns; UNPUBLISHED DATA Abbott; Unpublished data Divalproex ER N=150; 10-17 y.o. Copyright © The REACH Institute. All rights reserved. RESOURCE SLIDE Industry DB Placebo RCTs for Pediatric Bipolar and Related Disorders: Atypicals Study/ Sponsor Ref N Olanz./ Lilly Tohen Am J Psych. 161 Risper./ Janssan AACAP 2007 Aripip/ BMS Duration (Days) Dose (mg/day) Response Rate (YMRS) Mean Weight Gain (kg) DBPCRT 2:1 21 10.4 +4.5 49% 3.66 +2.18 BPD I Manic, Mixed DBPCRT 1:1:1 21 0.5-2.5 3-6 59% 63% 1.9 1.4 10-17 BPD I Manic, Mixed DBPCRT 1:1:1 28 10 30 45% 64% 0.9 0.54 M 10-17 BPD I Manic DBPCRT 1:1:1 21 400 600 64% 58% 1.7 M 10-17 BPD I Manic, Mixed DBPCRT 2:1 28 80-160 -13.83 (Zipras) -8.61 (PBO) - Sites Age Range Yr. DX 26 10-17 BPD I Manic, Mixed 169 M 10-17 ACNP 2007 296 M Que/ AstraZeneca ACNP 2007 284 Zipras/ Pfizer APA 2008 238 Design Copyright ©2014The REACH Institute. All rights reserved. RESOURCE SLIDE Other DB Placebo RCTs for Pediatric Bipolar and Related Disorders: Atypicals Authors DelBello et al. (2002) Treatment Quetiapine as adjunct to Divalproex Sample Diagnosis Results N=30; 12-18 y.o. Bipolar-I, manic or mixed episode Significant decreases in YMRS scores after 6 wks. N=43; 8-17 y.o. BD-I or II and comorbid ADHD? Aripiprazole > Placebo for YMRS Did not improve ADHD symptoms UNPUBLISHED DATA Luis Rohde, Unpublished Data Aripiprazole Copyright © The REACH Institute. All rights reserved. RESOURCE SLIDE. Treatment Options for Pediatric Bipolar Disorder: Selected Open Trials Authors Treatment Sample Diagnosis Results MOOD STABILIZERS Kafantaris et al. (2003) Lithium N=100; 15.2 ± 1.9 y.o. (12-18); Inpatient BD-I manic or mixed episode ≥33% improvement on YMRS: 63%; 26% remission Patel et al. (2006) Lithium N=27; 15.6 y.o. (1218); Inpatient Bipolar; during depressive episode ↓ CDRS-R; 48% response; 30% remission Kowatch et al. (2000) Lithium vs. Divalproex vs. Carbamazepine N=42; 11.4 y.o. (618); Outpatient Bipolar-I or II All three efficacious; DVP > Li = CBZ (response rates and effect size) Pavuluri et al. (2006) Lithium (+ risperidone for non-responders) N=38; 11.4 ± 3.8 y.o. (4-17); Outpatient Preschool-onset bipolar ≥50% decrease on YMRS: 17/38 on Li alone; 18/21 with risperidone Findling et al. (2006) Lithium/Divalproex (after success w/ Li/DVP and relapse w/ monotherapy) N=38; 10.5 y.o. (517); Outpatient Bipolar-I or II 34 (89.5%) responded Dineen-Wagner et al. (2002) Divalproex N=40; 12.1 ± 3.6 y.o. (7-19); In/Outpatient Bipolar-I or II, manic, mixed, or hypomanic 22 (61%) improved on YMRS Chang et al. (2006) Lamotrigine (alone or added to current medications) N=20; 15.8 ± 1.7 y.o. (12-17); Outpatient Bipolar- I, II, NOS; during depressive episode 16 (84%) improved on CGI; 12 (63%) ↓ CDRS-R; 11 (58%) remitted Biederman et al. (2005) Risperidone N=30; 10.1 ± 2.5 y.o. (6-17) Bipolar- I, II or NOS 70% response (based on CGI); ↓ YMRS scores Frazier et al. (2001) Olanzapine N=23; 10.3 ± 2.9 y.o. (5-14); Outpatient BD-I manic, mixed, or hypomanic Response rate: 14/23 (61%) ATYPICALS Copyright © The REACH Institute. All rights reserved. RESOURCE SLIDE Higher Level of Suspicion • Family history of mood disorders • Red Flag symptoms that occur together • Early age of onset for depression • Mood disorder with psychotic features • Recurrent depressive episodes resistive to treatment • Episodic presentation of ADHD Copyright © The REACH Institute. All rights reserved. RESOURCE SLIDE DSM-5 Hypomanic Episode • A distinct period of sustained elevated, expansive, or irritable mood for 4 days • At least three: – Inflated self esteem or grandiosity – Decreased need for sleep – More talkative than usual – Flight of ideas or racing thoughts – Distractibility – Increase in goal-directed activity or psychomotor agitation – Excessive involvement in pleasurable activities with potential for painful consequences • Unequivocal change in functioning observable by others • Does not cause a marked impairment in occupational or social functioning or necessitate hospitalization Copyright © The REACH Institute. All rights reserved. RESOURCE SLIDE Mania vs. Hypomania Criteria Mood Symptoms Duration Number of Symptoms Impairment Manic Episode Hypomanic Episode “DISTINCT PERIOD OF Abnormally & persistently elevated, expansive, or irritable mood.” Same 7 days At least 4 days 3 or more (4 if only irritable) Same Marked Does not cause marked impairment; unequivocal change in functioning; observable by others Copyright © The REACH Institute. All rights reserved. RESOURCE SLIDE Variations in BP Illness Courses Bipolar I Disorder: Depression Followed by Mania Bipolar I Disorder: Single Manic Episode Severe Moderate Mild Time ----> Mild Time ----> Euthymic Depression Euthymic Depression Moderate Mild Moderate Severe Time Bipolar II Disorder: Depression Followed by Hypomania Mild Moderate Severe Time Mood Cycling Across A Lifetime MANIA Mania Severe DEPRESSION Moderate Mild Depression Euthymic Mild Moderate Severe Time Copyright © The REACH Institute. All rights reserved. Time Copyright © The REACH Institute. All rights reserved. Mania Mania Severe RESOURCE SLIDE Distribution of Reported BD Age of Onset (yr.) Goodwin & Jamison 2007 Copyright © The REACH Institute. All rights reserved. RESOURCE SLIDE: Mood Swings Quick Guide Copyright © The REACH Institute. All rights reserved. RESOURCE SLIDE: Rates of Disorder: Children of Bipolar Parents vs. Control Parents 60 52 Bipolar Offspring 50 40 30 Control Offspring 29 26 24 21 17 % 20 11 10 4 11 0.8 11 4 3 3.6 0 Birmaher et al Arch Gen Psychiatry 2009:6 Copyright © The REACH Institute. All rights reserved. RESOURCE SLIDE: Red Flag Symptoms Symptom Rages/Aggression Not Bipolar When told “no”, short, 5-10 min. Possibly BP Disorder or BP Spectrum 4-5 Xs/day, hours at a time, little provocation, “Egg Shell” sign Decreased Need for Initial/middle insomnia Sleep because of anxiety 3-4 day periods of “I only slept 4 hours and am feeling fine.” Spontaneous Mood Shifts Silly/giddly for hours in the AM; depressed and suicidal in the PM Moody/angry around sibs and parents High Risk Behaviors Project X Grandiosity “I can get into college somewhere with my 2.0 GPA” Agitation with Antidepressant/SSR Not if it resolves Is Risky Business “I don’t need to go to college to start the next Facebook” Possibly, if manic SXs continue after SSRI is stopped. Copyright © The REACH Institute. All rights reserved. RESOURCE SLIDE: The Diagnosis of Bipolar Disorder in Children & Adolescents… A Clinical Diagnosis Screening Instruments CBCL or Parent GBI Helpful, but not Diagnostic Sensitive but not Specific Interview of the Parent & Child/Adolescent Requires the clear history of an EPISODE, different from the child’s normal self Family History Medical History Past Responses to Psychotropics? Copyright © The REACH Institute. All rights reserved. RESOURCE SLIDE: Pharmacologic Treatments for Pediatric Bipolar Disorder: A Review & Meta-analysis. Liu HY, Potter MP, Woodword Y, et. al. • PubMed from 1989 through 2010 for open-label and randomized controlled • Trials published in English on the pharmacotherapy of pediatric mania. • 46 open-label and randomized clinical trials of antimanic agents in pediatric bipolar disorder encompassing 2,666 subjects Copyright © The REACH Institute. All rights reserved. Copyright © The REACH Institute. All rights reserved. RESOURCE SLIDE: Liu et al., 2011 Pharmacotherapy of Juvenile Bipolar Disorder: # of Studies, # of Subjects, & Treatment Type Copyright © The REACH Institute. All rights reserved. RESOURCE SLIDE: Mood Stabilizers Copyright © The REACH Institute. All rights reserved. RESOURCE SLIDE: Mood Stabilizers vs. Antipsychotics Copyright © The REACH Institute. All rights reserved. RESOURCE SLIDE: Mood Stabilizers Traditional New/Novel * Lithium Valproate (Sodium Divalproex) Carbamazepine Gabapentin Lamotrigine Topiramate Tiagabine Oxcarbazepine Levetiracetam Zonisamide * Not recommended for PCPs’ initiation Copyright © The REACH Institute. All rights reserved.