Bipolar Disorder in Adolescents: What Primary Care Providers Need to Know Moira Rynn, MD Associate Professor of Clini

1. Bipolar Disorder in Adolescents: What Primary Care Providers Need to KnowMoira Rynn, MDAssociate Professor of Clinical PsychiatryDeputy Director of ResearchNew York State Psychiatric Institute/Columbia UniversityPamela Murray, MD, MHP, FAAPChief of Adolescent MedicineCo-Chair of the Division of General Pediatrics & Adolescent MedicineWest Virginia University School of MedicineFebruary 29, 2012

2. Presentation Outline Defining the illness Epidemiology Signs and Symptoms Risk Factors Comorbid Diagnoses (psychiatric & medical) Consequences if Untreated Presentation in the Primary Care Setting Treatment Modalities Coordination of Care

3. Definition of Mania A distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting at least 1 wk (or any duration if hospitalization is necessary). Must be severe to cause marked functional impairment or to necessitate hospitalization to prevent harm to self or others May or may not occur with psychotic features

4. Definition of Mania During this mood phase, 3 of the 7 following symptoms, or if mood is only irritable, 4 of 7, must be present to a significant degree: 1. Inflated self-esteem or grandiosity 2. Decreased need for sleep (e.g., feels rested after only 3 hrs of sleep) 3. More talkative than usual or pressure to keep talking 4. Flight of ideas or subjective experience that thoughts are racing 5. Distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli) 6. Increase in goal-directed activity (socially, at work or school, or sexually) or psychomotor agitation 7. Excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments)

5. Definition of Hypomania A distinct period of persistently elevated, expansive, or irritable mood, lasting throughout at least 4 days, that is clearly different from the usual non-depressed mood. Clearly different from usual baseline mood state Clear change in functioning that is uncharacteristic for that individual However, the impairment is such that hospitalization is not indicated and there are no symptoms of psychosis Same required number of symptoms as in Mania

6. Definition of Mixed Episode The criteria are met both for a Manic Episode and for a Major Depressive Episode (except for duration) nearly every day during at least a 1-week period The mood disturbance is sufficiently severe to cause marked impairment in occupational functioning or in usual social activities or relationships with others, or to necessitate hospitalization to prevent harm from self or others, or there are psychotic features The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication, or other treatment) or a general medical condition (e.g., hyperthyroidism) Note: Mixed-like episodes that are clearly caused by somatic antidepressant treatment (e.g., medications, electroconvulsive therapy, light therapy) should not count towards a diagnosis of Bipolar I Disorder

7. Bipolar Disorders Bipolar I Disorder: one or more Manic or Mixed Episodes, usually accompanied by Major Depressive Episodes Bipolar II Disorder: one or more Major Depressive Episodes accompanied by at least one Hypomanic Episode

8. Bipolar Disorders Cyclothymic Disorder: at least 2 years of numerous periods of hypomanic symptoms that do not meet criteria for a Manic Episode and numerous periods of depressive symptoms that do not meet criteria for a Major Depressive Episode Bipolar Disorder Not Otherwise Specified: included for coding disorders with bipolar features that do not meet criteria for any of the specific Bipolar Disorders (or bipolar symptoms about which there is inadequate or contradictory information)

9. Epidemiology

11. Antipsychotic Medication Prescriptions

12. Mood States

13. Adolescent Symptoms of Bipolar Disorder Elevated, expansive, or irritable mood Grandiosity Decreased need for sleep Racing thoughts Poor judgment or hypersexuality Distractibility Pressured speech Comoridity predicts functional impairment and age of onset duration Comoridity predicts functional impairment and age of onset duration

14. Younger Children Irritability and belligerence than euphoria Many diagnosed with ADHD and ODD Difficulty sleeping Aggression At baseline very ill (explosive)

15. Comparison Between Bipolar Disorder and ADHD 60 outpatient children with bipolar disorder (mean age = 11.0 years) 60 outpatient children with ADHD (mean age = 9.6 years)

16. Distinction Between Bipolar Disorder and ADHD Bipolar disorder group had the following as compared to the ADHD group Elevated mood Grandiosity Hypersexuality Decreased need for sleep Racing thoughts

17. Bipolar Disorder vs. ADHD Symptoms of bipolar disorder mistaken for ADHD symptoms: High energy Short attention spans Low tolerance for frustration Suspect bipolar disorder instead of ADHD if: Disruptive behaviors appear later in life (after 10 years of age) Disruptive behaviors come and go and tend to occur with mood changes The child has periods of exaggerated elation, depression, no need for sleep, and inappropriate sexual behaviors The child has severe mood swings, temper outbursts, or rages The child has hallucinations or delusions There is a strong family history of bipolar disorder

18. Bipolar Mood State vs. ADHD

19. Non-episodic Irritability Symptoms: chronic versus episodic Elation versus irritability There are children suffering from severe irritability and ADHD symptoms without distinct mood episodes

20. Normal Child vs. Child Mania: Elated Mood

21. Normal Child vs. Child Mania: Grandiose Behavior

22. Normal Child vs. Child Mania:Decreased Need for Sleep

23. Normal Child vs. Child Mania:Racing Thoughts

24. Normal Child vs. Child Mania:Hypersexual Behaviors

25. Risk Factors � Why Family History? Most highly familial of psychiatric disorders When a parent has bipolar disorder increased risk of Bipolar spectrum disorder (BPSD) in offspring (OR=13) 90% of school-age children do not have BPD 2x risk for mood and disruptive behavior disorders Increased risk with Antecedent anxiety and disruptive behavior disorders Increased genetic load - 2 parents with bipolar disorder Earlier age onset of depression in parent(s) Absence of clinically useful genetic/metabolic markers Birmaher et al, 2009 Pgh bipolar offspring study (n-338) Birmaher 2009 Bpsd- bipolar spectrum disorders (I,II oe NOS) Not always sure that diagnosis or medication is correct, but still helpful clues 2 parent risk � Goldstein 2010Pgh bipolar offspring study (n-338) Birmaher 2009 Bpsd- bipolar spectrum disorders (I,II oe NOS) Not always sure that diagnosis or medication is correct, but still helpful clues 2 parent risk � Goldstein 2010

26. Risk Factors � Getting the Family History History of depression or bipolar disorder in parent or first degree relative Mania Diagnoses Medications Medication response Hospitalizations Legal problems Suicides Substance use Pgh bipolar offspring study (n-338) Birmaher 2009 Bpsd- bipolar spectrum disorders (I,II oe NOS) Not always sure that diagnosis or medication is correct, but still helpful cluesPgh bipolar offspring study (n-338) Birmaher 2009 Bpsd- bipolar spectrum disorders (I,II oe NOS) Not always sure that diagnosis or medication is correct, but still helpful clues

27. Risk Factors: Premorbid Psychiatric Diagnoses Previous psychiatric disorders Depression 15-20% develop BD in 3-6 years of depression (MDD) diagnosis Rapid onset, psychotic features, treatment-associated mania, family burden of mood disorders Anxiety Oppositional defiant and conduct disorders (ODD/CD) ADHD Pseudo-ADHD - non-sleeping, dysregulated, aggressive child

28. Risk Factors Severe stressors Exposure to violence Prenatal and perinatal factors Prenatal exposure to drugs � 6-fold risk Birth complications Timing of puberty Early puberty may be risk factor for girls Chronic illness Increased incidence with epilepsy, inflammatory bowel disease, Type 1 diabetes Pavuluri 0 case control 2006Pavuluri 0 case control 2006

29. Psychiatric Comorbidities Influence Treatment Response ADHD and BPD Decreased response to mood-stabilizing medications Substance use disorder and BPD Increased suicide attempts, legal problems and teen pregnancies Psychiatric comorbidity Greater depression severity Reduced efficacy of anti-manic treatment Sub use risks, Hunt 2009Sub use risks, Hunt 2009

30. Psychiatric Comorbidities are Normative Pediatric and adolescent population ADHD (62%) ODD (53%) Anxiety disorders (27%) Conduct disorder (19%) Substance use disorders (12%) Adults - 2 or more other psychiatric conditions Anxiety Substance use disorder (33-65%) Meta-analysis of children by Kowatch (2005); more adhd in prepubertal, more panic, conduct and substance problems in adols Meta-analysis of children by Kowatch (2005); more adhd in prepubertal, more panic, conduct and substance problems in adols

31. Consequences of Untreated Bipolar Disorder Depression is the dominant mood in BPD Disengagement, hopelessness School/work underachievement and failure Attendance Neurocognitive functioning Classroom placement and environment Medication effects Peer and family relationship problems Long-term educational and social difficulties

32. Consequences of Bipolar Disorder Manic behaviors and consequences Sex, sexting, spend, squander, sneak, suicide, substances, sleeplessness, superpowers Substance abuse, antisocial behavior, high-risk sexual behavior Legal complications Suicide ideation, attempts, completed suicide Accidental injury and death

33. Presentation in Primary Care Clinical Vignette: A 16 year old boy was first treated for ADHD at the age of 9. His parents have maintained his ADHD medication, but are now concerned about his �mood swings�. His mood alternates between irritable apathy and an impulsive high energy state that requires adult redirection. His parents report concern about alcohol and drug use. They are worried he is recently sexually active. His sleep is an ongoing concern. They don�t know his friends or where he is much of the time�. They don�t know his friends or where he is much of the time�.They don�t know his friends or where he is much of the time�.

34. Presentation in Primary Care Parent/provider questions Is ADHD a risk? Is ADHD the correct diagnosis? Is irritability a symptom of another problem? Is his high energy, the absence or irritability/low energy or true excess? Is substance use the underlying problem or a co-morbidity? Is his sexual interest/activity developmentally appropriate � or out of the norm? Is is sleep cycle shifted or is his sleep requirement reduced? What else is he doing that we don�t know about? What is going on inside of his head?

35. Screening Tools Child Mania Rating Scale-Parent Version (CMRS-P) This is an assessment tool that helps to differentiate bipolar disorder from other psychiatric disorders (Pavuluri et al., 2006) Altman Self-Rating Mania Scale (ASRM) A 5-item self-rating mania scale, designed to assess the presence and/or severity of manic symptoms (Altman et al., 1997)

36. Presentation in Primary Care�when it sounds like mania or BPD Mania cycles � you may not see it yourself An evaluation by a child psychiatrist/behavioral health professional is the �diagnostic test� to order when bipolar disorder is on the differential diagnosis list Medical considerations Differential diagnosis at presentation Treatment/medication side effects Known medical comorbidities Known psychiatric comorbidities Refer when you have a suspicion, not a diagnosis Sleep- decreased need, not shift Mood interferes with functioning � �too happy� or �too sad� to attend to usual activities; not more joy in the usual No goals, no controls Grandiosity, invulnerability, special abilities and talents Rage � physical, verbal aggression Mania with anti-depressants May recognize evolution and spectrum of sx over time Refer when you have a suspicion, not a diagnosis Sleep- decreased need, not shift Mood interferes with functioning � �too happy� or �too sad� to attend to usual activities; not more joy in the usual No goals, no controls Grandiosity, invulnerability, special abilities and talents Rage � physical, verbal aggression Mania with anti-depressants May recognize evolution and spectrum of sx over time

37. Presentation in Primary Care Differential diagnosis at presentation � medical/somatic causes Endocrine disorders Hyperthyroid, Cushings disease Autoimmune disorders with CNS disease Lupus, MS Infections Lyme, syphilis Systemic/metabolic disorders Wilson�s, porphyria Substance use Amphetamines, cocaine, hallucinogens, PCP, marijuana

38. Presentation in Primary Care Treatment/medication side effects Steroids Prescription stimulants Ketamine Beta-agonists Antidepressants Antiepileptic drugs Felbamate, levetiracetam Manic side effect does not diagnose bipolar disorderManic side effect does not diagnose bipolar disorder

39. Primary Care Considerations Medical comorbidities Multiple medical conditions in ~ 30% (v 8%) Metabolic syndrome components prevalent and often precede BPD diagnosis Migraines, asthma, epilepsy/neurologic conditions Obesity and overweight correlate with History of physical abuse Substance use disorders Psychiatric hospitalizations Multiple classes of mood-stabilizing medications Jerrell 2002 Evans-Lacko 2009 Goldstein 2008 - obesityJerrell 2002 Evans-Lacko 2009 Goldstein 2008 - obesity

40. Primary Care Considerations Pregnancy risk Birth control, long-acting reversible contraception Condoms, emergency contraception Preconception counseling and vitamins, especially folate Pregnancy and breast feeding Medication risk/benefit Adult medical comorbidities Cardiovascular disease Increased prevalence and early onset ->excess mortality Metabolic syndrome components � hypertension, hyperglycemia, dyslipidemia, obesity Associated with more functional impairment, suicide attempts, manic and depressive episodes CV disease prevalence noted before complicating medications Fagiolini 2003 � metabolic syndrome/obesity correlatesCV disease prevalence noted before complicating medications Fagiolini 2003 � metabolic syndrome/obesity correlates

41. Treatment

42. Mood Stabilizers

43. Lithium: Adverse Events

44. Depakote: Adverse Events

45. Collaborative Lithium Trial (CoLT) Aim: To comprehensively examine lithium in the treatment of pediatric participants with bipolar I disorder Consists of four treatment phases: Phase 1 - Efficacy Phase: Randomized (2 Li: 1 placebo), 8-week, double-blind, parallel group, placebo-controlled acute trial of lithium. Ativan is the only rescue medication for this phase. Phase 2 � Long Term Effectiveness Phase (24 weeks): Responders to the efficacy phase can continue in the open label treatment with lithium, adjunctive medication is allowed as clinically indicated Phase 3 � Discontinuation Phase (28 weeks): Responders to phase 2 randomized double-blind to receive either continued treatment with lithium or placebo Phase 4 � Restabilization Phase: 8-week, open label lithium treatment for participants who experience significant deterioration during the Discontinutation Phase

46. Collaborative Lithium Trial (CoLT) http://clinicaltrials.gov/ct2/show/NCT01166425 NICHD-2005-07-2 Participating Sites: University Hospital Case Medical Center, Cleveland, OH Children�s National Medical Center, Washington, DC University of Illinois at Chicago University of Kansas School of Medicine University of Massachusetts Medical School The Zucker Hillside Hospital, Glen Oaks, NY Columbia University/New York State Psychiatric Institute

47. Atypical Antipsychotics

48. Atypical Antipsychotics: Adverse Events

49. Treatment for Bipolar Depression Psychotherapy (First line) Cognitive Behavioral Therapy (CBT) Interpersonal Psychotherapy (IPT) Family Focused Therapy Lithium SSRIs (as adjunctive treatment to mood stabalizer) Bupropion (as adjunctive treatment to mood stabilizer) Lamotrigine Divalproex ECT

50. Antidepressant Induced Mania

51. Psychotherapy for BPD Psychoeducation-based approaches Multi-Family Psychotherapy Group and Individual Family Therapy (Fristad 2002, 2005) Family-Focused Treatment (Miklowitz, 2004) Links to fewer relapses, longer delay to relapse Child and Family Focused CBT Manualized PT, CBT+FFT Dialectic Behavior Therapy Supportive Therapy Interpersonal and social-rhythm therapy (IPSRT)

52. Obtain detailed history on symptoms of elated mood, grandiosity, decreased need for sleep, hypersexuality, racing thoughts. Use screening instruments Examine for discrete mood episodes and determine baseline functioning Take a careful psychiatric family history Obtain collateral information Obtain a careful longitudinal history of the symptoms Final Points

53. Multiple therapeutic modalities Be clear about medication rationale Poly-pharmacy may be indicated Be clear on the target symptoms Measure symptom change over time from multiple informants Select a psychosocial treatment approach along with the medication treatment Final Points

54. Primary Care Medical Home Model Provide non-judgmental and supportive care Psycho-education - answer questions and concerns within your scope � recovery and recurrence are normative Denial may be part of the illness Recognize and respond to stigma around psychiatric diagnoses and care Co-manage disease and medication co-morbidities Prevention and treatment of metabolic syndrome components (atypical antipsychotics, Lithium) Diet, exercise and glucophage Endocrine, dermatologic, renal, etc. side effects (e.g. Lithium) Relapse prevention/recognition

55. Management & Coordination of Care When referring to a mental health specialist: Convey results of previous assessments and intervention efforts Maintain an openness to discuss case Obtain written consent to provide to mental health specialist to convey interest and facilitate communication Track children who have been referred for specialty treatment

56. Management & Coordination of Care If family is unsuccessful in acquiring evaluation or treatment in a timely way: Offer to continue generic intervention efforts Initiate treatment for some diagnoses Not generally advised for bipolar disorder Contact mental health provider/agency directly Know when to cry �Bipolar disorder!� Expect that some of your referrals will not have that diagnosis Make periodic telephone contact to monitor for worsening or emergent problems Have emergency/urgency plan In some instances it may be necessary to use emergency procedures in order to obtain needed services.

57. Management & Coordination of Care Once specialist has met with child: Primary care clinicians need feedback Forms for exchange of information may facilitate this process Telephone, EMR and email contact may be helpful Attend to confidentiality issues Face-to-face meeting involving all providers involved in the care of the child Primary care clinicians need to know about treatment including medications Awareness of possible side effects Implement Chronic Care Model Consider your role in medication maintenance once stabile Transition plan for changing acuity, emerging adulthood, changes in schools, providers, geography, health insurance Methods used to monitor children with chronic medical conditions such as asthma and diabetes can be useful in the care of children with mental health and substance abuse conditions. �Strategies for Preparing a Primary Care Practice� describes steps in implementing chronic care methods for children with mental health problems, as for other children and youth with special health care needs.Methods used to monitor children with chronic medical conditions such as asthma and diabetes can be useful in the care of children with mental health and substance abuse conditions. �Strategies for Preparing a Primary Care Practice� describes steps in implementing chronic care methods for children with mental health problems, as for other children and youth with special health care needs.

58. Resources American Academy of Child and Adolescent Psychiatry : www.aap.org/mentalhealth Bipolar Parents Medication Guide http://www.aacap.org/galleries/default-file/aacap_bipolar_medication_guide.pdf Treatment recommendation algorithm 1). www.jaacap.com/article/S0890-8567(09)61467-2/abstract 2). http://pediatrics.aappublications.org/content/125/Supplement_3/S109.full.pdf Altman Self-Rating Mania Scale: www.cqaimh.org/pdf/tool_asrm.pdf Child Mania Rating Scale-Parent: www.dbsalliance.org/pdfs/ChildManiaSurvey.pdf PHQ-9 Scale: http://www.teenscreen.org/images/stories/PDF/PHQ-9-1-5-12.pdf Geller et al 2002 article: http://www.thebalancedmind.org/sites/default/files/geller.pdf Child & Adolescent Psychosocial Intervention Chart: http://www2.aap.org/commpeds/dochs/mentalhealth/docs/CR%20Psychosocial%20Interventions.F.0503.pdf Strategies for Preparing a Primary Care Practice: http://pediatrics.aappublications.org/content/125/Supplement_3/S87.full.pdf

59. TeenScreen National Center Contact Info: Website: www.teenscreen.org Email: teenscreeninfo@nyspi.columbia.edu AAP Contact Info: Website: www.aap.org/mentalhealth Email: mentalhealth@aap.org Contact