Presentation Outline

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 APA, 2000

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) APA, 2000

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 APA, 2000

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 APA, 2000

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 APA, 2000

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) APA, 2000

9. Epidemiology Van Meter et al., 2011

10. Diagnosis of Pediatric Bipolar Disorder Moreno et al., 2007

11. Antipsychotic Medication Prescriptions Olfson et al., 2006

12. Mood States Manic Episode Symptomatic Euthymic Symptom change from Baseline Symptomatic Depressive Episode

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

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) Geller et al., 1998

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 Geller et al., 1998

17. Bipolar Disorder vs. ADHD AACAP, 2010 • 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 Manic Episode Symptomatic ADHD Baseline Symptoms Symptom change from Baseline Symptomatic Depressive Episode

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 Leibenluft et al., 2003

20. Normal Child vs. Child Mania: Elated Mood Geller et al., 2002

21. Normal Child vs. Child Mania: Grandiose Behavior Geller et al., 2002

22. Normal Child vs. Child Mania:Decreased Need for Sleep Geller et al., 2002

23. Normal Child vs. Child Mania:Racing Thoughts Geller et al., 2002

24. Normal Child vs. Child Mania:Hypersexual Behaviors Geller et al., 2002

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

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

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

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

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%)

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….

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) A5-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

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

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

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

41. Treatment Psychoeducation Psychotherapy Medication

42. Mood Stabilizers Findling, 2008 & AACAP 2010

43. Lithium: Adverse Events AACAP, 2010 Findling, 2008

44. Depakote: Adverse Events AACAP, 2010 Findling, 2008

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 Funded by NICHD

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 AACAP, 2010 & Findling et al., 2008 & Kowatch et al., 2005

48. Atypical Antipsychotics: Adverse Events AACAP, 2010

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 Kowatch et al., 2005

50. Antidepressant Induced Mania • 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)