Bipolar Disorder in children and adolescents

1. Bipolar Disorderin children and adolescents E. Lila Amirali, MD, FRCPC Assistant Professor McGill University

2. Overview • Examining the validity of Bipolar in Children and Adolescents : Historical Overview, Epidemiology,Neurobiology and Genetics • Establishing the Diagnosis: Diagnostic Criteria and Challenges • Pharmacological Treatment • Psychotherapeutic interventions

3. Historical Overview • Kraepelin (1800s): 0.4% before 10 yo • Antony and Scott (1960) • Weinberg and Brumback (1976): DSM-III • Davis (1979):”softer” criteria • 1980- : adult criteria with some modifications

5. Continuity into adulthood • Review articles: • Jairam R et al, 2008 • Chang K, 2007 • Youngstrom E et al, 2006 • Carlson and Meyer, 2006 • Craney and Geller, 2003 • Harrington and Myatt, 2003

6. Epidemiology • Follow-up studies of clinical samples • High risk offspring studies (cross-sectional and longitudinal) • Continuity of MDD, dysthymia and minor depressive episodes • Does an early exposure to stimulants and/or antidepressants unmask/modify bipolar? • Pediatric bipolar remains to be validated • Duffy A, Can J Psychiatry, 2007

7. Epidemiology • 1% lifetime prevalence • 0.13% 1-year incidence • Lewinsohn et al (JAACAP 1995;34: 454-463) • Mean age of onset 11.75 (2.96) years • No difference between male and female • Suicidality: extremely HIGH risk (Geller et al,2002; Lewinsohn et al, 1995)

8. Neurobiology Neuroimaging studies: prefrontal-limbic structures and circuits Amygdala: 1. relative overactivation in children and adults with performance of emotional tasks (non-specific) 2. volume (exposure to mood stabilizers) Prefrontal Cortex: 1.Adults have decreased prefrontal gray matter (decreased neuronal and glial density in the DLPFC, decreased subgenual prefrontal gray matter and glial cell density and decreased prefrontal gray matter volumes bilaterally) but not children 2.Spectroscopy studies of prefrontal NAA (N-acetylaspartate) may be compatible with neurodegeneration, pointing to continuity across the life span. 3. Functional studies fit the model of abnormal PFC functioning (including DLPFC, medial and ventral PFC) from overactivation in childhood to decreased activation in adulthood.

10. Genetics • Candidate genes in adults: • COMT (catechol-O-methyltransferase) • SERT (serotonin transporter) NOT found to be associated with pediatric cohorts but: • small sample size (low power vs genetic differences?) • Chang K, 2007; Kloos A and Weller, 2008; DelBello and Strakowski 2006

11. Challenges for accurate diagnosis • Clinical bias against diagnosis of mania in childhood • Low base rate of bipolar in childhood • Symptom overlap with other illnesses • Developmental constraints and variability in symptom expression and clinical presentation

12. DSM IV Criteria • Manic or hypomanic episode: • Elated mood >1wk or requiring hospitalization • 3 symptoms: grandiosity(G), decreased need for sleep(S), flight of ideas(F), pressured speech/talkative(T), distractibility(D), psychomotor agitation/increased activity(I), hypersexuality/activities with bad outcomes(A) • Significantly impaired functioning or psychosis • Mass General H: DIGFAST

13. Mania • Mixed or dysphoric picture • Intense mood lability and irritability: severe mood dysregulation with multiple, intense, prolonged mood swings each day • (Findling et al, 2001; Geller at al, 2000; Wozniak et al, 1995)

14. Differential DiagnosisMedical Conditions Mimic Mania: • Temporal Lobe Epilepsy • Hyperthyroidism • Closed or open head injury • Multiple sclerosis • Systemic lupus erythematosus • Alcohol-related neurodevelopmental disorder • Wilson’s disease • JAACAP, 2005

15. Differential DiagnosisMedical Conditions Increase Mood Cycling: TCAs SSRIs SNRIs Aminophylline Corticosteroids Sympathomimetic amines (eg Pseudoephedrine) Antibiotics (clarithromycin, erythromycin, amoxicillin etc) JAACAP, 2005

16. Differential DiagnosisPsychiatric Conditions • ADHD (chronic, persistent) • Disruptive Behaviour (low self-esteem) • Conduct Disorder (chronic, lacks remorse, calculating, vindictive) • PDD spectrum (early onset, catastrophic anxiety, premorbid language and communication) • Psychosis (mood congruent)

17. Comorbidity with mania • Externalizing Disorders: 93% (88% co, 59% ao) • Depressive Disorders(MDD,DD): 60% (64% co, 76% ao) • Anxiety Disorders: 56% (44% co, 59% ao) • Substance Disorders: 0 (9% co, 35% ao) • Tic/Tourette’s: 26% (32% co, 41% ao) • Psychosis: 31% (56% co, 35% ao) • Faraone SV et al, JAACAP, 1997;36:1046-1055 • CO: child onset • AO: adolescent onset

18. Mania • Elated mood • Grandiosity • Irritability (MDD, ADHD, ODD, Anxiety) • Hyperactivity/agitation (MDD, ADHD, Anxiety) • Distractibility (MDD, ADHD, Anxiety) • Flight of ideas (ADHD, Communication Dx) • Poor judgment (ADHD/impulsivity) • Reduced sleep (MDD, ADHD, Anxiety) • FIND: frequency, intensity, number, duration

19. Diagnosis • Careful history, medical history, substance abuse, family psychiatric history, current level of functioning and MSE with symptom scales that address: • ADHD • Depression • Mania • Social phobia • PDD • Psychosis

20. Diagnosis • “Rages”:monitor frequency, intensity, duration and precipitating factors • Multiple informants: parents, school, extracurricular activities • Prospective Mood Charting: Daily logs tracking mood, energy, sleep and unusual behavior • Timeline for Comorbidity: BAMO (behavior, anxiety, mood and other) (Cerel and Fristad, 2001)

21. Diagnosis 1. Structured Interviews • Children’s Interview for Psychiatric Syndromes (ChIPS) • Diagnostic Interview Schedule for Children (DISC) • Diagnostic Interview for Children and Adolescents-Revised (DICA-R) 2. Parent /Teacher/Child Rating Scales • Child/Adolescent Symptom Inventory • CBCL/YSR • Conners Rating Scale 3. Interview Scales • Young-Mania Rating Scale (Y-MRS) • Children’s Atypical Development Scale

22. Course and Prognosis • High Rate of Relapse • > 2 episodes over the 5-year follow-up • More prolonged early course • Less responsive to treatment • Approximately half are significantly impaired • Comorbid Substance Abuse further increases the risk of suicide

23. Pharmacological treatment Acute Phase: • Min of 4-6 weeks at therapeutic blood levels and/or adequate dose for each medication trial (up to 8 weeks for lithium) • Algorithm for BPD-1, Manic or Mixed without psychosis: monotherapy plus augmentation, progressing to combination treatment. Finally ECT and clozapine are the final choices. • Monotherapy: Mood Stabilizers or Atypical Antipsychotics • JAACAP, 2005

24. Pharmacological treatment Acute phase • Algorithm for BPD-1, Manic or Mixed with Psychosis: mood stabilizer and Atypical, followed by augmentation and combinations • Algorithm for BPD-1 Depressed: Lithium, SSRI and Bupropion as adjunctive treatment after mood is stabilized, CBT, IPT, DBT. Lamotrigine still used with precautions. • JAACAP, 2005

25. Treatment of Comorbid Disorders ADHD: • Treat bipolar first to stabilize the mood • Use the stimulants very carefully • Psychosocial interventions, including parent behavior management and school consultation and support

26. Treatment of Comorbid Disorders ODD and CD: • Mood Stabilizers and Atypicals • Parent behavior Management • Stimulants, if ADHD comorbid • Consider treating the Substance Abuse, if comorbid • Consider residential setting for treatment

27. Treatment of Comorbid Disorders Anxiety Disorders: • Careful use of SSRIs. May need to use a mood stabilizer first. • CBT Substance abuse: • Treat for both simultaneously • Lithium may be an option (Geller et al, 1998) • Consider Rehabilitation • Family therapy

28. Pharmacological Treatment Maintenance/ Continuation: • Panel recommendation to continue for a min of 12-24 months after remission • Factors to consider: severity, clarity of the diagnosis, history of suicidal behavior, severe aggression and psychosis • Tapering slowly, at the least stressful time, in the most stable, supportive and adequately monitoring environment

29. Pharmacological Treatment Monitor: • Weight gain and Diabetes (fhx of obesity, cardiovascular disease, diabetes, hypertension and dyslilidemia, BMI, waist circumference, BP, fasting lipid profile) Reassess at 4, 8 12 wks • Cognitive Side Effects (neuropsychological evaluation) • Polycystic Ovary Syndrome(Initial menstrual hx and subsequent charting, pelvic ultrasound) • Thyroid function for Lithium and Pancreatitis for Divalproex • Movement disorders and prolactine for antipsychotics

30. Psychotherapeutic Interventions • Psychoeducation • Cognitive Behavioral Therapy (Adult controlled studies : Cochran, 1984, Perry 1998, Scott, 2001, Lam, 2003 and 2004, Colom 2003 Miklowitz, 2003) • Interpersonal Therapy and Social Rhythm Therapy (Frank) • Family Focused Treatment (Miklowitz)

31. Bipolar Disorder Model (Goodwin, 1990) Biological vulnerability Non compliance Rx Disturbed Social Rhythm Event with personal significance Disturbed Sleep Mania

32. CBT Model Environment thoughts body behavior feelings

33. CBT Model for Bipolar Disorder (Scott, 2001) Mood Changes Mania Physical Symptoms Cognitive Changes Insomniaoverestimation of the abilities underestimation of risk Stress Behavioral Changes sexual promiscuity Psychosocial Problems Legal problems Psychosocial Dysfunction

34. Intervention Strategies • Evaluation • Problem List and Goals • Psychoeducation • Self-observation, life routines and Sleep • Medication Compliance/Adherence • Early identification and management of the prodromal symptoms • Prevention and treatment of comorbidities • Focus on the Cognitive Vulnerability • Social and Family Aspects

35. Life Chart Severe Moderate Light Mania Depression Light Moderate Severe Events Medication School/Work

36. Problem List and Goals Problems Goals Accept the diagnosis/uncertainty Discuss the illness Prevent Relapse Recognize the signs and symptoms and plan the follow-up School attendance Plan support and setting Substance abuse Rehab and support

37. Psychoeducation • Symptoms and their consequences • Causes • The role of stress • Evolution of the illness • Treatment and prognosis • Encourage active participation in the treatment plan • Educational books and pamphlets/ other resources (www.bpkids.org)

38. Psychoeducation Risk Factors Protective Factors Substance abuse Medication Bad sleeping Habits Good social and family support Regular daily routines Use of mental health resources Stressful events Good communication skills Conflict or family distress Problem resolution

39. Self-observation and stabilization of Social rhythms Life chart and mood chart to make the link between: • Symptoms • Daily routines (sleeping, eating, activities, stimulation) • Treatment • Events Help the patient to see the difference between the euthymic/ depressive/ manic /hypomanic state

40. Prevention Strategies Biological: • Medication • Avoid stimulants Behavioral: • Planning of activities (adequate sleep, more quiet time, lower stimulation activities) • Minimize environmental stimulation • Relaxation • Take the time to do things (sit down to eat, speak more slowly etc) • Avoid confrontations Social: • Make the intervention plan with the collaboration of the family • Make rules in order to avoid impulsive actions

41. Prevention Strategies Cognitive: • Self-talk (“relax...” “One thing at a time”) • Cards and post-it (“ write down a good idea that worked for you”) • Before making a decision: cost-benefit analysis(2 columns) • Delay at least 48 hours any big decision, get feedback from 2 other people • Anticipatory Problem resolution • Imagine and prepare for the negative consequences

42. Cognitive restructuring During a manic episode: • Why do I have to act now? Could this wait? • Did I already have ideas that sounded great at the time but that ended up disastrous? • What is the worst that can happen if I wait for a few days? • What would my best friend advise me to do ? What would I advise my best friend? • What can I do to make sure that this is the right decision? After the episode: • Reframe the grandiose ideas as signs of mania • Discuss the wish to remain in the manic state

43. Target the Cognitive Vulnerability Basic schemas I am not up to part Conditional schemas • Autonomy • Extreme striving attitude If I am not the best I am worthless • Perfectionism If I am not the best they won’t accept me • Need to please I have to work very hard Focusing only at work/school to make up for lost time Vicious circle Stress, fatigue, insomnia Relapse

44. How can the family help? • Help the pt to obtain services • Support the use of medication • Keep a calm and tolerant atmosphere at home • Have realistic expectations • Encourage participation in the treatment process and diminish stress • Problem resolution • Express positive emotion • Active listening • Encourage proper assertiveness and appropriate expression of negative emotion Miklowitz, 1997

45. Conclusion • Much more common than once thought • Still rare in children • Very often comorbid • Very severe consequences • Important role for medication and psychotherapy, individual and family