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Bipolar Disorder

Pathways. Bipolar Disorder. from Jamison KEY: H= Asylum or psychiatric hospital; S= Suicide; SA = Suicide Attempt

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Bipolar Disorder

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  1. Pathways Bipolar Disorder

  2. from Jamison KEY:H= Asylum or psychiatric hospital; S= Suicide; SA = Suicide Attempt WritersHans Christian Andersen, Honore de Balzac, James Barrie, William Faulkner (H), F. Scott Fitzgerald (H), Ernest Hemingway (H, S), Hermann Hesse (H, SA), Henrik Ibsen, Henry James, William James, Samuel Clemens (Mark Twain), Joseph Conrad (SA), Charles Dickens, Isak Dinesen (SA), Ralph Waldo Emerson, Herman Melville, Eugene O'Neill (H, SA), Mary Shelley, Robert Louis Stevenson, Leo Tolstoy, Tennessee Williams (H), Mary Wollstonecraft (SA), Virginia Woolf (H, S) ComposersHector Berlioz (SA), Anton Bruckner (H), George Frederic Handel, Gustav Holst, Charles Ives, Gustav Mahler, Modest Mussorgsky, Sergey Rachmaninoff, Giocchino Rossini, Robert Schumann (H, SA), Alexander Scriabin, Peter Tchaikovsky Nonclassical composers and musiciansIrving Berlin (H), Noel Coward, Stephen Foster, Charles Mingus (H), Charles Parker (H, SA), Cole Porter (H) PoetsWilliam Blake, Robert Burns, George Gordon, Lord Byron, Samuel Taylor Coleridge, Hart Crane (S) , Emily Dickinson, T.S. Eliot (H), Oliver Goldsmith, Gerard Manley Hopkins, Victor Hugo, Samuel Johnson, John Keats, Vachel Lindsay (S), James Russell Lowell, Robert Lowell (H), Edna St. Vincent Millay (H), Boris Pasternak (H), Sylvia Plath (H, S), Edgar Allan Poe (SA), Ezra Pound (H), Anne Sexton (H, S), Percy Bysshe Shelley (SA), Alfred, Lord Tennyson, Dylan Thomas, Walt Whitman ArtistsRichard Dadd (H), Thomas Eakins, Paul Gauguin (SA), Vincent van Gogh (H, S), Ernst Ludwig Kirchner (H, S), Edward Lear, Michelangelo, Edvard Meunch (H), Georgia O'Keeffe (H), George Romney, Dante Gabriel Rossetti (SA)

  3. DIAGNOSIS

  4. DSM-IV-TR • Five types of episodes • Four subtypes • Four severity levels • Three course specifiers American Psychiatric Association. (2000). Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revision. Washington, DC: Author.

  5. Manic Episode Symptoms: • Inflated self-esteem or grandiosity • Decreased need for sleep • Pressured speech or more talkative than usual • Flight of ideas or racing thoughts • Distractibility • Psychomotor agitation or increase in goal-directed activity • Hedonistic interests

  6. Hypomanic Episode • Similarities with Manic Episode = • Same symptoms • Differences = • Length of time • Impairment not as severe

  7. Hypomanic Episode • Similarities with Manic Episode = • Same symptoms • Differences = • Length of time • Impairment not as severe

  8. Major Depressive Episode Symptoms: • Depressed mood (in children can be irritable) • Diminished interest in activities • Significant weight loss or gain • Insomnia or hypersomnia • Psychomotor agitation or retardation • Fatigue/loss of energy • Feelings of worthlessness/inappropriate guilt • Diminished ability to think or concentrate/indecisiveness • Suicidal ideation or suicide attempt

  9. Mixed Episode Both Manic and Major Depressive Episode criteria are met nearly every day for a least a one week period.

  10. Subtypes Bipolar Disorder I = more classic form; clear episodes of depression & mania Bipolar Disorder II = presents with less intense and often unrecognized manic phases Cyclothymia = chronic moods of hypomania & depression, often evolves into a more serious type Bipolar Disorder Not Otherwise Specified (NOS) = largest group of individuals

  11. EPIDEMIOLOGY

  12. Prevalence • Estimated between 3-6% • Subsyndromal bipolar disorder • Equal distribution across gender variables • Average age @ onset = 20 years old

  13. Course • Initial cycle typically major depressive episode • Recovery • Relapse • Rapid Cycling • Rapid cycling=4 episodes/year • Ultrarapid cycling=5-364 episodes/year • Ultradian cycling=>365 episodes/year

  14. Age at Onset • Pediatric, prepubertal, or early adolescent (prior to age 12) • Adolescent (12 - 18 years) • Adult onset (+ 18 years)

  15. IMPAIRMENTS

  16. Comorbidity • Attention Deficit Hyperactivity Disorder (ADHD) • Between 60-80%

  17. ADHD Often talks excessively Is often easily distracted by extraneous stimuli Is often “on the go” or often acts as if “driven by a motor” Criteria Comparison Bipolar Disorder (mania) • More talkative than usual, or pressure to keep talking • Distractibility • Increase in goal directed activity or psychomotor agitation Differentiation= elated mood, grandiosity, decreased need for sleep, hypersexuality, and irritable mood.

  18. Comorbidity(cont.) • Oppositional Defiant Disorder (ODD) & Conduct Disorder (CD) • 70-75% • Substance Abuse • 40-50% • Anxiety Disorders • 35-40%

  19. Suicidal Behaviors • Prevalence of suicide attempts • 40-45% • Age of first attempt • Multiple attempts • Severity of attempts • Suicidal ideation

  20. Cognitive Deficits • Executive Functions • Attention • Memory • Sensory-Motor Integration • Nonverbal Problem-Solving • Academic Deficits • Mathematics

  21. Psychosocial Deficits • Relationships • Peers • Family members • Recognition and Regulation of Emotion • Social Problem-Solving • Self-Esteem • Impulse Control

  22. TREATMENT APPROACHES

  23. MANIA Mood Stabillizers Aypical Antipsychotics Anti-Anxiety Psychopharmacological DEPRESSION • Mood Stabilizers • Anti-Obsessional • Anti-Depressant • Atypical Antipsychotics

  24. Lithium: Pharmacology • Not liver metabolized. Kidney excreted • Not protein bound • 70-80% reabsorb prox Tubule, Na comp: Na (dehydr, thiazide diuret) Li level • Excretion related to GFR:elder preg • Half-life 24 hrs (HS), steady state 5 days • Peak Levels 2 hrs, SR 4-4.5 • fast release: N/V, slow rel: diarrhea

  25. Predictors: Good Li Response • Past Li response (personal or family) • Euphoric, pure (classic) mania • Sequence Mania-Depr-Euthymia • No psychosis • No Rapid Cycling

  26. Predictors: Poor Li Response[Good response to anticonvulsants] • Mixed mania (adolescents) • Irritable mania • Secondary mania (geriatric) • Psychotic Sx • Rapid Cycling • Depression-Mania-Euthymia • Comorbid substance abuse

  27. Lithium: Common Side Effects • GI distress: upper LiCO3, lower GI SR. • Polyuria / polydipsia • Sedation-lethargy • Cognitive (memory, concentr, slow) • Wt. Gain • Poor coordination, tremor • Skin (worse acne)

  28. Lithium: Serious SE • Renal • nephrogenic diabetes insipidus • tubular interstitial nephritis • Hypothyroidism • Psoriasis (onset or worsening) • Cardiac: EKG flat T, SA dysfx, tachicardia • Li Tox. N/V/D, delirium, ataxia, stupor • Tx dyalisis if >3.0, correct fluid-electrolites

  29. Li: Interactions & Use • Li levels: • diuretics, • NSAIDs (ASA OK) • ACE-inhibitors • Starting: • Baseline Renal, TFT, HCG, EKG, UA, weight, medical Hx • 300-600 mg/day divided doses • Levels in 5 days • Increase 300-900 mg/day q 5-7 days

  30. Valproate • FDA Sz ‘78, BP ‘96 • Effective antimanic, BP depression • Therapeutic effect 2 d. level 50-125 mg/l • oral loading 20-30 mg/kg/day • Elderly & hypomania responde to lower? • Mixed, rapid cycling, schizoaffective

  31. Valproate • FDA Sz ‘78, BP ‘96 • Effective antimanic, BP depression • Therapeutic effect 2 d. level 50-125 mg/l • oral loading 20-30 mg/kg/day • Elderly & hypomania responde to lower? • Mixed, rapid cycling, schizoaffective

  32. Valproate • Increases GABA levels • Effects 2nd Messenger, Prot-Kinase-C • 80-95 % Protein bound • Liver Metabolized p450 (inhibitor) • Half life 8-17 hrs

  33. VPA: Common Side Effects • GI distress • Sedation • Liver transaminase elevation • Tremor • Hair loss • Weight gain-increased appetite • Thrombocitopenia (elders) • Teratogenic: neural tube, cranio-facial

  34. VPA: Less Common SE • Neutropenia • Coagulopathies, platelet Function • endocrine abnormalities • Amenorrhea, policystic ovary? • Hypothyroidism • Hypocortisolemia

  35. VPA: Rare Dangerous SE • Idiosincratic Hepatic Failure • lethargy, anorexia, N/V, bleed, edema • Risk: <2 yo, many anticonvuls, Dev. Delay • Remote risk in >10yo psychiatric patients • Acute Hemorrhagic Pancreatitis • Bone Marrow Supression

  36. VPA Use • Baseline: • Medical Hx, CBC-diff, LFT (LDH, SGOT, SGPT, bili, Alk. Phos, GGT), HCG, PT,PTT if bleeding abnorm, amylase? • Warn about hepatic, pancreatic, hematologic, teratogenic risks • Load 20 mg/kg/day, lower outpt hypom • Level 50-120 (check in 1-5 days) • Monitor LFT, CBC

  37. Carbamazepine • Effective antimanic, Tx-refract Depr • Onset 2 wks, antidepr 4-6 wk • Ther. Levels: 4-12 or 15 mg/L • Half life decreases to 12-17 hrs • p450 liver induction

  38. CBZ: Side Effects • Less cognitive probl than Li • Less Wt gain, hair loss, tremor than VPA • Neuro: Diplopia,blurr vision, fatigue/sed • GI: Naus/diarr, Dry mouth • Leukopenia, thrombocitopenia, rash • LFT • Agranulocytosis (, Liver fail, pancreatitis, Stevens-Johnson (exfol skin), neuroteratogenic

  39. CBZ: Interactions (Many) • p450 induction, CBZlevels of: CBZ, VPA, lamotrig, TCAs, prednisone, theophiline, warfarin, benzos, & oral contraceptives • p450 inhibitors: acetazolamide, Ca-channe blockers [diltiazem & verapamil, but not nifedipine], danazol, erythromycin, fluoxetine, isoniazid, VPA all CBZ levels

  40. CBZ: Use • Baseline: Medical Hx, CBC+diff,LFT, Renal, TFT, HCG, ferritin • Start low: • 100-400 mg/day, • 100-200 mg every several days, bid (occasionally qd) • Follow CBC, LFT • clinical monitoring more effective than labs

  41. Therapy • Psychoeducation • Family Interventions • Cognitive-Behavioral Therapy • RAINBOW Program • Interpersonal and Social Rhythm Therapy • Schema-focused Therapy

  42. Biological mechanisms • Macro • Micro

  43. MACRO • Which parts of the brain are relevant to BP

  44. ▲ volumes • amygdala • ↑ at later phases of the disease (drugs ?) (Strakowski, 2012) • ↓ at the first episode (Bitter, 2011) • VPC and striatum • ↓ volume inversely correlated with age (Blumberg, 2006; Sanches, 2009)

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