Bipolar Disorder

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Bipolar Disorder
2011-01-13 13:15:00
Bipolar Disorder PHPR521

Bipolar Disorder
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  1. What is the definition of bipolar disorder?
    a disorder of mood or affect defined by the presence of at least 1 manic episode at some point in the pts life
  2. What is the definition of mania?
    an abnormally and persistently elevated, expansive, or irritable mood that lasts at least 1 wk and causes marked impairment in functioning
  3. What is the definition of hypomania?
    an abnormally and persistently, elevated, expanxive, or irritable mood that lasts at least 4d but does not cause marked impairment in functioning
  4. What is the definition of mixed episode?
    criteria for both a major depressive episode and manic episode occur nearly every day for at least 1 wk
  5. What is the definition of bipolar Type I?
    manic episode +/- major depressive or mixed episode
  6. What is the definition of bipolar Type II?
    major depressive episode +/- hypomanic episode
  7. What is the definition of dysthymic disorder?
    chronic subsyndromal depressive episodes
  8. What is the definition of cyclothymic disorder?
    chronic fluctuations b/w subsyndromal depressive and hypomanic episodes (2y for adults; 1y for children and adolescents)
  9. What is the definition of bipolar disorder not otherwise specified?
    mood states do not meet criteria for any specific bipolar disorder
  10. What is the definition of rapid cycling?
    4 major depressive or manic episodes (manic, mixed, or hypomanic) in 12mo
  11. When does bipolar usually show up?
    • usually b/w 15 and 30
    • average age = 21
    • after 60 is rare and usually medically induced
  12. What type of bipolar episode is usually first for women?
    major depressive
  13. What type of bipolar episode is usually first for men?
  14. Which sex is more likely to have mixed, depressive, or rapid cycling?
  15. What types of bipolar is CBZ useful for ?
    mixed states, rapid cycling....but second line due to poorly tolerated SE and DI
  16. What is the most common serum concentration of CBZ?
    6-12 Mcg/ml
  17. What are the advantages of CBZ?
    • effective for broad spectrum of bipolar pts
    • ER capsules available
    • relatively cheap for standard dosage forms (cheaper than Depakote)
  18. What are the disadvantages of CBZ?
    • CNS SE not well tolerated (but can develop tolerance and dose-dependent)
    • rashes - rarely severe
    • blood dyscrasias
    • many DI
    • teratogenic
  19. What are some DI of CBZ?
    • Fluoxetine
    • Fluvoxamine
    • VPA
    • antibiotics (esp. erythro)
    • many antipsychotics
    • warfarin

    Induces it's own metabolism so check levels after couple wks
  20. Carbamazepine
    Decreased neurotransmitter turnover, increased substance P, Na+ channel blockade, et al

    • diplopia
    • blurred vision
    • nystagmus
    • ataxia
    • dizziness
    • HA
    • sedation
    • rashes
    • leukopenia
    • thrombocytopenia
    • anemia
    • aplastic anemia - very rare
    • hepatitis - very rare
  21. What antipsychotics are approved for bipolar acute mania?
    • olanzapine
    • risperidone
    • quetiapine
    • aripiprazole
    • ziprasidone
    • asenapine
  22. Which antipsychotics are good for mixed states?
    • aripiprazole
    • risperidone
    • olanzapine
  23. Which antipsychotic is approved for treatment of bipolar depression?
    quetiapine (the only first line alternative for this)
  24. Which antipsychotic is approved for maintenance treatment of bipolar?
  25. Which antipsychotic is associated with frequent akathisia?
  26. What are the concerns of using FGA's for adjunct treatment of bipolar?
    tardive dyskinesia (greater than in SCZ)
  27. What are the advantages of antipsychotics in bipolar disorder?
    • FGA's have fast onset on some behaviors (within a week)
    • helpful in partial responders and manic pts with psychotic features
    • some available as immediate release injectables
  28. Which antipsychotics are available as immediate release injectables?
    olanzapine, ziprasidone, aripiprazole
  29. What are the disadvantages of antipsychotics in treatment of bipolar disorder?
    • bipolar pts at higher risk of FGA SE than other pts (esp. TD)
    • some SGAs are VERY expensive
    • use lowest effective doses to avoid SE
  30. Lamotrigine
    anti-convulsant ("novel mood stabilizer")

    • For maintenance of stabilized patients only
    • 1st line for bipolar depression

    • Nausea
    • anorexia
    • sedation
    • tremor
    • ataxia
    • dizziness
    • HA
    • blurred vision
    • insomnia
    • aseptic meningitis - rare
    • rash (Stevens-Johnson) - tritrate SLOWLY and do not use with VPA
  31. Oxcarbazepine
    anti-convulsant ("novel mood stabilizer")

    fewer DI and better tolerance than CBZ

    • sedation
    • rash (benign)
    • HA
    • dizziness
    • NV
    • hyponatremia - mainly in elderly

    induces metabolism of oral contraceptives
  32. Tamoxifen
    Protein Kinase C inhibitor ("novel mood stabilizer")

    experimental ONLY for BD acute mania
  33. What does Switch mean in bipolar depression?
    time from depression to mania may be shortened by antidepressants
  34. What is first line therapy for bipolar depression?
    • Li
    • quetiapine
    • lamotrigine
    • VPA

    • any of the above + antidepressant (esp. SSRI or bupropion)
    • AVOID antidepressant monotherapy - combine with a mood stabilizer or AAP
  35. What is second line treatment for bipolar depression?
    • quetiapine + CBZ or Li
    • add CBZ to existing regimen
    • Li or VPA + lamotrigine
    • olanzapine + fluoxetine
    • Li or VPA + olanzapine

    AVOID venlafaxine, it seems to have higher risk of Switch than other ADs
  36. Quetiapine is approved for what type of depression?
    bipolar depression ONLY (not major depression)
  37. What drugs are used for bipolar disorder?
    • Li
    • VPA
    • CBZ
    • Lamotrigine
    • Oxcarazepine
    • AP
    • AD
    • BZD
    • CCB (for HTN comorbidity)
  38. How long does it take to see a response from mood stabilizers in bipolar pts?
    1-2 wks
  39. What is the efficacy of mood stabilizers in bipolar pts?
    • better for mania than depression
    • better for acute episodes than for prophylaxis
  40. Why should Li, VPA, and CBZ be avoided during pregnancy?
    they are all known teratogens
  41. Which drug is the DOC for classic, euphoric mania?
    Li, but 20-30% may not respond to tx
  42. What is the problem with taking pts off of Li or pts who are intermittently compliant?
    10% may experience withdrawal-induced refractoriness, but this is RARE
  43. Why is Li the "kineticist's dreamdrug"?
    • 100% absorption
    • 0 PPB
    • 0 metabolism
  44. How is Li excreted?
    • 96% in urine
    • 4% in sweat
    • 80% is reabsorbed at the proximal tubule
    • Cl = 0.2 x CrCl
  45. What are the target plasma concentrations of Li?
    • 0.8-1.2 meq/L for acute mania
    • 0.6-1.0 meq/L for maintenance tx
  46. When must a sample be drawn to ensure Li has reached steady state?
    4-5d after initiation of tx and 12h after last dose
  47. What are the advantages of Li?
    • yrs of experience
    • best mood stabilizer for manic or depressive (lamotrigine or quetiapine?) episodes
    • cheap
  48. What are the disadvantages of Li?
    • toxic in OD
    • teratogenic
    • requires therapeutic monitoring
    • many DI
    • many SE
  49. What are the SE of Li?
    • sedation
    • polyuria
    • polydipsia (thirst)
    • NVD
    • anorexia
    • wt gain
    • fine tremor
    • edema
    • cystic acne
    • leukocytosis
    • t-wave inversion resembling hypokalemia
  50. What are the acute toxic effects of Li?
    • persistent vomiting/diarrhea
    • muscle weakness
    • coarse tremor
    • ataxia
    • dysarthria
    • irritability or agitation
    • lethargy
    • somnolence
    • seizures
    • coma
    • death
  51. What are the chronic toxic effects of Li?
    • goitrogenic hypothyroidism (levothyroxin - but reversibility is questionable)
    • Renal tubular necrosis (stop Li)
    • diabetes insipidus syndrome (stop Li)
  52. If Li levels are 0.4-0.8 and pt has insomnia, what should be done?
    increase dose, they are not controlled (Li is sedating)
  53. What labs should be drawn prior to Li institution?
    • BUN
    • Scr
    • urinalysis
    • serum electrolytes
    • thyroid fx
    • ECG
    • CBC w/ differential
    • pregnancy test
  54. What DI should you worry about with Li?
    • NSAIDs - decrease clearance of Li (ASA and sulindac ok)
    • diuretics - increase clearance of Li (thiazides, not loops)
    • ACEI and ARBs increase Li concentrations
    • significant changes in salt intake
  55. What is first line tx for bipolar according to CANMAT?
    • Li
    • VPA
    • Aripiprazole
    • Risperidone
    • Ziprasidone
  56. What are the advantages of VPA (Depakote)?
    • well tolerated
    • efficacy includes rapid cyclers, mixed states and presence of EEG abnormalities
    • safer than Li
    • DR form is generic
  57. What are the disadvantages of VPA (Depakote)?
    • expensive (except DR)
    • not as effective for depressive episodes
    • hepatotoxic (all were in kids on multiple antiepileptics)
    • teratogenic
    • many SE
  58. What are the SE of VPA (Depakote)?
    • hyperammonemia (usually benign - monitor for hepatic and CNS toxicity)
    • wt gain
    • increased appetite or anorexia
    • NVD (use enteric coated, give w/food, or add H2 blocker)
    • cramping
    • ataxia (modify dose)
    • drowsiness/sedation (modify dose
    • tremor (modify dose or add BBL)
    • alopecia (hair loss - tolerance possible, reversible; try Zn and Se supplements)
    • menstrual irregularities
    • thrombocytopenia (modify dose)
    • elevated liver enzymes (usually benign, educate pt on signs of liver failure, modify dose, d/c if >2x normal)
    • hepatotoxicity (rare - d/c drug)
    • pancreatitis (rare - d/c drug)