Bipolar Disorders

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Bipolar Disorders

  1. 1. BIPOLAR DISORDERS :(: Dapinderjit Gill, Ross University Bergen Regional Medical Center, Psych Clerkship
  2. 2. DEFINITIONS
  3. 3. BIPOLAR DISORDERDEFINITIONCharacterized by mania (i.e., have a manic or hypomanic episode) either alone or incombination with depression – Introductory Textbook of PsychiatryAny of several psychological disorders of mood characterized usually by alternatingepisodes of depression and mania – Merriam-Webster’s Dictionary Psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevate energy levels, cognition, and mood with or without one or more depressive episodes – Wikipedia.org
  4. 4. EPISODES Major Depressive Episode  5 of 9 sx. of depression (one must be depressed mood or loss of interest or pleasure) and must be present for at least 2 weeks. Manic Episode  3 of 7 sx. plus presence of an abnormally elevated, expansive, or irritable mood lasting at least one week. Mixed Episode  Full criteria for both a manic and a depressive episode be met within a 1- week period Hypomanic Episode  Elevated mood and other classic sx. that define mania but are not accompanied by delusional beliefs or hallucinations and are not severe enough to require hospitalization or markedly impair social and occupational functioning
  5. 5. CLASSIFICATIONS
  6. 6. CLASSIFICATIONSBIPOLAR DISORDERSBipolar IBipolar IICyclothymic disorderBipolar disorder not otherwise specified
  7. 7. EPIDEMIOLOGY
  8. 8. EPIDEMIOLOGYRecent National Comorbidity StudyLifetime prevalence of nearly 2% for bipolar I and II combined.More common in women than in men 3:2 but men tend to have earlieronset than womenMedian age of onset 25 yearsThe Global Burden of DiseaseBipolar disorders rank sixthamong the world’s most disabling illnesses
  9. 9. ETIOLOGY ANDPATHOPHYSIOLOGY
  10. 10. ETIOLOGY AND PATHOPHYSIOLOGYGENETICSignificantly increases rates of bipolar disorder in first degree relatives ofbipolar parentsTwin and adoption studies have provided evidence that mood disordersare genetic in addition to being familial  Monozygotic-to-dizygotic ratio approx. 4:1Genes of interest:  Associations with bipolar disorder include D-amino0acid oxidase gene (G72), brain0derived neurotrophic factor gene (BDNF), neuregulin 1 gene (NRG1), dysbindin (DTNBP1)  Genes associated with circadian rhythm (CLOCK, TIMELESS, PERIOD3) have also been implicated
  11. 11. DSM-VI-TR BIPOLARDISORDERS
  12. 12. BIPOLAR I
  13. 13. BIPOLAR I Occurrence of at least one manic or mixed episodeDSM-VI-TR Six separate criteria sets  Single Manic Episode  Most Recent Episode Hypomanic  Most Recent Episode Manic  Most Recent Episode Mixed  Most Recent Episode Depressed  Most Recent Episode Unspecified
  14. 14. BIPOLAR ISINGLE MANIC EPISODE 296.0xAPresence of only one Manic Episode and no past MDEBThe Manic Episode is not better accounted for bySchizoaffective Disorder and is not superimposed onSchizophrenia, Schizophreniform Disorder, Delusional Disorder,or Psychotic Disorder Not Otherwise Specified
  15. 15. BIPOLAR IMOST RECENT EPISODE HYPOMANIC 296.40ACurrently (or most recently) in a Hypomanic EpisodeBThere has previously been at least one Manic Episode or MixedEpisodeCThe mood sx. cause clinically significant distress or impairment insocial, occupational, or other important areas of functioningDThe mood episodes in Criteria A and B are not better accounted for bySchizoaffective Disorder and are not superimposed on Schizophrenia,Schizophreniform Disorder, Psychotic Delusional Disorder NotOtherwise Specified
  16. 16. BIPOLAR IMOST RECENT EPISODE MANIC 296.4xACurrently (or most recently) in a Manic EpisodeBThere has previously been at least one Major Depressive Episode,Manic Episode, or Mixed EpisodeCThe mood episodes in Criteria A and B are not better accounted for bySchizoaffective Disorder and are not superimposed on Schizophrenia,Schizophreniform Disorder, Psychotic Delusional Disorder NotOtherwise Specified
  17. 17. BIPOLAR IMOST RECENT EPISODE MIXED 296.6xACurrently (or most recently) in a Mixed EpisodeBThere has previously been at least one Major Depressive Episode,Manic Episode, Mixed EpisodeCThe mood episodes in Criteria A and B are not better accounted for bySchizoaffective Disorder and are not superimposed on Schizophrenia,Schizophreniform Disorder, Psychotic Delusional Disorder NotOtherwise Specified
  18. 18. BIPOLAR IMOST RECENT EPISODE DEPRESSED 296.5xACurrently (or most recently) in a Major Depressive EpisodeBThere has previously been at least one Manic Episode or MixedEpisodeCThe mood episodes in Criteria A and B are not better accounted for bySchizoaffective Disorder and are not superimposed on Schizophrenia,Schizophreniform Disorder, Psychotic Delusional Disorder NotOtherwise Specified
  19. 19. BIPOLAR IMOST RECENT EPISODE UNSPECIFIED 296.7ACriteria, except for duration, are currently (or mostly recently) met for a Manic, aHypomanic, a Mixed, or a Major Depressive EpisodeBThere has previously been at least one Manic Episode or Mixed EpisodeCThe mood sx. cause clinically significant distress or impairment in social, occupational,or other important areas of functioningDThe mood episodes in Criteria A and B are not better accounted for by SchizoaffectiveDisorder and are not superimposed on Schizophrenia, Schizophreniform Disorder,Psychotic Delusional Disorder Not Otherwise SpecifiedEThe mood symptoms in Criteria A and B are not due to the direct physiological effectsof a substance or a general medical condition
  20. 20. BIPOLAR II
  21. 21. BIPOLAR II Characterized by periods of hypomania that typically occur either before or after periods of depression but also may occur independently May lead to personal, social, or work difficulties but are not sufficiently severe to require hospitalization High rate of comorbidity with other disorders such as substance abuse Experience greater burden of depressive sx. than bipolar I
  22. 22. BIPOLAR IIRECURRENT MAJOR DEPRESSIVE EPISODES WITH HYPOMANIC EPISODES 269.89APresence (or history) of one or more Major Depressive EpisodesBPresence (or history) of at least one Hypomanic EpisodeCThere has never been a Manic Episode or Mixed EpisodeDThe mood episodes in Criteria A and B are not better accounted for bySchizoaffective Disorder and are not superimposed on Schizophrenia,Schizophreniform Disorder, Psychotic Delusional Disorder Not Otherwise SpecifiedEThe sx. cause clinically significant distress or impairment in social, occupational, orother important areas of functioning
  23. 23. CYCLOTHYMICDISORDER
  24. 24. CYCLOTHYMIC DISORDER Mildest form of bipolar disorders Mild swings between two poles of depression and hypomania In hypomania, patient is not socially or professionally incapacitated During depressed phase, patient has some sx. of depression but these are not severe enough to meet criteria a full major depressive episode
  25. 25. CYCLOTHYMIC DISORDER301.13AFor at least 2 years, the presence of numerous periods with hypomanic sx. and numerousperiods with depressive sx. that do not meet criteria for a Major Depressive Episode.BDuring the above 2 year period, the person has not been without the sx. in Criterion A formore than 2 months at a timeCNo Major Depressive Episode, Manic Episode, or Mixed Episode has been present during thefirst 2 years of the disturbanceDThe sx. in Criterion A are not better accounted for by Schizoaffective Disorder and are notsuperimposed on Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or PsychoticDisorder Not Otherwise Specified.EThe sx. are not due to direct physiological effects of substance or a general medical conditionFThe sx. cause clinically significant distress or impairment in social, occupational, or otherimportant areas of functioning
  26. 26. BIPOLAR DISORDERNOT OTHERWISE SPECIFIED
  27. 27. BIPOLAR DISORDER NOT OTHERWISESPECIFIED296.801Very rapid alternation (over days) between manic sx. and depressive sx. that meet sx.threshold criteria but not minimal duration criteria for Manic, Hypomanic, or MajorDepressive Episodes2Recurrent Hypomanic Episodes without intercurrent depressive sx.3A Manic or Mixed Episode superimposed on Delusional Disorder, residual Schizophrenia, or Psychotic Disorder Not Otherwise Specified4Hypomanic Episodes, along with chronic depressive symptoms, that are too infrequent to qualify for a diagnosis of Cyclothymic Disorder5Situations in which the clinician has concluded that a Bipolar Disorder is present but isunable to determine whether it is primary, due to a general medical condition, orsubstance induced
  28. 28. DIFFERENTIALDIAGNOSIS
  29. 29. DIFFERENTIAL DIAGNOSIS General Medical conditions  Such as hypothyroidism and SLEs Specific extrinsic factors  Drugs of abuse, sedatives, tranquilizers, antihypertensives, glucocorticoids etc. Mania vs. Schizophrenia Bereavement  presence of the sx. considered a normal reaction in this case
  30. 30. TREATMENT
  31. 31. TREATMENT Lithium, Valproate, and Carbamazepine FDA approved for acute Mania Lamotrigine and a few others are approved for maintenance treatment of bipolar disorders Other anticonvulsant drugs (gabapentin and topiramate) have been used to treat bipolar patients but have had mixed results All SGAs (expect clozapine) approved to treat acute mania, and several have received indications for maintenance treatment of bipolar disorder or as adjuncts to lithium or valproate. Electroconvulsive therapy is highly effective in treatment of manic patients when medication is ineffective
  32. 32. LITHIUMLITHIUM CARBONATE (Eskaliath, Eskalith CR)Cap: 300 mg; Manic episode  >= 12yo 1800mg/d in divided doses given TID or QID. Desired serum level 1- 1.5mEq/L  Long-term: 300mg TID or QIDTab,ER: 450mg BID  Desired serum levels of 0.6-1.2mEq/L  Pregnancy rating: C: not rated; contraindicated for breast feedingLITHIUM CITRATESyr: 300mg/5ml; Manic episode>= 12 yo 600mg TID to serum level 1-15.mEq/LLong-term: 300mg TID or QID to serum level 0.6-1.2mEq/LPregnancy rating: D: Positive evidence of risk : use only when no saferalternative exists for a serious problem; contraindicated for breast feeding
  33. 33. DIVALPROEX SODIUM (DEPAKOTE) Valproate sodium and Valproic acid in a 1:1 ratio; Tab, delay: 125mg, 250mg, 500mg Bipolar Disorder: Manic Episodes: Adult: Initial 750mg divided doses; Titrate rapidly to clinical effect; Max: 60mg/kg Hepatotoxic, teratogenic, pancreatitis Pregnancy rating: D: positive evidence of risk: use only when no safer alternative exists for a serious problem Contraindicated in breast feeding
  34. 34. CARBAMAZEPINE (EQUETRO) Cap, ER: 100mg, 200mg, 300mg Bipolar I: Acute Manic and Mixed Episodes Adult: Initial 400mg/d divided dose BID; Titrate to 200mg/d; Max: 1600mg/d Pregnancy rating: D: positive evidence of risk: use only when no safer alternative exists for a serious problem Contraindicated in breast feeding
  35. 35. LAMOTRIGINE (LAMICTAL) Chewtab: 2mg, 5mg, 25mg; Tab: 25mg, 100mg, 150mg, 200mg Bipolar I: Maintenance: Adults: Patient not taking Carbamazepine, other enzyme-inducing drugs (if pt. is on these drugs please refer to PDR):  Week 1+2: 25mg/d; Week 3+4: 50mg/d; Week 5: 100mg/d; Week 6+7: 200mg/d Serious rash, Steven-Johnson syndrome Adjust dose for hepatic and renal insufficiency Pregnancy rating: C: risk cannot be ruled out Contraindicated in breast feeding
  36. 36. ARIPIPRAZOLE (ABILIFY) Atypical antipsychotic Inj: 7.5 mg/ml; Sol: 1mg/ml; Tab: 2mg, 5mg, 10mg, 15mg, 20mg, 30mg Adults: Bipolar Disorder: Acute Manic and Mixed Episodes  PO: Initial 30mg QD; Titrate Agitation Associated with Bipolar Disorder, Manic or Mixed  Inj: Initial 9.75mg IM; Max: 30mg/d; Initiate PO therapy as soon as possible Pregnancy rating: D: positive evidence of risk: use only when no safer alternative exists for a serious problem Contraindicated in breast feeding
  37. 37. RISPERIDONE (RISPERDAL) Atypical antipsychotic Sol: 1mg/ml; Tab: 0.25mg, 0.5mg, 1mg, 2mg, 3mg, 4mg Bipolar I Disorder: Acute Manic and Mixed Episodes: Adults: Monotherapy or Adjunct Therapy with Lithium or Valproate  Initial 2-3mg QD; Titrate: increase by 1mg QD; Max: 6mg/d Adjust dose for hepatic and renal insufficiency Pregnancy rating: C: risk cannot be ruled out Contraindicated in breast feeding
  38. 38. ZIPRASODONE (GEODON) Atypical antipsychotic Cap: 20mg, 40mg, 60mg, 80mg Bipolar Disorder: Acute Manic and Mixed Episodes: Adults:  Initial 40mg BID with food; Titrate: increase to 60-80mg BID on second day of treatment and maintain 40-80mg BID Pregnancy rating: C: risk cannot be ruled out Contraindicated in breast feeding
  39. 39. QUETIAPINE FUMARATE (SEROQUEL) Atypical antipsychotic Tab: 25mg, 50mg, 100mg, 200mg, 300mg, 400mg Bipolar I Disorder: Acute Manic and Mixed Episodes: Adults: Monotherapy or Adjunct Therapy with Lithium or Valproate  Initial 100mg/d BID; Titrate: increase to 400mg/d on day 4 with increments of up to 100mg/d BID. Adjust doses up to 800mg/d by day 6 in increments of not greater than 200mg/d; Max: 800mg/d Adjust dose for hepatic insufficiency Pregnancy rating: C: risk cannot be ruled out Contraindicated in breast feeding
  40. 40. OLANZAPINE (ZYPREXA) Atypical antipsychotic; combination with Fluoxetine HCl (Symbyax, different strengths and dosages, refer to PDR) Inj: 10mg; Tab: 2.5mg, 5mg, 7.5mg, 10mg, 15mg, 20mg; Tab, dissolve: 5mg, 10mg, 15mg, 20mg Bipolar I Disorder: Acute Manic and Mixed Episodes: Adults: Monotherapy: PO: Initial 10-15mg QD Adjunct Therapy with Lithium or Valproate: Initial 10mg QD; Titrate: adjust by 5mg/d; Max: 20mg/d Maintenance: Monotherapy: 5-20mg/d Agitation associated with bipolar mania: Inj: Initial 10mg IM; Max: 3 doses of 10mg IM q2-4h. May initiate PO therapy when clinically appropriate. Pregnancy rating: C: risk cannot be ruled out; Contraindicated in breast feeding
  41. 41. TREATMENTKEY POINTSAfter an episode of mania, patient should receive maintenancemedicationAdvise the importance of getting sufficient sleep and followingsensible sleep hygiene measuressupportive psychotherapy to help them cope with consequences and maintain their self-esteem
  42. 42. THANK YOU
  43. 43. REFERENCES Donald W. Black, Nancy C. Andreasen. Introductory Textbook of Psychiatry. 5th Edition. pp. 141-168. Merriam-Webster’s Dictionary Wikipedia.org, “Bipolar Disorders”. Last accessed April 20 2011. http://en.wikipedia.org/wiki/Bipolar_disorder# Signs_and_symptoms PDR Pharmacopoeia Pocket Dosing Guide. 2007.Bristol- Myers Squibb and Otsuka America Pharmaceuticals, Inc. pp. 266- 269

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