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Practical Approaches for Optimizing Management of Patients with Bipolar Disorder

Practical Approaches for Optimizing Management of Patients with Bipolar Disorder. Learning Objectives. Utilize available screening tools to improve the diagnosis of bipolar disorder in primary care and mental health settings

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Practical Approaches for Optimizing Management of Patients with Bipolar Disorder

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  1. Practical Approaches for Optimizing Management of Patients with Bipolar Disorder

  2. Learning Objectives • Utilize available screening tools to improve the diagnosis of bipolar disorder in primary care and mental health settings • Appropriately apply clinical practice guidelines into the management of patients with bipolar disorder • Improve coordination of care among primary care providers and mental health specialists for patients with bipolar disorder • Enhance clinician-patient communication through the use of condition-specific education to improve outcomes and adherence

  3. Mood Disorders: DSM-IV Classification DSM-IV Mood Disorders Depressive disorders Bipolar disorders Substance-induced Due to general medical condition Dysthymicdisorder MDD BP II DepressivedisorderNOS BP I BP NOS Cyclothymia MDD = Major depressive disorder NOS = Not otherwise specified Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), 4th ed. American Psychiatric Association, 1994.

  4. Bipolar Disorder: The Ingredients MANIA HYPOMANIA* MIXED EPISODE† NORMALMOOD SUBSYNDROMAL DEPRESSION DEPRESSION *Hypomania is milder form of mania with similar yet less severe symptoms and less overall impairment. †Mixed episode is an episode that simultaneously presents symptoms of both depression and mania. Stahl SM. Essential Psychopharmacology, 2nd Edition.New York, NY: Cambridge University Press; 2000.

  5. Bipolar Terminology A distinct period of abnormally and persistently elevated, expansive, or irritable mood • Mania • Lasting at least 1 week with a significant decline in function • Hypomania • Lasting at least 4 days, (clearly different from the usual non-depressed mood), but without a significant decline in function and no psychosis American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association; 2000.

  6. Diagnostic Criteria for Major Affective Disorders (DSM-IV) *NOS = Not otherwise specified Adapted from the American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association; 2000:345-428.

  7. Spent in Specific Affective Symptoms Bipolar II Patients 86 patients followed for 13.4 years % of Weeks Ratio of 3:1 Depressed vs Manic/Hypomanic Ratio of 39:1 Depressed vs Manic/Hypomanic Judd LL, et al. Arch Gen Psychiatry. 2002;59:531-537. Judd LL, et al. Arch Gen Psychiatry. 2003;60:261-269.

  8. Racing thoughts Distractibility Flight of ideas Inattentiveness Delusions Hallucinations BipolarDisorder Symptom Domains of Bipolar Disorder Dysphoric or Negative Mood and Behavior Manic Mood and Behavior • Euphoria • Grandiosity • Pressured speech • Impulsivity • Excessive libido • Recklessness • Social intrusiveness • Diminished need for sleep • Depression • Anxiety • Irritability • Hostility • Violence • Suicide Psychotic Symptoms Cognitive Symptoms Culpepper L. Prim Care Companion J Clin Psychiatry. 2010;12(S1):4-9.

  9. Prevalence of Bipolar Spectrum Disorder: National Comorbidity Survey Replication • Nationally representative sample of 9,282 adults (≥ 20 years) • Direct interviews, Version 3.0 World Health Organization Composite International Diagnostic Interview for assessment of DSM-IV lifetime and 12-month Axis I disorders. February 2001–April 2003 • Subthreshold BPD is common, clinically significant, and underdetected • 75% of subthreshold BPD lifetime cases received no medication Merikangas K, et al. Arch Gen Psychiatry. 2007;64:543-552.

  10. Epidemiology • Bipolar disorder is estimated to affect approximately 3.7%of the US population1 • Disease onset at 15 to 24 years of age, but accurate diagnosis may take 5 to 10 years1,2 • Equal incidence in men and women2 1. Hirschfeld RMA, et al. J Clin Psychiatry. 2003;64:53-59. 2. Evans DL. J Clin Psychiatry. 2000;61(suppl 13):26-31.

  11. Bipolar Disorder Diagnosis Is Often Missed • Positive screen rate for bipolar illness: 3.7% (> 6 million people in US) • 66.8% response rate> 85,000 US Adults Surveyed No Bipolar Dx 80.2% Bipolar Dx 19.8% 3.7% 96.3% Only 20% of those with a positive screen had been told by their doctors that they had bipolar disorder Hirschfeld RM, et al. J Clin Psychiatry. 2003;64:53-59.

  12. Misdiagnosis of Bipolar Disorder 2000 NDMDA initial diagnosis (69%) 60 60 50 Depression Anxiety 40 Percent Schizophrenia 30 Cluster B 26 Alcohol abuse 20 18 17 10 14 0 NDMDA = National Depressive and Manic-Depressive Association; N = 400 Hirschfeld R, et al. J Clin Psychiatry.2003;64:161-174.

  13. Diagnostic Challenges • Bipolar disorder is a longitudinal syndrome • Prior history is often poorly documented • Absence of collateral informants • Vague diagnostic criteria • Mixed manic/depressive symptoms are common • Depression is often the first presentation • Current affective state influences perceptions and reporting • Poor memory of emotion • Comorbid conditions are common • Lack of validated biological markers Adapted from Sachs G. FOCUS. 2007;5(1):3-13.

  14. Bipolar Disorder and ADHD Common features • Impulsivity – Substance use • Attention problems – Poor school or work performance • Conduct problems – Relationship problems Distinguishing features Comorbidity more common in childhood than adult onset bipolar disorder Slide courtesy of Roger McIntyre, MD, and Robert M Post, MD.

  15. The Hazards of Misdiagnosis and Delayed Diagnosis in Bipolar Disorder Increased risk of: Treatment resistance Rapid cycling or mixed features Violent behavior; impulsive behavior Sexual and other indiscretions Worsening substance abuse Loss of job or significant other Suicide attempts or completion

  16. Factors Distinguishing Bipolar and Unipolar Depression Manning JS. Prim Care Companion J Clin Psychiatry. 2010;12(S1):17-22.

  17. Tools Differentiate Bipolar Disorder from Unipolar Depression • Screening Tools • MDQ (Mood Disorder Questionnaire) • WHO CIDI 3.0 (Composite International Diagnostic Interview) • Interview Questions Hirschfeld R, et al. Am J Psychiatry. 2000;157:1873-1875. Kessler R, et al. J Affect Disord. 2006;96:259-269.

  18. Unipolarvs Bipolar Depression • Have you experienced sustained periods of feeling uncharacteristically energetic? • Have you had periods of not sleeping but not feeling tired? • Have you felt that your thoughts were racing and couldn’t be slowed down? • Have you had periods where you were excessive in sexual interest, spending money, or taking unusual risks? →Screening Tool: Mood Disorders Questionnaire (MDQ) Perlis RH, et al. Am J Psychiatry. 2006;163:225-231. Hirschfeld RM, et al. Am J Psychiatry. 2000;157:1873-1875.

  19. The Mood Disorder QuestionnaireSelf-Report Instrument Important symptoms: • Hyper or more energetic than usual • Predominately or thematically irritable • Distinctly self-confident, positive or self-assured • Less sleep than usual • More talkative or speaking faster than usual • Racing thoughts • Easily distracted • Problems at work and socially • More interest in sex • Taking unusual risks • Excessive spending Hirschfeld RM, et al. Am J Psychiatry. 2000;157:1873-1875. Hirschfeld RM, et al. J Clin Psychiatry Prim Care Comp. 2002;4:9-11.

  20. WHO CIDI 3.0Clinician-Administered Screening Tool Euphoria Stem Question 1. Some people have periods lasting several days when they feel much more excited and full of energy than usual. Their minds go too fast. They talk a lot. They are very restless or unable to sit still and they sometimes do things that are unusual for them, such as driving too fast or spending too much money. Have you ever had a period like this lasting several days or longer? Irritability Stem Question 2. Have you ever had a period lasting several days or longer when most of the time you were so irritable or grouchy that you started arguments, shouted at people or hit people? Criterion B Screening Question 3. People who have episodes like this often have changes in their thinking and behavior at the same time, like being more talkative, needing very little sleep, being very restless, going on buying sprees, and behaving in many ways they would normally think inappropriate. Did you ever have any of these changes during your episodes of being exited and full of energy or very irritable or grouchy? Criterion B Symptom Questions 9 Questions ….. If “Yes’ Kessler R, et al. J Affect Disord. 2006;96:259-269.

  21. Bipolar vsUnipolar Depression • Comparison of data from large multicenter trials • Bipolar Depression • Family history of bipolar disorder • Earlier age of onset • Greater number of previous depressive episodes • Higher sense of “fear” on MADRS • Unipolar Depression • Sadness, insomnia, cognitive, somatic complaints and depressed behavior Perlis R, et al. Am J Psychiatry. 2006;163:225-231.

  22. Problems with Treatment of Bipolar Depression • Standard mood stabilizers much more effective for “high” than for “low” • Antidepressants can precipitate manic episode or increase mood lability • Antidepressants may be less effective (or completely ineffective) in bipolar depression

  23. Consider the Following: • The age at onset of symptoms • Frequency of previously recognized depressive episodes • Previous response to antidepressants • The presence of family members with episodes of mania/hypomania • History of attempted suicide • Comorbid substance use STABLE Resource Toolkit. http://www.cqaimh.org/pdf/tool_interview.pdf. Accessed March 2011.

  24. Lifetime Prevalence of Substance Use Disorder Highest in Bipolar Disorder 9 – 70 8 61% – 60 7 – 50 6 5 – 40 48% 47% Percent Odds Ratio 4 – 30 36% 3 33% 31% – 20 27% 2 – 10 1 – 0 0 Major Depression OCD Panic Bipolar I Bipolar II Dysthymia Schizophrenia Regier DA, et al. JAMA. 1990;264:2511-2518.

  25. Impact of Substance Abuse on Bipolar Course of Illness • Less • Compliance • Symptom remission • Treatment (lithium) response More • Early onset - unmasking • Suicidality • Mixed states • Rapid cycling • Impulsivity • Aggression • ER visits and hospitalizations • Neuronal loss? Goodwin F, Jamison K. Manic Depressive Illness 2ndEdition. Oxford University Press, NY,2007. Goldberg JF, et al. J Clin Psychiatry. 1999;60:733-740. Frye MA, et al. Mod Probl Pharm. 1997;25:88-113. Strakowski SM, et al. Int J Psychiatry Med. 1994;24:305-328.

  26. Substance Use and Switch from a Depressive Episode to Manic/Hypomanic/Mixed Episode Statistically Significant Current alcohol use disorder vs never P = 0.001 Past alcohol use disorder vs never P = 0.01 Statistically Significant Current drug use disorder vs never P = 0.005 Past drug use disorder vs never P = 0.05 Ostacher M, et al. Am J Psychiatry. 2010;167(3):289-297.

  27. Cumulative Probability of Death and Comorbid Substance Use Disorders, 1999–2006 Male Bipolar Disorder Deaths, n = 4,925 Female Bipolar Disorder Deaths, n = 6,934 1.0 1.0 0.8 0.8 0.6 0.6 Cumulative Probability of Death 0.4 0.4 0.2 0.2 0.0 0.0 20 30 40 50 60 70 80 20 30 40 50 60 70 80 Age (years) Age (years) Drug Use Disorder Alcohol Use Disorder, only No Substance Use Disorder Yoon, YH, et al. Compr Psychiatry. 2010 Dec 10. [Epub ahead of print].

  28. Screening for Substance Use/Abuse AUDIT-C • 1. How often do you have a drink containing alcohol? • Never • Monthly or less • 2-4 times a month • 2-3 times a week • 4 or more times a week • How many standard drinks containing alcohol do you have on a typical day? • 1 or 2 • 3 or 4 • 5 or 6 • 7 to 9 • 10 or more • How often do you have six or more drinks on one occasion? • Never • Less than monthly • Monthly • Weekly • Daily or almost daily Brown RL, Rounds LA. Wis Med J. 1995;94(3):135-140. Bush K, et al. Arch Int Med. 1998;158(16):1789-1795.

  29. Clinical Response for Individuals who Screen Positive for Substance Use/Dependence • Brief interventions • Increase insight and awareness • Increase motivation toward behavioral change • Referral to treatment • Access to specialty care as needed WIPHL. http://www.wiphl.com/about/index.php?category_id=3197. Accessed May 2011.

  30. Psychiatric Diagnosis and Suicide in Veterans Health Administration Patients, 1999-2006 Hazard Ratio N = 3,291,891 used VHA services during 1999; in the following 7 years, 7684 died by suicide Ilgen M, et al. Arch Gen Psychiatry. 2010;67(11):1152-1158.

  31. 12 months, NCS and NCS-R NCS NCS-R 35 31.8 31.0 30 25.4 25 22.1 20.5 18.8 20 Percent 15 10.6 9.8 10 5 0 Ideation Plan Gesture Attempt Prevalence of Bipolar I and II Among Survey Respondents With Suicide-Related Behavior NCS = 1990-1992 National Comorbidity Survey NCS-R = 2001-2003 National Comorbidity Survey Replication Kessler RC, et al. JAMA. 2005;293:2487-2495.

  32. Factors Associated With SuicideAttempts in Bipolar Illness Course of Illness Increased Cycling Severity of Depression Comorbidities Suicide Attempts Genetic Suicidal (D) and (M), Severity of Mania, More time III, Early Onset Axis I: Anxiety and Eating Disorders, Comorbidities, Axis II: A, B, C Family HX: Depression, Bipolar, Alcohol, Other Psych. Illnesses Drug Abuse, Alcohol Abuse, PTSD Suicide and Drug Abuse Problems with Health Ins, and Access to Health Care Death of Imp. Other, Lack of Confidence Occupational, Financial and Health Care Adversities Social Occupational, Financial, Legal and Housing Problems Loss of Social Support, Social Role Demands, Problems with Spouse (most recent episode) Post RM, et al. Bipolar Disord. 2003;5:310-319.

  33. Suicide Risk Assessment • 3 to 20% of patients with bipolar disorder die by suicide • 25 to 50% of patients with bipolar disorder make at least 1 attempt at • suicide • Routinely assess for suicide risk • Identify high-risk tendencies • Hopelessness and despair • Prior suicide attempts • Access to means; plan in mind • Lethality of plans or attempts • Substance abuse • Family history of suicide or suicide attempts • Acute psychosocial crises and chronic psychosocial stressors American Foundation for Suicide Prevention. http://www.afsp.org/index.cfm?fuseaction=home.viewPage&page_id=050CDCA2-C158-FBAC-16ACCE9DC8B7026C#bipolar. Accessed March 2011. APA Practice Guidelines. http://www.psychiatryonline.com/pracGuide/pracGuideTopic_14.aspx. Accessed March 2011.

  34. Suicide Behaviors Questionnaire-Revised (SBQ-R) • Have you ever thought about or attempted to kill yourself? (check one only) • 1.Never • 2. It was just a brief passing thought • 3a. I have had a plan at least once to kill myself but not try to do it • 3b. I have had a plan at least once to kill myself and really wanted to die • 4a. I have attempted to kill myself, but did not want to die • 4b. I have attempted to kill myself, and really hoped to die • How often have you thought about killing yourself in the past year? (check one only) • 1. Never • 2. Rarely (1 time) • 3. Sometimes (2 times) • 4. Often (3-4 times) • 5. Very often (5 or more times) • Have you ever told someone that you were going to commit suicide, or that you might do it? (check one only) • 1. No • 2a. Yes, at one time, but not really want to die • 2b. Yes, at one time, and really wanted to die • 3a. Yes, more than once, but did not want to do it • 3b. Yes, more than once, and really wanted to do it • How likely is it that you will attempt suicide someday? (check one only) • 0. Never 4. Likely • 1. No chance at all 5. Rather likely • 2. Rather unlikely 6. Very likely • 3. Unlikely Osman A, et al. Assessment. 2001;8:443-454.

  35. Overall Treatment Goals • Reduce acute mood symptoms • Restore psychosocial functioning • Relationships, work, school, living situation • Prevent relapse • Minimize frequency, duration, and severity of • depressive and manic symptoms • Help patients achieve their goals

  36. Treatment at Entry to STEP-BDSystematic Treatment Enhancement Program for Bipolar Disorder • Data from First 1000 Subjects • 7.5% on NO medication • Of patients taking medications • Average of 2.42 drugs • 59% on an adequate dose of mood stabilizer • 26% on antipsychotic • 44% on antidepressant without adequate mood stabilizer • 72% had significant comorbidity Simon N, et al. J ClinPsychopharmacol. 2004;24:512-520.

  37. Initiating Medical Treatment • Is the medication effective for bipolar mania (bipolar depression)? • What are the published studies? • How good are the published studies? • What about established clinical practice? • Is the medication safe? • What do the published studies suggest? • What risks are emphasized in the product information? • Is the medication tolerable? • Not entirely the same as safety • Arguably one of the strongest predictors of compliance • Is the medication practical? • Can my patient obtain the medication? • Can my patient afford to pay for, or otherwise obtain the medication? • Will this medication interact with my patient’s other medications? Adapted from Grunze H, et al. World J Biol Psychiatry.2009;10(2):85-116.

  38. Many Medications with Bipolar Mania Indication *adjunctively with lithium or divalproex ** monotherapy or adjunctively with lithium or divalproex 2010 Physicians’ Desk Reference. Available at: http://www.pdr.net.Accessed March 2011. FDA. http://www.accessdata.fda.gov/Scripts/cder/DrugsatFDA/. Accessed March 2011.

  39. Pharmacological Treatment of Acute Mania–CANMAT Guidelines Yatham LN, et al. Bipolar Disord. 2009;11(3):225-255.

  40. Simplified Algorithm for Bipolar Mania Step 1: Monotherapy with a first-line agent Step 1b: Severely ill patients might benefit from beginning with combination therapy Step 2: Add on additional agent or change monotherapy - Add second, first-line agent - Combine lithium/anticonvulsant with an atypical antipsychotic - Adjunctive benzodiazepines can be helpful Step 3: Add on additional agent - Add third-line agent - Clozapine* may be particularly effective - ECT may be particularly effective Step 4: Continue to combine interventions Step 5: Psychosocial interventions (self-management, psychotherapy, social support) Also: Psychoeducation throughout *Clozapine is not FDA-approved for bipolar mania Adapted from Yatham LN, et al. Bipolar Disord. 2009;11(3):225-255.

  41. Lithium Carbonate/Citrate for Bipolar Mania -First medication FDA approved for bipolar mania -Most algorithms include lithium as first line -Recent meta-analyses confirm lithium efficacy -Most studies recommend serum level of 0.8-1.2 mEq/L -Generally well tolerated -Very cost effective Grunze H, et al. World J Biol Psychiatry. 2009;10(2):85-116. Smith LA, et al. Bipolar Disord. 2007;9(6):551-560. Yatham LN, et al. Bipolar Disord. 2009;11(3):225-255.

  42. Lithium–Safety Adapted from Correll CU. Current Psychiatry. 2010;9(11):49-81.

  43. Valproic Acid/Divalproex for Bipolar Mania • First-line recommendation in most algorithms • Serum levels of 50-125 mg/L • Can be loaded rapidly • Might be more effective in rapid cycling • Generally well tolerated Bowden C, et al.Am J Psychiatry.1996;153(6):765-770. Grunze H, et al. World J Biol Psychiatry.2009;10(2):85-116. Yatham LN, et al. Bipolar Disord. 2009;11(3):225-255.

  44. Divalproex/Valproic Acid:Safety Adapted from Correll CU. Current Psychiatry. 2010;9(11):49-81.

  45. Carbamazepine for Bipolar Mania • Not first line in all algorithms • May be less evidence for efficacy than lithium or divalproex • Traditional recommendations called for serum levels of 4-15 µg/mL • More recent studies suggest no connection with efficacy • A lot of potential drug-drug interactions • Generally well tolerated Grunze H, et al. World J Biol Psychiatry.2009;10(2):85-116. Weisler RH, et al. J Clin Psychiatry.2004;65(4):478-484. Yatham LN, et al. Bipolar Disord. 2009;11(3):225-255.

  46. Carbamazepine: Safety Adapted from Correll CU. Current Psychiatry. 2010;9(11):49-81.

  47. Atypical Antipsychotics Approved for Bipolar Mania • - No evidence for differences in efficacy • between atypical antipsychotic medications • Medications vary a great deal in likely • adverse effects • Some evidence for greater efficacy of atypical • antipsychotic medications versus lithium and • divalproex Aripiprazole Asenapine Olanzapine Quetiapine Risperidone Ziprasidone Correll CU, et al. Bipolar Disord. 2010;12(2):116-141. Yildiz A, et al. Neuropsychopharmacology. 2011;36(2):375-389.

  48. Tolerability of Atypical Antipsychotics Adapted from McIntyre R, Konarski J. J Clin Psychiatry. 2005;66(S3):28-36.

  49. 24 22 20 16 12 8 8 4 4 0 0 0 0 4 4 8 8 12 12 16 16 20 20 24 24 28 28 32 32 36 36 40 40 44 44 48 48 52 52 One-Year Weight Gain: Mean Change From Baseline Weight 14 Olanzapine (15 mg) Olanzapine (All doses) Quetiapine Risperidone Ziprasidone Aripiprazole 12 10 8 Change From Baseline Weight (kg) Change From Baseline Weight (lb) 6 4 2 0 Weeks Nemeroff CB. J Clin Psychiatry.1997;58(suppl 10):45-49. Kinon BJ. J Clin Psychiatry.1998;59(suppl 19):18-22. Brecher M, et al. Neuropsychopharmacology. 2004;29:S109.

  50. Monitoring Protocol† for Patients Treated with Atypical Antipsychotics †More frequent assessments may be warranted based on clinical status Adapted from American Diabetes Association; American Psychiatric Association; American Association of Clinical Endocrinologists; North American Association for the Study of Obesity. Diabetes Care. 2004;27:596-601.

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