Faculty. Disclosures. Overcoming Pitfalls in the Diagnosis of Bipolar Disorder 10/13/16. Emerging Challenges in Primary Care: 2016

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1 10/13/16 Emerging Challenges in Primary Care: 2016 Overcoming Pitfalls in the Diagnosis of Bipolar Disorder Faculty Richard H. Anderson, MD, PhD Principal Partner, St. Charles Psychiatric Associates, Midwest Research Group Clinical Faculty, Washington University School of Medicine, Department of Psychiatry St. Louis, MO 2 Disclosures Richard H. Anderson, MD, PhD serves as a speaker for Takeda Pharmaceuticals. 3 1

2 Learning Objectives After participating in the proposed educational activities, clinicians should be better able to: 1. Recognize the the high prevalence of bipolar disorder in patients who experience depression 2. Describe the high rate of misdiagnosis of patients with BD 3. Develop a knowledge of the key criteria that differentiate unipolar depression from BD 4. Provide information and tools for successful screening and recognition of patients with BD 4 Pre-Test Questions 5 Pre-test ARS Question 1 On a scale of 1 to 5, please rate how confident you would be in the diagnosis and management of a patient with Bipolar Disorder: 1. Not at all confident 2. Slightly confident 3. Moderately confident 4. Pretty much confident 5. Very confident 6 2

3 Pre-test ARS Question 2 Which of the following is true regarding the high prevalence of Bipolar Disorder in patients who experience depression? 1. Bipolar I patients are symptomatic almost half their lives 2. Depressive episodes are indistinct between Major Depressive Disorder and Bipolar Affective Disorder in a depressed episode 3. In Bipolar Disorder, patients are asymptomatic close to half of the time 4. The most common variant episode of Bipolar disorder is the depressed state 5. All of the above 7 Pre-test ARS Question 3 Which of the following is false in describing the high rate of misdiagnosis of patients with Bipolar Disorder? 1. The prevalence of bipolar disorder may be higher than previously estimated 2. 50% of individuals with positive screens for bipolar I or II disorders reported they had previously received a diagnosis of bipolar disorder from a physician 3. Up to 80% of patients who screen positive for bipolar disorder have not been previously diagnosed with bipolar disorder 4. The Mood Disorder Questionnaire (MDQ) is a validated screening instrument for Bipolar I and II disorders 88 Pre-test ARS Question 4 In developing knowledge of the key criteria that differentiate unipolar depression from Bipolar Disorder, is the following statement true or false? Depression is the initial symptom reported by the majority of patients with bipolar disorder. 1. True 2. False 9 3

4 Pre-test ARS Question 5 Which of the following statements regarding the recognition and initial management of Bipolar Disease is false? 1. Treatment of Bipolar Depression requires starting antidepressants first at illness onset to reduce suicidal risk and improve social adjustment, then adding a mood stabilizer once the depressive symptoms begin to improve 2. Bipolar disorder is most frequently misdiagnosed as unipolar depression 3. It takes up to 10 years before being accurately diagnosed in many BD patients 4. Antidepressants, in the absence of mood stabilizers, may induce mania or hypomania and worsen the course of bipolar disorder by accelerating cycling frequency 10 Primary Care Practitioners They are the backbone of America s mental health care system, providing a larger percentage of mental health care services than specialists in mental and addictive disorders In many communities, they are the only professionals with mental health care training Norquist GS, Regier DA (1996), Annu Rev Med 47: Stigma of Mental Health Diagnosis The public identifies mental illnesses with violence and danger, which trigger the desire to maintain social distance from these patients 1 The patient s perception and concern about stigma are associated with greater impairment in social functioning with persons outside of the family circle, but not with family members 2 Greater concern about stigma is associated with greater severity of mental disorder Patient withdrawal from society in response to concerns with stigma Absence of close or confiding relationships is associated with greater risk of relapse or nonremission among individuals with depression 1 Link BG et al. (1999), Am J Public Health 89(9): ; 2 Perlick DA et al. (2001), Psychiatr Serv 52(12):

5 Patient Access to Mental Health Care Socioeconomic status plays a role in patient access to mental health treatment The highest rates for bipolar disorder diagnosis are among the poorest respondents (annual income < $20,000) Majority of the participants who screened positive for bipolar disorder are not previously diagnosed by a healthcare professional, although they sought professional help for these symptoms and had been previously diagnosed with another mental health condition Poor patients are less likely to receive mental health care and, if they do, are comparatively less likely to receive treatment from a mental health specialist Das AK et al. (2005), JAMA 293(8): Potential Consequences of Unfocused Treatment Antidepressant monotherapy may worsen disease course Creation of mania or mixed states Accelerated mood cycling More suicide attempts More hospitalizations More comorbidities Greater psychosocial impairment Greater healthcare costs Goldberg JF, Ernst CL (2002), J Clin Psychiatry 63(11): ; Goldberg JF, Truman CJ (2003), Bipolar Disord 5(6): Standardized Mortality Ratio Bipolar Disorder: Untreated vs. Treated Standardized Mortality Ratios Zurich Cohort (N=406) * * 2.2* * 2.2* Neoplasm Cardiovascular Cerebro- Accidents Suicide Other All Causes vascular *p<0.001; p<0.05; Angst F et al. (2002), J Affect Disord 68(2-3): Untreated Treated 15 5

6 Need for Improved Recognition 16 Positive Mood Disorder Questionnaire for Bipolar Disorder in the Community Neither Bipolar Disorder Nor Depression Diagnosis 49% 20% 31% Diagnosed With Bipolar Disorder Diagnosed With Depression, But Not Bipolar Disorder 80% of Patients Who Screened Positive for Bipolar Disorder Had Not Been Diagnosed With Bipolar Disorder * N=85,358 participants (3.7% screened positive for BD); *49% (neither BD nor depression diagnosis) + 31% (diagnosed with depression but not bipolar disorder); Hirschfeld RM et al. (2003), J Clin Psychiatry 17 64(1):53-59; Hirschfeld RM et al. (2003), J Clin Psychiatry 64(2): Underrecognition of Bipolar Disorder in Patients in a General Medicine Clinic Patients Screened While Seeking Primary Care 10% screened positive for lifetime history of BD Depression, but Not BD Was 10% Most Common Diagnosis 79.5% N=1,146; Das AK et al. (2005), JAMA 293(8):

7 Underrecognition of Bipolar Disorder Patients Treated for Depression in a Family Medicine Clinic 649 outpatients receiving treatment for depression Screened positive for BD: 21%* Estimated bipolar prevalence among 649 depressed patients ~28% MDQ sensitivity = 58% MDQ specificity = 93%; based on SCID *Using the MDQ; Hirschfeld RM et al. (2005), J Am Board Fam Pract 18(4): Patients With BD-I Are Symptomatic Almost Half Their Lives NIMH Collaborative Depression Study Weeks Manic/Hypomanic Weeks Cycling/Mixed 9% 6% Weeks Depressed 32% 53% Weeks Asymptomatic N=146 patients followed every 6 months over 2-20 years; Mean follow-up = 12.8 years; Judd LL et al. (2002), Arch Gen Psychiatry 59(6): Percent of Time Patients With BD-II Have Depressive Symptoms NIMH Collaborative Depression Study 86 patients followed every 6 months over 13.4 years Depressed 51% Hypomanic 1% Cycling/Mixed 2% Asymptomatic 46% Judd LL et al. (2003), Arch Gen Psychiatry 60(3):

8 Longitudinal Assessment of Bipolar Disorder Is Critical Mania Polarity of Symptoms Euthymia Hypomania Subsyndromal Depression Depression Depression 22 Bipolar Hypomanic Episode Increased mental/physical activity Decreased need for sleep Talkative and/or distinctly more social Mood irritable or elated Tendency for impairment of social judgment No adequate cause for symptoms Labile Recurrent Hypersomnic, Retarded Depression Escalating Irritability a.m. HS 1-3 Days Modal Duration a.m. HS Euthymic Mood HS = hora somni (bedtime); Manning JS et al. (1999), Psychiatr Clin North Am 22(3): Hypersomnic, Retarded Depression 23 Screening From the General to the More Specific 24 8

9 Whom Do I Screen for Bipolar Disorder? Patient types Every person with depressed mood Every person with generalized anxiety disorder Persons with behavioral disruptions Persons with history of substance abuse FDA health advisory Screen for bipolar disorder before initiating antidepressant treatment FDA Public Health Advisory (2004). Available at: Accessed June 2, Helpful Mnemonics to Assist Clinicians in the Identification of Mental Health Problems SOAP: problem-oriented medical record BATHE: general psychosocial assessment SIG E CAPS: diagnosis of depression DIGFAST: symptoms of hypomania/ mania 26 SOAP: Problem-Oriented Medical Record Subjective the patient s stated reason for the visit to the clinician Objective the findings (e.g., physical, laboratory, imaging) immediately prior to, at the time of or following a visit Assessment what is the clinician s overall determination of the patient s status based on the information obtained in the 2 previous steps? Plan what the clinician proposes to do regarding the patient s situation Weed LJ (1971), Ann Clin Res 3(3):

10 Percentage of Physical Complaints With Identified vs. Unidentified Organic Causes Over a 3-Year Period 3-Year Incidence (%) Chest Pain Fatigue Dizziness Headache Edema Back Pain No organic cause identified Organic cause identified Dyspnea Insomnia Abdominal Pain Numbness 28 Kroenke K, Mangelsdorff AD (1989), Am J Med 86(3): The BATHE Technique Background: What is going on in your life? Affect/feeling: How do you feel about that? Trouble: What about that troubles you (most)? Handling: How are you handling that? Empathy: That must be very difficult Stuart MR, Lieberman JA (2002), The Fifteen Minute Hour: Practical Therapeutic Interventions Stuart in Primary MR, Lieberman Care, JA 3rd (2002), ed. The Philadelphia: Fifteen Minute Hour: Saunders Practical Therapeutic Interventions in Primary Care, 29 3rd ed. Philadelphia: Saunders Detection of Depression 2 questions In the past 2 weeks, have you often been bothered by feeling down, depressed or hopeless? In the past 2 weeks, have you often been bothered by having little interest or pleasure in doing things? A yes to either or both questions is a positive screen for depression Pignone MP et al. (2002), Ann Intern Med 136(10):

11 SIG E CAPS ( Prescribe Energy Capsules ) 31 Wise MG, Rundell JR (1994), Concise Guide to Consultation Psychiatry, 2nd ed. Washington, D.C.: American Psychiatric Press, pp55-56 SIG E CAPS S increased or decreased sleep and sexual desire I decreased interest or pleasure in almost all activities G inappropriate guilt or feelings of worthlessness/ hopelessness E decreased energy or fatigue C decreased concentration A increased or decreased appetite, with weight gain or loss P psychomotor agitation or retardation S suicidal ideation, plan or attempt Wise MG, Rundell JR (1994), Concise Guide to Consultation Psychiatry, 2nd ed. Washington, D.C.: American Psychiatric Press, pp SIG E CAPS (Cont.) If a patient has 5 positive responses, at least 1 of which is either depressed mood or anhedonia, for 2 weeks, and this represents a change from previous behavior, then he/she meets DSM-IV criteria for major depressive disorder Wise MG, Rundell JR (1994), Concise Guide to Consultation Psychiatry, 2nd ed. Washington, D.C.: American Psychiatric Press, pp

12 DIGFAST: Symptoms of Hypomania and Mania Distractibility: poorly focused, multitasking Insomnia: decreased need for sleep Grandiosity: inflated self-esteem Flight of ideas: complaints of racing thoughts Activities: increased goal-directed activities Speech: pressured or more talkative Thoughtlessness: risk-taking behaviors sexual, financial, travel, driving Ghaemi SN (2001), Primary Psychiatry 8: Criteria for Manic Episode Elevated, expansive or irritable mood lasting 1 week (or any duration if hospitalization is required) Plus: 3* of the following symptoms: Inflated self-esteem/grandiosity Decreased need for sleep Overly talkative (pressured speech) Racing thoughts/flight of ideas Distractibility Increased activity/agitation Excessive involvement in high-risk pleasurable activities *For predominantly irritable mood, 4 or more symptoms needed for diagnosis; APA (2000), Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision. Washington, D.C.: American Psychiatric Publishing, Inc. 35 Diagnosis of Bipolar Disorder Is it just depression? Is your depressed patient bipolar? Not all depression is unipolar 1/3 of bipolar disorder in the general population is misdiagnosed as unipolar depression Unipolar depression is a diagnosis of exclusion Hirschfeld RM et al. (2003), J Clin Psychiatry 64(2):

13 Why Does It Matter if Bipolar Disorder Is Misdiagnosed? APA (2002), Am J Psychiatry 159(4 Suppl):1-50; Frye MA et al. (2004), Depress Anxiety 19(4): When Are Symptoms of Depression Part of Bipolar Disorder Rather Than Unipolar Disorder? In a survey of 600 patients with BD, more than 1/3 sought help within 1 year of symptom onset 69% were not diagnosed with BD most frequent diagnosis was major depression Mean number of physicians consulted before correct diagnosis: 4 1/3 did not receive a BD diagnosis for 10 years Hirschfeld RM et al. (2003). J Clin Psychiatry 64(2): Differential Diagnosis: Unipolar or Bipolar? 5. Associated features Unevenness in intimate relationships Frequent career changes Substance use disorders 1. Family history Higher rates of psychiatric illness 4. Mania symptoms Distractibility Insomnia Activities Grandiosity Pressured speech Flight of ideas Thoughtlessness Positive for bipolar disorder 2. Course of illness Age of 1st mania/ Key Elements depression Duration of episodes Frequency of episodes Seasonality 3. Treatment response Multiple treatment failures Nonresponse or erratic response to 39 antidepressants 13

14 Unipolar vs. Bipolar Depression Substance abuse Family history loaded for mood disorders 1st episode <25 years Seasonality Highly recurrent depression Antidepressant misadventures Rapid on/off pattern Postpartum depression Mixed depression/hypomania/mania Kaye NS (2005), J Am Board Fam Pract 18(4): Bipolar Unipolar Very high Moderate Common Sometimes Very common Sometimes Common Occasional More Common Less Common Common Less Common Common Unusual Common Sometimes Common Absent 40 Diagnosing Unipolar vs. Bipolar Disorder: The Critical Role of Past History Presenting symptoms do not tell the whole story Ask the patient about: Past (hypo)manic symptoms, including overactivity as well as euphoric or irritable mood Impulsive behaviors, divorce/separation, job changes Medication-response history Multiple antidepressant failures? Apparent rapid recovery? Insomnia on antidepressants? Family history of mood disorders Bipolar disorder may be progressive APA (2002), Am J Psychiatry 159(4 Suppl):1-50; Akiskal HS et al. (2000), J Affect Disord 59 (suppl 1):S5-S30; Angst J et al. 41 (2003), Eur Neuropsychopharmacol 13(suppl 2):S43-S50; Katzow JJ et al. (2003), Bipolar Disord 5(6): ; Stahl SM (2005), PsychEd Up 1(8):6-7; Frye MA et al. (2004), Depress Anxiety 19(4): Diagnosing Unipolar vs. Bipolar Disorder: The Critical Role of Outside Observers Patients Underreport Manic Symptoms % Experiencing Symptom Prolonged Sadness Loss of Energy Depression Mania Heightened Increased Mood Activity % Not reporting % Reporting N=600; Hirschfeld RM et al. (2003), J Clin Psychiatry 64(2):

15 Onset Age in Bipolar Disorder: NDMDA * Survey Percent of Members Ages* <5-14 = 33% in 2000 Ages* = 27% in 2000 Ages* = 39% in < Age (Years) NDMDA = National Depressive and Manic-Depressive Association; *Now the Depression and Bipolar Support Alliance (DBSA); Lish JD et al. (1994), J Affect Disord 31(4): ; Hirschfeld RM et al. (2003), J Clin Psychiatry 64(2): Tools for Diagnosing Unipolar vs. Bipolar Disorder Correctly Can use patient health questionnaire (PHQ-9) as a screening tool for symptoms of depression Cannot tell if depressive symptoms are part of a unipolar depression episode or bipolar disorder without also explicitly asking about current or past (hypo)manic symptoms Can use MDQ as a screening tool for bipolar disorder Additional tools Bipolar Spectrum Diagnostic Scale (BSDS) Hypomania Checklist (HCL-32) Kroenke K et al. (2001), J Gen Intern Med 16(9): ; PHQ-9, Available at: phq-9.pdf. Accessed May 16, 2006; Akiskal HS et al. (2000), J Aff Disord 59(suppl 1):S5-S30; Angst J et al. (2003), Eur Neuropsychopharmacol 13(suppl 2):S43-S50; Hirschfeld RM et al. (2000), Am J Psychiatry 157(11): ; MDQ, 44 Available at: Accessed May 16, 2006 Documenting Baseline and Follow-Up Depression Symptoms PHQ-9 Over the last 2 weeks, how often have you been bothered by any of the following problems? Read each item carefully, and insert the number of your response (Key: not at all = 0; several days = 1; more than half the days = 2; nearly every day = 3) 1. Little interest or pleasure in doing things 2. Feeling down, depressed, or hopeless 3. Trouble falling asleep, staying asleep, or sleeping too much 4. Feeling tired or having little energy 5. Poor appetite or overeating 6. Feeling bad about yourself, feeling that you are a failure, or feeling that you have let yourself or your family down 7. Trouble concentrating on things such as reading the newspaper or watching television 8. Moving or speaking so slowly that other people could have noticed. Or being so fidgety or restless that you have been moving around a lot more than usual 9. Thinking that you would be better off dead or that you want to hurt yourself in some way 45 Kroenke K et al. (2001), J Gen Intern Med 16(9):

16 Documenting Baseline and Follow-Up Depression Symptoms PHQ-9 (Cont.) Total score for questions 1-9: Scoring key: minimal <5; mild 5-9; moderate 10-14; moderately severe 15-19; severe >19 Impairment: if you checked off any problem on this questionnaire so far, how difficult have these problems made it for you to do your work, take care of things at home, or get along with other people? Key: not difficult at all = 0; somewhat difficult = 1; very difficult = 2; extremely difficult = 3 Kroenke K et al. (2001), J Gen Intern Med 16(9): Screening Tool: Mood Disorder Questionnaire Hirschfeld RM et al. (2000), Am J Psychiatry 157(11): Mood Disorder Questionnaire Patients answer yes or no to a series of questions Has there ever been a time in your life when you were not your usual self and (while not using drugs or alcohol? 13 questions If you checked yes to more than one of the above, have several of these ever happened during the same period of time? How much of a problem did any of these cause like being unable to work; having family, money or legal troubles; getting into arguments or fights? Family history of mood disorders and substances abuse Has a health professional ever told you that you have manic-depressive illness or bipolar disorder? Hirschfeld RM et al. (2000), Am J Psychiatry 157(11): ; MDQ, Available at: Accessed May 16,

17 Criteria for a Positive MDQ Screen A positive screen Requires 7 or more yes responses Symptom co-occurrence and moderate-tosevere functional impairment as rated by the patient The level of functional impairment due to symptoms is queried on a 4-point scale, ranging from no problem to serious problem Hirschfeld RM et al. (2000), Am J Psychiatry 157(11): Hypomania Checklist Self-administered inventory to help clinicians diagnose BD-II and minor bipolar disorders 32 yes/no items used to identify hypomanic component in patients with depressive episodes Designed to assess personal and social role consequences of hypomanic symptoms Takes into account the subjects current overall affective status as a potentially interfering variable in answering the questions Can reveal the extent to which the patient has insight into the condition 50 Bipolar Spectrum Diagnostic Scale Scale to identify BD-II and NOS conditions Validated self-rating scale For entire bipolar spectrum Supplement to clinician s semi-structured interview 2 sections Part I: a paragraph with 19 positively identified sentences (describing many of the symptoms of BD) followed by an underline space for participants to place a checkmark if it applies to them Part II: 1 multiple choice question asking subjects to rate how well the paragraph describes them overall 51 17

18 When There s Not a Lot of Time: 3 Key Questions To Ask How is your sleep? How much sleep do you require? How have you responded to antidepressants in the past? Do you have a family member with a mood disorder? Also Seek a Caregiver s Perspective Remember the importance of seeking the comments of the patient s relative or caregiver 52 Comorbidities: The Rule, Not the Exception The Multidimensionality of BD McIntyre RS et al. (2004), Hum Psychopharmacol 19(6): Comorbidities: Medical Psychiatric 53 Patients With BD Affected (%) Lifetime Substance Use Comorbidity in BD Any SUD EtOH THC Cocaine Others* *Stimulants, sedatives, hallucinogens, opiates; THC = δ-9-tetrahydrocannabinol; McElroy SL et al. (2001), Am J Psychiatry 158(3):

19 Suicide Risk Factors in BD Early age at disease onset High number of depressive episodes Comorbid alcohol abuse History of antidepressant-induced mania Family history of suicidal behavior Traits of hostility and impulsivity Slama F et al. (2004), J Clin Psychiatry 65(8): ; Michaelis BH et al. (2004), Suicide Life Threat Behav 34(2): Suicide Lethality Risk: Unipolar vs. Bipolar Patients Unipolar Bipolar 20 0 Patients with BD are 6x more likely to make a highly lethal suicide attempt than unipolar patients N=2,395; Raja M, Azzoni A (2004), J Affect Disord 82(3): Candidates for Consultation or Referral Diagnostic uncertainty or dilemma Treatment refractory Acuity/severity Danger to self/others mandating inpatient status Need for intensive outpatient therapy Patient-provider mismatch Clinician or patient preference Jackson WC (2005), Drug Benefit Trends 17(Suppl A):

20 Obstacles to Consultation and Referral Availability Provider scarcity Long waiting times Negative stigmatization Patient perceptions Provider perceptions Co-management Legal issues Care coordination Financial Reimbursement rates Carveouts Others 58 Potential Benefits of Shared Care Patient Intensity of focus on a complex illness Open communication between primary care and mental health care providers Referring provider Learning through focused questions to experts Building relationships Consultant Interaction of mental and general medical care providers 59 Summary Symptoms of depression can be due to major depressive disorder or to bipolar disorder An accurate diagnosis can be made by taking a history not only of current symptoms, but also of past symptoms, and by getting additional information from family members Diagnostic screening tools can help make a diagnosis 60 20

21 Summary (Cont.) 1/3 of bipolar disorder in the general population is misdiagnosed as unipolar depression Unipolar depression is a diagnosis of exclusion An awareness of cultural variability with affective disorders is critical in the clinical setting Hirschfeld RM et al. (2003), J Clin Psychiatry 64(1):53-59; Das AK et al. (2005), JAMA 293(8): Post-Test Questions 62 Post-test ARS Question 1 Which of the following is true regarding the high prevalence of Bipolar Disorder in patients who experience depression? 1. Bipolar I patients are symptomatic almost half their lives 2. Depressive episodes are indistinct between Major Depressive Disorder and Bipolar Affective Disorder in a depressed episode 3. In Bipolar Disorder, patients are asymptomatic close to half of the time 4. The most common variant episode of Bipolar disorder is the depressed state 5. All of the above 63 21

22 Post-test ARS Question 2 Which of the following is false in describing the high rate of misdiagnosis of patients with Bipolar Disorder? 1. The prevalence of bipolar disorder may be higher than previously estimated 2. 50% of individuals with positive screens for bipolar I or II disorders reported they had previously received a diagnosis of bipolar disorder from a physician 3. Up to 80% of patients who screen positive for bipolar disorder have not been previously diagnosed with bipolar disorder 4. The Mood Disorder Questionnaire (MDQ) is a validated screening instrument for Bipolar I and II disorders 64 Post-test ARS Question 3 In developing knowledge of the key criteria that differentiate unipolar depression from Bipolar Disorder, is the following statement true or false? Depression is the initial symptom reported by the majority of patients with bipolar disorder. 1. True 2. False 65 Post-test ARS Question 4 Which of the following statements regarding the recognition and initial management of Bipolar Disease is false? 1. Treatment of Bipolar Depression requires starting antidepressants first at illness onset to reduce suicidal risk and improve social adjustment, then adding a mood stabilizer once the depressive symptoms begin to improve 2. Bipolar disorder is most frequently misdiagnosed as unipolar depression 3. It takes up to 10 years before being accurately diagnosed in many BD patients 4. Antidepressants, in the absence of mood stabilizers, may induce mania or hypomania and worsen the course of bipolar disorder by accelerating cycling frequency 66 22

23 Post-test ARS Question 5 On a scale of 1 to 5, please rate how confident you would be in the diagnosis and management of a patient with Bipolar Disorder: 1. Not at all confident 2. Slightly confident 3. Moderately confident 4. Pretty much confident 5. Very confident 67 23