CLINICAL EXPERTS IN BIPOLAR DEPRESSION Navigating Diagnosis in Bipolar Depression PRESENTATION This promotional, non-cme content is intended only for US health care professionals involved in the treatment of adult patients with bipolar disorder and is sponsored by Sunovion Pharmaceuticals Inc. F A C U LT Y Gregory W. Mattingly, MD Psychiatrist Department of Psychiatry Washington University School of Medicine St. Louis, Missouri President St. Charles Psychiatric Associates St. Charles, Missouri Disclosure Dr. Mattingly serves or has served as a consultant, speaker, and researcher for various pharmaceutical companies, including Sunovion. Among patients diagnosed with bipolar disorder, 50% experience a major depressive episode (MDE) first, before a manic episode1 Depression predominates symptomatic time2 The diagnostic criteria for an MDE are the same regardless of whether the MDE occurs in the context of major depressive disorder (MDD) or bipolar disorder3 One of the greatest diagnostic challenges is that early in bipolar disorder, an individual may not have had enough episodes to have had a history of mania, which is necessary for diagnosing the illness. Further, people often do not recognize manic or hypomanic symptoms as part of the illness; rather, they are typically motivated by depressed states to seek help. Maintain a high level of suspicion for bipolar depression in anyone presenting with an MDE; 1 in 5 patients being treated for depression in primary care actually has bipolar I or II disorder4,5 Be vigilant for clusters of symptoms and features that may suggest bipolar depression - Strong indicators are4,6,7: Family history of bipolar disorder in a first-degree relative History of antidepressant-induced mania or hypomania Early age of onset Recurrent pattern of illness Atypical symptoms of depression (eg, hypersomnia, hyperphagia, fatigue) - Suggestive features include4,6,7: Psychotic features Lack of response to antidepressant therapy Abrupt onset of and end to MDE An MDE is like a fever in that a number of things could be causing it. The patient has the symptom of depression, but underneath it, what is the driving condition? 1
HISTORY Patients with bipolar disorder typically are complex: Comorbid psychiatric illnesses are commonly seen in these patients and can confound diagnosis8 In the landmark STEP-BD trial, the most frequent lifetime comorbidities in patients with bipolar disorder were8: - Anxiety disorder - Substance use disorder - ADHD - Eating disorder When I take a history, I explore the past with my patient to look for a pattern that has been building over time, such as a childhood diagnosis of ADHD that was difficult to manage followed by high levels of anxiety and irritability in adulthood. This longitudinal perspective is important. Look beyond the comorbidities, which might be marked and predominate the clinical picture, and dig under the surface to determine whether bipolar disorder lies underneath. For a patient who presents with an MDE, investigate whether mania has occurred in the past, because the diagnosis of bipolar I disorder requires a lifetime history of at least 1 manic episode3 Utilize a mnemonic such as DIGFAST to guide questions that can help uncover past manic or hypomanic episodes9 - D = Distractibility - I = Indiscretion or disinhibition - G = Grandiosity - F = Flight of ideas - A = Activity increase - S = Sleep deficit or decreased need for sleep - T = Talkativeness In my practice, when I ask a patient about history, I start with strengths. I ask, What were you good at? Then, What were your challenges? Quite often with bipolar disorder, you will see that there were roots of it earlier in a patient s life. So, I ask the same questions about each life stage childhood, adolescence, and adulthood to establish a developmental history, all the while looking for episodes of mania or hypomania. Then, I obtain the patient s family and medical histories. Gathering collateral information from a patient s partner, family members, or caregivers with the patient s consent is also an important aspect of history-taking. I can obtain additional perspectives on the patient s past mood episodes and be alerted to current issues. I always let the patient know when I ve spoken to someone they trust. In my experience, this candor helps strengthen the therapeutic alliance. 2
SCREENING Up to 69% of patients with bipolar disorder are initially misdiagnosed10 Patients with bipolar disorder go through a mean of 3.5 other diagnoses and 4 HCPs before receiving an accurate diagnosis10 The most common misdiagnoses in patients with bipolar disorder are10: - MDD - Anxiety disorder - Schizophrenia - Personality disorder - Substance use disorder Once a suspicion of bipolar disorder is raised on the basis of the patient s presentation and history, use screening tools designed to help evaluate and differentiate mood symptoms to recognize patients who are likely to have the diagnosis. Screeners help you quickly and effectively gather meaningful data upfront, before you conduct a detailed clinical interview. Per current guidelines, use a screening tool or other structured instrument for documenting mania to decrease the potential for bipolar disorder to be missed or confused with another diagnosis11 - One such tool is the MDQ, a 13-item patient questionnaire that assesses past symptoms, as well as their concurrence and the degree to which they have caused problems for the patient12 Additionally, to further aid the diagnostic process, screeners may help quantify a patient s current depression. The PHQ-9 is a 9-item questionnaire via which the patient indicates the frequency of depressive symptoms experienced over the past 2 weeks and specifies the extent of functional difficulty associated with them13 In my practice, we administer the PHQ-9 and MDQ to all patients who present with an MDE. I believe these 2 screeners are commonly used tools because they can provide systematic data that anyone on the multidisciplinary care team can collect; they can also be downloaded for free. Several other instruments are also widely accessible. Regardless of your choice, I believe the most important point is that screeners play a key role in the diagnostic process. I think of it like an internist s knowledge that a patient s blood pressure is elevated before a detailed clinical interview: It informs the conversation and next steps. Further, some screeners, like the PHQ-9, can be administered throughout the management process to assess the patient s progress and response to treatment. 3
INTERVIEW Screeners are not validated diagnostic instruments14 Using the internist metaphor again, the clinician knows that a patient s blood pressure is elevated but must figure out why. Similarly, a clinician whose patient screens positive on the PHQ-9 or the MDQ must now investigate further with a detailed clinical interview the last step in the process before a formal diagnosis can be made. For a patient who screens positive for an MDE or a lifetime history of mania, conduct a detailed clinical interview to confirm the diagnosis of bipolar disorder and exclude other diagnoses. The interview comprehensively evaluates the patient s history, including duration and severity of episodes, impact of the episodes on psychosocial functioning, and previous treatments and response15 A detailed clinical interview may also include a complete medical history, physical examination, and laboratory tests, in part to thoroughly assess the patient for comorbid medical conditions15 - As many as 55% of patients with bipolar disorder have at least 1 medical condition, and metabolic comorbidities are the most prevalent.16 The etiology of these abnormalities is complex; factors such as lifestyle choices, genetic vulnerability, and the use of certain medications may play a role17,18 There are many details about a patient s illness, such as sleep and sleep cycles, impulsivity, school- or work-related issues, and relationship difficulties, that can offer important insights to the clinician but that a simple history or screener may not fully elucidate. The patient interview can help us dig deeper. Thoroughly exploring a patient s medical history and assessing metabolic risk factors are important for 2 reasons: They can rule out other causes of depressive symptoms, such as fatigue associated with hypothyroidism, and they can inform treatment decisions with respect to the risk-benefit ratios of various medications. Therefore, in my practice, in addition to weighing patients, I usually order lab tests for thyroid function, vitamin D, and testosterone (in men), as well as a complete blood count and a metabolic panel. Over time, metabolic parameters should be routinely monitored in patients with severe mental illness, including bipolar disorder, due to their increased risk for CVD compared with the general population. 4
References: 1. Suppes T, Leverich GS, Keck PE, et al. The Stanley Foundation Bipolar Treatment Outcome Network. II. Demographics and illness characteristics of the first 261 patients. J Affect Disord. 2001;67(1-3):45-59. 2. Judd LL, Akiskal HS, Schettler PJ, et al. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry. 2002;59(6):530-537. 3. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Washington, DC: American Psychiatric Publishing; 2013. 4. Berk M, Berk L, Moss K, Dodd S, Malhi GS. Diagnosing bipolar disorder: how can we do it better? Med J Aust. 2006;184(9):459-462. 5. Hirschfeld RM, Cass AR, Holt DCL, Carlson CA. Screening for bipolar disorder in patients treated for depression in a family medicine clinic. J Am Board Fam Pract. 2005;18(4):233-239. 6. Bowden CL. A different depression: clinical distinctions between bipolar and unipolar depression. J Affect Disord. 2005;84 (2-3):117-125. 7. Bowden CL. Strategies to reduce misdiagnosis of bipolar depression. Psychiatr Serv. 2001;52(1):51-55. 8. Simon NM, Otto MW, Weiss RD, et al. Pharmacotherapy for bipolar disorder and comorbid conditions: baseline data from STEP-BD. J Clin Psychopharmacol. 2004;24(5):512-520. 9. Lewis FT, Kass E, Klein RM. An overview of primary care assessment and management of bipolar disorder. J Am Osteopath Assoc. 2004;104(6 suppl 6):S2-S8. 10. Hirschfeld RM, Lewis L, Vornik LA. Perceptions and impact of bipolar disorder: how far have we really come? Results of the National Depressive and Manic-Depressive Association 2000 survey of individuals with bipolar disorder. J Clin Psychiatry. 2003;64(2):161-174. 11. Goodwin GM, Haddad PM, Ferrier IN, et al. Evidence-based guidelines for treating bipolar disorder: revised third edition recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2016;30(6):495-553. 12. Hirschfeld RM, Williams JB, Spitzer RL, et al. Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire. Am J Psychiatry. 2000;157(11):1873-1875. 13. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16(9):606-613. 14. Hirschfeld RM, Calabrese JR, Weissman MM, et al. Screening for bipolar disorder in the community. J Clin Psychiatry. 2003;64(1):53-59. 15. Culpepper L. The diagnosis and treatment of bipolar disorder: decision-making in primary care. Prim Care Companion CNS Disord. 2014;16(3). http://www.ncbi.nlm.nih.gov/pmc/articles/pmc4195640/. Published June 19, 2014. Accessed February 22, 2018. 16. Maina G, Bechon E, Rigardetto S, Salvi V. General medical conditions are associated with delay to treatment in patients with bipolar disorder. Psychosomatics. 2013;54(5):437-442. 17. de Almeida KM, Moreira CL, Lafer B. Metabolic syndrome and bipolar disorder: what should psychiatrists know? CNS Neurosci Ther. 2012;18(2):160-166. 18. American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004;27(2):596-601. ADHD, attention-deficit/hyperactivity disorder; CVD, cardiovascular disease; HCPs, health care professionals; MDQ, Mood Disorder Questionnaire; PHQ-9, Patient Health Questionnaire 9 Item; STEP-BD, Systematic Treatment Enhancement Program for Bipolar Disorder. This clinical resource was developed in collaboration with expert faculty and is brought to you by The clinical expert commentary reflects the view of an actual licensed clinician who has been engaged by Sunovion Pharmaceuticals Inc. to provide input. The information contained herein is intended for general informational purposes only and is not a substitute for your professional medical advice and judgment. SUNOVION and are registered trademarks of Sumitomo Dainippon Pharma Co., Ltd. Sunovion Pharmaceuticals Inc. is a U.S. subsidiary of Sumitomo Dainippon Pharma Co., Ltd. 2018 Sunovion Pharmaceuticals Inc. All rights reserved. 03/18 LAT478-18 5