Toward a Better Understanding of the Bipolar Depression Spectrum
Expired
Roger S. McIntyre, MD, FRCPC
BOTTOM LINE:Toward a Better Understanding of the Bipolar Depression Spectrum |
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Depressive symptoms and episodes are the predominant presentation of bipolar disorder and account for much of the morbidity associated with the illness. Mixed features in bipolar disorder are common, associated with a more complex and severe illness presentation, linked to suicide and comorbidity (eg, obesity), and often lead to misdiagnosis. |
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Introduction
Bipolar disorder (BD) is a severe, lifelong disorder associated with high rates of nonrecovery, chronicity, and premature mortality.1 The actionable opportunity for reducing the morbidity and mortality of BD is to address current unmet needs. Herein, we review the current unmet needs in BD: (1) suboptimal diagnostic accuracy/ timeliness; (2) insufficient treatments for bipolar depression, anxiety, and cognitive symptoms; (3) the management of comorbidity; and (4) treatments capable of improving functional
recovery/integration (Table 1).

Bipolar Depression: Diagnostic Dilemmas to Innovative Treatments
This activity is intended for physicians, physician assistants, nurse practitioners, and registered nurses engaged in the care of patients with major depression.
Supported by an educational grant from:
Allergan
Activity Information
Expired
Release date: October 1, 2019
Expiration date: September 30, 2020
Estimated time to complete activity: 1 AMA Category 1 Credit™ 1 ANCC contact hours
Expired
EDUCATIONAL OBJECTIVES
After completing this activity, the participant should be better able to:
• Discuss the prevalence of bipolar disorder in different psychiatric patients.
• Describe the different symptoms that occur in children, adolescents, and adults.
• Use the evidence base, including FDA approval for different treatments, to inform therapy for bipolar depression.
• Provide details to ensure that physicians consider the potential metabolic profile of antipsychotics when choosing agents.
FACULTY
![]() | Roger S. McIntyre, MD, FRCPC | |
![]() | Lakshmi N. Yatham, MBBS FRCPC |
Jairo Vinícius Pinto, MD
Department of Psychiatry, University of British Columbia
Department of Psychiatry, Federal University of Rio Grande do Sul
Gayatri Saraf, MD
Department of Psychiatry, University of British Columbia
JOINT ACCREDITATION STATEMENT

In support of improving patient care, this activity has been planned and implemented by the Postgraduate Institute for Medicine and Global Medical Education. Postgraduate Institute for Medicine is jointly accredited by the American Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the health care team.
PHYSICIAN CONTINUING MEDICAL EDUCATION
The Postgraduate Institute for Medicine designates this enduring material for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
CONTINUING NURSING EDUCATION
The maximum number of hours awarded for this Continuing Nursing Education activity is 1 contact hour.
Designated for 0.6 contact hours of pharmacotherapy credit for Advance Practice Registered Nurses.
DISCLOSURE OF CONFLICTS OF INTEREST
Postgraduate Institute for Medicine (PIM) requires instructors, planners, managers and other individuals who are in a position to control the content of this activity to disclose any real or apparent conflict of interest (COI) they may have as related to the content of this activity. All identified COI are thoroughly vetted and resolved according to PIM policy. PIM is committed to providing its learners with high quality CME activities and related materials that promote improvements or quality in health care and not a specific proprietary business interest of a commercial interest.
Faculty
Roger S. McIntyre, MD, FRCPC
Consulting Fees: Lundbeck, Pfizer, AstraZeneca, Eli Lilly,
JanssenOrtho, Purdue, Johnson & Johnson, Moksha8,
Sunovion, Mitsubishi, Takeda, Forest, Otsuka, Bristol-Myers
Squibb, Shire
Speakers’ Bureau: Lundbeck, Pfizer, AstraZeneca, Elli Lilly,
JanssenOrtho, Purdue, Johnson & Johnson, Moksha8,
Sunovion, Mitsubishi, Takeda, Forest, Otsuka, Bristol-Myers Squibb, Shire
Research Grants: Lundbeck, JanssenOrtho, Shire, Purdue,
AstraZeneca, Pfizer, Otsuka, Allergan
Lakshmi N. Yatham, MBBS, FRCPC
Consulting Fees: Allergan, DSP, Everest Clinical Research,
Lundbeck, Otsuka
Research Support: DSP, Lundbeck, Valeant
Ownership Interest: Biogen, Amgen
Jairo Vinícius Pinto, MD
Scholarship: National Council for Scientific and Technological
Development, Ministry of Science and Technology, Brazil
(Conselho Nacional de Desenvolvimento Científico
e Tecnológico, CNPq).
Dr. Pinto reports no biomedical financial interests
or potential conflicts of interest.
Gayatri Saraf, MD
Dr. Saraf reports no biomedical financial interests or potential
conflicts of interest.
PLANNERS AND MANAGERS
The PIM planners and managers have nothing to disclose. The Global Medical Education planner and manager,
Prakash Masand, MD, has disclosed the following: Consulting Fees: Allergan, Lundbeck, Sunovion, Takeda
Speakers’ Bureau: Allergan, Lundbeck, Sunovion, Takeda Contracted Research: Allergan
DISCLOSURE OF UNLABELED USE
This educational activity may contain discussion of published and/or investigational uses of agents that are
not indicated by the FDA. The planners of this activity do not recommend the use of any agent outside of the
labeled indications. The opinions expressed in the educational activity are
those of the faculty and do not necessarily represent the views of the planners. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.
Disclaimer
Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses
of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications and/
or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.
METHOD OF PARTICIPATION AND INSTRUCTIONS FOR CREDIT
During the period October 1, 2019, through September 30,
2020 participants must read the learning objectives and
disclosures, study the educational activity and complete
the post-test with a score of 75% or better and the activity
evaluation. Please follow the steps below:
Go to www.cmeuniversity.com
- Register or Login (will take less than 1 minute)
- Type in 14313 at the top of the page, “Find Post-Test/Evaluation by Course”, click enter
- Click on activity title when it appears
- Choose the type of credit you would like
- Complete the activity post-test
- Complete online Evaluation
- Receive an immediate CME Certificate to download and/or print for your files
References
- Alonso J, Vilagut G, Mortier P, et al. The role impairment associated with mental disorder risk profiles in the WHO World Mental Health International College Student Initiative. Int J Methods Psychiatr Res. 2019;28(2):e1750.
- Phillips ML, Kupfer DJ. Bipolar disorder diagnosis: challenges and future directions. Lancet. 2013;381(9878):1663-1671.
- 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.
- Carta MG, Angst J. Screening for bipolar disorders: a public health issue. J Affect Disord. 2016;205:139-143.
- Zimmerman M. Screening for bipolar disorder: lessons not yet learned. Evid Based Ment Health. 2016;19(3):e16.
- Jain R, Maletic V, McIntyre RS. Diagnosing and treating patients with mixed features. J Clin Psychiatry. 2017;78(8):1091-1102.
- Stahl SM, Morrissette DA, Faedda G, et al. Guidelines for the recognition and management of mixed depression. CNS Spectr. 2017;22(2):203-219.
- Li CT, Bai YM, Huang YL, et al. Association between antidepressant resistance in unipolar depression and subsequent bipolar disorder: cohort study. Br J Psychiatry. 2012;200(1):45-51.
- Earley W, Burgess MV, Rekeda L, et al. Cariprazine treatment of bipolar depression: a randomized double-blind placebo-controlled phase 3 study. Am J Psychiatry. 2019;176(6):439-448.
- Ragguett RM, McIntyre RS. Cariprazine for the treatment of bipolar depression: a review. Expert Rev Neurother. 2019;19(4):317-323.
- Karasinska JM, George SR, El-Ghundi M, et al. Modification of dopamine D1 receptor knockout phenotype in mice lacking both dopamine D1 and D3 receptors. Eur J Pharmacol. 2000;399(2):171-181.
- Sienaert P, Lambrichts L, Dols A, et al. Evidence-based treatment strategies for treatment-resistant bipolar depression: a systematic review. Bipolar Disord. 2013;15(1):61-69.
- Leverich GS, Altshuler LL, Frye MA, et al. Risk of switch in mood polarity to hypomania or mania in patients with bipolar depression during acute and continuation trials of venlafaxine, sertraline, and bupropion as adjuncts to mood stabilizers. Am J Psychiatry. 2006;163(2):232-239.
- Altshuler LL, Sugar CA, McElroy SL, et al. Switch rates during acute treatment for bipolar II depression with lithium, sertraline, or the two combined: a randomized double-blind comparison. Am J Psychiatry. 2017;174(3):266-276.
- Miskowiak KW, Burdick KE, Martinez-Aran A, et al. Methodological recommendations for cognition trials in bipolar disorder by the International Society for Bipolar Disorders Targeting Cognition Task Force. Bipolar Disord. 2017;19(8):614-626.
- Raust A, Daban C, Cochet B, Henry C, Bellivier F, Scott J. Neurocognitive performance as an endophenotype for bipolar disorder. Front Biosci (EliteEd). 2014;E6(1):89-103.
- Kessing LV. Course and cognitive outcome in major affective disorder. Dan Med J. 2015;62(11):B5160.
- McIntyre RS, Lophaven S, Olsen CK. A randomized, double-blind, placebo-controlled study of vortioxetine on cognitive function in depressed adults. Int J Neuropsychopharmacol. 2014;17(10):1557-1567.
- McIntyre RS, Anderson N, Baune BT, et al. Expert consensus on screening and assessment of cognition in psychiatry. CNS Spectr. 2019;24(1):154-162.
- Rosenblat JD, McIntyre RS. Bipolar disorder and inflammation. PsychiatrClin North Am. 2016;39(1):125-137.
- Moraes JB, Maes M, Barbosa DS, et al. Elevated C-reactive protein levels in women with bipolar disorder may be explained by a history of childhood trauma, especially sexual abuse, body mass index and age. CNS Neurol Disord Drug Targets. 2017;16(4):514-521.
- McIntyre RS, Subramaniapillai M, Lee Y, et al. Efficacy of adjunctive infliximab vs placebo in the treatment of adults with bipolar I/II depression: a randomized clinical trial [published ahead of print May 8, 2019]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2019.0779.
- McIntyre RS. Is obesity changing the phenotype of bipolar disorder from predominately euphoric toward mixed presentations? Bipolar Disord. 2018;20(8):685-686.
- Vieta E, Torrent C, Martínez-Arán A. Functional remediation in bipolar disorder. In: Functional Remediation for Bipolar Disorder. Cambridge, UK: Cambridge University Press; 2014:23-30. doi:10.1017/CBO9781107415867.004.
- McHugh ML. Interrater reliability: the kappa statistic. Biochem Med. 2012;22(3):276-282.
- McIntyre RS. Mixed features and mixed states in psychiatry: from calculus to geometry. CNS Spectr. 2017;22(2):116-117.