Criteria for Diagnosis of Bipolar 1 Disorder: A Comprehensive Guide for Clinicians

Introduction

Bipolar disorder, a significant contributor to global disability, is marked by recurrent mood episodes of mania or hypomania and depression. Often initially misdiagnosed, bipolar disorder requires careful evaluation and ongoing management. This article delves into the critical aspects of bipolar disorder, with a specific focus on the Criteria For Diagnosis Of Bipolar 1 disorder, aiming to enhance diagnostic accuracy and treatment strategies for healthcare professionals. Effective management strategies encompass pharmacotherapy and psychosocial interventions, yet relapse and incomplete responses, especially in depressive phases, necessitate continuous monitoring and treatment adjustments. Comorbid psychiatric and medical conditions further complicate management, highlighting the need for a holistic approach. This comprehensive review addresses the etiology, classification, evaluation, management, and prognosis of bipolar disorder, emphasizing the crucial role of an interprofessional team in optimizing patient care, particularly in the context of establishing clear criteria for diagnosis of bipolar 1.

Etiology of Bipolar Disorder

The precise cause of bipolar disorder remains elusive, but current understanding points to a complex interplay of genetic predispositions, epigenetic modifications, neurochemical imbalances, and environmental influences. The heritability of bipolar disorder is well-documented, with numerous genetic loci identified as potential risk factors. Early research in 1987 highlighted “DNA markers” on chromosome 11, and subsequent studies have linked at least 30 genes to an increased risk.

Environmental factors, particularly early life stressors, also play a significant role. Childhood maltreatment, especially emotional abuse or neglect, is associated with an increased risk of developing bipolar disorder later in life. Other stressful life events such as childbirth, divorce, unemployment, disability, and early parental loss have also been implicated. In adults with bipolar disorder, a substantial proportion report experiencing a stressful life event in the six months preceding a manic or depressive episode.

Neurochemically, bipolar disorder is thought to involve disruptions in neurotransmitter systems, particularly monoamines like dopamine and serotonin, and intracellular signaling pathways that regulate mood. However, a single, unifying neurotransmitter dysfunction has not been identified. Neuroimaging studies using techniques like MRI have revealed structural and functional brain alterations in individuals with bipolar disorder, including reduced subcortical volumes, decreased cortical thickness, and altered white matter integrity compared to healthy individuals. Changes in functional connectivity within brain networks have also been observed.

Epidemiology of Bipolar Disorder

Global prevalence studies indicate a remarkably consistent international rate of bipolar spectrum disorders (including Bipolar I, Bipolar II, and subthreshold bipolar disorder), with similar severity, impact, and comorbidity patterns across different regions. The aggregate lifetime prevalence of bipolar spectrum disorder is estimated at 2.4%. Specifically, Bipolar I disorder has a lifetime prevalence of approximately 0.6%.

The onset of bipolar disorder typically occurs during two peak age ranges: 15-24 years and 45-54 years. Notably, over 70% of individuals with bipolar disorder exhibit clinical symptoms before the age of 25. Bipolar disorder affects individuals across genders, ethnicities, and geographic locations (urban vs. rural) with relatively equal distribution. Cyclothymic disorder, a milder form of bipolar disorder, has a lifetime prevalence of about 0.4-1%.

Pathophysiology of Bipolar Disorder

Similar to its etiology, the pathophysiology of bipolar disorder is not fully understood and is believed to involve intricate interactions among genetic, neurochemical, and environmental factors. Research has highlighted genetic components, signaling pathways, biochemical changes, and neuroimaging findings associated with bipolar disorder.

Evidence strongly supports a genetic contribution, as well as epigenetic influences that modify gene expression. Studies in humans have shown alterations in neurotrophic factors such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) in individuals with bipolar disorder. These findings suggest that disruptions in neurotrophic signaling, which is crucial for neuroplasticity, are involved in the pathophysiology. Other proposed mechanisms include mitochondrial dysfunction, oxidative stress, immune-inflammatory imbalances, and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis.

Neuroimaging studies have provided further insights, demonstrating changes in regional brain activity, functional connectivity, neuronal activity, and brain energy metabolism in bipolar disorder. Anatomical studies of post-mortem brain tissue from individuals with bipolar disorder have revealed dendritic spine loss in the dorsolateral prefrontal cortex, a region critical for executive functions and emotional regulation. As previously mentioned, imbalances in monoamine neurotransmitter systems, particularly dopamine and serotonin, and intracellular signaling pathways are implicated, although no single neurotransmitter dysfunction has been definitively identified.

History and Physical Examination in Bipolar Disorder Diagnosis

Diagnosing bipolar disorder is primarily a clinical process, relying on a comprehensive clinical assessment. This assessment includes a detailed patient interview, ideally supplemented by interviews with family members, and a thorough review of the patient’s longitudinal history of mood symptoms. Currently, there are no definitive biomarkers or neuroimaging tests to diagnose bipolar disorder.

A significant challenge in diagnosis is the delay between symptom onset and accurate diagnosis. On average, patients with bipolar disorder are not correctly diagnosed until 6 to 10 years after their initial contact with healthcare providers, despite exhibiting clinical features of the condition. This diagnostic delay highlights the need for increased awareness and improved diagnostic approaches.

Distinguishing between unipolar major depressive disorder (MDD) and bipolar depression is particularly crucial, as depressive episodes in both conditions share similar diagnostic criteria. Clinicians must actively inquire about past manic, hypomanic, and depressive episodes in patients presenting with depressive symptoms. This is particularly important for patients with early-onset depression (before age 25), those with a high number of lifetime depressive episodes (five or more), and those with a family history of bipolar disorder, as these factors increase the likelihood of a bipolar diagnosis.

Other indicators that may suggest a shift from an initial diagnosis of MDD to bipolar disorder include the presence of psychotic symptoms, lack of response to antidepressants, antidepressant-induced mania or hypomania, and polymorbidity (three or more comorbid conditions). Screening tools, such as the Mood Disorders Questionnaire (MDQ) and the Hypomania Checklist 32 (HCL-32), can aid in identifying potential bipolar disorder cases, although they are not highly sensitive or specific and should be followed by a comprehensive clinical assessment if positive.

Evaluation: DSM-5 Diagnostic Criteria for Bipolar 1 Disorder

The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) provides specific criteria for diagnosis of bipolar 1 disorder. According to DSM-5, the essential criterion for bipolar 1 disorder is the occurrence of at least one manic episode. A manic episode is defined by a distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased activity or energy, lasting at least one week and present most of the day, nearly every day (or any duration if hospitalization is necessary).

Specific Criteria for a Manic Episode in Bipolar 1 Disorder Diagnosis (DSM-5):

During the period of mood disturbance and increased energy or activity, three (or more) of the following symptoms (four if the mood is only irritable) are present to a significant degree and represent a noticeable change from usual behavior:

1. Inflated self-esteem or grandiosity: This can range from unwarranted self-confidence to delusions of grandeur.
2. Decreased need for sleep: Feeling rested after only a few hours of sleep, or not feeling the need for sleep at all.
3. More talkative than usual or pressure to keep talking (pressured speech): Rapid, incessant speech that is difficult to interrupt.
4. Flight of ideas or racing thoughts: Subjective experience of thoughts racing through the mind, or abruptly jumping from one idea to another.
5. Distractibility: Attention too easily drawn to unimportant or irrelevant external stimuli.
6. Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation (purposeless non-goal-directed activity): Increased involvement in multiple projects or activities, or restless physical agitation.
7. Excessive involvement in activities that have a high potential for painful consequences: Engaging in risky behaviors without considering negative consequences, such as unrestrained buying sprees, sexual indiscretions, or foolish business investments.

Important Considerations for Bipolar 1 Diagnosis:

• Severity: The mood disturbance is sufficiently severe to cause marked impairment in social or occupational functioning or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features.
• Exclusion: The episode is not attributable to the physiological effects of a substance (e.g., drug of abuse, medication, other treatment) or another medical condition.
• Episode Precedence: While a manic episode is required for the diagnosis of Bipolar 1 disorder, individuals may also experience hypomanic or major depressive episodes before or after the manic episode. However, these are not required for the diagnosis of bipolar 1.

Alt text: Diagram illustrating the bipolar spectrum, differentiating between Bipolar I, Bipolar II, and Cyclothymia based on the severity and duration of manic and depressive episodes, crucial for accurate bipolar 1 diagnosis.

Differential Diagnosis within Bipolar Spectrum:

It’s important to differentiate Bipolar 1 disorder from other bipolar and related disorders:

• Bipolar II Disorder: Characterized by at least one hypomanic episode and at least one major depressive episode, but no manic episodes. The absence of a full manic episode distinguishes Bipolar II from Bipolar I.
• Cyclothymic Disorder: Involves numerous periods with hypomanic symptoms that do not meet full hypomanic episode criteria and depressive symptoms that do not meet full major depressive episode criteria for at least two years (one year in children and adolescents).
• Specified and Unspecified Bipolar and Related Disorders: These categories are used when bipolar-like symptoms do not fully meet the criteria for Bipolar I, Bipolar II, or cyclothymic disorder.

Treatment and Management of Bipolar 1 Disorder

Managing bipolar 1 disorder effectively requires a multifaceted approach, including pharmacological and psychosocial interventions. Acute mania, a hallmark of Bipolar 1 disorder, often necessitates psychiatric hospitalization to stabilize the patient, manage agitation, and prevent dangerous behaviors. Initial treatment focuses on rapid stabilization, often using a combination of mood stabilizers and antipsychotics. Benzodiazepines may be used adjunctively for managing acute agitation and promoting sleep.

Pharmacological Treatment:

• Acute Mania: First-line treatments include mood stabilizers like lithium and valproate, and atypical antipsychotics such as aripiprazole, asenapine, cariprazine, quetiapine, and risperidone. Combination therapy (e.g., lithium or valproate plus an antipsychotic) may be necessary for severe or treatment-resistant mania. Electroconvulsive therapy (ECT) is also considered for severe, treatment-resistant mania, or in pregnant women with severe mania. Valproate should be avoided in women of childbearing potential due to teratogenic risks.
• Acute Bipolar Depression: Treatment focuses on managing depressive episodes while minimizing the risk of switching to mania. First-line monotherapy options include quetiapine, olanzapine, or lurasidone. Combination therapies such as olanzapine-fluoxetine, lithium plus lamotrigine, or lurasidone plus lithium or valproate may also be effective. Antidepressants should generally be avoided as monotherapy in bipolar depression due to the risk of manic switch or mood destabilization.
• Maintenance Treatment: Long-term maintenance treatment is crucial to prevent mood episode recurrence and improve functioning. Mood stabilizers (lithium, lamotrigine, valproate) and atypical antipsychotics are the mainstays of maintenance pharmacotherapy, often used in combination. Lithium is particularly effective in preventing both manic and depressive relapse and is associated with a reduced risk of suicide in bipolar disorder.

Psychosocial Interventions:

Psychotherapy plays a vital role in the comprehensive management of bipolar 1 disorder. Cognitive behavioral therapy (CBT), interpersonal and social rhythm therapy (IPSRT), and family-focused therapy are evidence-based psychosocial treatments that can improve mood stability, medication adherence, and overall functioning. Psychoeducation for patients and families is also essential, helping them understand bipolar disorder, recognize early warning signs of mood episodes, and develop coping strategies.

Differential Diagnosis of Bipolar 1 Disorder

The differential diagnosis of bipolar 1 disorder includes several conditions that share overlapping symptoms, such as mood lability, impulsivity, and psychosis. Key differential diagnoses include:

• Major Depressive Disorder (MDD): Distinguishing bipolar 1 disorder from MDD is crucial but challenging, especially in the initial presentation when only depressive symptoms are present. A thorough history of manic or hypomanic episodes is essential to differentiate these conditions.
• Schizophrenia and Schizoaffective Disorder: Psychotic symptoms can occur in both bipolar 1 disorder and schizophrenia spectrum disorders. The presence of prominent mood episodes (mania or depression) in conjunction with psychosis favors a diagnosis of bipolar disorder, while schizophrenia is characterized by persistent psychosis in the absence of prominent mood episodes. Schizoaffective disorder involves psychotic symptoms that occur concurrently with mood episodes and also independently for a period of time.
• Anxiety Disorders: Anxiety symptoms are common in bipolar disorder and can sometimes be the primary presenting complaint. However, the presence of distinct manic or hypomanic episodes differentiates bipolar 1 disorder from primary anxiety disorders.
• Substance Use Disorders: Substance use can mimic or exacerbate symptoms of bipolar disorder. It is important to differentiate substance-induced mood disorders from primary bipolar disorder.
• Borderline Personality Disorder (BPD): Mood lability and impulsivity are features of both BPD and bipolar disorder. However, the mood shifts in BPD are typically more rapid and reactive to interpersonal events, while bipolar disorder is characterized by distinct mood episodes lasting for days to weeks.
• Attention-Deficit/Hyperactivity Disorder (ADHD): In children and adolescents, ADHD can sometimes be mistaken for early-onset bipolar disorder due to overlapping symptoms like hyperactivity and impulsivity. Careful assessment of the episodic nature of mood symptoms is crucial for differentiation.

Prognosis and Complications of Bipolar 1 Disorder

Bipolar disorder, including Bipolar 1, is a chronic condition associated with significant morbidity and mortality. It is a leading cause of disability worldwide and is associated with a reduced life expectancy, with an estimated 13 years of potential life lost compared to the general population. Mortality in bipolar disorder is elevated due to both natural causes (cardiovascular, respiratory, and endocrine illnesses) and unnatural causes, particularly suicide. The suicide rate in bipolar disorder is estimated to be 20 to 30 times higher than in the general population.

Complications of bipolar disorder are multifaceted and include:

• Medical Comorbidities: Individuals with bipolar disorder have a higher risk of medical conditions such as cardiovascular disease, metabolic syndrome, obesity, diabetes, and migraine.
• Psychiatric Comorbidities: Anxiety disorders, substance use disorders, and personality disorders, particularly borderline personality disorder, are commonly comorbid with bipolar disorder, often leading to a more severe course and poorer outcomes.
• Suicide Risk: The risk of suicide is significantly elevated throughout the course of bipolar disorder, particularly during depressive episodes and mixed episodes.
• Functional Impairment: Bipolar disorder can significantly impact social, occupational, and interpersonal functioning, leading to difficulties in work, relationships, and overall quality of life.

Deterrence and Patient Education in Bipolar 1 Disorder

Psychoeducation is a cornerstone of bipolar disorder management, aiming to empower patients and families with knowledge and skills to manage the condition effectively. Key components of psychoeducation include:

• Symptom Recognition: Teaching patients and families to recognize early warning signs of mania and depression to facilitate timely intervention.
• Medication Adherence: Emphasizing the importance of consistent medication adherence for mood stabilization and relapse prevention.
• Lifestyle Modifications: Educating patients about healthy lifestyle choices, such as maintaining regular sleep patterns, avoiding stimulants like excessive caffeine and alcohol, and engaging in regular physical activity.
• Coping Strategies: Providing patients with coping skills to manage stress, improve emotional regulation, and navigate daily challenges associated with bipolar disorder.
• Relapse Prevention Planning: Developing individualized relapse prevention plans that outline strategies to manage triggers and early symptoms of mood episodes.

Enhancing Healthcare Team Outcomes in Bipolar 1 Disorder Management

Optimal management of bipolar 1 disorder requires a collaborative, interprofessional team approach. This team may include psychiatrists, primary care physicians, psychiatric nurse practitioners, physician assistants, psychologists, social workers, pharmacists, and case managers. An integrated care model, incorporating both psychiatric and medical healthcare, is essential to address the complex needs of individuals with bipolar 1 disorder and comorbid conditions.

Key elements of effective team-based care include:

• Shared Decision-Making: Engaging patients in treatment planning and decision-making to enhance treatment adherence and patient satisfaction.
• Collaborative Care Models: Implementing structured collaborative care models that integrate mental health services into primary care settings, improving access to and coordination of care.
• Medication Management: Pharmacists play a crucial role in medication reconciliation, monitoring for drug interactions, and educating patients about their medications.
• Psychosocial Support: Social workers and case managers can connect patients with community resources, support groups, and vocational rehabilitation services.
• Ongoing Monitoring and Follow-up: Regular monitoring of symptoms, medication effectiveness, and side effects, as well as proactive follow-up, are essential to optimize outcomes and prevent relapse.

By fostering effective communication, collaboration, and shared expertise among interprofessional team members, healthcare providers can significantly improve the lives of individuals living with bipolar 1 disorder, helping them achieve functional recovery and improved quality of life.

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References

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1.Chakrabarti S. Bipolar disorder in the International Classification of Diseases-Eleventh version: A review of the changes, their basis, and usefulness. World J Psychiatry. 2022 Dec 19;12(12):1335-1355. [PMC free article: PMC9791613] [PubMed: 36579354]

2.Merikangas KR, Jin R, He JP, Kessler RC, Lee S, Sampson NA, Viana MC, Andrade LH, Hu C, Karam EG, Ladea M, Medina-Mora ME, Ono Y, Posada-Villa J, Sagar R, Wells JE, Zarkov Z. Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Arch Gen Psychiatry. 2011 Mar;68(3):241-51. [PMC free article: PMC3486639] [PubMed: 21383262]

3.McGuffin P, Rijsdijk F, Andrew M, Sham P, Katz R, Cardno A. The heritability of bipolar affective disorder and the genetic relationship to unipolar depression. Arch Gen Psychiatry. 2003 May;60(5):497-502. [PubMed: 12742871]

4.Barnett JH, Smoller JW. The genetics of bipolar disorder. Neuroscience. 2009 Nov 24;164(1):331-43. [PMC free article: PMC3637882] [PubMed: 19358880]

5.Craddock N, Sklar P. Genetics of bipolar disorder. Lancet. 2013 May 11;381(9878):1654-62. [PubMed: 23663951]

6.Rybakowski J. Etiopathogenesis of bipolar affective disorder – the state of the art for 2021. Psychiatr Pol. 2021 Jun 30;55(3):481-496. [PubMed: 34460876]

7.Rowland TA, Marwaha S. Epidemiology and risk factors for bipolar disorder. Ther Adv Psychopharmacol. 2018 Sep;8(9):251-269. [PMC free article: PMC6116765] [PubMed: 30181867]

8.Miklowitz DJ, Johnson SL. The psychopathology and treatment of bipolar disorder. Annu Rev Clin Psychol. 2006;2:199-235. [PMC free article: PMC2813703] [PubMed: 17716069]

9.Ching CRK, Hibar DP, Gurholt TP, Nunes A, Thomopoulos SI, Abé C, Agartz I, Brouwer RM, Cannon DM, de Zwarte SMC, Eyler LT, Favre P, Hajek T, Haukvik UK, Houenou J, Landén M, Lett TA, McDonald C, Nabulsi L, Patel Y, Pauling ME, Paus T, Radua J, Soeiro-de-Souza MG, Tronchin G, van Haren NEM, Vieta E, Walter H, Zeng LL, Alda M, Almeida J, Alnaes D, Alonso-Lana S, Altimus C, Bauer M, Baune BT, Bearden CE, Bellani M, Benedetti F, Berk M, Bilderbeck AC, Blumberg HP, Bøen E, Bollettini I, Del Mar Bonnin C, Brambilla P, Canales-Rodríguez EJ, Caseras X, Dandash O, Dannlowski U, Delvecchio G, Díaz-Zuluaga AM, Dima D, Duchesnay É, Elvsåshagen T, Fears SC, Frangou S, Fullerton JM, Glahn DC, Goikolea JM, Green MJ, Grotegerd D, Gruber O, Haarman BCM, Henry C, Howells FM, Ives-Deliperi V, Jansen A, Kircher TTJ, Knöchel C, Kramer B, Lafer B, López-Jaramillo C, Machado-Vieira R, MacIntosh BJ, Melloni EMT, Mitchell PB, Nenadic I, Nery F, Nugent AC, Oertel V, Ophoff RA, Ota M, Overs BJ, Pham DL, Phillips ML, Pineda-Zapata JA, Poletti S, Polosan M, Pomarol-Clotet E, Pouchon A, Quidé Y, Rive MM, Roberts G, Ruhe HG, Salvador R, Sarró S, Satterthwaite TD, Schene AH, Sim K, Soares JC, Stäblein M, Stein DJ, Tamnes CK, Thomaidis GV, Upegui CV, Veltman DJ, Wessa M, Westlye LT, Whalley HC, Wolf DH, Wu MJ, Yatham LN, Zarate CA, Thompson PM, Andreassen OA., ENIGMA Bipolar Disorder Working Group. What we learn about bipolar disorder from large-scale neuroimaging: Findings and future directions from the ENIGMA Bipolar Disorder Working Group. Hum Brain Mapp. 2022 Jan;43(1):56-82. [PMC free article: PMC8675426] [PubMed: 32725849]

10.Scaini G, Valvassori SS, Diaz AP, Lima CN, Benevenuto D, Fries GR, Quevedo J. Neurobiology of bipolar disorders: a review of genetic components, signaling pathways, biochemical changes, and neuroimaging findings. Braz J Psychiatry. 2020 Sep-Oct;42(5):536-551. [PMC free article: PMC7524405] [PubMed: 32267339]

11.Kato T. Current understanding of bipolar disorder: Toward integration of biological basis and treatment strategies. Psychiatry Clin Neurosci. 2019 Sep;73(9):526-540. [PubMed: 31021488]

12.Nowrouzi B, McIntyre RS, MacQueen G, Kennedy SH, Kennedy JL, Ravindran A, Yatham L, De Luca V. Admixture analysis of age at onset in first episode bipolar disorder. J Affect Disord. 2016 Sep 01;201:88-94. [PubMed: 27182964]

13.Moreno C, Laje G, Blanco C, Jiang H, Schmidt AB, Olfson M. National trends in the outpatient diagnosis and treatment of bipolar disorder in youth. Arch Gen Psychiatry. 2007 Sep;64(9):1032-9. [PubMed: 17768268]

14.Kroon JS, Wohlfarth TD, Dieleman J, Sutterland AL, Storosum JG, Denys D, de Haan L, Sturkenboom MC. Incidence rates and risk factors of bipolar disorder in the general population: a population-based cohort study. Bipolar Disord. 2013 May;15(3):306-13. [PubMed: 23531096]

15.Van Meter AR, Youngstrom EA, Findling RL. Cyclothymic disorder: a critical review. Clin Psychol Rev. 2012 Jun;32(4):229-43. [PubMed: 22459786]

16.Konopaske GT, Lange N, Coyle JT, Benes FM. Prefrontal cortical dendritic spine pathology in schizophrenia and bipolar disorder. JAMA Psychiatry. 2014 Dec 01;71(12):1323-31. [PMC free article: PMC5510541] [PubMed: 25271938]

17.Dagani J, Signorini G, Nielssen O, Bani M, Pastore A, Girolamo G, Large M. Meta-analysis of the Interval between the Onset and Management of Bipolar Disorder. Can J Psychiatry. 2017 Apr;62(4):247-258. [PMC free article: PMC5407546] [PubMed: 27462036]

18.McIntyre RS, Berk M, Brietzke E, Goldstein BI, López-Jaramillo C, Kessing LV, Malhi GS, Nierenberg AA, Rosenblat JD, Majeed A, Vieta E, Vinberg M, Young AH, Mansur RB. Bipolar disorders. Lancet. 2020 Dec 05;396(10265):1841-1856. [PubMed: 33278937]

19.Angst J, Cui L, Swendsen J, Rothen S, Cravchik A, Kessler RC, Merikangas KR. Major depressive disorder with subthreshold bipolarity in the National Comorbidity Survey Replication. Am J Psychiatry. 2010 Oct;167(10):1194-201. [PMC free article: PMC3145248] [PubMed: 20713498]

20.Wang YY, Xu DD, Liu R, Yang Y, Grover S, Ungvari GS, Hall BJ, Wang G, Xiang YT. Comparison of the screening ability between the 32-item Hypomania Checklist (HCL-32) and the Mood Disorder Questionnaire (MDQ) for bipolar disorder: A meta-analysis and systematic review. Psychiatry Res. 2019 Mar;273:461-466. [PubMed: 30684793]

21.Mitchell PB, Goodwin GM, Johnson GF, Hirschfeld RM. Diagnostic guidelines for bipolar depression: a probabilistic approach. Bipolar Disord. 2008 Feb;10(1 Pt 2):144-52. [PubMed: 18199233]

22.Bobo WV. The Diagnosis and Management of Bipolar I and II Disorders: Clinical Practice Update. Mayo Clin Proc. 2017 Oct;92(10):1532-1551. [PubMed: 28888714]

23.Parker GB, Graham RK, Tavella G. Is there consensus across international evidence-based guidelines for the management of bipolar disorder? Acta Psychiatr Scand. 2017 Jun;135(6):515-526. [PubMed: 28260229]

24.Gomes FA, Cerqueira RO, Lee Y, Mansur RB, Kapczinski F, McIntyre RS, Yatham LN, Berk M, Milev R, Brietzke E. What not to use in bipolar disorders: A systematic review of non-recommended treatments in clinical practice guidelines. J Affect Disord. 2022 Feb 01;298(Pt A):565-576. [PubMed: 34758372]

25.National Collaborating Centre for Mental Health (UK). Bipolar Disorder: The NICE Guideline on the Assessment and Management of Bipolar Disorder in Adults, Children and Young People in Primary and Secondary Care. The British Psychological Society and The Royal College of Psychiatrists; London: Sep, 2014. [PubMed: 29718639]

26.Goodwin GM, Haddad PM, Ferrier IN, Aronson JK, Barnes T, Cipriani A, Coghill DR, Fazel S, Geddes JR, Grunze H, Holmes EA, Howes O, Hudson S, Hunt N, Jones I, Macmillan IC, McAllister-Williams H, Miklowitz DR, Morriss R, Munafò M, Paton C, Saharkian BJ, Saunders K, Sinclair J, Taylor D, Vieta E, Young AH. Evidence-based guidelines for treating bipolar disorder: Revised third edition recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2016 Jun;30(6):495-553. [PMC free article: PMC4922419] [PubMed: 26979387]

27.Fountoulakis KN, Grunze H, Vieta E, Young A, Yatham L, Blier P, Kasper S, Moeller HJ. The International College of Neuro-Psychopharmacology (CINP) Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD-2017), Part 3: The Clinical Guidelines. Int J Neuropsychopharmacol. 2017 Feb 01;20(2):180-195. [PMC free article: PMC5408976] [PubMed: 27941079]

28.Yatham LN, Kennedy SH, Parikh SV, Schaffer A, Bond DJ, Frey BN, Sharma V, Goldstein BI, Rej S, Beaulieu S, Alda M, MacQueen G, Milev RV, Ravindran A, O’Donovan C, McIntosh D, Lam RW, Vazquez G, Kapczinski F, McIntyre RS, Kozicky J, Kanba S, Lafer B, Suppes T, Calabrese JR, Vieta E, Malhi G, Post RM, Berk M. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018 Mar;20(2):97-170. [PMC free article: PMC5947163] [PubMed: 29536616]

29.Shah N, Grover S, Rao GP. Clinical Practice Guidelines for Management of Bipolar Disorder. Indian J Psychiatry. 2017 Jan;59(Suppl 1):S51-S66. [PMC free article: PMC5310104] [PubMed: 28216785]

30.Grande I, Berk M, Birmaher B, Vieta E. Bipolar disorder. Lancet. 2016 Apr 09;387(10027):1561-1572. [PubMed: 26388529]

31.Ferrari AJ, Stockings E, Khoo JP, Erskine HE, Degenhardt L, Vos T, Whiteford HA. The prevalence and burden of bipolar disorder: findings from the Global Burden of Disease Study 2013. Bipolar Disord. 2016 Aug;18(5):440-50. [PubMed: 27566286]

32.Chan JKN, Tong CHY, Wong CSM, Chen EYH, Chang WC. Life expectancy and years of potential life lost in bipolar disorder: systematic review and meta-analysis. Br J Psychiatry. 2022 Sep;221(3):567-576. [PubMed: 35184778]

33.Hayes JF, Miles J, Walters K, King M, Osborn DP. A systematic review and meta-analysis of premature mortality in bipolar affective disorder. Acta Psychiatr Scand. 2015 Jun;131(6):417-25. [PMC free article: PMC4939858] [PubMed: 25735195]

34.Plans L, Barrot C, Nieto E, Rios J, Schulze TG, Papiol S, Mitjans M, Vieta E, Benabarre A. Association between completed suicide and bipolar disorder: A systematic review of the literature. J Affect Disord. 2019 Jan 01;242:111-122. [PubMed: 30173059]

35.Roshanaei-Moghaddam B, Katon W. Premature mortality from general medical illnesses among persons with bipolar disorder: a review. Psychiatr Serv. 2009 Feb;60(2):147-56. [PubMed: 19176408]

36.Maina G, Salvi V, Vitalucci A, D’Ambrosio V, Bogetto F. Prevalence and correlates of overweight in drug-naïve patients with bipolar disorder. J Affect Disord. 2008 Sep;110(1-2):149-55. [PubMed: 18234351]

37.Fagiolini A, Frank E, Scott JA, Turkin S, Kupfer DJ. Metabolic syndrome in bipolar disorder: findings from the Bipolar Disorder Center for Pennsylvanians. Bipolar Disord. 2005 Oct;7(5):424-30. [PubMed: 16176435]

38.Fagiolini A, Kupfer DJ, Houck PR, Novick DM, Frank E. Obesity as a correlate of outcome in patients with bipolar I disorder. Am J Psychiatry. 2003 Jan;160(1):112-7. [PubMed: 12505809]

39.Hossain S, Mainali P, Bhimanadham NN, Imran S, Ahmad N, Patel RS. Medical and Psychiatric Comorbidities in Bipolar Disorder: Insights from National Inpatient Population-based Study. Cureus. 2019 Sep 12;11(9):e5636. [PMC free article: PMC6822913] [PubMed: 31700739]

40.Yapici Eser H, Kacar AS, Kilciksiz CM, Yalçinay-Inan M, Ongur D. Prevalence and Associated Features of Anxiety Disorder Comorbidity in Bipolar Disorder: A Meta-Analysis and Meta-Regression Study. Front Psychiatry. 2018;9:229. [PMC free article: PMC6030835] [PubMed: 29997527]

41.Messer T, Lammers G, Müller-Siecheneder F, Schmidt RF, Latifi S. Substance abuse in patients with bipolar disorder: A systematic review and meta-analysis. Psychiatry Res. 2017 Jul;253:338-350. [PubMed: 28419959]

42.Onyeka IN, Collier Høegh M, Nåheim Eien EM, Nwaru BI, Melle I. Comorbidity of Physical Disorders Among Patients With Severe Mental Illness With and Without Substance Use Disorders: A Systematic Review and Meta-Analysis. J Dual Diagn. 2019 Jul-Sep;15(3):192-206. [PubMed: 31164045]

43.Latalova K, Prasko J, Kamaradova D, Sedlackova J, Ociskova M. Comorbidity bipolar disorder and personality disorders. Neuro Endocrinol Lett. 2013;34(1):1-8. [PubMed: 23524617]

44.McElroy SL, Winham SJ, Cuellar-Barboza AB, Colby CL, Ho AM, Sicotte H, Larrabee BR, Crow S, Frye MA, Biernacka JM. Bipolar disorder with binge eating behavior: a genome-wide association study implicates PRR5-ARHGAP8. Transl Psychiatry. 2018 Feb 02;8(1):40. [PMC free article: PMC5804024] [PubMed: 29391396]

45.Fisher A, Manicavasagar V, Kiln F, Juraskova I. Communication and decision-making in mental health: A systematic review focusing on Bipolar disorder. Patient Educ Couns. 2016 Jul;99(7):1106-1120. [PubMed: 26924609]

46.Susman JL. Improving outcomes in patients with bipolar disorder through establishing an effective treatment team. Prim Care Companion J Clin Psychiatry. 2010;12(Suppl 1):30-4. [PMC free article: PMC2902190] [PubMed: 20628504]

47.Salloum IM, Thase ME. Impact of substance abuse on the course and treatment of bipolar disorder. Bipolar Disord. 2000 Sep;2(3 Pt 2):269-80. [PubMed: 11249805]

48.van der Voort TY, van Meijel B, Goossens PJ, Hoogendoorn AW, Draisma S, Beekman A, Kupka RW. Collaborative care for patients with bipolar disorder: randomised controlled trial. Br J Psychiatry. 2015 May;206(5):393-400. [PubMed: 25792695]

49.Kern JS, Cerimele JM. Collaborative Care for Patients With a Bipolar Disorder: A Primary Care FQHC-CMHC Partnership. Psychiatr Serv. 2019 Apr 01;70(4):353. [PubMed: 30929615]

Disclosure: Ankit Jain declares no relevant financial relationships with ineligible companies.

Disclosure: Paroma Mitra declares no relevant financial relationships with ineligible companies.