apa research paper on bipolar disorder

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• April 01, 2024 | VOL. 181, NO. 4 CURRENT ISSUE pp.255-346
• March 01, 2024 | VOL. 181, NO. 3 pp.171-254
• February 01, 2024 | VOL. 181, NO. 2 pp.83-170
• January 01, 2024 | VOL. 181, NO. 1 pp.1-82

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Advances in Understanding and Treating Mood Disorders

• Ned H. Kalin , M.D.

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Mood disorders, primarily major depression and bipolar disorder, are among the most debilitating psychiatric illnesses. Although significant progress has been made, there is much to be learned about their pathophysiology and much to be improved upon regarding their treatment. It is important to acknowledge that considerable work in the past has enhanced our understanding and treatment of mood disorders as evidenced by currently available effective treatments, which range from specific psychotherapies to psychopharmacology to neuromodulation. Still, many of our patients fail to fully respond to treatment or stay chronically ill.

Significant advances have been made in relation to the neurobiology underlying emotion, cognition, and behavior, and multitudes of studies have been performed in clinically ill populations; however, we are still far away from applying most of these findings to the clinical setting. From neuroimaging studies, we have developed a reasonable understanding of the circuity underlying negative emotion, reward, fear, anxiety, cognition, and behavior and have characterized various abnormalities in task and “resting-state” brain function in populations of patients with depression and bipolar disorder. Replicability of many of these findings, especially those in patient populations, has become an issue. Genetic studies are identifying structural genetic variants associated with the likelihood of developing mood disorders. However, the effect size of the influence of any one single-nucleotide polymorphism is quite small, and as with most psychiatric illness, we are understanding that many genes interact to increase susceptibility or provide protection. The use of polygenic risk scores appears to be an effective way to capture the complex genetics of these disorders, and over time this approach has potential to inform clinical care. Environmental factors also play a prominent role in the expression of mood disorders: advances are being made at the molecular level in understanding how environmental events are epigenetically programmed to result in altered gene expression that is informative for understanding the gene-by-environment interactions relevant to mood disorders. Most in the field believe that new effective treatment development depends on elucidating a fundamental understanding of mood disorder–related alterations in specific neural circuits and the molecules within these circuits. In addition, the use of machine learning to capitalize on combining critical components of large data sets (i.e., genetic, epigenetic, circuit function, and environmental events) holds promise for personalized psychiatric treatment approaches.

This issue of the Journal is devoted to providing our readership with a better understanding of where the field is in relation to our understanding and treatment of mood disorders, as well as introducing our readers to new promising findings. The centerpiece of this issue is a broad overview on depression by Dr. Charles Nemeroff, chair of the Department of Psychiatry and Behavioral Sciences at the University of Texas Dell Medical School in Austin. In his insightful and thought-provoking overview ( 1 ), Dr. Nemeroff provides his perspective on how we can conceptualize and integrate the multitude of findings and issues relevant to understanding the heterogeneity of depression, diagnostic criteria, mechanisms associated with depression-related pathophysiology, and insights into current and future treatments. This overview is followed by a comprehensive review focused on the use of hormonal treatment strategies for major depression ( 2 ). Dysregulated hormonal systems (e.g., pituitary-adrenal, thyroid, and gonadal) have long been associated with mood alterations and have been a focus of a vast number of studies investigating the potential role of specific hormonal systems in the pathophysiology and treatment of depression. This review, a product of the APA Council of Research Task Force on Novel Biomarkers and Treatments, synthesizes findings from the existing literature to provide clinicians and researchers with a resource for the evidence underlying hormonal treatment strategies. I particularly want to acknowledge the two co-first authors of this review, Dr. Jennifer Dwyer and Dr. Awais Aftab, who at the time were trainee members on the research council. I had the privilege of working closely with Drs. Dwyer and Aftab on this review and personally thank them for their insights and considerable efforts, which they relate in further detail in this month’s AJP Audio podcast episode.

This issue of the Journal also presents original research articles that address topics related to the treatment of bipolar disorder, the use of a new transcranial magnetic stimulation (TMS) strategy for treatment of refractory depression, and the effects of gender-affirming interventions on the treatment of mood and anxiety disorders in transgender individuals.

Using data from the National Ambulatory Medical Care Survey from 1997 to 2016, Rhee et al. ( 3 ) statistically characterize 20-year trends in the pharmacological treatment of bipolar disorder. Although it is probably not a surprise to somewhat older practitioners who have lived these changes, an important finding from this study is documenting the dramatic increase in the use of second-generation antipsychotics with the co-occurrence of a large reduction in the use of traditional mood stabilizers, such as lithium or valproic acid. The authors also report a considerable decrease in the use of psychotherapy, which may be problematic given the considerable psychosocial issues faced by patients with bipolar disorder. Dr. Michael Thase, from the University of Pennsylvania and an expert in the development and evaluation of new treatments for mood disorders, contributes an editorial that provides further historical context for these changes in treatment as well as the implications of these changes ( 4 ).

In another article, the Stanford group presents extremely promising data toward improving TMS methods for treatment-resistant depression ( 5 ). Capitalizing on intermittent theta-burst stimulation (iTBS), which is approved for the treatment of depression, Cole and coworkers report findings from an open-label trial of 22 patients who underwent an intensive iTBS treatment over the course of 5 consecutive days. Importantly, this early study used resting-state functional connectivity MRI to individualize the treatment target region within the left dorsolateral prefrontal cortex, such that stimulation was placed over the area that was most negatively correlated with the functional MRI signal in the subgenual anterior cingulate cortex (sgACC). This targeting strategy was used as the sgACC is a neural hub that receives the confluence of prefrontal cortical and subcortical information that is relevant to emotion and mood regulation, as well as to depression. One important outcome of the study is the demonstration that this intensive theta-burst treatment protocol was safe for patients. Treatment efficacy was rapid, with a remarkable remission rate of approximately 90%. Drs. Carpenter and Philip, from the Brown Department of Psychiatry and Human Behavior and experts in TMS neuromodulation, provide an editorial emphasizing the exciting treatment prospects supported by the data from this study (6). They also discuss these findings in relation to existing TMS treatment strategies and study design issues, including the small sample size and open-label nature of the study.

Also in this issue, along with an accompanying editorial by Dr. Sven Mueller from Ghent University ( 7 ), is an article that addresses the very important concern regarding the mental well-being of transgender individuals, specifically the effects of gender-affirming treatments on their mental health ( 8 ). In their article, Bränström and Pachankis use Swedish registries to assess mental health visits and outcomes after hormonal and surgical gender-affirming interventions. Compared with the general population, the results demonstrate that transgender individuals had higher numbers of clinical visits for the treatment of depression and anxiety prior to the interventions. The authors initially concluded, and presented in their article, that gender-affirming surgery, and not hormonal treatment, was associated with a subsequent reduction in the need for mental health intervention. However, when the article was initially available online, concerns were raised by some of our readers regarding the conclusions. Based on these concerns, we solicited secondary reviews of the article, including statistical consultation that recommended additional analyses. Among these analyses, the authors compared matched groups of gender identity patients who did and did not receive gender-affirming surgery, which resulted in the revised conclusion that gender-affirming surgery did not provide an advantage in relation to mental health outcomes. A robust discussion of this issue, and other methodologic and interpretive concerns, can be found in the numerous accompanying letters to the editor ( 9 – 15 ), published along with Bränström and Pachankis’ response to these letters ( 16 ) and a note from myself regarding the corrections and the process the Journal followed to vet the concerns that were raised ( 17 ). In addition to a published erratum notice, the Bränström and Pachankis article now includes an addendum referring to this postpublication discussion.

Two articles in this issue address environmental influences on mental health and depression, though in very different ways. One article examines the effects of air pollution on increasing hospital admissions for depression in China, and another article focuses on mechanisms involved in the intergenerational transmission of the effects of trauma. In their article, Gu et al. ( 18 ) present information building on earlier work that draws an association between short-term ambient air pollutant concentration and hospital admissions for depression. Using daily assessments of air pollutant concentrations across 75 cities and admission data from more than 111,000 hospitals, the authors found that from 2013 to 2017, increasing exposure to fine particles (<2.5 μm) and inhalable particles (<10 μm) was associated with increased rates of hospitalization. This association was demonstrated to be present within 7 days of increasing pollutant exposure, and the effects appeared to be particularly strong for nitrogen dioxide. It should be emphasized that in interpreting these findings, there are important methodologic issues that the authors discuss in the limitations paragraph of the article’s Discussion section. Furthermore, these findings represent associational data, which do not address causality. Nonetheless, the authors speculate on the possibility that pollutant-induced oxidative stress and inflammation may be underlying factors that could mediate this interesting and troubling association with depression.

Moving from an epidemiological level of analysis toward a molecular one, the article in this issue by Bierer et al. ( 19 ) characterizes epigenetic changes associated with the intergenerational transfer of traumatic experiences. This article focuses on the FKBP5 gene, which makes a protein that regulates glucocorticoid receptor responsivity. In addition, variation in the FKBP5 gene has been shown to be associated with posttraumatic stress disorder. This article speaks to how traumatic experiences in parents prior to conception may influence the biology and behavior of their offspring. Specifically, the authors replicate and extend an earlier finding in which they demonstrated reduced methylation at a specific site of the FKBP5 gene when measured in blood from the offspring of mothers who survived the Holocaust. The authors show that this effect was strongest in the offspring of mothers who were exposed to the Holocaust at younger ages and that reduced methylation of this site on the FKBP5 gene was associated with lower levels of anxiety and higher levels of basal cortisol levels. Because of the association between reduced anxiety and decreased FKBP5 methylation, the authors speculate that this epigenetic alteration may serve to protect offspring from the influences of stress exposure. The article also provides a helpful, in-depth discussion of the function of the FKBP5 gene and its protein and how this gene may be causally related to the effects of trauma and to pituitary-adrenal function. The present finding, which is an important replication of earlier work, along with other numerous relevant discoveries involving the FKBP5 gene, supports further serious attention to FKBP5 as a risk factor and mediator of stress-related psychopathology.

The disruption of hedonic processes is a cardinal feature of depression, and it is well established that depression is associated with alterations in the activation of reward-related circuits. The article by Rappaport and coauthors ( 20 ) addresses depression at a neural systems level of analysis by focusing on reward-related circuitry and development. This circuitry is complex and brain-wide, including regions such as brainstem dopaminergic nuclei, the ventral and dorsal striatum (i.e., the nucleus accumbens and caudate, respectively), the prefrontal cortex, and limbic structures (e.g., the amygdala, hypothalamus, and hippocampus). In the study presented here, the researchers used a monetary reward task to examine activation of reward-related neural circuitry in adolescents in relation to current symptoms of depression as well as in relation to their lifetime history of depression. The sample used is unique in that prospective assessments of symptoms began at between 3 and 5 years of age. The findings demonstrate the importance of examining both the state and “trait-like” aspects of depression, as the data revealed different patterns of neural alterations in relation to current symptoms compared with an individual’s life history of depression. Specifically, current depression was characterized by blunted activation of the nucleus accumbens when anticipating reward, whereas a cumulative history of depression involved a blunted response across a broader network of cortical and striatal regions. These findings are intriguing and potentially very important. Above and beyond the specific findings, the analytic strategy used in this study emphasizes the value of parsing current symptoms from illness history when characterizing the biology of our patients. The findings suggest that different mechanisms, even within the same general circuitry, may be at play in relation to understanding current symptoms in contrast to longer-term vulnerabilities. The developmental nature of this study is also highly important, as the findings shed light on the earliest manifestations of depression and its potential cumulative effects over development on neural circuit dysfunction. In her accompanying editorial ( 21 ), Dr. Erika Forbes, an expert in mechanisms underlying adolescent depression, highlights the importance of neurodevelopmental research while reviewing and discussing the relevance of these new findings.

In conclusion, this issue presents an in-depth view into important clinical and research issues relevant to mood disorders. The overview on depression presents our readership with where we are in the field and the challenges we face in improving outcomes for patients with depression. The review on the use of hormonal treatments and the articles on treatment trends in bipolar disorder and on gender-affirming interventions in transgender individuals provide information that is immediately applicable to clinical practice. Other exciting findings reveal insights into alterations in reward processing in adolescents with depression, an understanding of how environmental influences affect the risk for developing stress-related psychopathology, and groundbreaking new neuromodulation strategies that may significantly impact treatment outcomes in patients with treatment-resistant depression. It is my hope that this issue of the Journal will enthuse, and provide optimism to, readers about the potential for further advances that will benefit our patients suffering from mood disorders.

Disclosures of Editors’ financial relationships appear in the April 2020 issue of the Journal .

1 Nemeroff CB : The state of our understanding of the pathophysiology and optimal treatment of depression: glass half full or half empty? Am J Psychiatry 2020 ; 177:671–685 Link ,  Google Scholar

2 Dwyer JB, Aftab A, Widge A, et al. : Hormonal treatments for major depressive disorder: state of the art . Am J Psychiatry 2020 ; 177:686–705 Link ,  Google Scholar

3 Rhee TG, Olfson M, Nierenberg AA, et al. : 20-year trends in the pharmacologic treatment of bipolar disorder by psychiatrists in outpatient care settings . Am J Psychiatry 2020 ; 177:706–715 Link ,  Google Scholar

4 Thase ME : Charting sea changes in outpatient pharmacotherapy of bipolar disorder (editorial). Am J Psychiatry 2020 ; 177:651–653 Abstract ,  Google Scholar

5 Cole EJ, Stimpson KH, Bentzley BS, et al. : Stanford Accelerated Intelligent Neuromodulation Therapy for treatment-resistant depression . Am J Psychiatry 2020 ; 177:716–726 Link ,  Google Scholar

6 Carpenter LL, Philip NS : The future is now? Rapid advances by brain stimulation innovation (editorial). Am J Psychiatry 2020 ; 177:654–656 Abstract ,  Google Scholar

7 Mueller SC : Mental health treatment utilization in transgender persons: what we know and what we don’t know (editorial). Am J Psychiatry 2020 ; 177:657–659 Abstract ,  Google Scholar

8 Bränström R, Pachankis JE : Reduction in mental health treatment utilization among transgender individuals after gender-affirming surgeries: a total population study . Am J Psychiatry 2020 ; 177:727–734 Abstract ,  Google Scholar

9 Anckarsäter H, Gillberg C : Methodological shortcomings undercut statement in support of gender-affirming surgery (letter). Am J Psychiatry 2020 ; 177:764–765 Abstract ,  Google Scholar

10 Van Mol A, Laidlaw MK, Grossman M, et al. : Gender-affirmation surgery conclusion lacks evidence (letter). Am J Psychiatry 2020 ; 177:765–766 Abstract ,  Google Scholar

11 Curtis D : Study of transgender patients: conclusions are not supported by findings (letter). Am J Psychiatry 2020 ; 177:766 Abstract ,  Google Scholar

12 Malone WJ, Roman S : Calling into question whether gender-affirming surgery relieves psychological distress (letter). Am J Psychiatry 2020 ; 177:766–767 Abstract ,  Google Scholar

13 Landén M : The effect of gender-affirming treatment on psychiatric morbidity is still undecided (letter). Am J Psychiatry 2020 ; 177:767–768 Abstract ,  Google Scholar

14 Wold A : Gender-corrective surgery promoting mental health in persons with gender dysphoria not supported by data presented in article (letter). Am J Psychiatry 2020 ; 177:768 Abstract ,  Google Scholar

15 Ring A, Malone WJ : Confounding effects on mental health observations after sex reassignment surgery (letter). Am J Psychiatry 2020 ; 177:768–769 Abstract ,  Google Scholar

16 Bränström R, Pachankis JE : Toward rigorous methodologies for strengthening causal inference in the association between gender-affirming care and transgender individuals’ mental health: response to letters (letter). Am J Psychiatry 2020 ; 177:769–772 Abstract ,  Google Scholar

17 Kalin NH : Reassessing mental health treatment utilization reduction in transgender individuals after gender-affirming surgeries: a comment by the editor on the process (letter). Am J Psychiatry 2020 ; 177:764 Abstract ,  Google Scholar

18 Gu X, Guo T, Si Y, et al. : Association between ambient air pollution and daily hospital admissions for depression in 75 Chinese cities . Am J Psychiatry 2020 ; 177:735–743 Link ,  Google Scholar

19 Bierer LM, Bader HN, Daskalakis NP, et al. : Intergenerational effects of maternal Holocaust exposure on FKBP5 methylation . Am J Psychiatry 2020 ; 177:744–753 Link ,  Google Scholar

20 Rappaport BI, Kandala S, Luby JL, et al. : Brain reward system dysfunction in adolescence: current, cumulative, and developmental periods of depression . Am J Psychiatry 2020 ; 177:754–763 Link ,  Google Scholar

21 Forbes EE : Chasing the Holy Grail: developmentally informed research on frontostriatal reward circuitry in depression (editorial). Am J Psychiatry 2020 ; 177:660–662 Abstract ,  Google Scholar

• Cited by None

• Second-Generation Antipsychotics
• Bipolar and Related Disorders
• Depressive Disorders
• Environmental Risk Factors
• Inflammation
• Transgender (LGBT) Issues
• Neurostimulation
• Pharmacotherapy

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• Spring 2024 | VOL. 22, NO. 2 Autism Across the Lifespan CURRENT ISSUE pp.147-262
• Winter 2024 | VOL. 22, NO. 1 Reproductive Psychiatry: Postpartum Depression is Only the Tip of the Iceberg pp.1-142

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Bipolar II Disorder: Understudied and Underdiagnosed

• Holly A. Swartz , M.D. , and
• Trisha Suppes , M.D., Ph.D.

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Despite its inclusion as a distinct entity in APA’s Diagnostic and Statistical Manual of Mental Disorders since 1994, bipolar II disorder remains a surprisingly neglected psychiatric condition. Understudied and underrecognized, bipolar II disorder is often misdiagnosed and misunderstood, even by experienced clinicians. As a result, patients typically experience symptoms for more than 10 years before receiving the correct diagnosis. Incorrect diagnosis leads to incorrect treatment, including overuse of monoaminergic antidepressant medications, with resultant declines in functioning and worse quality of life. Perhaps because of its underrecognition, treatment studies of bipolar II disorder are limited, and, too often, results of bipolar I disorder studies are applied to bipolar II disorder, with no direct evidence supporting this practice. Bipolar II disorder is an understudied and unmet treatment challenge in psychiatry. In this review, the authors provide a broad overview of bipolar II disorder, including differential diagnosis, course of illness, comorbid conditions, and suicide risk. The authors summarize treatment studies specific to bipolar II disorder, identifying gaps in the literature. This review reveals similarities between bipolar I and bipolar II disorders, including risks of suicide and predominance of depression over the course of illness, but also differences between the phenotypes in treatment response, for example, to antidepressant medications.

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• Cited by None

• Bipolar and Related Disorders
• Bipolar II Disorder
• Pharmacotherapy

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Special Report: Bipolar Disorder II—Frequently Neglected, Misdiagnosed

• Trisha Suppes , M.D., Ph.D. ,
• Holly A. Swartz , M.D. ,
• Sara Schley

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Unlike its cousin, bipolar I disorder, which has been extensively studied and depicted in popular literature and on screen, bipolar II disorder is poorly understood, underdiagnosed, and insufficiently treated. This has often resulted in an over 10-year delay in diagnosis.

Even experienced clinicians know surprisingly little about bipolar II disorder (BD II), despite its inclusion as a distinct entity in DSM since 1994. An abundance of studies supports conceptualization of BD II as a unique phenotype within the bipolar illness spectrum, although many fail to recognize it as distinct disorder apart from bipolar I disorder (BD I).

Alternatively, BD II is considered a “lesser form” of BD I, despite numerous studies showing comparable illness severity and risk of suicide in these two BD subtypes. Perhaps because of its under-recognition, treatment studies of BD II are limited, and too often results from studies of patients with BD I are simply applied to those with BD II with no direct evidence supporting this practice. BD II is an understudied and unmet treatment challenge in psychiatry.

In this review, we will provide a broad overview of BD II including differential diagnosis, course of illness, comorbidities, and suicide risk. We will summarize treatment studies specific to BD II, identifying gaps in the literature. This review will reveal similarities between BD I and II, including suicide risk and predominance of depression over the course of illness, but also differences between the phenotypes in treatment response, for example to antidepressants.

We highlight the perspective of an expert by experience who discusses her lived experiences of BD II in an accompanying interview ( Interview With an Expert by Lived Experience ).

Diagnosis History

Alternating states of mania and melancholia are among the earliest described human diseases, first noted by ancient Greek physicians, philosophers, and poets. Hippocrates (460-337 B.C.E.), who formulated the first known classification of mental disorders, systematically described bipolar mood states: melancholia, mania, and paranoia. More than two millennia later, Emil Kraepelin, recognized as one of the founders of modern psychiatry, described manic-depressive illness as a singular disease characterized by alternating cycles of mania or melancholia. However, Kraepelin was more focused on mood changes and cycling than the polarity of episodes per se. Thus, his concept included what we now term recurrent major depressive disorder (MDD) . Nevertheless, his and other formulations from this period provide background for our modern concepts of bipolar disorder, differentiating it from unipolar depression (MDD and related disorders).

The hiding in plain sight of patients with BD II was brought to awareness by David L. Dunner, M.D., in the 1960s. When examining a cohort of individuals with mood disorders in a study by the National Institute of Mental Health (NIMH), he identified a subgroup of patients with recurrent episodes of depression who also had a history of at least one period of hypomania and a strong family history of bipolar disorder. This subgroup was found to have a different course of illness compared with those with recurrent depression and a history of mania (BD I). Thanks to this work, BD II was recognized as a distinct disorder, separate from BD I. It finally entered the DSM lexicon in 1994 in DSM-IV and was added to ICD-10 even more recently.

Conceptualization of bipolar disorders continues to evolve as the field learns more; for example, changes were made to the DSM-5 diagnostic criteria for BD such that Criteria A for both mania and hypomania now include increased energy as well as elevated or irritable mood (see Table 1). Thus, BD II is now recognized as a disorder of energy as well as mood.

DSM focuses on categorial diagnoses—that is, thresholds for absence or presence of disease. In parallel to this framework, many have argued for considering bipolar disorders along a continuous spectrum of illness. Thus, the term bipolar spectrum is used to describe both the spectrum of severity across BD symptoms as well as combinations of mood symptoms with manic/hypomanic and depressive components. Some refer to BD II as a part of the bipolar spectrum. These concepts reflect a growing awareness that dimensional descriptions of mood disorders may better map onto continuous biological markers of disease, compared with DSM ’s categorical approach, but the debate about diagnostic boundaries and disease etiology continues. Importantly, conceptualizations of BD as a spectrum condition versus discrete diagnostic categories (that is, BD I or BD II) are not mutually exclusive but rather speak to ongoing efforts to understand and best describe the phenomenology of BD.

Differential Diagnosis

The validity of BD II as a separate disorder has been reified through multiple empirical studies. The clinical diagnosis is reliably separable from BD I, as seen in APA clinical trials preparing for DSM-5 and in careful clinical interviews. In DSM-5 field trials to assess reliability of diagnoses, BD I was among the most recognizable, but BD II fell in the acceptable range and well above MDD as a reliable diagnostic entity. Family studies also support the diagnosis of BD II as an independent entity with distinct familial heritability, according to a 1976 study by Dunner et al. and a 1990 study by J. Raymond DePaulo, M.D., et al., and the authors of this report. Finally, genetic studies have found correlations suggesting the heterogeneity between BD I and BD II is “nonrandom,” supporting the concept of distinct conditions.

BD II diagnosis requires at least one lifetime hypomanic episode and one major depressive episode. Despite clarity of BD II diagnostic criteria, clinicians struggle to accurately identify it in practice. BD II is often either missed or incorrectly diagnosed, resulting in an over 10-year delay in diagnosis. Difficulties in accurate diagnosis arise from several sources. First, DSM-5 criteria for the depressive phase of BD II are identical to those required for a major depressive episode, which make BD II and MDD cross-sectionally indistinguishable. This is particularly notable as MDD diagnoses make up a substantial percent of the incorrect diagnoses for patients with BD II. Second, hypomania, which by definition is a less severe form of mania, may be difficult for patients to distinguish from a “normal” mood state when accompanied by extra energy and good mood. Third, mixed hypomanic mood states are very common in BD II, and in fact more common than euphoric hypomanic states. Mixed mood states are characterized by the presence of symptoms of opposite polarity during a depressive or hypomanic episode. In a mixed hypomania, patients might believe they are simply irritable and angry in the context of depression rather than recognizing the additional hypomanic symptoms warranting a diagnosis of mixed hypomanic state. Finally, patients rarely present for treatment in the midst of a hypomanic episode, a mood state that is either perceived as ego-syntonic or simply not identified as part of their illness during mixed hypomania.

The primary reason patients with BD II seek care is depression. Depression dominates the course of BD II, both in the early and late stages. However, retrospectively identifying episodes of hypomania during a depressive episode can be challenging. Further, many individuals see hypomania (either the euphoric or mixed variant) as part of “normal” mood rather than part of a bipolar spectrum, contributing to misreporting of mood episodes. Especially after unrelenting episodes of depression, it is understandable that many would perceive hypomania as a return to baseline. However, under-recognition of hypomania contributes to incorrect diagnoses. In sum, many individuals with BD II fail to recall, recognize, or report histories of hypomania, leading to an MDD (mis)diagnosis.

In psychiatry, all diagnoses are a one-way road. Individuals who have ever met criteria for a manic episode will continue to carry the diagnosis of BD I—even without further manic episodes. Similarly, patients who have a distant episode of hypomania and at least one prior major depressive episode would be considered to have BD II disorder, even in the absence of additional hypomanic episodes that meet symptom and duration criteria. Thus, accurate diagnosis of BD II relies on careful history taking. To improve diagnostic acumen, it is essential that clinicians systematically screen all patients with MDD for BD and ask careful questions about prior episodes of hypomania.

Course of Illness and Comorbidity

Kraepelin noted before the medication era that the course of illness for patients with BD generally progresses into more persistent and severe depression with aging. While he was primarily referring to manic-depressive illness, which we would call BD I today, the same principle applies to patients with BD II. In the NIMH collaborative study by Lewis Judd, M.D., et al., which included long-term follow-up of up to 20 years, patients with BD II experienced a course of illness characterized by more depressive episodes and fewer well intervals over time.

There is a longstanding debate in the literature whether patients with BD II suffer the same impairments and risks as those with BD I. BD II was previously—and incorrectly—labeled a “less severe” version of BD I. In fact, studies consistently show comparable disease burden in BD I and II. A recent Swedish study by Alina Karanti, M.D., et al. reported higher rates of depressive episodes, illness onset at a younger age, and significantly higher rates of psychiatric comorbidity (anxiety disorders, eating disorders, and ADHD) among patients with BD II compared with those with BD I. In this Swedish sample, (n>8,700) no differences were noted in substance abuse between BD I and BD II. Interestingly, individuals with BD II generally obtained more education and achieved a higher level of independence than those with BD I.

High rates of psychiatric comorbidity in patients with BD II further compound the challenge of differential diagnosis. There is considerable overlap between BD II and anxiety disorders. Attention-deficit/hyperactivity disorder also frequently co-occurs. Approximately 20% of individuals with BD II also meet criteria for borderline personality disorder (BPD), and up to 40% of those with BPD are incorrectly diagnosed as having BD I or II. Tables 2 and 3 show estimated co-occurring psychiatric illnesses for patients with BD II. The diagnosis of BD II requires a careful clinical interview of both past and current symptomatology.

Suicide is a significant risk for all patients with BD, and historically patients with BD I were viewed as having a higher risk than BD II due to the extremities of mania. However, data from a number of sources support that suicide risk is high across all patients with BD, and relatively little difference is found in risk for patients with BD I versus BD II. Older studies have suggested this risk may be higher for patients with BD II than BD I, and, indeed, the Swedish bipolar registry database study recently indicated that the rate of suicide attempts was significantly higher in patients with BD II though no data on completed suicides were provided. Overall, the reports from the International Society for Bipolar Disorders Task Force on Suicide found that the risk for suicide was estimated at 164 of 100,000 per year in patients with BD versus 10 of 100,000 per year in the general population (see the reference by Ayal Schaffer, M.D., at the end of this report).

Treatment of BD II

Treatment guidelines for bipolar disorder often give only a passing nod to distinguishing appropriate treatments for BD I versus BD II. The combined guidelines by the Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) were unusual in making a point of distinguishing the evidence base for BD I versus BD II. They are reported in a 2018 paper by Lakshmi N. Yatham, M.D., et al. (see reference at end of article).

These guidelines have a separate section devoted to BD II, and they clearly state that one cannot directly apply studies on patients with BD I to management of patients with BD II. The conclusion of these guidelines is that there are too few controlled studies in patients with BD II to make detailed evidence-based recommendations or develop evidence-based treatment algorithms. Below is a brief overview of our current knowledge of treatments for patients with BD II with medication and/or psychotherapy.

Antidepressants

It is worth highlighting that, while monotherapy antidepressants would be viewed as an inappropriate practice for patients with BD I depression, studies suggest that the risks and benefits may be different for those with BD I and BD II. In at least one study, risk of switching to hypomania was no greater with lithium than with sertraline monotherapy. Other studies have shown antidepressant monotherapy to be an efficacious monotherapy for BD II. Meta-analyses on risk of antidepressant-induced switches are inconclusive, though the risk of treatment-emergent (hypo)mania due to medication appears to be less in patients with BD II than in patients with BD I depression receiving monotherapy antidepressants. Absent conclusive data on antidepressant switch rates, without a past record of good response to antidepressant monotherapy, current treatment guidelines suggest starting with lithium or a mood stabilizer before adding or switching to antidepressant monotherapy. Additionally, it is important to note that antidepressants in some patients may worsen the overall course of illness and may not be efficacious in some patients with BD II. Any patient who experiences hypomania or mania (which must be distinguished from transient activation symptoms) while on antidepressant medication should be presumed to be on the bipolar spectrum.

Antipsychotics

Most atypical antipsychotics have not been studied for the treatment of both BD I and BD II depression, with two notable exceptions. Quetiapine registration trials included individuals with BD II, with post-hoc analyses demonstrating efficacy of quetiapine monotherapy for BD II depression. Lumateperone is the first antipsychotic formally studied for depression response in patients with BD II since quetiapine trials in the early 2000s. Lumateperone, in randomized, controlled trials, performed as well or better for BD II than BD I, according to a 2021 study by Joseph R. Calabrese, M.D., et al. Cariprazine and lurasidone, while both FDA approved to treat bipolar depression, were never formally studied in patients with BD II. There have been case series supporting their use in BD II depression, but no randomized, controlled trials have been carried out. FDA approval to treat patients with BD II depression with lumateperone came in 2021, 15 years after quetiapine was approved. This glacial rate of accruing new FDA-approved compounds for BD II speaks to the need for more studies in this population.

Lithium and Anticonvulsants

While we might expect lithium to be the frontrunner treatment for managing BD II, study results are varied. Certainly, for hypomania and maintenance treatment of patients with BD II, lithium is a top choice. Lithium has a disappointingly poor track record for treating BD II depression with little indication that response rates are superior to those of antidepressants and atypical antipsychotics. Lamotrigine has good evidence for preventing new depression episodes in the context of BD (both BD II and I). The evidence, however, is less robust for treating acute depression in patients with BD II. In clinical practice, many clinicians prescribe lamotrigine, especially as an adjunctive treatment, for BD II depression, but our ability to make firm recommendations with confidence about lamotrigine is limited.

Other Therapies

Rapid-acting therapies are on the rise across all treatments for depression. There has been a recent surge of clinical work and research examining transcranial magnetic stimulation (TMS), ketamine, and psychedelics and related compounds. More work is needed specifically focused on BD II depression before firm conclusions may be drawn.

There is limited evidence supporting the use of TMS for BD II depression. This evidence base is developing, and more information is forthcoming on the utility of TMS for BD II depression.

Ketamine and Psychedelic Studies

Racemic ketamine has been in use for many years as an anesthetic and more recently was approved by the FDA as intranasal esketamine (the s-enantiomer of racemic ketamine) as a treatment for MDD. Three small studies of racemic ketamine suggest that it is effective for BD II depression. A 2022 observational study by Farhan Fancy et al. assessing patients with BD I versus BD II treated with racemic ketamine included more than 60 patients (n=35 BD II). In this largest open observational study to date involving ketamine and BD, patients with BD II demonstrated a more robust response than those with BD I. More studies are in development exploring this new use of an old drug; to date, there is no information on the role of esketamine for bipolar depression, let alone BD II.

Recently, it’s been difficult to pick up a journal or look at other media without seeing something about psychedelics and related compounds. There is a surge of interest in psychedelics for MDD, although evidence about their effectiveness is still early and with rare exceptions involves small samples. There is one report on treatment of depression with psilocybin in patients with BD II. In this pilot study, 15 patients with BD II were given a one-time dose of psilocybin (25 mg) and provided preparatory, dosing, and integration therapy consistent with psilocybin studies in MDD. In this small open study by Scott Aaronson, M.D., et al., the rate of response at 3 and 12 weeks was more robust than has been observed in MDD studies. An ongoing study is assessing the durability of patients’ response to psilocybin administered one time for patients with BD II depression. While no notable adverse events or increased mood lability were noted in this small sample to date, further study is needed to assess benefits and harms.

Psychotherapy

Most information about psychotherapy for BD II is derived from trials of interventions for BD in general that also included a subset of individuals with BD II. A recent systematic review of psychotherapies for BD II identified over 1,000 individuals with BD II who participated in randomized, controlled trials testing psychosocial interventions to treat depression or prevent recurrence of mood symptoms. However, relatively few of these trials—only eight of 27—examined outcomes in those with BD II separately. From this review, we concluded that there is preliminary evidence supporting the efficacy of several evidence-based psychotherapies for BD II: cognitive-behavioral therapy, psychoeducation, family focused therapy, interpersonal and social rhythm therapy (IPSRT), and functional remediation. None of these psychotherapies have undergone rigorous testing in randomized, controlled trials focused specifically on BD II depression, with the exception of IPSRT, pointing to the need for additional research in this area. To our knowledge, no meta-analysis of psychotherapy for BD II has been published.

IPSRT, the only psychosocial intervention to be tested in a randomized, controlled trial consisting of participants with BD II only (rather than a mixed patient population of BD I and II), focuses on helping individuals develop more regular routines to stabilize underlying disturbances in circadian rhythms. Because abnormalities in circadian biology have been implicated in the genesis of bipolar disorders, including BD II, a chronobiologic behavioral approach may be especially helpful to mitigate BD II symptoms.

Conclusions

BD II is a relatively common disorder affecting approximately 0.4% of the population. Its prevalence, morbidity, and mortality are comparable to that of BD I. Evidence supports conceptualizing BD II as a distinct phenotype, separable from both BD I and MDD. Compared with BD I and MDD, far less is known about BD II and how to treat it. Further, despite being reliably diagnosed in DSM-5 field trials, BD II is frequently misdiagnosed in practice, resulting in a decade-long lag between onset of symptoms and appropriate diagnosis. A neglected condition, BD II causes unnecessary suffering in those who are misdiagnosed or for whom appropriate treatments are unclear. More research is urgently needed to improve identification and treatments for BD II. ■

David L. Dunner, M.D., et al. “ Heritable Factors in the Severity of Affective Illness ,” Biological Psychiatry , February 1976.

J. Raymond DePaulo, M.D., et al. “ Bipolar II Disorder in Six Sisters ,” Journal of Affective Disorders , August 1990.

Lewis Judd, M.D., et al. “ Long-Term Symptomatic Status of Bipolar I vs. Bipolar II Disorders ,” International Journal of Neuropsychopharmacology, June 2003.

Alina Karanti, Ph.D., et al. “ Characteristics of Bipolar I and II Disorder: A Study of 8766 Individuals ,” Bipolar Disorders , June 2020.

Ayal Schaffer, M.D., et al. “ A Review of Factors Associated With Greater Likelihood of Suicide Attempts and Suicide Deaths in Bipolar Disorder: Part II of a Report of the International Society for Bipolar Disorders Task Force on Suicide in Bipolar Disorder ,” Australian & New Zealand Journal of Psychiatry , November 2015.

Lakshmi N. Yatham, M.D., et al. “ 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 Disorders , March 2018.

Joseph R. Calabrese, M.D., et al. “ Efficacy and Safety of Lumateperone for Major Depressive Episodes Associated With Bipolar I or Bipolar II Disorder: A Phase 3 Randomized Placebo-Controlled Trial ,” American Journal of Psychiatry , December 2021.

Farhan Fancy, et al. “ Real-World Effectiveness of Repeated Ketamine Infusions for Treatment-Resistant Bipolar Depression ,” Bipolar Disorders , December 14, 2022.

Scott Aaronson, M.D., et al. “ COMP360 Psilocybin Therapy Shows Potential in Open-Label Study in Type II Bipolar Disorder ,” Global Newswire, December 8, 2022.

Trisha Suppes, M.D., Ph.D., is a professor of psychiatry, staff psychiatrist at the VA Palo Alto, and director of the Exploratory Therapeutics Laboratory at Stanford University.

Holly A. Swartz, M.D., is a professor of psychiatry at the University of Pittsburgh School of Medicine and director of the Center for Advanced Psychotherapy at Western Psychiatric Hospital.

They are co-editors of Bipolar II Disorder: Recognition, Understanding, and Treatment from APA Publishing. APA members may purchase the book at a discount.

Sara Schley is the author of Brainstorm: From Broken to Blessed on the Bipolar Spectrum (Seed Systems, 2022). She is the founder of a consulting business and has worked with hundreds of renowned companies worldwide.

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• Diagnosis and...

Diagnosis and management of bipolar disorders

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• Peer review
• Fernando S Goes , associate professor of psychiatry and behavioral sciences 1 2
• 1 Precision Medicine Center of Excellence in Mood Disorders, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
• 2 Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
• Correspondence to: F S Goes fgoes1{at}jhmi.edu

Bipolar disorders (BDs) are recurrent and sometimes chronic disorders of mood that affect around 2% of the world’s population and encompass a spectrum between severe elevated and excitable mood states (mania) to the dysphoria, low energy, and despondency of depressive episodes. The illness commonly starts in young adults and is a leading cause of disability and premature mortality. The clinical manifestations of bipolar disorder can be markedly varied between and within individuals across their lifespan. Early diagnosis is challenging and misdiagnoses are frequent, potentially resulting in missed early intervention and increasing the risk of iatrogenic harm. Over 15 approved treatments exist for the various phases of bipolar disorder, but outcomes are often suboptimal owing to insufficient efficacy, side effects, or lack of availability. Lithium, the first approved treatment for bipolar disorder, continues to be the most effective drug overall, although full remission is only seen in a subset of patients. Newer atypical antipsychotics are increasingly being found to be effective in the treatment of bipolar depression; however, their long term tolerability and safety are uncertain. For many with bipolar disorder, combination therapy and adjunctive psychotherapy might be necessary to treat symptoms across different phases of illness. Several classes of medications exist for treating bipolar disorder but predicting which medication is likely to be most effective or tolerable is not yet possible. As pathophysiological insights into the causes of bipolar disorders are revealed, a new era of targeted treatments aimed at causal mechanisms, be they pharmacological or psychosocial, will hopefully be developed. For the time being, however, clinical judgment, shared decision making, and empirical follow-up remain essential elements of clinical care. This review provides an overview of the clinical features, diagnostic subtypes, and major treatment modalities available to treat people with bipolar disorder, highlighting recent advances and ongoing therapeutic challenges.

Introduction

Abnormal states of mood, ranging from excesses of despondency, psychic slowness, diminished motivation, and impaired cognitive functioning on the one hand, and exhilaration, heightened energy, and increased cognitive and motoric activity on the other, have been described since antiquity. 1 However, the syndrome in which both these pathological states occur in a single individual was first described in the medical literature in 1854, 2 although its fullest description was made by the German psychiatrist Emil Kraepelin at the turn of the 19th century. 3 Kraepelin emphasized the periodicity of the illness and proposed an underlying trivariate model of mood, thought (cognition), and volition (activity) to account for the classic forms of mania and depression and the various admixed presentations subsequently know as mixed states. 3 These initial descriptions of manic depressive illness encompassed most recurrent mood syndromes with relapsing remitting course, minimal interepisode morbidity, and a wide spectrum of “colorings of mood” that pass “without a sharp boundary” from the “rudiment of more severe disorders…into the domain of personal predisposition.” 3 Although Kraepelin’s clinical description of bipolar disorder (BD) remains the cornerstone of today’s clinical description, more modern conceptions of bipolar disorder have differentiated manic depressive illness from recurrent depression, 4 partly based on differences in family history and the relative specificity of lithium carbonate and mood stabilizing anticonvulsants as anti-manic and prophylactic agents in bipolar disorder. While the boundaries of bipolar disorder remain a matter of controversy, 5 this review will focus on modern clinical conceptions of bipolar disorder, highlighting what is known about its causes, prognosis, and treatments, while also exploring novel areas of inquiry.

Sources and selection criteria

PubMed and Embase were searched for articles published from January 2000 to February 2023 using the search terms “bipolar disorder”, “bipolar type I”, “bipolar type II”, and “bipolar spectrum”, each with an additional search term related to each major section of the review article (“definition”, “diagnosis”, “nosology”, “prevalence”, “epidemiology”, “comorbid”, “precursor”, “prodrome”, “treatment”, “screening”, “disparity/ies”, “outcome”, “course”, “genetics”, “imaging”, “treatment”, “pharmacotherapy”, “psychotherapy”, “neurostimulation”, “convulsive therapy”, “transmagnetic”, “direct current stimulation”, “suicide/suicidal”, and “precision”). Searches were prioritized for systematic reviews and meta-analyses, followed by randomized controlled trials. For topics where randomized trials were not relevant, searches also included narrative reviews and key observational studies. Case reports and small observations studies or randomized controlled trials of fewer than 50 patients were excluded.

Modern definitions of bipolar disorder

In the 1970s, the International Classification of Diseases and the Diagnostic and Statistical Manual of Mental Disorders reflected the prototypes of mania initially described by Kraepelin, following the “neo-Kraepelinian” model in psychiatric nosology. To meet the primary requirement for a manic episode, an individual must experience elevated or excessively irritable mood for at least a week, accompanied by at least three other typical syndromic features of mania, such as increased activity, increased speed of thoughts, rapid speech, changes in esteem, decreased need for sleep, or excessive engagement in impulsive or pleasurable activities. Psychotic symptoms and admission to hospital can be part of the diagnostic picture but are not essential to the diagnosis. In 1994, Diagnostic and Statistical Manual of Mental Disorders , fourth edition (DSM-IV) carved out bipolar disorder type II (BD-II) as a separate diagnosis comprising milder presentations of mania called hypomania. The diagnostic criteria for BD-II are similar to those for bipolar disorder type I (BD-I), except for a shorter minimal duration of symptoms (four days) and the lack of need for significant role impairment during hypomania, which might be associated with enhanced functioning in some individuals. While the duration criteria for hypomania remain controversial, BD-II has been widely accepted and shown to be as common as (if not more common than) BD-I. 6 The ICD-11 (international classification of diseases, 11th revision) included BD-II as a diagnostic category in 2019, allowing greater flexibility in its requirement of hypomania needing to last several days.

The other significant difference between the two major diagnostic systems has been their consideration of mixed symptoms. Mixed states, initially described by Kraepelin as many potential concurrent combinations of manic and depressive symptoms, were more strictly defined by DSM as a week or more with full syndromic criteria for both manic and depressive episodes. In DSM-5, this highly restrictive criterion was changed to encompass a broader conception of subsyndromal mixed symptoms (consisting of at least three contrapolar symptoms) in either manic, hypomanic, or depressive episodes. In ICD-11, mixed symptoms are still considered to be an episode, with the requirement of several prominent symptoms of the countervailing mood state, a less stringent requirement that more closely aligns with Kraepelin's broader conception of mixed states. 7

Epidemiology

Using DSM-IV criteria, the National Comorbidity Study replication 6 found similar lifetime prevalence rates for BD-I (1.0%) and BD-II (1.1%) among men and women. Subthreshold symptoms of hypomania (bipolar spectrum disorder) were more common, with prevalence rate estimates of 2.4%. 6 Incidence rates, which largely focus on BD-I, have been estimated at approximately 6.1 per 100 000 person years (95% confidence interval 4.7 to 8.1). 8 Estimates of the incidence and lifetime prevalence of bipolar disorder show moderate variations according to the method of diagnosis (performed by lay interviewers in a research context v clinically trained interviews) and the racial, ethnic, and demographic context. 9 Higher income, westernized countries have slightly higher rates of bipolar disorder, 10 which might reflect a combination of westernized centricity in the specific idioms used to understand and elicit symptoms, as well as a greater knowledge, acceptance, and conceptualization of emotional symptoms as psychiatric disorders.

Causes of bipolar disorder

Like other common psychiatric disorders, bipolar disorder is likely caused by a complex interplay of multiple factors, both at the population level and within individuals, 11 which can be best conceptualized at various levels of analysis, including genetics, brain networks, psychological functioning, social support, and other biological and environmental factors. Because knowledge about the causes of bipolar disorder remains in its infancy, for pragmatic purposes, most research has followed a reductionistic model that will ultimately need to be synthesized for a more coherent view of the pathophysiology that underlies the condition.

Insights from genetics

From its earliest descriptions, bipolar disorder has been observed to run in families. Indeed, family history is the strongest individual risk factor for developing the disorder, with first degree relatives having an approximately eightfold higher risk of developing bipolar disorder compared with the baseline population rates of ~1%. 12 While family studies cannot separate the effects of genetics from behavioral or cultural transmission, twin and adoption studies have been used to confirm that the majority of the familial risk is genetic in origin, with heritability estimates of approximately 60-80%. 13 14 There have been fewer studies of BD-II, but its heritability has been found to be smaller (~46%) 15 and closer to that of more common disorders such as major depressive disorder or generalized anxiety. 15 16 Nevertheless, significant heritability does not necessarily imply the presence of genes of large effect, since the genetic risk for bipolar disorder appears likely to be spread across many common variants of small effect sizes. 16 17 Ongoing studies of rare variations have found preliminary evidence for variants of slightly higher effect sizes, with initial evidence of convergence with common variations in genes associated with the synapse and the postsynaptic density. 18 19

While the likelihood that the testing of single variants or genes will be useful for diagnostic purposes is low, analyses known as polygenic risk studies can sum across all the risk loci and have some ability to discriminate cases from controls, albeit at the group level rather than the individual level. 20 These polygenic risk scores can also be used to identify shared genetic risk factors across other medical and psychiatric disorders. Bipolar disorder has strong evidence for common variant based coheritability with schizophrenia (genetic correlation (r g ) 0.69) and major depressive disorder (r g 0.48). BD-I has stronger coheritability with schizophrenia compared with BD-II, which is more strongly genetically correlated with major depressive disorder (r g 0.66). 16 Lower coheritability was observed with attention deficit hyperactivity disorder (r g 0.21), anorexia nervosa (0.20), and autism spectrum disorder (r g 0.21). 16 These correlations provide evidence for shared genetic risk factors between bipolar disorder and other major psychiatric syndromes, a pattern also corroborated by recent nationwide registry based family studies. 12 14 Nevertheless, despite their potential usefulness, polygenic risk scores must currently be interpreted with caution given their lack of populational representation and lingering concerns of residual confounds such as gene-environment correlations. 21

Insights from neuroimaging

Similarly to the early genetic studies, small initial studies had limited replication, leading to the formation of large worldwide consortiums such as ENIGMA (enhancing neuroimaging genetics through meta-analysis) which led to substantially larger sample sizes and improved reproducibility. In its volumetric analyses of subcortical structures from MRI (magnetic resonance imaging) of patients with bipolar disorder, the ENIGMA consortium found modest decreases in the volume of the thalamus (Cohen’s d −0.15), the hippocampus (−0.23), and the amygdala (−0.11), with an increased volume seen only in the lateral ventricles (+0.26). 22 Meta-analyses of cortical regions similarly found small reductions in cortical thickness broadly across the parietal, temporal, and frontal cortices (Cohen’s d −0.11 to −0.29) but no changes in cortical surface area. 23 In more recent meta-analyses of white matter tracts using diffuse tension imaging, widespread but modest decreases in white matter integrity were found throughout the brain in bipolar disorder, most notably in the corpus callosum and bilateral cinguli (Cohen’s d −0.39 to −0.46). 24 While these findings are likely to be highly replicable, they do not, as yet, have clinical application. This is because they reflect differences at a group level rather than an individual level, 25 and because many of these patterns are also seen across other psychiatric disorders 26 and could be either shared risk factors or the effects of confounding factors such as medical comorbidities, medications, co-occurring substance misuse, or the consequences (rather than causes) of living with mental illness. 27 Efforts to collate and meta-analyze large samples utilizing longitudinal designs 28 task based, resting state functional MRI measurents, 29 as well as other measures of molecular imaging (magnetic resonance spectroscopy and positron emission tomography) are ongoing but not as yet synthesized in large scale meta-analyses.

Environmental risk factors

Because of the difficulty in measuring and studying the relevant and often common environmental risk factors for a complex illness like bipolar disorder, there has been less research on how environmental risk factors could cause or modify bipolar disorder. Evidence for intrauterine risk factors is mixed and less compelling than such evidence in disorders like schizophrenia. 30 Preliminary evidence suggests that prominent seasonal changes in solar radiation, potentially through its effects on circadian rhythm, can be associated with an earlier onset of bipolar disorder 31 and a higher likelihood of experiencing a depressive episode at onset. 31 However, the major focus of environmental studies in bipolar disorder has been on traumatic and stressful life events in early childhood 32 and in adulthood. 33 The effects of such adverse events are complex, but on a broad level have been associated with earlier onset of bipolar disorder, a worse illness course, greater prevalence of psychotic symptoms, 34 substance misuse and psychiatric comorbidities, and a higher risk of suicide attempts. 32 35 Perhaps uniquely in bipolar disorder, evidence also indicates that positive life events associated with goal attainment can also increase the risk of developing elevated states. 36

Comorbidity

Bipolar disorder rarely manifests in isolation, with comorbidity rates indicating elevated lifetime risk of several co-occurring symptoms and comorbid disorders, particularly anxiety, attentional disorders, substance misuse disorders, and personality disorders. 37 38 The causes of such comorbidity can be varied and complex: they could reflect a mixed presentation artifactually separated by current diagnostic criteria; they might also reflect independent illnesses; or they might represent the downstream effects of one disorder increasing the risk of developing another disorder. 39 Anxiety disorders tend to occur before the frank onset of manic or hypomanic symptoms, suggesting that they could in part reflect prodromal symptoms that manifest early in the lifespan. 37 Similarly, subthreshold and syndromic symptoms of attention deficit/hyperactivity disorder are also observed across the lifespan of people with bipolar disorder, but particularly in early onset bipolar disorder. 40 On the other hand, alcohol and substance misuse disorders occur more evenly before and after the onset of bipolar disorder, consistent with a more bidirectional causal association. 41

The association between bipolar disorder and comorbid personality disorders is similarly complex. Milder manifestations of persistent mood instability (cyclothymia) or low mood (dysthymia) have previously been considered to be temperamental variants of bipolar disorder, 42 but are now classified as related but separate disorders. In people with persistent emotional dysregulation, making the diagnosis of bipolar disorder can be particularly challenging, 43 since the boundaries between longstanding mood instability and phasic changes in mood state can be difficult to distinguish. While symptom overlap can lead to artificially inflated prevalence rates of personality disorders in bipolar disorder, 44 the elevated rates of most personality disorders in bipolar disorder, particularly those related to emotional instability, are likely reflective of an important clinical phenomenon that is understudied, particularly with regard to treatment implications. 45 In general, people with comorbidities tend to have greater symptom burden and functional impairment and have lower response rates to treatment. 46 47 Data on approaches to treat specific comorbid disorders in bipolar disorder are limited, 48 49 and clinicians are often left to rely on their clinical judgment. The most parsimonious approach is to treat primary illness as fully as possible before considering additional treatment options for remaining comorbid symptoms. For certain comorbidities, such as anxiety symptoms and disorders of attention, first line pharmacological treatment—namely, antidepressants and stimulants, should be used with caution, since they might increase the long term risks of mood switching or overall mood instability. 50 51

Like other major mental illnesses, bipolar disorder is also associated with an increased prevalence of common medical disorders such as obesity, hyperlipidemia, coronary artery disease, chronic obstructive pulmonary disease, and thyroid dysfunction. 52 These have been attributed to increase risk factors such as physical inactivity, poor nutrition, smoking, and increased use of addictive substances, 53 but some could also be consequences of specific treatments, such as the atypical antipsychotics and mood stabilizers. 54 Along with poor access to care, this medical burden likely accounts for much of the increased standardized mortality (approximately 2.6 times higher) in people with bipolar disorder, 55 highlighting the need to utilize treatments with better long term side effect profiles, and the need for better integration with medical care.

Precursors and prodromes: who develops bipolar disorder?

While more widespread screening and better accessibility to mental health providers should in principle shorten the time to diagnosis and treatment, early manifestation of symptoms in those who ultimately go on to be diagnosed with bipolar disorder is generally non-specific. 56 In particular, high risk offspring studies of adolescents with a parent with bipolar disorder have found symptoms of anxiety and attentional/disruptive disorders to be frequent in early adolescence, followed by higher rates of depression and sleep disturbance in later teenage years. 56 57 Subthreshold symptoms of mania, such as prolonged increases in energy, elated mood, racing thoughts, and mood lability are also more commonly found in children with prodromal symptoms (meta-analytic prevalence estimates ranging from 30-50%). 58 59 Still, when considered individually, none of these symptoms or disorders are sensitive or specific enough to accurately identify individuals who will transition to bipolar disorder. Ongoing approaches to consider these clinical factors together to improve accuracy have a promising but modest ability to identify people who will develop bipolar disorder, 60 emphasizing the need for further studies before implementation.

Screening for bipolar disorder

Manic episodes can vary from easily identifiable prototypical presentations to milder or less typical symptoms that can be challenging to diagnose. Ideally, a full diagnostic evaluation with access to close informants is performed on patients presenting to clinical care; however, evaluations can be hurried in routine clinical care, and the ability to recall previous episodes might be limited. In this context, the use of screening scales can be a helpful addition to clinical care, although screening scales must be regarded as an impetus for a confirmatory clinical interview rather than a diagnostic instrument by themselves. The two most widely used and openly available screening scales are the mood disorders questionnaire (based on the DSM-IV criteria for hypomania) 61 and the hypomania check list (HCL-32), 62 that represent a broader overview of symptoms proposed to be part of a broader bipolar spectrum.

Racial/ethnic disparities

Although community surveys using structured or semi-structured diagnostic instruments, have provided little evidence for variation across ethnic groups, 63 64 observational studies based on clinical diagnoses in healthcare settings have found a disproportionately higher rate of diagnosis of schizophrenia relative to bipolar disorder in black people. 65 Consistent with similar disparities seen across medicine, these differences in clinical diagnoses are likely influenced by a complex mix of varying clinical presentations, differing rates of comorbid conditions, poorer access to care, greater social and economic burden, as well as the potential effect of subtle biases of healthcare professionals. 65 While further research is necessary to identify driving factors responsible for diagnostic disparities, clinicians should be wary of making a rudimentary diagnosis in patients from marginalized backgrounds, ensuring comprehensive data gathering and a careful diagnostic formulation that incorporates shared decision making between patient and provider.

Bipolar disorder is a recurrent illness, but its longitudinal course is heterogeneous and difficult to predict. 46 66 The few available long term studies of BD-I and BD-II have found a consistent average rate of recurrence of 0.40 mood episodes per year in historical studies 67 and 0.44 mood episodes per year in more recent studies. 68 The median time to relapse is estimated to be 1.44 years, with higher relapse rates seen in BD-I (0.81 years) than in BD-II (1.63 years) and no differences observed with respect to age or sex. 1 2 In addition to focusing on episodes, an important development in research and clinical care of bipolar disorder has been the recognition of the burden of subsyndromal symptoms. Although milder in severity, these symptoms can be long lasting, functionally impairing, and can themselves be a risk factor for episode relapse. 69 Recent cohort studies have also found that a substantial proportion of patients with bipolar disorder (20-30%) continue to have poor outcomes even after receiving guideline based care. 46 70 Risk factors that contribute to this poor outcome include transdiagnostic indicators of adversity such as substance misuse, low educational attainment, socioeconomic hardship, and comorbid disorders. As expected, those with more severe past illness activity, including those with rapid cycling, were also more likely to remain symptomatically and psychosocially impaired. 46 71 72

The primary focus of treating bipolar disorder has been to manage the manic, mixed, or depressive episodes that present to clinical care and to subsequently prevent recurrence of future episodes. Owing to the relapse remitting nature of the illness, randomized controlled trials are essential to determine treatment efficacy, as the observation of clinical improvement could just represent the ebbs and flows of the natural history of the illness. In the United States, the FDA (Food and Drug Administration) requires at least two large scale placebo controlled trials (phase 3) to show significant evidence of efficacy before approving a treatment. Phase 3 studies of bipolar disorder are generally separated into short term studies of mania (3-4 weeks), short term studies for bipolar depression (4-6 weeks), and longer term maintenance studies to evaluate prophylactic activity against future mood episodes (usually lasting one year). Although the most rigorous evaluation of phase 3 studies would be to require two broadly representative and independent randomized controlled trials, the FDA permits consideration of so called enriched design trials that follow participants after an initial response and tolerability has been shown to an investigational drug. Because of this initial selection, such trials can be biased against comparator agents, and could be less generalizable to patients seen in clinical practice.

A summary of the agents approved by the FDA for treatment of bipolar disorder is in table 1 , which references the key clinical trials demonstrating efficacy. Figure 1 and supplementary table 1 are a comparison of treatments for mania, depression, and maintenance. Effect sizes reflect the odds ratios or relative risks of obtaining response (defined as ≥50% improvement from baseline) in cases versus controls and were extracted from meta-analyses of randomized controlled trials for bipolar depression 86 and maintenance, 94 as well as a network meta-analysis of randomized controlled trials in bipolar mania. 73 Effect sizes are likely to be comparable for each phase of treatment, but not across the different phases, since methodological differences exist between the three meta-analytic studies.

FDA approved medications for bipolar disorder

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Summary of treatment response rates (defined as ≥50% improvement from baseline) of modern clinical trials for acute mania, acute bipolar depression, and long term recurrence. Meta-analytic estimates were extracted from recent meta-analyses or network meta-analyses of acute mania, 73 acute bipolar depression, 86 and bipolar maintenance studies 94

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Acute treatment of mania

As mania is characterized by impaired judgment, individuals can be at risk for engaging in high risk, potentially dangerous behaviors that can have substantial personal, occupational, and financial consequences. Therefore, treatment of mania is often considered a psychiatric emergency and is, when possible, best performed in the safety of an inpatient unit. While the primary treatment for mania is pharmacological, diminished insight can impede patients' willingness to accept treatment, emphasizing the significance of a balanced therapeutic approach that incorporates shared decision making frameworks as much as possible to promote treatment adherence.

The three main classes of anti-manic treatments are lithium, mood stabilizing anticonvulsants (divalproate and carbamazepine), and antipsychotic medications. Almost all antipsychotics are effective in treating mania, with the more potent dopamine D2 receptor antagonists such as risperidone and haloperidol demonstrating slightly higher efficacy ( fig 1 ). 73 In the United States, the FDA has approved the use of all second generation antipsychotics for treating mania except for lurasidone and brexpriprazole. Compared with mood stabilizing medications, second generation antipsychotics have a faster onset of action, making them a first line treatment for more severe manic symptoms that require rapid treatment. 99 The choice of which specific second generation antipsychotic to use depends on a balance of efficacy, tolerability concerns, and cost considerations (see table 1 ). Notably, the FDA has placed a black box warning on all antipsychotics for increasing the risk of cerebral vascular accidents in the elderly. 100 While this was primarily focused on the use of antipsychotics in dementia, this likely class effect should be taken into account when considering the use of antipsychotics in the elderly.

Traditional mood stabilizers, such as lithium, divalproate, and carbamazepine are also effective in the treatment of active mania ( fig 1 ). Since lithium also has a robust prophylactic effect (see section on prevention of mood episodes below) it is often recommended as first line treatment and can be considered as monotherapy when rapid symptom reduction is not clinically indicated. On the other hand, other anticonvulsants such as lamotrigine, gabapentin, topiramate, and oxcarbazepine have not been found to be effective for the treatment of mania or mixed episodes. 101 Although the empirical evidence for polypharmacy is limited, 102 combination treatment in acute mania, usually consisting of a mood stabilizer and a second generation antipsychotic, is commonly used in clinical practice despite the higher burden of side effects. Following resolution of an acute mania, consideration should be given to transitioning to monotherapy with an agent with proven prophylactic activity.

Pharmacological approaches to bipolar depression

Depressed episodes are usually more common than mania or hypomania, 103 104 and often represent the primary reason for individuals with bipolar disorder to seek treatment. Nevertheless, because early antidepressant randomized controlled trials did not distinguish between unipolar and bipolar depressive episodes, it has only been in the past two decades that large scale randomized controlled trials have been conducted specifically for bipolar depression. As such trials are almost exclusively funded by pharmaceutical companies, they have focused on the second generation antipsychotics and newer anticonvulsants still under patent. These trials have shown moderate but robust effects for most recent second generation antipsychotics, five of which have received FDA approval for treating bipolar depression ( table 1 ). No head-to-head trials have been conducted among these agents, so the choice of medication depends on expected side effects and cost considerations. For example, quetiapine has robust antidepressant efficacy data but is associated with sedation, weight gain, and adverse cardiovascular outcomes. 105 Other recently approved medications such as lurasidone, cariprazine, and lumateperone have better side effect profiles but show more modest antidepressant activity. 106

Among the mood stabilizing anticonvulsants, lamotrigine has limited evidence for acute antidepressant activity, 107 possibly owing to the need for an 8 week titration to reach the full dose of 200 mg. However, as discussed below, lamotrigine can still be considered for mild to moderate acute symptoms owing to its generally tolerable side effect profile and proven effectiveness in preventing the recurrence of depressive episodes. Divalproate and carbamazepine have some evidence of being effective antidepressants in small studies, but as there has been no large scale confirmatory study, they should be considered second or third line options. 86 Lithium has been studied for the treatment of bipolar depression as a comparator to quetiapine and was not found to have a significant acute antidepressant effect. 88

Antidepressants

Owing to the limited options of FDA approved medications for bipolar depression and concerns of metabolic side effects from long term second generation antipsychotic use, clinicians often resort to the use of traditional antidepressants for the treatment of bipolar depression 108 despite the lack of FDA approval for such agents. Indeed, recent randomized clinical trials of antidepressants in bipolar depression have not shown an effect for paroxetine, 89 109 bupropion, 109 or agomelatine. 110 Beyond the question of efficacy, another concern regarding antidepressants in bipolar disorder is their potential to worsen the course of illness by either promoting mixed or manic symptoms or inducing more subtle degrees of mood instability and cycle acceleration. 111 However, the risk of switching to full mania while being treated with mood stabilizers appears to be modest, with a meta-analysis of randomized clinical trials and clinical cohort studies showing the rates of mood switching over an average follow-up of five months to be approximately 15.3% in people with bipolar disorder treated on antidepressants compared with 13.8% in those without antidepressant treatment. 111 The risk of switching appears to be higher in the first 1-2 years of treatment in people with BD-I, and in those treated with a tricyclic antidepressant 112 or the dual reuptake inhibitor venlafaxine. 113 Overall, while the available data have methodological limitations, most guidelines do not recommend the use of antidepressants in bipolar disorder, or recommend them only after agents with more robust evidence have been tried. That they remain so widely used despite the equivocal evidence base reflects the unmet need for treatment of depression, concerns about the long term side effects of second generation antipsychotics, and the challenges of changing longstanding prescribing patterns.

Pharmacological approaches to prevention of recurrent episodes

Following treatment of the acute depressive or manic syndrome, the major focus of treatment is to prevent future episodes and minimize interepisodic subsyndromal symptoms. Most often, the medication that has been helpful in controlling the acute episode can be continued for prevention, particularly if clinical trial evidence exists for a maintenance effect. To show efficacy for prevention, studies must be sufficiently long to allow the accumulation of future episodes to occur and be potentially prevented by a therapeutic intervention. However, few long term treatment studies exist and most have utilized enriched designs that likely favor the drug seeking regulatory approval. As shown in figure 1 , meta-analyses 94 show prophylactic effect for most (olanzapine, risperidone, quetiapine, aripiprazole, asenapine) but not all (lurasidone, paliperidone) recently approved second generation antipsychotics. The effect sizes are generally comparable with monotherapy (odds ratio 0.42, 95% confidence interval 0.34 to 0.5) or as adjunctive therapy (odds ratio 0.37, 95% confidence interval 0.25 to 0.55). 94 Recent studies of lithium, which have generally used it as a (non-enriched) comparator drug, show a comparable protective effect (odds ratio 0.46, 95% confidence interval 0.28 to 0.75). 94 Among the mood stabilizing anticonvulsant drugs, a prophylactic effect has also been found for both divalproate and lamotrigine ( fig 1 and supplementary table 1), although only the latter has been granted regulatory approval for maintenance treatment. While there are subtle differences in effect sizes in drugs approved for maintenance ( fig 1 and table 1 ), the overlapping confidence intervals and methodological differences between studies prevent a strict comparison of the effect measures.

Guidelines often recommend lithium as a first line agent given its consistent evidence of prophylaxis, even when tested as the disadvantaged comparator drug in enriched drug designs. Like other medications, lithium has a unique set of side effects and ultimately the decision about which drug to use among those which are efficacious should be a decision carefully weighed and shared between patient and provider. The decision might be re-evaluated after substantial experience with the medication or at different stages in the long term treatment of bipolar disorder (see table 1 ).

Psychotherapeutic approaches

The frequent presence of residual symptoms, often associated with psychosocial and occupational dysfunction, has led to renewed interest in psychotherapeutic and psychosocial approaches to bipolar disorder. Given the impairment of judgment seen in mania, psychotherapy has more of a supportive and educational role in the treatment of mania, whereas it can be more of a primary focus in the treatment of depressive states. On a broad level, psychotherapeutic approaches effective for acute depression, such as cognitive behavioral therapy, interpersonal therapy, behavioral activation, and mindfulness based strategies, can also be recommended for acute depressive states in individuals with bipolar disorder. 114 Evidence for more targeted psychotherapy trials for bipolar disorder is more limited, but meta-analyses have found evidence for decreased recurrence (odds ratio 0.56; 95% confidence interval 0.43 to 0.74) 115 and improvement of subthreshold interepisodic depressive and manic symptoms with cognitive behavioral therapy, family based therapy, interpersonal and social rhythm therapy, and psychoeducation. 115 Recent investigations have also focused on targeted forms of psychotherapy to improve cognition 116 117 118 as well as psychosocial and occupational functioning. 119 120 Although these studies show evidence of a moderate effect, they remain preliminary, methodologically diverse, and require replication on a larger scale. 121

The implementation of evidence based psychotherapy as a treatment faces several challenges, including clinical training, fidelity monitoring, and adequate reimbursement. Novel approaches, leveraging the greater tractability of digital tools 122 and allied healthcare workers, 123 are promising means of lessening the implementation gap; however, these approaches require validation and evidence of clinical utility similar to traditional methods.

Neurostimulation approaches

For individuals with bipolar disorder who cannot tolerate or do not respond well to standard pharmacotherapy or psychotherapeutic approaches, neurostimulation techniques such as repetitive transcranial magnetic stimulation or electric convulsive therapy should be considered as second or third line treatments. Electric convulsive therapy has shown response rates of approximately 60-80% in severe acute depressions 124 125 and 50-60% in cases with treatment resistant depression. 126 These response rates compare favorably with those of pharmacological treatment, which are likely to be closer to ~50% and ~30% in subjects with moderate to severe depression and treatment resistant depression, respectively. 127 Although the safety of electric convulsive therapy is well established, relatively few medical centers have it available, and its acceptability is limited by cognitive side effects, which are usually short term, but which can be more significant with longer courses and with bilateral electrode placement. 128 While there have been fewer studies of electric convulsive therapy for bipolar depression compared with major depressive disorder, it appears to be similarly effective and might show earlier response. 129 Anecdotal evidence also suggests electric convulsive therapy that is useful in refractory mania. 130

Compared with electric convulsive therapy, repetitive transcranial magnetic stimulation has no cognitive side effects and is generally well tolerated. Repetitive transcranial magnetic stimulation acts by generating a magnetic field to depolarize local neural tissue and induce excitatory or inhibitory effects depending on the frequency of stimulation. The most studied FDA approved form of repetitive transcranial magnetic stimulation applies high frequency (10 Hz) excitatory pulses to the left prefrontal cortex for 30-40 minutes a day for six weeks. 131 Like electric convulsive therapy, repetitive transcranial magnetic stimulation has been primarily studied in treatment resistant depression and has been found to have moderate effect, with about one third of patients having a significant treatment response compared with those treated with pharmacotherapy. 131 Recent innovations in transcranial magnetic stimulation have included the use of a novel, larger coil to stimulate a larger degree of the prefrontal cortex (deep transcranial magnetic stimulation), 132 and a shortened (three minutes), higher frequency intermittent means of stimulation known as theta burst stimulation that appears to be comparable to conventional (10 Hz) repetitive transcranial magnetic stimulation. 133 A preliminary trial has recently assessed a new accelerated protocol of theta burst stimulation marked by 10 sessions a day for five days. It found that theta burst stimulation had a greater effect on people with treatment resistant depression compared with treatment as usual, although larger studies are needed to confirm these findings. 134

Conventional repetitive transcranial magnetic stimulation (10 Hz) studies in bipolar disorder have been limited by small sample sizes but have generally shown similar effects compared with major depressive disorder. 135 However, a proof of concept study of single session theta burst stimulation did not show efficacy in bipolar depression, 136 reiterating the need for specific trials for bipolar depression. Given the lack of such trials in bipolar disorder, repetitive transcranial magnetic stimulation should be considered a potentially promising but as yet unproven treatment for bipolar depression.

The other major form of neurostimulation studied in both unipolar and bipolar depression is transcranial direct current stimulation, an easily implemented method of delivering a low amplitude electrical current to the prefrontal area of the brain that could lead to local changes in neuronal excitability. 137 Like repetitive transcranial magnetic stimulation, transcranial direct current stimulation is well tolerated and has been mostly studied in unipolar depression, but has not yet generated sufficient evidence to be approved by a regulatory agency. 138 Small studies have been performed in bipolar depression, but the results have been mixed and require further research before use in clinical settings. 137 138 139 Finally, the evidence for more invasive neurostimulation studies such as vagal nerve stimulation and deep brain stimulation remains extremely limited and is currently insufficient for clinical use. 140 141

Treatment resistance in bipolar disorder

As in major depressive disorder, the use of term treatment resistance in bipolar disorder is controversial since differentiating whether persistent symptoms are caused by low treatment adherence, poor tolerability, the presence of comorbid disorders, or are the result of true treatment resistance, is an essential but often challenging clinical task. Treatment resistance should only be considered after two or three trials of evidence based monotherapy, adjunctive therapy, or both. 142 In difficult-to-treat mania, two or more medications from different mechanistic classes are typically used, with electric convulsive therapy 143 and clozapine 144 being considered if more conventional anti-manic treatments fail. In bipolar depression, it is common to combine antidepressants with anti-manic agents, despite limited evidence for efficacy. 145 Adjunctive therapies such as bright light therapy, 146 the dopamine D2/3 receptor agonist pramipexole, 147 and ketamine 148 149 have shown promising results in small open label trials that require further study.

Treatment considerations to reduce suicide in bipolar disorder

The risk of completed suicide is high across the subtypes of bipolar disorder, with estimated rates of 10-15% across the lifespan. 150 151 152 Lifetime rates of suicide attempts are much higher, with almost half of all individuals with bipolar disorder reporting at least one attempt. 153 Across a population and, often within individuals, the causes of suicide attempts and completed suicides are likely to be multifactorial, 154 affected by various risk factors, such as symptomatic illness, environmental stressors, comorbidities (particularly substance misuse), trait impulsivity, interpersonal conflict, loneliness, or socioeconomic distress. 155 156 Risk is highest in depressive and dysphoric/mixed episodes 157 158 and is particularly high in the transitional period following an acute admission to hospital. 159 Among the available treatments, lithium has potential antisuicidal properties. 160 However, since suicide is a rare event, with very few to zero suicides within a typical clinical trial, moderate evidence for this effect emerges only in the setting of meta-analyses of clinical trials. 160 Several observational studies have shown lower mortality in patients on lithium treatment, 161 but such associations might not be causal, since lithium is potentially fatal in overdose and is often avoided by clinicians in patients at high risk of suicide.

The challenge of studying scarce events has led most studies to focus on the reduction of the more common phenomena of suicidal ideation and behavior as a proxy for actual suicides. A recent such multisite study of the Veterans Affairs medical system included a mixture of unipolar and bipolar disorder and was stopped prematurely for futility, indicating no overall effect of moderate dose lithium. 162 Appropriate limitations of this study have been noted, 163 164 including difficulties in recruitment, few patients with bipolar disorder (rather than major depressive disorder), low levels of compliance with lithium therapy, high rates of comorbidity, and a follow-up of only one year. Nevertheless, while the body of evidence suggests that lithium has a modest antisuicidal effect, its degree of protection and utility in complex patients with comorbidities and multiple risk factors remain matters for further study. Treatment of specific suicidal risk in patients with bipolar disorder must therefore also incorporate broader interventions based on the individual’s specific risk factors. 165 Such an approach would include societal interventions like means restriction 166 and a number of empirically tested suicide focused psychotherapy treatments. 167 168 Unfortunately, the availability of appropriate training, expertise, and care models for such treatments remains limited, even in higher income countries. 169

More scalable solutions, such as the deployment of shortened interventions via digital means could help to overcome this implementation gap; however, the effectiveness of such approaches cannot be assumed and requires empirical testing. For example, a recent large scale randomized controlled trial of an abbreviated online dialectical behavioral therapy skills training program was paradoxically associated with slightly increased risk of self-harm. 170

Treatment consideration in BD-II and bipolar spectrum conditions

Because people with BD-II primarily experience depressive symptoms and appear less likely to switch mood states compared with individuals with BD-I, 50 171 there has been a greater acceptance of the use of antidepressants in BD-II depression, including as monotherapy. 172 However, caution should be exercised when considering the use of antidepressants without a mood stabilizer in patients with BD-II who might also experience high rates of mood instability and rapid cycling. Such individuals can instead respond better to newer second generation antipsychotic agents such as quetiapine 173 and lumateperone, 93 which are supported by post hoc analyses of these more recent clinical trials with more BD-II patients. In addition, despite the absence of randomized controlled trials, open label studies have suggested that lithium and other mood stabilizers can have similar efficacy in BD-II, especially in the case of lamotrigine. 174

Psychotherapeutic approaches such as psychoeducation, cognitive behavioral therapy, and interpersonal and social rhythm therapy have been found to be helpful 115 and can be considered as the primary form of treatment for BD-II in some patients, although in most clinical scenarios BD-II is likely to occur in conjunction with psychopharmacology. While it can be tempting to consider BD-II a milder variant of BD-I, high rates of comorbid disorders, rapid cycling, and adverse consequences such as suicide attempts 175 176 highlight the need for clinical caution and the provision of multimodal treatment, focusing on mood improvement, emotional regulation, and better psychosocial functioning.

Precision medicine: can it be applied to improve the care of bipolar disorder?

The recent focus on precision medicine approaches to psychiatric disorders seeks to identify clinically relevant heterogeneity and identify characteristics at the level of the individual or subgroup that can be leveraged to identify and target more efficacious treatments. 1 177 178

The utility of such an approach was originally shown in oncology, where a subset of tumors had gene expression or DNA mutation signatures that could predict response to treatments specifically designed to target the aberrant molecular pathway. 179 While much of the emphasis of precision medicine has been on the eventual identification of biomarkers utilizing high throughput approaches (genetics and other “omics” based measurements), the concept of precision medicine is arguably much broader, encompassing improvements in measurement, potentially through the deployment of digital tools, as well as better conceptualization of contextual, cultural, and socioeconomic mechanisms associated with psychopathology. 180 181 Ultimately, the goal of precision psychiatry is to identify and target driving mechanisms, be they molecular, physiological, or psychosocial in nature. As such, precision psychiatry seeks what researchers and clinicians have often sought: to identify clinically relevant heterogeneity to improve prediction of outcomes and increase the likelihood of therapeutic success. The novelty being not so much the goals of the overarching approach, but the increasing availability of large samples, novel digital tools, analytical advances, and an increasing armamentarium of biological measurements that can be deployed at scale. 177

Although not unique to bipolar disorder, several clinical decision points along the life course of bipolar disorder would benefit from a precision medicine approach. For example, making an early diagnosis is often not possible based on clinical symptoms alone, since such symptoms are usually non-specific. A precision medicine approach could also be particularly relevant in helping to identify subsets of patients for whom the use of antidepressants could be beneficial or harmful. Admittedly, precision medicine approaches to bipolar disorder are still in their infancy, and larger, clinically relevant, longitudinal, and reliable phenotypes are needed to provide the infrastructure for precision medicine approaches. Such data remain challenging to obtain at scale, leading to renewed efforts to utilize the extant clinical infrastructure and electronic medical records to help emulate traditional longitudinal analyses. Electronic medical records can help provide such data, but challenges such as missingness, limited quality control, and potential biases in care 182 need to be resolved with carefully considered analytical designs. 183

Emerging treatments

Two novel atypical antipsychotics, amilsupride and bifeprunox, are currently being tested in phase 3 trials ( NCT05169710 and NCT00134459 ) and could gain approval for bipolar depression in the near future if these pivotal trials show a significant antidepressant effect. These drugs could offer advantages such as greater antidepressant effects, fewer side effects, and better long term tolerability, but these assumptions must be tested empirically. Other near term possibilities include novel rapid antidepressant treatments, such as (es)ketamine that putatively targets the glutamatergic system, and has been recently approved for treatment resistant depression, but which have not yet been tested in phase 3 studies in bipolar depression. Small studies have shown comparable effects of intravenous ketamine, 149 184 in bipolar depression with no short term evidence of increased mood switching or mood instability. Larger phase 2 studies ( NCT05004896 ) are being conducted which will need to be followed by larger phase 3 studies. Other therapies targeting the glutamatergic system have generally failed phase 3 trials in treatment resistant depression, making them unlikely to be tested in bipolar depression. One exception could be the combination of dextromethorphan and its pharmacokinetic (CYP2D6) inhibitor bupropion, which was recently approved for treatment resistant depression but has yet to be tested in bipolar depression. Similarly, the novel GABAergic compound zuranolone is currently being evaluated by the FDA for the treatment of major depressive disorder and could also be subsequently studied in bipolar depression.

Unfortunately, given the general efficacy for most patients of available treatments, few scientific and financial incentives exist to perform large scale studies of novel treatment in mania. Encouraging results have been seen in small studies of mania with the selective estrogen receptor modulator 185 tamoxifen and its active metabolite endoxifen, both of which are hypothesized to inhibit protein kinase C, a potential mechanistic target of lithium treatment. These studies remain small, however, and anti-estrogenic side effects have potentially dulled interest in performing larger studies.

Finally, several compounds targeting alternative pathophysiological mechanisms implicated in bipolar disorder have been trialed in phase 2 academic studies. The most studied has been N -acetylcysteine, a putative mitochondrial modulator, which initially showed promising results only to be followed by null findings in larger more recent studies. 186 Similarly, although small initial studies of anti-inflammatory agents provided impetus for further study, subsequent phase 2 studies of the non-steroidal agent celecoxib, 187 the anti-inflammatory antibiotic minocycline, 187 and the antibody infliximab (a tumor necrosis factor antagonist) 188 have not shown efficacy for bipolar depression. Secondary analyses have suggested that specific anti-inflammatory agents might be effective only for a subset of patients, such as those with elevated markers of inflammation or a history of childhood adversity 189 ; however, such hypotheses must be confirmed in adequately powered independent studies.

Several international guidelines for the treatment of bipolar disorder have been published in the past decade, 102 190 191 192 providing a list of recommended treatments with efficacy in at least one large randomized controlled trial. Since effect sizes tend to be moderate and broadly comparable across classes, all guidelines allow for significant choice among first line agents, acknowledging that clinical characteristics, such as history of response or tolerability, severity of symptoms, presence of mixed features, or rapid cycling can sometimes over-ride guideline recommendations. For acute mania requiring rapid treatment, all guidelines prioritize the use of second generation antipsychotics such as aripiprazole, quetiapine, risperidone, asenapine, and cariprazine. 102 192 193 Combination treatment is considered based on symptom severity, tolerability, and patient choice, with most guidelines recommending lithium or divalproate along with a second generation antipsychotic for mania with psychosis, severe agitation, or prominent mixed symptoms. While effective, haloperidol is usually considered a second choice option owing to its propensity to cause extrapyramidal symptoms. 102 192 193 Uniformly, all guidelines agree on the need to taper antidepressants in manic or mixed episodes.

For maintenance treatment, guidelines are generally consistent in recommending lithium if tolerated and without relative contraindications, such as baseline renal disease. 194 The second most recommended maintenance treatment is quetiapine, followed by aripiprazole for patients with prominent manic episodes and lamotrigine for patients with predominant depressive episodes. 194 Most guidelines recommend considering prophylactic properties when initially choosing treatment for acute manic episodes, although others suggests that acute maintenance treatments can be cross tapered with maintenance medications after several months of full reponse. 193

For bipolar depression, recent guidelines recommend specific second generation antipsychotics such as quetiapine, lurasidone, and cariprazine 102 192 193 For more moderate symptoms, consideration is given to first using lamotrigine and lithium. Guidelines remain cautious about the use of antidepressants (selective serotonin reuptake inhibitors, venlafaxine, or bupropion) in patients with BP-I, restricting them to second or third line treatments and always in the context of an anti-manic agent. However, for patients with BP-II and no rapid cycling, several guidelines allow for the use of carefully monitored antidepressant monotherapy.

Bipolar disorder is a highly recognizable syndrome with many effective treatment options, including the longstanding gold standard therapy lithium. However, a significant proportion of patients do not respond well to current treatments, leading to negative consequences, poor quality of life, and potentially shortened lifespan. Several novel treatments are being developed but limited knowledge of the biology of bipolar disorder remains a major challenge for novel drug discovery. Hope remains that the insights of genetics, neuroimaging, and other investigative modalities could soon be able to inform the development of rational treatments aimed to mitigate the underlying pathophysiology associated with bipolar disorder. At the same time, however, efforts are needed to bridge the implementation gap and provide truly innovative and integrative care for patients with bipolar disorder. 195 Owing to the complexity of bipolar disorder, few patients can be said to be receiving optimized care across the various domains of mental health that are affected in those with bipolar disorder. Fortunately, the need for improvement is now well documented, 196 and concerted efforts at the scale necessary to be truly innovative and integrative are now on the horizon.

Questions for future research

Among adolescents and young adults who manifest common mental disorders such as anxiety or depressive or attentional disorders, who will be at high risk for developing bipolar disorder?

Can we predict the outcomes for patients following a first manic or hypomanic episode? This will help to inform who will require lifelong treatment and who can be tapered off medications after sustained recovery.

Are there reliable clinical features and biomarkers that can sufficiently predict response to specific medications or classes of medication?

What are the long term consequences of lifelong treatments with the major classes of medications used in bipolar disorder? Can we predict and prevent medical morbidity caused by medications?

Can we understand in a mechanistic manner the pathophysiological processes that lead to abnormal mood states in bipolar disorder?

Series explanation: State of the Art Reviews are commissioned on the basis of their relevance to academics and specialists in the US and internationally. For this reason they are written predominantly by US authors

Contributors: FSG performed the planning, conduct, and reporting of the work described in the article. FSG accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish.

Competing interests: I have read and understood the BMJ policy on declaration of interests and declare no conflicts of interest.

Patient involvement: FSG discussed of the manuscript, its main points, and potential missing points with three patients in his practice who have lived with longstanding bipolar disorder. These additional viewpoints were incorporated during the drafting of the manuscript.

Provenance and peer review: Commissioned; externally peer reviewed.

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Bipolar disorders

Affiliations.

• 1 Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada; Brain and Cognition Discovery Foundation, Toronto, ON, Canada. Electronic address: [email protected].
• 2 Institute for Mental and Physical Health and Clinical Translation Strategic Research Centre, School of Medicine, Deakin University, Melbourne, VIC, Australia; Mental Health Drug and Alcohol Services, Barwon Health, Geelong, VIC, Australia; Orygen, The National Centre of Excellence in Youth Mental Health, Melbourne, VIC, Australia; Centre for Youth Mental Health, Florey Institute for Neuroscience and Mental Health, Melbourne, VIC, Australia; Department of Psychiatry, The University of Melbourne, Melbourne, VIC, Australia.
• 3 Department of Psychiatry, Adult Division, Kingston General Hospital, Kingston, ON, Canada; Department of Psychiatry, Queen's University School of Medicine, Queen's University, Kingston, ON, Canada; Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada.
• 4 Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Centre for Youth Bipolar Disorder, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
• 5 Department of Psychiatry, Faculty of Medicine, University of Antioquia, Medellín, Colombia; Mood Disorders Program, Hospital Universitario San Vicente Fundación, Medellín, Colombia.
• 6 Copenhagen Affective Disorders Research Centre, Psychiatric Center Copenhagen, Rigshospitalet, Copenhagen, Denmark; Department of Psychiatry, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
• 7 Discipline of Psychiatry, Northern Clinical School, University of Sydney, Sydney, NSW, Australia; Department of Academic Psychiatry, Northern Sydney Local Health District, Sydney, Australia.
• 8 Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
• 9 Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Dauten Family Center for Bipolar Treatment Innovation, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
• 10 Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
• 11 Hospital Clinic, Institute of Neuroscience, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain.
• 12 Department of Psychiatry, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Psychiatric Research Unit, Psychiatric Centre North Zealand, Hillerød, Denmark.
• 13 Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London and South London and Maudsley National Health Service Foundation Trust, Bethlem Royal Hospital, London, UK.
• 14 Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
• PMID: 33278937
• DOI: 10.1016/S0140-6736(20)31544-0

Bipolar disorders are a complex group of severe and chronic disorders that includes bipolar I disorder, defined by the presence of a syndromal, manic episode, and bipolar II disorder, defined by the presence of a syndromal, hypomanic episode and a major depressive episode. Bipolar disorders substantially reduce psychosocial functioning and are associated with a loss of approximately 10-20 potential years of life. The mortality gap between populations with bipolar disorders and the general population is principally a result of excess deaths from cardiovascular disease and suicide. Bipolar disorder has a high heritability (approximately 70%). Bipolar disorders share genetic risk alleles with other mental and medical disorders. Bipolar I has a closer genetic association with schizophrenia relative to bipolar II, which has a closer genetic association with major depressive disorder. Although the pathogenesis of bipolar disorders is unknown, implicated processes include disturbances in neuronal-glial plasticity, monoaminergic signalling, inflammatory homoeostasis, cellular metabolic pathways, and mitochondrial function. The high prevalence of childhood maltreatment in people with bipolar disorders and the association between childhood maltreatment and a more complex presentation of bipolar disorder (eg, one including suicidality) highlight the role of adverse environmental exposures on the presentation of bipolar disorders. Although mania defines bipolar I disorder, depressive episodes and symptoms dominate the longitudinal course of, and disproportionately account for morbidity and mortality in, bipolar disorders. Lithium is the gold standard mood-stabilising agent for the treatment of people with bipolar disorders, and has antimanic, antidepressant, and anti-suicide effects. Although antipsychotics are effective in treating mania, few antipsychotics have proven to be effective in bipolar depression. Divalproex and carbamazepine are effective in the treatment of acute mania and lamotrigine is effective at treating and preventing bipolar depression. Antidepressants are widely prescribed for bipolar disorders despite a paucity of compelling evidence for their short-term or long-term efficacy. Moreover, antidepressant prescription in bipolar disorder is associated, in many cases, with mood destabilisation, especially during maintenance treatment. Unfortunately, effective pharmacological treatments for bipolar disorders are not universally available, particularly in low-income and middle-income countries. Targeting medical and psychiatric comorbidity, integrating adjunctive psychosocial treatments, and involving caregivers have been shown to improve health outcomes for people with bipolar disorders. The aim of this Seminar, which is intended mainly for primary care physicians, is to provide an overview of diagnostic, pathogenetic, and treatment considerations in bipolar disorders. Towards the foregoing aim, we review and synthesise evidence on the epidemiology, mechanisms, screening, and treatment of bipolar disorders.

Copyright © 2020 Elsevier Ltd. All rights reserved.

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• Research Support, Non-U.S. Gov't
• Anticonvulsants / therapeutic use
• Antidepressive Agents / therapeutic use
• Antimanic Agents / therapeutic use
• Antipsychotic Agents / therapeutic use
• Bipolar Disorder / classification*
• Bipolar Disorder / drug therapy*
• Bipolar Disorder / genetics
• Bipolar Disorder / psychology
• Carbamazepine / therapeutic use
• Cardiovascular Diseases / complications
• Cardiovascular Diseases / mortality
• Child Abuse / psychology
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• Depressive Disorder, Major / drug therapy*
• Depressive Disorder, Major / genetics
• Depressive Disorder, Major / psychology
• Environmental Exposure / adverse effects
• Lamotrigine / therapeutic use
• Lithium / therapeutic use
• Mania / drug therapy
• Mania / psychology
• Suicide / psychology
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• Valproic Acid / therapeutic use
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Master's apa research paper on bipolar disorder.

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This sample psychology paper explores bipolar disorder. It defines the mental illness, explains the symptoms and treatment options. This APA-style research paper was written at the Master level to serve as a sample for the Ultius blog.

Understanding the symptoms and treatment of bipolar disorder

Bipolar disorder is a mood disorder that presents with symptoms of cycling between periods of extreme excitement (mania) and sadness; it is hereditary and often linked to brain injury (Mitchell, 2013; Duarte, Becerra & Cruise, 2016). Between one and two percent of all Australians suffer from bipolar disorder, although in many the symptoms are mild and have limited impact on functioning (Mitchell, 2013; Kulkarni et al., 2012). For those with severe cases, symptoms can impact all major life areas, including work, school, and interpersonal and community relationships (Bullock, Murray & Meyer, 2017).

This makes understanding important for the social work professional, as social work practice will likely deal with many persons suffering from bipolar disorder, particularly if that practice involves the mental health field. Without a clear understanding of the shifting mood and behavior of those with bipolar disorder, the social worker may attempt to meet the client in their current state, without understanding that this state may be vastly different tomorrow (Grande et al., 2016). In addition, the social worker may form expectations of the ability of the client to undertake certain things independently that are not realistic expectations, leading to poor outcomes (Hampson, Hicks & Watt, 2016). Understanding the nature of bipolar disorder and its effect on client functioning provides social workers a foundation from which to effectively address these clients’ various needs within the consideration of their mental health issues (Martín-Subero et al., 2014).

Diagnosing bipolar disorder

A brief review of literature reveals some disagreement about what constitutes bipolar disorder and its diagnosis (Benti et al., 2014; Grande et al., 2016). This dispute involves the severity of symptoms required to justify a bipolar disorder (Benti et al., 2014; Grande et al., 2016). However, most scholars recognize that periods of extreme mood, often accompanied by psychotic elements, are common in the severe form of the disease (Bullock, Murray & Meyer, 2017). There is also agreement of the effects of these mood swings.

Duarte, Becerra and Cruise (2016) examined English-language research over a 23 year period, and found that bipolar disorder negatively impacted patients’ educational attainment, occupational success, and stability in relationships . Those diagnosed at early ages were more likely to suffer from damaging effects; those with an age of onset of 15-19, the most common range for those with severe bipolar disorder, were less likely to be successfully married, gainfully employed, or have completed their basic education (Duarte, Becerra & Cruise, 2016; Joyce, Thompson & Marwaha, 2016). These findings were consistent with several of the solitary research studies include in this review, such as Chatzidamianos, Lobban and Jones (2015), Hampson, Hicks and Watt (2016), Martín-Subero et al (2014), and Kulkarni et al. (2012).

Symptoms of bipolar disorder

Symptoms of the disease are behavioral, with limited and disputed indications of change of brain activity during certain mood episodes (Bullock, Murray & Meyer, 2017). Bullock, Murray and Meyer (2017), in a study of the effects of environmental factors on bipolar mood episodes, found that few clear physiological tests exist. Further, there are not consistent environmental factors beyond a slight correlation with increased environment temperature that would predict when mood changes might occur. Periods of extreme mood can last anywhere from a few hours to weeks at a time, making differentiation between symptoms and the patient’s normal functioning even more difficult, particularly in early stages of the disease (Joyce, Thompson & Marwaha, 2016).

Treatment of bipolar disorder

This literature indicates social work practitioners act based on some theoretical framework, which guides their decisions regarding how to approach a patient with bipolar disorder (Kulkarni et al, 2012). This may determine both how they approach the client and the treatment plans created to assist them (Kulkarni et al, 2012). For example, Systems Theory maintains that humans are systems, with each component of the system affecting other components (Hampson, Hicks & Watt, 2016). It is therefore impossible to look only at a mental illness without considering the rest of the person (Grande et al., 2016). In addition, the context in which people live involves systems, and these systems impact the systems of the individual (Hampson, Hicks & Watt, 2016). The whole picture must be considered and dealt with when providing assistance to an individual (Hampson, Hicks & Watt, 2016).

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In this framework, the social worker identifies areas of system failure and seeks to assist the client in obtaining the skills, knowledge, or community in which he or she will have the most positive outcomes (Grande et al., 2016). This differs from Ecological Theory, which holds that humans respond to factors in their environments, and environmental change will result in behavioral change (Mitchell, 2013). From this perspective, the social worker is tasked with assisting the client in locating environments and environmental factors that promote their well-being and avoiding those that do not (Mitchell, 2013). Different social workers will practice based on different frameworks, causing varied responses to similar symptoms.

Literature reveals both pharmaceutical and therapeutic treatment is typical in medical provision for bipolar disorder. Lithium is the most common and effective drug treatment for bipolar disorder in Australia (Kulkarni et al., 2012). An element found in nature, it is not clear how Lithium relieves symptoms, but it is known to alter the messenger relays in the brain and change brain activity, and to have an anti-manic effect without increasing depression (Duarte, Becerra & Cruise, 2016).

On the other end of the symptom spectrum, antidepressants may also be used for patients with long depressive mood episodes; however, their effectiveness in treating bipolar is limited and may exacerbate mood periods of excitement (Kulkarni et al., 2012). Other pharmaceutical treatments involve the use of anti-psychotic medications such as Lurasidone, although these are only generally prescribed in more severe bipolar cases (Kulkarni et al., 2012). Of note, Chatzidamianos, Lobban and Jones (2015) found as part of their study in family support that few patients or family members have clear understanding or realistic expectations of the result of medication, making both medication compliance and consistency in therapeutic treatment more erratic.

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This is a concern, as therapeutic treatment is an important component of managing bipolar disorder. Of the six articles examined and the four articles used for additional information, all in one way or another supported the importance of individual and group therapies in maintaining mood stability. In addition, several contend this type of treatment more effective than medical treatment, if only one can be used (Hampson, Hicks & Watt, 2016; Joyce, Thompson & Marwaha, 2016). One study, Martín-Subero et al (2014), found that a naturalistic approach to managing mood swings can be effective without additional medications.

Literature indicates that modern treatments for bipolar disorder combine medication with behavioral therapies for better symptom control (Hampson, Hicks & Watt, 2016). These therapies attempt to support patient self-care, rather than relying on medical providers to manage their illness (Hampson, Hicks & Watt, 2016). One foundational therapy in this approach is cognitive behavior therapy , which is founded on groups involving patients with similar disorders and symptoms (Kulkarni et al., 2012). These groups, led by an experienced counselor, help the patient identify areas of behavioral concern, create plans to address these areas, and improvement and maintain steps to control symptoms in everyday life (Kulkarni et al., 2012).

Another common therapy is family therapy, which involves persons from the patient’s family or support population in a similar process (Chatzidamianos, Lobban & Jones, 2015). Employing the family unit in assisting the patient in maintaining stability was shown to be very effective in studies by Chatzidamianos, Lobban and Jones (2015), who report that the continued presence of family members can lead to quick recognition of symptoms, and assist in timely response to onset of symptoms, as well as help patients become more aware of their conditions and when to act in response to them.

Conclusions

Bipolar disorder remains a difficult mental illness , particularly as it does not present consistently over time. However, useful frameworks for social work practice and appropriate modern therapy approaches can enable the social worker to effectively assist client with bipolar disorder.

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Butler M, Urosevic S, Desai P, et al. Treatment for Bipolar Disorder in Adults: A Systematic Review [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2018 Aug. (Comparative Effectiveness Review, No. 208.)

Treatment for Bipolar Disorder in Adults: A Systematic Review [Internet].

• Cite this Page Butler M, Urosevic S, Desai P, et al. Treatment for Bipolar Disorder in Adults: A Systematic Review [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2018 Aug. (Comparative Effectiveness Review, No. 208.) References.
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Treatment, Symptoms, and Prevention of Bipolar Disorder Essay

Introduction.

Bipolar disorder is a mental disorder that is manifested by drastic mood changes — bipolar manifests in two main extremes, namely depression, and mania (Peacock, 2000). Depression manifests when an individual feels tired and sad. On the other hand, mania manifests when an individual experiences periods of extreme excitement and restlessness. Symptoms of bipolar depend on the extreme that individual experiences at a certain period.

In many cases, an individual is diagnosed with clinical depression and later with bipolar. During an episode of depression, individuals experience feelings that include hopelessness, extreme sadness, worthlessness, lethargy, and irritability (Peacock, 2000). In severe cases, an individual might contemplate suicide. On the other hand, episodes of mania are characterized by feelings of happiness, joy, irritability, and extreme creativity.

Prevalence and incidence

According to the World Health Organization, more than 10 million individuals have bipolar in the United States (Peacock, 2000). The disorder is a leading cause of disability in the world. It has a lifetime prevalence of approximately 3% around the globe. Statistics have revealed that more than 0.8% of the American population experiences at least a manic episode at one time in their life.

On the other hand, 0.5% of the population experiences a hypomanic episode. 6.4% of the American population has been shown to have bipolar spectrum disorder (Peacock, 2000). Studies have revealed that the incidence of bipolar disorder among men and women is the same. The incidence rate is similar across people of different origins and ethnic backgrounds.

However, its severity varies across the world. In the U.S., the rate of incidence is higher among African Americans than among Americans of European descent (Peacock, 2000). The disorder affects people mainly in their adolescence and early adulthood years. In many cases, individuals with experienced bipolar episodes of mania after the age of fifty.

Symptoms of bipolar disorder depend on the mood that an individual experiences at a certain period. Individuals experience extreme mood changes that affect their behaviors and thinking patterns. Mania is characterized by over-excitement, while depression is characterized by extreme sadness.

During episodes of depression, individuals experience feelings of sadness, hopelessness, worthlessness, and loss of interest in activities they previously enjoyed, such as sex and social interaction (Fink & Kraynak, 2012). Their thinking is predominantly negative, and they rarely see the positive aspects of their lives. Their behavior also changes. They are restless, irritable, indecisive, and insomniac. Moreover, they experience problems with concentration and memory (Peacock, 2000).

Symptoms of mania

Symptoms of mania include hyperactivity, high quantities of energy, extreme irritability, impulsive behavior, restlessness, risk-taking, extreme happiness, and excitement, as well as unrealistic belief in personal capabilities (Fink & Kraynak, 2012).

Hypomania is a less severe form of mania that is characterized by moderate productivity and happiness. In other cases, both episodes of depression and mania might manifest at the same time. During such episodes, individuals become insomniac, agitated, and may harbor sundial thoughts (Fink & Kraynak, 2012).

Treatment of bipolar disorder includes us of both medication and therapy (Miklowitz, 2011). Bipolar is a disorder that affects individuals for the rest of their lives. Therefore, combining medication with therapy lowers the prevalence of the various mood changes associated with the disorder (Fink & Kraynak, 2012).

The recurrence of a maniac and depressive episodes makes life difficult for victims. Successful treatment of bipolar disorder involves the use of different treatment remedies. According to studies, medication alone is not enough to treat bipolar disorder effectively. One of the most important aspects of bipolar treatment is education and awareness about causes and ways of management.

Victims should read extensively about the disorder, join support groups, and make lifestyle changes that enable them to manage their symptoms (Ketter, 2007). The most common treatment methods for bipolar include medication, psychotherapy, education, lifestyle changes, and support. Drugs such as mood stabilizers aid in the minimization of symptoms. The most common and most effective mood stabilizer used to treat bipolar is lithium (Ketter, 2007).

Antidepressants such as Prozac and Amitriptyline are also used. Antipsychotic medications include Ariplazole, Quetiapine, Risperidone, and Clozapine (Ketter, 2007). Other drugs used together with mood stabilizers include Lamictal, Symbax, Zyprexa, and Seroquel. Psychotherapy teaches individuals different ways of coping with difficult times and different mood changes (Fink & Kraynak, 2012). Types of therapy available to individuals include cognitive-behavioral therapy and family-focused therapy (Ketter, 2007).

Education involves understanding the various symptoms of bipolar and their management. Finally, support involves interacting with individuals with the disorder for moral, emotional, and psychological support. Support groups facilitate the sharing of experiences that could be helpful to other individuals with similar challenges (Ketter, 2007). Complementary treatments include acupuncture, deep meditation, as well as light and dark therapy.

Prevention of a bipolar disorder

To prevent bipolar disorder, it is important to learn about it to control mood changes and other symptoms. It is also important to practice lifestyle management. Lifestyle management involves changes such as alcohol avoidance, practicing meditation, physical exercise, and thinking positively (Miklowitz, 2011).

Prevention of bipolar disorder mainly focuses on stress reduction. High levels of stress increase the risk of developing bipolar for genetically susceptible individuals. Stress reduction can be achieved through regular physical exercise and participating in relaxation methods such as meditation and yoga (Ketter, 2007).

Risk factors

Bipolar disorder’s risk factors include genetics, lifestyle, alcohol and drug abuse, high-stress levels, environment, and major life changes. Research has revealed that bipolar disorder has a basis in the genes of individuals. Therefore, the risk is very high for individuals who come from families with a history of the disorder. Research has shown that children from families in which one or both the parents have the disorder have a high risk of developing the disorder (Fink & Kraynak, 2012).

Major life changes such loss of a loved one, sexual abuse, or traumatic events such as accidents increase the risk of developing the disorder. Individuals who undergo prolonged periods of stress are also at high risk of developing the disorder (Fink & Kraynak, 2012). Medical practitioners recommend physical exercise and meditation as two of the most effective methods of reducing stress. Alcohol and drug abuse also increase the risk of developing the disorder.

Environment plays a critical role in the development o bipolar disorder. For instance, children who grow in abusive and violent families have a very high risk of developing bipolar (Miklowitz, 2011). Stressful environments play a key role in triggering depressive episodes that herald the development of bipolar.

Diagnosis is carried out through evaluation by a medical professional following diagnosis guidelines as provided in the Diagnostic and Statistical Manual of Mental disorder (DSM) (Fink & Kraynak, 2012). Successful diagnosis is mainly based on the observation of major changes in mood patterns and behavior. After a successful diagnosis, a patient is given medication based on past medical history and the severity of the condition.

Bipolar disorder is a mental disorder that is characterized by extreme mood changes that range from mania to depression. Risk factors include lifestyle, genetics, environment, drug and alcohol abuse, and major life changes such as death or abuse. Symptoms depend on the type of mod. Symptoms observed during the mania phase include hyperactivity, risk-taking, restlessness, and unrealistic belief in one’s capabilities.

During the depression phase, symptoms include insomnia, poor concentration, lack of appetite, loss of interest in activities that were once enjoyable, and feelings of hopelessness as well as helplessness. In severe cases, individuals contemplate suicide. Effective treatment involves the use of both drugs and psychotherapy. Drugs used include mood stabilizers, antidepressants, and psychotic medication.

Forms of therapy applied to include cognitive-behavioral therapy, family-centered therapy, as well as interpersonal and social rhythm therapy. Prevention involves participation in physical exercise and stress reduction activities such as meditation and yoga. According to the World Health Organization, more than 10 million individuals have bipolar in the United States.

On the other hand, 3% of the world’s population suffers from the disorder. Research has revealed that bipolar disorder has a basis in the genes of individuals. Therefore, the risk is very high for individuals who come from families with a history of the disorder. Research has shown that children from families in which one or both the parents have the disorder have a high risk of developing the disorder.

Fink, C., & Kraynak, J. (2012). Bipolar Disorder for Dummies . New York: John Wiley & sons.

Ketter, T. (2007). Advances in Treatment of Bipolar Disorder . New York: American Psychiatric Publishers.

Miklowitz, D. J. (2011). The Bipolar Disorder Survival Guide, Second Edition: What You and your Family Need to Know . New York: Gilford Press.

Peacock, J. (2000). Bipolar Disorder . New York: Capstone.

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IvyPanda. (2020, April 5). Treatment, Symptoms, and Prevention of Bipolar Disorder. https://ivypanda.com/essays/bipolar-disorder-essay/

"Treatment, Symptoms, and Prevention of Bipolar Disorder." IvyPanda , 5 Apr. 2020, ivypanda.com/essays/bipolar-disorder-essay/.

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IvyPanda . 2020. "Treatment, Symptoms, and Prevention of Bipolar Disorder." April 5, 2020. https://ivypanda.com/essays/bipolar-disorder-essay/.

1. IvyPanda . "Treatment, Symptoms, and Prevention of Bipolar Disorder." April 5, 2020. https://ivypanda.com/essays/bipolar-disorder-essay/.

Bibliography

IvyPanda . "Treatment, Symptoms, and Prevention of Bipolar Disorder." April 5, 2020. https://ivypanda.com/essays/bipolar-disorder-essay/.

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