Bipolar Disorder Part II

 

Rapid cycling

Most people who meet criteria for bipolar disorder experience a number of episodes, on average 0.4 to 0.7 per year, lasting three to six months. Rapid cycling, however, is a course specifier that may be applied to any bipolar subtype. It is defined as having four or more mood disturbance episodes within a one-year span. Rapid cycling is usually temporary but is common amongst people with bipolar disorder and affects between 25.8 and 45.3% of them at some point in their life. These episodes are separated from each other by a remission (partial or full) for at least two months or a switch in mood polarity (i.e., from a depressive episode to a manic episode or vice versa). The definition of rapid cycling most frequently cited in the literature (including the DSM-V and ICD-11) is that of Dunner and Fieve: at least four major depressive, manic, hypomanic or mixed episodes during a 12-month period. The literature examining the pharmacological treatment of rapid cycling is sparse and there is no clear consensus with respect to its optimal pharmacological management. People with the rapid cycling or ultradian subtypes of bipolar disorder tend to be more difficult to treat and less responsive to medications than other people with bipolar disorder.

Coexisting psychiatric conditions

The diagnosis of bipolar disorder can be complicated by coexisting (comorbid) psychiatric conditions including obsessive–compulsive disorder, substance-use disorder, eating disorders, attention deficit hyperactivity disorder, social phobia, premenstrual syndrome (including premenstrual dysphoric disorder), or panic disorder. A thorough longitudinal analysis of symptoms and episodes, assisted if possible by discussions with friends and family members, is crucial to establishing a treatment plan where these comorbidities exist. Children of parents with bipolar disorder more frequently have other mental health problems.

Children

Lithium is the only medication approved by the FDA for treating mania in children.

In the 1920s, Kraepelin noted that manic episodes are rare before puberty. In general, bipolar disorder in children was not recognized in the first half of the twentieth century. This issue diminished with an increased following of the DSM criteria in the last part of the twentieth century. The diagnosis of childhood bipolar disorder, while formerly controversial, has gained greater acceptance among childhood and adolescent psychiatrists. American children and adolescents diagnosed with bipolar disorder in community hospitals increased 4-fold reaching rates of up to 40% in 10 years around the beginning of the 21st century, while in outpatient clinics it doubled reaching 6%. Studies using DSM criteria show that up to 1% of youth may have bipolar disorder. The DSM-5 has established a diagnosis—disruptive mood dysregulation disorder—that covers children with long-term, persistent irritability that had at times been misdiagnosed as having bipolar disorder, distinct from irritability in bipolar disorder that is restricted to discrete mood episodes.

Elderly

Bipolar disorder is uncommon in older patients, with a measured lifetime prevalence of 1% in over 60s and a 12-month prevalence of 0.1 to 0.5% in people over 65. Despite this, it is over-represented in psychiatric admissions, making up 4 to 8% of inpatient admission to aged care psychiatry units, and the incidence of mood disorders is increasing overall with the aging population. Depressive episodes more commonly present with sleep disturbance, fatigue, hopelessness about the future, slowed thinking, and poor concentration and memory; the last three symptoms are seen in what is known as pseudo-dementia. Clinical features also differ between those with late-onset bipolar disorder and those who developed it early in life; the former group present with milder manic episodes, more prominent cognitive changes and have a background of worse psycho-social functioning, while the latter present more commonly with mixed affective episodes, and have a stronger family history of illness. Older people with bipolar disorder experience cognitive changes, particularly in executive functions such as abstract thinking and switching cognitive sets, as well as concentrating for long periods and decision-making.

Prevention

Attempts at prevention of bipolar disorder have focused on stress (such as childhood adversity or highly conflictual families) which, although not a diagnostically specific causal agent for bipolar, does place genetically and biologically vulnerable individuals at risk for a more severe course of illness. Longitudinal studies have indicated that full-blown manic stages are often preceded by a variety of prodromal clinical features, providing support for the occurrence of an at-risk state of the disorder when an early intervention might prevent its further development and/or improve its outcome.

Management

The aim of management is to treat acute episodes safely with medication and work with the patient in long-term maintenance to prevent further episodes and optimize function using a combination of pharmacological and psycho-therapeutic techniques. Hospitalization may be required especially with the manic episodes present in bipolar I. This can be voluntary or (local legislation permitting) involuntary. Long-term inpatient stays are now less common due to deinstitutionalization, although these can still occur. Following (or in lieu of) a hospital admission, support services available can include drop-in centers, visits from members of a community mental health team or an Assertive Community Treatment team, supported employment, patient-led support groups, and intensive outpatient programs. These are sometimes referred to as partial-inpatient programs.

Psycho-social

Psychotherapy aims to assist a person with bipolar disorder in accepting and understanding their diagnosis, coping with various types of stress, improving their interpersonal relationships, and recognizing prodromal symptoms before full-blown recurrence. Cognitive behavioral therapy, family-focused therapy, and psycho-education have the most evidence for efficacy in regard to relapse prevention, while interpersonal and social rhythm therapy and cognitive-behavioral therapy appear the most effective in regard to residual depressive symptoms. Most studies have been based only on bipolar I, however, and treatment during the acute phase can be a particular challenge. Some clinicians emphasize the need to talk with individuals experiencing mania, to develop a therapeutic alliance in support of recovery.

Medication

Lithium is often used to treat bipolar disorder and has the best evidence for reducing suicide.

Medications are often prescribed to help improve symptoms of bipolar disorder. Medications approved for treating bipolar disorder including mood stabilizers, anti-psychotics, and antidepressants. Sometimes a combination of medications may also be suggested. The choice of medications may differ depending on the bipolar disorder episode type or if the person is experiencing unipolar or bipolar depression. Other factors to consider when deciding on an appropriate treatment approach includes if the person has any comorbidities, their response to previous therapies, adverse effects, and the desire of the person to be treated.

Mood-stabilizers

Lithium and the anticonvulsants carbamazepine, lamotrigine, and valproic acid are classed as mood stabilizers due to their effect on the mood states in bipolar disorder. Lithium has the best overall evidence and is considered an effective treatment for acute manic episodes, preventing relapses, and bipolar depression. Lithium reduces the risk of suicide, self-harm, and death in people with bipolar disorder. Lithium is preferred for long-term mood stabilization. Lithium treatment is also associated with adverse effects and it has been shown to erode kidney and thyroid function over extended periods. Valproate has become a commonly prescribed treatment and effectively treats manic episodes. Carbamazepine is less effective in preventing relapse than lithium or valproate. Lamotrigine has some efficacy in treating depression, and this benefit is greatest in more severe depression. It has also been shown to have some benefit in preventing bipolar disorder relapses, though there are concerns about the studies done, and is of no benefit in rapid cycling subtype of bipolar disorder. Valproate and carbamazepine are teratogenic and should be avoided as a treatment in women of childbearing age, but discontinuation of these medications during pregnancy is associated with a high risk of relapse. The effectiveness of topiramate is unknown. Carbamazepine effectively treats manic episodes, with some evidence it has greater benefit in rapid-cycling bipolar disorder, or those with more psychotic symptoms or more symptoms similar to that of schizoaffective disorder.

Mood stabilizers are used for long-term maintenance but have not demonstrated the ability to quickly treat acute bipolar depression.

Anti-psychotics

Anti-psychotic medications are effective for short-term treatment of bipolar manic episodes and appear to be superior to lithium and anticonvulsants for this purpose. Atypical anti-psychotics are also indicated for bipolar depression refractory to treatment with mood stabilizers. Olanzapine is effective in preventing relapses, although the supporting evidence is weaker than the evidence for lithium. A 2006 review found that haloperidol was an effective treatment for acute mania, limited data supported no difference in overall efficacy between haloperidol, olanzapine or risperidone, and that it could be less effective than aripiprazole.

Anti-depressants

Antidepressants are not recommended for use alone in the treatment of bipolar disorder and do not provide any benefit over mood stabilizers. Atypical anti-psychotic medications (e.g., aripiprazole) are preferred over antidepressants to augment the effects of mood stabilizers due to the lack of efficacy of antidepressants in bipolar disorder. Treatment of bipolar disorder using antidepressants carries a risk of affective switches; where a person switches from depression to manic or hypomanic phases. The risk of affective switches is higher in bipolar I depression; antidepressants are generally avoided in bipolar I disorder or only used with mood stabilizers when they are deemed necessary. There is also a risk of accelerating cycling between phases when antidepressants are used in bipolar disorder.

Combined treatment approaches

Anti-psychotics and mood stabilizers used together are quicker and more effective at treating mania than either class of drug used alone. Some analyses indicate anti-psychotics alone are also more effective at treating acute mania. A first-line treatment for depression in bipolar disorder is a combination of olanzapine and fluoxetine.

Other drugs

Short courses of benzodiazepines are used in addition to other medications for calming effect until mood stabilizing become effective. Electroconvulsive therapy (ECT) is an effective form of treatment for acute mood disturbances in those with bipolar disorder, especially when psychotic or catatonic features are displayed. ECT is also recommended for use in pregnant women with bipolar disorder. It is unclear if ketamine (a common general dissociative anesthetic used in surgery) is useful in bipolar disorder.

Children

Treating bipolar disorder in children involves medication and psychotherapy. The literature and research on the effects of psycho-social therapy on bipolar spectrum disorders are scarce, making it difficult to determine the efficacy of various therapies. Mood stabilizers and atypical anti-psychotics are commonly prescribed. Among the former, lithium is the only compound approved by the FDA for children. Psychological treatment combines normally education on the disease, group therapy, and cognitive behavioral therapy. Long-term medication is often needed.

Resistance to treatment

The occurrence of poor response to treatment in has given support to the concept of resistance to treatment in bipolar disorder. Guidelines to the definition of such treatment resistance and evidence-based options for its management were reviewed in 2020.

Prognosis

A lifelong condition with periods of partial or full recovery in between recurrent episodes of relapse, bipolar disorder is considered to be a major health problem worldwide because of the increased rates of disability and premature mortality. It is also associated with co-occurring psychiatric and medical problems, higher rates of death from natural causes (e.g., cardiovascular disease), and high rates of initial under- or misdiagnosis, causing a delay in appropriate treatment and contributing to poorer prognoses. When compared to the general population, people with bipolar disorder also have higher rates of other serious medical comorbidities including diabetes mellitus, respiratory diseases, HIV, and Hepatitis C virus infection. After a diagnosis is made, it remains difficult to achieve complete remission of all symptoms with the currently available psychiatric medications and symptoms often become progressively more severe over time.

Compliance with medications is one of the most significant factors that can decrease the rate and severity of relapse and have a positive impact on overall prognosis. However, the types of medications used in treating BD commonly cause side effects and more than 75% of individuals with BD inconsistently take their medications for various reasons. Of the various types of the disorder, rapid cycling (four or more episodes in one year) is associated with the worst prognosis due to higher rates of self-harm and suicide. Individuals diagnosed with bipolar who have a family history of bipolar disorder are at a greater risk for more frequent manic/hypomanic episodes. Early onset and psychotic features are also associated with worse outcomes, as well as subtypes that are non-responsive to lithium.

Early recognition and intervention also improve prognosis as the symptoms in earlier stages are less severe and more responsive to treatment. Onset after adolescence is connected to better prognoses for both genders, and being male is a protective factor against higher levels of depression. For women, better social functioning before developing bipolar disorder and being a parent are protective towards suicide attempts.

Functioning

Changes in cognitive processes and abilities are seen in mood disorders, with those of bipolar disorder being greater than those in major depressive disorder. These include reduced attentional and executive capabilities and impaired memory. People with bipolar disorder often experience a decline in cognitive functioning during (or possibly before) their first episode, after which a certain degree of cognitive dysfunction typically becomes permanent, with more severe impairment during acute phases and moderate impairment during periods of remission. As a result, two-thirds of people with BD continue to experience impaired psycho-social functioning in between episodes even when their mood symptoms are in full remission. A similar pattern is seen in both BD-I and BD-II, but people with BD-II experience a lesser degree of impairment.

When bipolar disorder occurs in children, it severely and adversely affects their psycho-social development. Children and adolescents with bipolar disorder have higher rates of significant difficulties with substance abuse, psychosis, academic difficulties, behavioral problems, social difficulties, and legal problems. Cognitive deficits typically increase over the course of the illness. Higher degrees of impairment correlate with the number of previous manic episodes and hospitalizations, and with the presence of psychotic symptoms. Early intervention can slow the progression of cognitive impairment, while treatment at later stages can help reduce distress and negative consequences related to cognitive dysfunction.

Despite the overly ambitious goals that are frequently part of manic episodes, symptoms of mania undermine the ability to achieve these goals and often interfere with an individual's social and occupational functioning. One-third of people with BD remain unemployed for one year following a hospitalization for mania. Depressive symptoms during and between episodes, which occur much more frequently for most people than hypomanic or manic symptoms over the course of illness, are associated with lower functional recovery in between episodes, including unemployment or underemployment for both BD-I and BD-II. However, the course of illness (duration, age of onset, number of hospitalizations, and the presence or not of rapid cycling) and cognitive performance are the best predictors of employment outcomes in individuals with bipolar disorder, followed by symptoms of depression and years of education.

Recovery and recurrence

A naturalistic study in 2003 by Tohen and coworkers from the first admission for mania or mixed episode (representing the hospitalized and therefore most severe cases) found that 50% achieved syndromal recovery (no longer meeting criteria for the diagnosis) within six weeks and 98% within two years. Within two years, 72% achieved symptomatic recovery (no symptoms at all) and 43% achieved functional recovery (regaining of prior occupational and residential status). However, 40% went on to experience a new episode of mania or depression within 2 years of syndromal recovery, and 19% switched phases without recovery.

Symptoms preceding a relapse (prodromal), especially those related to mania, can be reliably identified by people with bipolar disorder. There have been intents to teach patients coping strategies when noticing such symptoms with encouraging results.

Suicide

Bipolar disorder can cause suicidal ideation that leads to suicide attempts. Individuals whose bipolar disorder begins with a depressive or mixed affective episode seem to have a poorer prognosis and an increased risk of suicide. One out of two people with bipolar disorder attempt suicide at least once during their lifetime and many attempts are successfully completed. The annual average suicide rate is 0.4%, which is 10–20 times that of the general population. The number of deaths from suicide in bipolar disorder is between 18 and 25 times higher than would be expected in similarly aged people without bipolar disorder. The lifetime risk of suicide has been estimated to be as high as 20% in those with bipolar disorder.

Risk factors for suicide attempts and death from suicide in people with bipolar disorder include older age, prior suicide attempts, a depressive or mixed index episode (first episode), a manic index episode with psychotic symptoms, hopelessness or psycho-motor agitation present during the episodes, co-existing anxiety disorder, a first degree relative with a mood disorder or suicide, interpersonal conflicts, occupational problems, bereavement or social isolation.

Epidemiology

Burden of bipolar disorder around the world: disability-adjusted life years per 100,000 inhabitants in 2004.

Bipolar disorder is the sixth leading cause of disability worldwide and has a lifetime prevalence of about 1 to 3% in the general population. However, a reanalysis of data from the National Epidemiological Catchment Area survey in the United States suggested that 0.8% of the population experience a manic episode at least once (the diagnostic threshold for bipolar I) and a further 0.5% have a hypomanic episode (the diagnostic threshold for bipolar II or cyclothymia). Including sub-threshold diagnostic criteria, such as one or two symptoms over a short time-period, an additional 5.1% of the population, adding up to a total of 6.4%, were classified as having a bipolar spectrum disorder. A more recent analysis of data from a second US National Comorbidity Survey found that 1% met lifetime prevalence criteria for bipolar I, 1.1% for bipolar II, and 2.4% for sub-threshold symptoms. Estimates vary about how many children and young adults have bipolar disorder. These estimates range from 0.6 to 15% depending on differing settings, methods, and referral settings, raising suspicions of over-diagnosis. One meta-analysis of bipolar disorder in young people worldwide estimated that about 1.8% of people between the ages of seven and 21 have bipolar disorder. Similar to adults, bipolar disorder in children and adolescents is thought to occur at a similar frequency in boys and girls.

There are conceptual and methodological limitations and variations in the findings. Prevalence studies of bipolar disorder are typically carried out by lay interviewers who follow fully structured/fixed interview schemes; responses to single items from such interviews may have limited validity. In addition, diagnoses (and therefore estimates of prevalence) vary depending on whether a categorical or spectrum approach is used. This consideration has led to concerns about the potential for both under-diagnosis and over-diagnosis.

The incidence of bipolar disorder is similar in men and women as well as across different cultures and ethnic groups. A 2000 study by the World Health Organization found that prevalence and incidence of bipolar disorder are very similar across the world. Age-standardized prevalence per 100,000 ranged from 421.0 in South Asia to 481.7 in Africa and Europe for men and from 450.3 in Africa and Europe to 491.6 in Oceania for women. However, severity may differ widely across the globe. Disability-adjusted life year rates, for example, appear to be higher in developing countries, where medical coverage may be poorer and medication less available. Within the United States, Asian Americans have significantly lower rates than their African American and European American counterparts. In 2017, the Global Burden of Disease Study estimated there were 4.5 million new cases and a total of 45.5 million cases globally.

History

German psychiatrist Emil Kraepelin first distinguished between manic–depressive illness and "dementia praecox" (now known as schizophrenia) in the late 19th century.

In the early 1800s, French psychiatrist Jean-Étienne Dominique Esquirol's lypemania, one of his affective monomanias, was the first elaboration on what was to become modern depression. The basis of the current conceptualization of bipolar illness can be traced back to the 1850s. In 1850, Jean-Pierre Falret described "circular insanity" (la folie circulaire, French pronunciation: ​la fɔli siʁ.ky.lɛʁ]); the lecture was summarized in 1851 in the "Gazette des hôpitaux" ("Hospital Gazette"). Three years later, in 1854, Jules-Gabriel-François Baillarger (1809–1890) described to the French Imperial Académie Nationale de Médecine a biphasic mental illness causing recurrent oscillations between mania and melancholia, which he termed folie à double forme (French pronunciation: [fɔli a dubl fɔʀm], "madness in double form"). Baillarger's original paper, "De la folie à double forme," appeared in the medical journal Annales médico-psychologiques (Medico-psychological annals) in 1854.

These concepts were developed by the German psychiatrist Emil Kraepelin (1856–1926), who, using Kahlbaum's concept of cyclothymia, categorized and studied the natural course of untreated bipolar patients. He coined the term manic depressive psychosis, after noting that periods of acute illness, manic or depressive, were generally punctuated by relatively symptom-free intervals where the patient was able to function normally.

The term "manic–depressive reaction" appeared in the first version of the DSM in 1952, influenced by the legacy of Adolf Meyer. Sub-typing into "unipolar" depressive disorders and bipolar disorders has its origin in Karl Kleist's concept – since 1911 – of unipolar and bipolar affective disorders, which was used by Karl Leonhard in 1957 to differentiate between unipolar and bipolar disorder in depression. These subtypes have been regarded as separate conditions since publication of the DSM-III. The subtypes bipolar II and rapid cycling have been included since the DSM-IV, based on work from the 1970s by David Dunner, Elliot Gershon, Frederick Goodwin, Ronald Fieve, and Joseph Fleiss.

Society and culture

Singer Rosemary Clooney's public revelation of bipolar disorder made her an early celebrity spokesperson for mental illness.

Cost

The United States spent approximately $202.1 billion on people diagnosed with bipolar I disorder (excluding other subtypes of bipolar disorder and undiagnosed people) in 2015. One analysis estimated that the United Kingdom spent approximately £5.2 billion on the disorder in 2007. In addition to the economic costs, bipolar disorder is a leading cause of disability and lost productivity worldwide. People with bipolar disorder are generally more disabled, have a lower level of functioning, longer duration of illness, and increased rates of work absenteeism and decreased productivity when compared to people experiencing other mental health disorders. The decrease in the productivity seen in those who care for people with bipolar disorder also significantly contributes to these costs.

Advocacy

There are widespread issues with social stigma, stereotypes, and prejudice against individuals with a diagnosis of bipolar disorder. In 2000, actress Carrie Fisher went public with her bipolar disorder diagnosis. She became one of the most well-recognized advocates for people with bipolar disorder in the public eye and fiercely advocated to eliminate the stigma surrounding mental illnesses, including bipolar disorder. Stephen Fried, who has written extensively on the topic, noted that Fisher helped to draw attention to the disorder's chronicity, relapsing nature, and that bipolar disorder relapses do not indicate a lack of discipline or moral shortcomings. Since being diagnosed at age 37, actor Stephen Fry has pushed to raise awareness of the condition, with his 2006 documentary Stephen Fry: The Secret Life of the Manic Depressive. In an effort to ease the social stigma associated with bipolar disorder, the orchestra conductor Ronald Braunstein cofounded the ME/2 Orchestra with his wife Caroline Whiddon in 2011. Braunstein was diagnosed with bipolar disorder in 1985 and his concerts with the ME/2 Orchestra were conceived in order to create a welcoming performance environment for his musical colleagues, while also raising public awareness about mental illness.

Notable cases

Numerous authors have written about bipolar disorder and many successful people have openly discussed their experience with it. Kay Redfield Jamison, a clinical psychologist and professor of psychiatry at the Johns Hopkins University School of Medicine, profiled her own bipolar disorder in her memoir An Unquiet Mind (1995). Several celebrities have also publicly shared that they have bipolar disorder; in addition to Carrie Fisher and Stephen Fry these include Catherine Zeta-Jones, Mariah Carey, Kanye West, Jane Pauley, Demi Lovato, Selena Gomez, and Russell Brand.

Media portrayals

Several dramatic works have portrayed characters with traits suggestive of the diagnosis which have been the subject of discussion by psychiatrists and film experts alike.

In Mr. Jones (1993), (Richard Gere) swings from a manic episode into a depressive phase and back again, spending time in a psychiatric hospital and displaying many of the features of the syndrome. In The Mosquito Coast (1986), Allie Fox (Harrison Ford) displays some features including recklessness, grandiosity, increased goal-directed activity and mood lability, as well as some paranoia. Psychiatrists have suggested that Willy Loman, the main character in Arthur Miller's classic play Death of a Salesman, has bipolar disorder.

The 2009 drama 90210 featured a character, Silver, who was diagnosed with bipolar disorder. Stacey Slater, a character from the BBC soap EastEnders, has been diagnosed with the disorder. The storyline was developed as part of the BBC's Headroom campaign. The Channel 4 soap Brookside had earlier featured a story about bipolar disorder when the character Jimmy Corkhill was diagnosed with the condition. 2011 Showtime's political thriller drama Homeland protagonist Carrie Mathison has bipolar disorder, which she has kept secret since her school days. The 2014 ABC medical drama, Black Box, featured a world-renowned neuroscientist with bipolar disorder. In the TV series Dave, the eponymous main character, played by Lil Dicky as a fictionalized version of himself, is an aspiring rapper. Lil Dicky's real-life hype man GaTa also plays himself. In one episode, after being off his medication and having an episode, GaTa tearfully confesses to having bipolar disorder. GaTa has bipolar disorder in real life but, like his character in the show, he is able to manage it with medication.

Creativity

A link between mental illness and professional success or creativity has been suggested, including in accounts by Socrates, Seneca the Younger, and Cesare Lombroso. Despite prominence in popular culture, the link between creativity and bipolar has not been rigorously studied. This area of study also is likely affected by confirmation bias. Some evidence suggests that some heritable component of bipolar disorder overlaps with heritable components of creativity. Probands of people with bipolar disorder are more likely to be professionally successful, as well as to demonstrate temperamental traits similar to bipolar disorder. Furthermore, while studies of the frequency of bipolar disorder in creative population samples have been conflicting, full-blown bipolar disorder in creative samples is rare.

Research

Research directions for bipolar disorder in children include optimizing treatments, increasing the knowledge of the genetic and neurobiological basis of the pediatric disorder and improving diagnostic criteria. Some treatment research suggests that psycho-social interventions that involve the family, psycho-education, and skills building (through therapies such as CBT, DBT, and IPSRT) can benefit in addition to pharmocotherapy.