Bipolar disorder


Lifelong psychiatric illness which is multifaceted.

Bipolar disorder affects approximately 8 million adults in the US.

Also known as manic-depressive illness.

Characterized by alternating episodes of depression, and either mania (bipolar 1) or hypomania (bipolar II).

While mania and hypomania are the defining features of BD, patients typically seek treatment during a depressive phase.

In bipolar disorder self-awareness changes with mood.

Bipolar disorder, a manic-depressive illness, , is a brain disorder that causes unusual and dramatic shifts in mood, energy, activity levels, ranging from high-highs and low-lows. 

Bipolar 1 is defined by manic symptoms, severe enough to require inpatient treatment.

Bipolar II involves milder, hypomanic episodes, not sufficiently severe to require hospitalization, but still capable of affecting relationships, finances, and physical health.

Diagnosis of BD requires a presence of at least one episode of mania or hypo mania.

Mania is characterized by elevated, expansive, or irritable mood lasting at least one week with significant consequences that often require hospitalization.

Mania symptoms include: mood, elevation, grandiosity, impulsivity risk taking, restlessness, racing thoughts, reduced need for sleep, increased productivity, inflated self-confidence, impaired judgment, irritability, and agitation.

Hypomania, along with a previous depressive episode, is a milder form of mania, requiring at least four consecutive days of elevated irritable mood and increased energy and goal directed behavior (bipolar II).

Bipolar disorder can make it difficult for an individual to carry out day-to-day tasks.


Less than 3 percent of the population experience it every year and 4.4 percent in their lifetime.


Over 80 percent of cases are classified as severe.

Ranks as the 17th leading source of disability among all disease is worldwide.

Often misclassified as a major depressive disorder.

A serious, chronic psychiatric illness characterized by alternating episodes of mania or hypomania and depression, or mixtures of manic and depressive features.

The probability of first onset peaks at approximately 15 years of age, and the median age of onset is approximately 20 years.

Bipolar II is more common in females, and bipolar I is equal prevalent in males and females.

Etiology of bipolar disorders is unknown but probably involves abnormalities in the neuroendocrine, neurotransmitter, and intracellular signaling systems that regulate mood and neuronal functioning.

No single factor can adequately explain symptoms or variations in treating outcomes in affected patients.

The proportion of disorder risk in the population attributable to genetic variation of bipolar disorders ranges from 73 to 93 percent.

The concordance rates for bipolar disorders is substantially higher for identical twins, 39-43 percent, than for dizygotic twins, 5-6 percent.

Annual incidence of bipolar disorders ranges from 3-10 cases per hundred thousand population, and the lifetime prevalence estimated to be 3-7%.

Reported as a lifetime and 12 month prevalence estimates of 2.4% and 1.5%, respectively.

It’s prevalence varies by country.

Bipolar I disorder is similar for males and females, whereas bipolar II disorder occurs more frequently among females.

An episodic illness with the variable course that can result in functional and cognitive impairment and reduction in quality of life.

Major characteristic separating bipolar disorders from other affective disorders is the presence of recurrent manic or hypomanic episodes that may alternate with depressive episodes.
Early recognition and treatment in bipolar disorder is important because treatment response is greater in early stage disease.
The time between the first depressive episode, and a clinical diagnosis of bipolar disorder is approximately nine years.
13 signs that may signal bipolar disorder.

Great mood, always-happy-bipolar-symptoms.


Characterized by up-and-down episodes of mania and depression.


During a manic phase, some patients can have a total break from reality.


Hypomania, a symptom of the disorder, is a high-energy state in which a person feels exuberant but hasn’t lost his or her grip on reality.


Inability to complete tasks


Individuals go from task to task, planning grand, unrealistic projects that are never finished before moving on to something else.


Bipolar disorder can have a seriously negative impact on individual’s sex life, with a variety of sexual expressions.


However, they may also completely avoid sex.




Typical antidepressants alone do not  work well in patients who are bipolar. 


Typical antidepressants in bipolar disease can even make people cycle more frequently, worsening their condition, or provoke a break-with-reality episode, or mania.






Some people with bipolar disorder condition suffer from “mixed mania,” : symptoms of mania and depression at the same time. 


During mixed mania patients are often extremely irritable.


Rapid speech


Negative words and pressured speech, talking over others.


Loss of time, with impairment in  concept of time. 


Trouble at work, with problems completing tasks, difficulty sleeping, irritability, inflated ego during a manic phase, and depression at other times, which causes excessive sleeping and additional mood problems.


Alcohol or drug abuse


About 50% of people with bipolar disorder also have a substance abuse problem, particularly alcohol use.


Many people will drink when they are in a manic phase to slow themselves down, and use alcohol to improve their mood when they are depressed.


Erratic behavior:spending sprees and unusual sexual behavior.


Grandiosity-center of attention


Sleep problems


Flight of ideas

One of the world’s 10 most disabling clinical conditions.

Peak incidence of BP-I and BP- II occurs between 12-30 years of age.

Has profound negative public health impact.

Characterized by disruptive mood swings, with intervals of partial or full recovery.

Symptoms are persistent, particularly depressive symptoms.

Patients with bilpolar disorders die an average of 8-20 years sooner than the general population.

Typically associated with cognitive disturbances such delusions, and inability to concentrate, racing thoughts, and a false belief of superiority.

Has tentative associations among irritable bowel syndrome, and adversity in childhood.

Estimated $151 billion spent on direct and indirect costs in the US in 2009.

Up to 15% of individuals with bipolar disorder die by suicide.

Suicide occurs 14 times as often in patients with bipolar disorder compared with the general population.

Suicide attempts and suicide deaths, are at least 18 times as common during depressive episodes as during manic episodes in bipolar I disorder.

Annual suicide attempt rates are approximately 30 to 60 times higher than the general population.

Higher rates of completed suicide in bipolar patients include: male sex, living alone, divorced status, unemployment, white race, age younger than 35 years or older than 75 years.

Patients with bipolar disorder have a much higher proportion of the deaths due to natural causes related to comorbidity obesity, cardiovascular, metabolic diseases and other comorbiditties of chronic health conditions and complications related to smoking.

Persons with bipolar disorder have approximately twice the risk of death, attributable to both suicide and higher rates of physical diseases in this population.

Comorbid obesity is associated with more severe and chronic bipolar illness course, poor response to drug therapy, and heightened suicide risk.

Associated with general medical processes including obesity, cardiovascular diseases, type 2 diabetes, autoimmune diseases, and malignancies, and with high rates of smoking.

Approximately 65% of individuals with BD have comorbid psychiatric illness.

Associated with episodic recurrent mania or hypomania.

Presence of manic or hypomanic episodes is the hallmark of the disorder and is distinguishes it from other conditions such is unipolar major depression.

Commonly misdiagnosed.

The time lag to accurate diagnosis of bipolar-1 and bipolar- II is more than 10 years.

A clinical diagnosis and diagnostic tests do not presently exists.

High index of suspicion is required for diagnosis.

Characterized by episodes of both elevated or irritable mood and depression.

Manic or hypomanic episodes are states of elevated mood and increased motor drive that are finite in time and differ in severity and length.

May be associated with psychotic features such as hallucinations.

Manic episodes impair social, and occupational functioning and may be associated with psychotic symptoms.

Affective disorders are classified along a spectrum defined by extent and severity of mood elevation, from unipolar, bipolar II to bipolar I.

Because bipolar disorder is mainly diagnosed in young adulthood it affects the economically active population and is associated with high cost to society.

Onset of mania later in life may be an indication of an underlying medical comorbidity.

Previously known as manic depressive illness.

Bipolar disorders clasified acccording to their longitudinal course.

Mild presentations are difficult to distinguish from normal mood fluctuations and features of personality, particularly in the early stages of the disease.

The clinical picture is distorted frequently by comorbid anxiety or development mixed states characterized by coterminous symptoms of depression and mania.

Patients with bipolar disorder have high rates of coexisting psychiatric conditions, including anxiety estimated to be present and 71% of patients, substance use in 56%, personality disorders in 36% and attention deficit hyperactivity disorder in 10 to 20%.
The burden of illness when there are additional psychiatric problems worsens the prognosis.
Additional disorders that patients with bipolar disorder have include:  a higher prevalence of chronic medical conditions such as metabolic syndrome affecting 37% of patients, migraine 35%, obesity 21%, and type two diabetes 14%.
Comorbid psychiatric illness and bipolar disorder is approximately 65%: anxiety disorders are particularly common at 71%, substance-abuse approximately 56%, personality disorder is approximately 36%, attention deficit disorder approximately 10 to 20%.
Women, with bipolar disorder have higher rates of anxiety and eating disorders than men.
Men with bipolar disorder are more likely to have substance use disorders and alcohol misuse, than women.

Bipolar I disorder has a more tortuous evolution and severe prognosis then bipolar II disorder because of symptom severity, bipolar II has a high episode frequency, higher rates of psychiatric comorbidities, and recurrent suicidal behaviors that impair quality of life

Bipolar 1 disorder is defined by the presence of manic episodes, including overconfidence, grandiosity, talkativeness, extreme disinhibition, irritability, decreased need for sleep, and highly elevated mood.

Bipolar 1 Is associated with psychotic symptoms such as delusions and hallucinations it up to 75% of manic episodes, and episodes of any severity may compromise psychosocial functioning to the pointed hospitalization is required.

Mania-Bipolar I disorder.

Hypomania-Bipolar II disorder.

Bipolar I more severe derangement than Bipolar type II disorder.

Patients with Bipolar II disease infrequently seek care.

Around 25% of patients with bipolar disorder may present with a depressive seasonal pattern, which is associated with bipolar II disorder, rapid cycling, eating disorders, and more depressive episodes.

Seasonal affective disorder (SAD) is most prevalent in patients with early-onset bipolar II disorder, compared with other early-onset mood disorders and healthy control subjects.


Seasonal impairment is greater in patients with mood disorders compared with healthy controls.


Among patients with mood disorders, those with bipolar II disorder had the highest prevalence of SAD.


SAD affects 23% of participants with bipolar II disorder, compared with approximately 10% of participants with major depressive disorder and bipolar I disorder and just 6% of healthy controls. 


Many patients present with one or more depressive episodes of major depression before the first manic or hypomanic episode that establishes the bipolar diagnosis.

Highly heritable biologic illness.

Genetic component estimated to be in the range of 60-85%.

30 significant genomewide loci have been associated with bipolar disorder.
It is proposed that these gene influences increase stress sensitization leading to bipolar disorder.
Duration of illness has been associated with a reduced cortical thickness of brain regions such as the prefrontal cortex and may play a role in stress regulation.

Aberrations in the hypothalamus-pituitary-adrenal axis also os thought to play a role in the pathophysiology and progression of bipolar disorder.

In adults the hallmark is a manic episode with a period of abnormal and elevated, expansive, or irritable mood, with accompany symptoms lasting at least 1 week.

Concordance rates for bipolar disorder in monozygotic twins are approximately 65% to 70% and approximately 14% for dizygotic twins.

Type I-mania and usually recurrent depression, type II recurrent major depression with hypomania.

Lifetime prevalence 1%-1.6% of adults and 1.2% of children.

Affects populations irrespective of nationality, ethnic origin, or socioeconomic status.

Is one of the leading causes of disabilities among young people.

Bipolar I disorder affects men and women equally, where is bipolar II disorder is most common in women.

Lifetime prevalence in a US study 4.5% with 1% for Bipolar I disorder, 1.1% for Bipolar II, and 2.4% for for manic and depressive symptoms that fall short of diagnostic criteria for Type I and II bipolar disorder (Merikangas ME et al).

Bipolar disorder types I and II affect at least 2% of the worlds population and sub threshold forms affect another 2%.

Inclusion of more broadly defined conditions increases the prevalence to 2-5%.

Median age of onset is 18 years.

Often starts in childhood and adolescence with 15-28% of cases with onset before the age of 13 years and 50-66% with onset before age 19 years.

An earlier onset is associated with a poor prognosis, longer treatment delays, more severe depressive episodes, higher prevalence of concurrent anxiety and substance use disorders.
The first episode of bipolar disorder is usually depressive, and for most patients with either bipolar I or bipolar II, depressive episodes last significantly longer than manic or hypomanic episodes throughout the course of illness.
Bipolar disorder typically first arises during the formative years in children and adolescents and affects developmental, educational and occupational milestones.

Cognitive and psychosocial dysfunction with acute episodes compound patient’s problems.

In youngest children irritability, affective lability, decreased need for sleep may be present.

Most children with bipolar disorder do not have discrete episodes of mania, but instead have chronic and severe irritable mood as manifested by explosive, aggressive behavior, or rapid cycling between elevated and depressive moods in a single day.

Later problems in children include suicidal and homicidal ideation, delusions, hallucinations with precocious sexual interests.

80%-90% have recurrent illness after and initial manic episode.

Depression can be present during 20-30% of a patient’s time, even during prophylactic treatment.

Three phases to illness: acute episodes, continuation phase and maintenance phase.

Acute phase usually lasts a couple of months.

Associated with premature death.


The goal of acute treatment for depressive episodes is remission, which requires several weeks to occur, and includes reduction in the number and severity of mood symptoms with resolution of suicidal ideation and psychotic features.

Pharmacological therapy is the primary treatment, and should be tailored to the clinical presentation – depression, or hypomania/mania.

Optimal management of bipolar disorder, emphasize combined, psychological, and psychosocial treatments.

Psychoeducation provides patients with information about BD, the importance of medication adherence, ability to recognize early signs of mood episodes, and how to develop strategies to manage symptoms and potential adverse effects of medications.

Five antipsychotic drugs or drug combinations are approved for acute bipolar depression: olanzapine/fluoxetine combination, quetiapine, lurasidone, cariprazine, and lumateperone.

These agents, have a 50-50 percent reduction in depressive scores.

Atypical antipsychotics have efficacy in bipolar depression, but often lead to weight gain, even with short term use.

Treatment in patients with acute depressive episode includes management of comorbid substance use disorders.

Approximately 5% suicide rate among non-hopitalized patients, and up to 25% for those in the early course of disease (Tondo L et al, Inskip et al).

A leading cause for disability among individuals 15-44 years of age (Murray CJ, Lopez AD).

When patients improve after the acute phase but not yet functionally recovered they move into the continuation phase, which may take a few months to a year.

The maintenance phase reflects functional improvement and stability.

Course has two extreme patterns-1-episodic and 2-unstable.

In the pure episodic type patients have a depressed episode or a manic one, but not a mixed episode.

The episodic event is followed by a relatively stable period lasting longer intervals with infrequent episodes and few complications.

The unstable course is manifested by mixed episodes of depression and mania with earlier onset, more complications and stronger genetic component.

Most disability associated with the depressive phase of the disease, while mania is more evident.

Approximately 25% of patients with bipolar disorders fully recover from an acute depressive episode, and such patients have a rate of illness relapse and disability which remains quite high despite treatment adherence.

BP-I depressive episodes account for greater disability and adverse functional impact than manic or hypomanic episodes.

Few medications have been shown to be effective for treating acute bipolar depressive episodes.

Mood stabilizers that include lithium, valproate, lamotrigine along with atypical psychotic drugs, such as quetiapine, ariprazole, and cariprazine, are recommended  pharmacological therapies for acute and long-term management of bipolar disorder.

Pharmacological treatment for bipolar I and bipolar II is similar.

Monotherapy with quetiapine or lurasidone and combination of therapy with lithium and lamotrigine, and either quetiapine or lurasidone plus a mood stabilizer, are high priority treatment options for BP- I depression.

The effectiveness of lithium monotherapy for acute bipolar depression is less well-established than that for treating of acute mania or for maintenance treatment.

Lithium has a significant effect for reducing suicide attempts and deaths in patients with bipolar disorder as compared with antidepressants or other mood stabilizers.

Lithium’s maintenance phase advocacy is well-established and can be considered either as monotherapy or as an adjunct for some patients with acute BP-1 depression, particularly those struggling with suicidal impulses.

MRI studies have shown abnormalities in the structure and function of pre-frontal and other brain regions implicated in emotional regulation and cognition.

Treatment with mood stabilizers and other medications can improve symptoms and the natural course of bipolar disorders, but relapses are frequent and symptomatic remission and functional recovery is difficult to achieve.

Adherence to recommended therapy is a major problem, and this is especially true early in the illness.

Most patients that seek treatment have bipolar depression, but there is evidence for misdiagnosis and misclassification as having unipolar major depression.

Certain comorbid psychiatric disorders predict for overdiagnosis of bipolar disorder and include;borderline personality disorder, post-traumatic stress disorder, other anxiety disorders and impulse control disorders.

More than one-third of patients with bipolar disorders have a comorbid personality disorder, particularly borderline personality disorder.

Patients with comorbid personality disorders have more frequent mood episodes, shorter euthymic intervals, and higher rates of alcohol and substance use disorders and suicidality.

Episodes of bipolar depression and unipolar major depression have similar diagnostic criteria, however the history of manic or hypomanic episodes distinguishes bipolar depression from unipolar depression.

Psychiatric comorbidity is present in 50 – 70% of patients with BP disorders.

The presence of psychiatric comorbidities in patients with bipolar disorder is associated with a worsening longitudinal course, more frequent mood episodes and suicide attempts, and poor quality of life and functioning.

The most common associated psychiatric comorbidities with BP are anxiety disorders, making up to 70%, and alcohol and other substance abuse disorders making up 40 to 50% of patients.

Episodes of bipolar depression and unipolar major depression have similar diagnostic criteria, however the history of manic or hypomanic episodes distinguishes bipolar depression from unipolar depression.

Psychiatric comorbidity is present in 50 – 70% of patients with BP disorders.

The most common associated psychiatric comorbidities with BP are anxiety disorders, making up to 70%, and alcohol and other substance abuse disorders making up 40 to 50% of patients.

Frequently occurs with eating disorders and impulse control disorders.

Generally can be managed with appropriate drugs and targeted psychosocial interventions, but residual clinical symptoms and dysfunction can persist.

Treatment is generally of two phases: acute-phase treatment, and maintenance-phase treatment.

Acute-phase treatment is focused on the management of acute episodes such as manic, hypo manic or depressive.

Acute bipolar depressive episodes are generally managed in an ambulatory setting.

Psychiatric hospitalizations are required for bipolar depressed patients at risk for suicide, and those with severe agitation or psychotic features, or those with severe loss of functioning.

Hypomanic episodes are not associated with either psychosis or significant dysfunction and are managed in an outpatient setting.

Drug therapy for hypomania are similar to those for Mania.

Similar principles of treatment are used to assess and manage mania are applied to hypomania and treatment options are the same.

Treatment involves discontinuing agents that may exacerbate or prolong symptoms – anti-depressants, stimulants.

Mood stabilizers with or without benzodiazepines can be used for the initial treatment of hypomanic episodes.

Guidelines recommend mood stabilizing agents, such as lithium, valproate, and atypical, antipsychotic agents, alone or in combination

Maintenance-phase treatment is focused on preventing occurrences of acute episodes.

Patients must be continually reevaluated for their mood symptoms and functioning capabilities.

Mood stabilizers are the first line of treatment.

Lithium is the first line choice for maintenance treatment reducing risks of relapse and suicide.

Lithium reduces risk of relapse by 4-fold.

Long-term lithium monotherapy can reduce mania or hypomania and depression by about two thirds.

Among patients with bipolar 1 disorder, and recently remitted depression episode, the addition of escitalopram or bupropion XL, continued for 52 weeks did not show a significant benefit as compared with treatment for eight weeks in preventing relapse of any mood episode (BEAM BD Trial,group

Many patients are highly responsive with a near total resolution of symptoms however, at least 30% of patients are only partially responsive, and 30% have no clinical response to lithium.

Good responders to lithium are more likely to have a family history of bipolar disorder than poor responders.

Patients who stabilize on the lithium tend to aggregate within families.

Treatment for mania include monotherapies with lithium, divalproex (Depakote), olanzapine (Zyprexa) , risperidone (Risperdal), quetiapine (Seraquel), ziprasidone (Geodon), aripiprazole (Abilify) and extended release carbamazepine.

Mania is considered a medical emergency, often requires hospitalization.

Goals of treatment include rapid stabilization of manic symptoms and dangerous behaviors, reestablishing sleep, and frequently concurrent management of withdrawing from drugs and alcohol.

Nearly all antipsychotic drugs and mood stabilizers are effective for treating manic episodes.

Antipsychotics are routinely used, often in conjunction with mood stabilizers such as lithium/valproate, as a first-line treatment for manic and mixed episodes associated with bipolar disorder.

Divalproex is an effective antimanic agent.

Carbamazepine sometimes used to treat acute Mania that does not respond to lithium.

Typical antipsychotics such as haloperidol, are effective for acute mania, but they are not used beyond the acute phase of treatment because of high incidence of neuromuscular adverse affects, hyperprolactinemia, and long-term risk of tardive dyskinesia.

For most patients acute antimanic effects manifest almost always within three weeks.

Manic episodes that do not respond to conventional drug therapy may respond to clozapine or electroconvulsive therapy.

Aripiprazole is first once-monthly, long-acting injectable approved for maintenance monotherapy treatment of bipolar I disorder in adults.

Combination of atypical antipsychotics with lithium or divalproex and clozapine (Clozaril) and electroshock therapy are to be considered when other treatments do not work.

Approximately 80% of patients with bipolar I disease treated with lithium have at least a partial response, 30% have an excellent response with complete remission of symptoms.

Patients with good responses to lithium clustering families, suggesting familial clustering can predict for a recurrence of symptoms.

Lithium  remains the first line treatment of mood stabilization and long-term treatment with bipolar disorder.

Lithium prevents both manic and depressive episodes.

Lithium use has decreased due to the addition of new antipsychotic agents and concerns about lithium tolerability and potential adverse effects including Kidney, Thyroid/parathyroid function.

Lithium is associated with increase rates of hypothyroidism and hyperparathyroidism.

Bipolar II is characterized by episodes of depression but alternating with hypo mania rather than mania.
The presence of at least one hypomanic episode in the life trajectory is considered to be consistent with a diagnosis of bipolar II disorder.
During periods of height and mood patients with bipolar disorder may also paradoxically be affected by depressive symptoms.
Changes in brain structure and cellular function, neuroprogression, is found in patients with recurrent episodes of affective disorder.
Long duration of illness is associated with decreased cortical thickness in brain regions such as the prefrontal cortex and epigenetic mechanisms the regulate mitochondrial function and neuroplasticity, inflammation and increase in oxidative and nitrosative stress are probable factors they promote  neuroprogression in the context of bipolar disorder.

Antidepressants are adjunctive therapies in  patients in whom bipolar depression is resistant to treatment with mood stabilizers and antipsychotics.

Anti-depressants have limited evidence of efficacy, and may increase rates of mania or hypomania.
Electroconvulsive therapy is reserved for patients with bipolar depression, refractory to medications, , and is considered the most effective treatment for severe and treatment resistant depression, including bipolar depression.
Most patients with bipolar disorder require lifelong treatment to reduce relapse rates, improve functioning, and quality of life.
Patients require a moodstabilizer, such as lithium, valproate, or lamotrigine, either alone, or in combination with atypical antipsychotic agents, such as quetiapine, ariprazole, asenapine, or lurasidone.
Cognitive behavioral therapy is associated with fewer depressive symptoms, improve social/occupational functioning compared with the usual treatments.
The prognosis of BD is variable, and the greater disease duration, the more episodes of depression, mania, and hypomania are associated with higher rates of recurrence and greater impairment in mental, physical health, and cognitive function performance.
Both types of bipolar disorder experience symptoms, approximately half of all days.
Patients with type I BD experience, more frequent switches between depression and mania and higher prevalence of episodes with mixed features when depression and hypomania co-occur compared with bipolar II.
Patients with bipolar II experience symptoms more often with major depressive symptoms predominating.

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