Background

• Bipolar disorder, or manic-depressive illness, is a mental health condition characterized by extreme mood swings that include periods of elevated or irritable mood (mania or hypomania) and depressive episodes. These mood episodes can last for days, weeks, or even months, significantly impacting a person’s ability to function and maintain stable relationships.

Epidemiology

• The estimated lifetime prevalence of bipolar I disorder, according to the National Institute of Mental Health in the United States, is approximately 2.6%. The prevalence of bipolar II disorder is estimated to be around 0.5%-1%.
• The onset of bipolar disorder occurs in late adolescence or early adulthood, with an average age of onset being around 25 years.
  Bipolar disorder often coincides with other mental health conditions. Common comorbidities include anxiety disorders, substance use disorders, attention-deficit/hyperactivity disorder (ADHD), and eating disorders.
• Bipolar disorder affects both males and females, but there are some gender differences in the presentation of the illness. Bipolar I disorder affects males and females equally, while bipolar II disorder may be slightly more common in females.

Anatomy

Pathophysiology

• Imbalanced neurotransmitters, chemical messengers in the brain, are thought to play a significant role in bipolar disorder. Specifically, abnormalities in serotonin, norepinephrine, and dopamine levels or functioning have been observed. These imbalances can disrupt mood regulation, leading to the characteristic mood swings reported in bipolar disorder.
• Neuroimaging studies portray structural and functional differences in the brains of individuals with bipolar disorder. These differences involve regions responsible for emotional regulation, like the amygdala, prefrontal cortex, and hippocampus. Changes in these brain areas may affect mood stability and emotional processing.

Etiology

The etiology of bipolar disorder involves a combination of genetic, biological, environmental, and psychosocial factors. While the exact cause is not fully understood, research suggests the following factors contribute to the development of bipolar disorder:
• Genetic Factors: Bipolar disorder has a significant genetic component. Family and twin studies have demonstrated a higher risk of the disorder in individuals with close relatives who have bipolar disorder. Specific genes and genetic variations are being studied better to understand their role in the disorder’s etiology.
• Neurobiological Factors: Imbalances in neurotransmitters, such as serotonin, norepinephrine, and dopamine, are thought to contribute to the etiology of bipolar disorder. Abnormalities in the functioning and regulation of these neurotransmitters can disrupt mood regulation and lead to the characteristic mood swings seen in the disorder.
• Environmental Factors: Stressful events, such as trauma, loss, or significant life changes, may trigger mood episodes. Substance abuse, including alcohol and drug use, can also contribute to developing and exacerbating bipolar disorder. Additionally, disruptions in sleep patterns, social support, and interpersonal relationships may impact the course of the disorder.
• Psychosocial Factors: Psychosocial factors, such as childhood adversity, early life trauma, and dysfunctional family dynamics, increase the risk of developing bipolar disorder. These factors can contribute to the vulnerability and expression of the disorder through their impact on stress response systems, coping mechanisms, and emotional regulation.

Genetics

Prognostic Factors

Clinical History

Non-specific signs & symptoms:
• Mood swings
• Hypomania
• Depression
• Mania
• Irritability
• Impulsiveness
• Loss of interest
• Changes in appetite
• Cognitive impairment
Systemic signs & symptoms
• Fatigue
• Weight disturbances

Physical Examination

When evaluating a patient with suspected bipolar disorder, a comprehensive physical examination is typically conducted to rule out any underlying medical conditions that may contribute to the symptoms or affect treatment decisions. While bipolar disorder primarily involves mood and behavioral symptoms, a physical examination helps assess the patient’s overall health and identify any physical signs that may be relevant. Here are some components of a physical examination that may be performed:
• Vital Signs: Measure blood pressure, heart rate, respiratory rate, and body temperature to assess the patient’s basic physiological parameters.
• General Appearance: Observing the patient’s overall appearance, including their level of distress, hygiene, grooming, and any significant physical abnormalities.
• Neurological Examination: Assessing the patient’s neurological function, including coordination, muscle strength, reflexes, sensation, and cranial nerve examination.
• Cardiovascular Examination: Evaluating the heart and blood vessels, including auscultating the heart sounds, checking for any murmurs or abnormalities, and assessing peripheral pulses.
• Respiratory Examination: Assessing the lungs and respiratory system, including auscultating breath sounds and evaluating the respiratory effort.
• Abdominal Examination: Palpating the abdomen for tenderness, masses, or organ enlargement. Checking for liver or spleen enlargement.
• Skin Examination: Inspect the skin for rashes, lesions, or other dermatological findings relevant to the patient’s health.
• Weight and Body Mass Index (BMI): Measuring the patient’s weight and calculating their BMI to assess any significant weight changes or abnormalities.

Age group

Associated comorbidity

• Substance abuse
• Anxiety disorders
• Attention deficit hyperactivity disorder
• Eating disorders
• Sleep disturbances
• Cardiovascular disease
• Diabetes

Associated activity

Acuity of presentation

• The acuity of presentation in bipolar disorder refers to the severity and intensity of symptoms at the time of diagnosis or assessment. It can vary depending on the phase of the illness and the specific episode experienced. The different levels of acuity commonly observed in the presentation of bipolar disorder are acute manic episodes, acute depressive episodes, mixed episodes, and chronic mood instability.

Differential Diagnoses

• Major depressive disorder
• Schizophrenia
• Anxiety disorders
• Substance use disorder
• Borderline personality disorder
• Attention deficit hyperactivity disorder in pediatrics

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

• The treatment of bipolar disorder typically involves a combination of medication, psychotherapy, and lifestyle modifications.
• Electroconvulsive therapy: Electroconvulsive therapy (ECT) is a medical procedure that involves inducing controlled seizures in a person’s brain using electrical currents. It is sometimes used as a treatment option for bipolar disorder, particularly when other treatments have been ineffective or when rapid and significant improvement is necessary.

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Atypical antipsychotic medications, such as aripiprazole, quetiapine, olanzapine, and risperidone, are commonly prescribed in bipolar disorder treatment. They can help manage acute manic or mixed episodes, reduce agitation, stabilize mood, and prevent future episodes. Atypical antipsychotics can be used as monotherapy or in combination with mood stabilizers.

• Aripiprazole:
  aripiprazole modulates the activity of neurotransmitters in the brain, including dopamine and serotonin. It acts as a partial agonist at dopamine D2 receptors and a partial agonist at serotonin 5-HT1A receptors. This unique pharmacological profile is believed to contribute to its mood-stabilizing effects.
• Quetiapine:
  quetiapine is primarily used to stabilize mood and help prevent episodes of mania or depression in individuals with bipolar disorder. It can effectively reduce the intensity and frequency of manic and depressive episodes.
  quetiapine is also approved for treating bipolar depression, which refers to the depressive phase of bipolar disorder. It can help alleviate symptoms such as sadness, loss of interest, sleep disturbances, and changes in appetite.
• Olanzapine:
  olanzapine is primarily used as a mood stabilizer in treating bipolar disorder. It helps to regulate and stabilize mood, reducing the severity and frequency of manic and depressive episodes.
  olanzapine is particularly effective in treating the manic phase of bipolar disorder. It can help alleviate symptoms such as elevated mood, irritability, racing thoughts, and increased energy level.
• Risperidone:
  risperidone is particularly effective in treating the manic phase of bipolar disorder. It can help alleviate agitation, irritability, impulsivity, and psychosis.
  risperidone may also be used for long-term maintenance treatment to prevent the recurrence of manic or depressive episodes in individuals with bipolar disorder. It can help maintain stability and reduce the risk of relapses.
• Antidepressants: While the use of antidepressants in bipolar disorder is somewhat controversial due to the risk of triggering manic episodes or rapid cycling, they may be cautiously prescribed in some cases. Antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs), may be used during depressive episodes in combination with mood stabilizers. Close monitoring is crucial to minimize the risk of inducing manic symptoms.
• Benzodiazepines: Benzodiazepines, such as lorazepam or clonazepam, are sometimes prescribed for short-term use in managing acute anxiety, insomnia, or agitation associated with bipolar disorder. These medications have sedating properties and can help calm and stabilize mood during high anxiety or agitation episodes.
• Anticonvulsants:     Besides traditional mood stabilizers like lithium and valproate, other anticonvulsant medications, such as carbamazepine and gabapentin, may be used to treat bipolar disorder. They can help stabilize mood, manage agitation, and reduce impulsivity.

The management of bipolar disorder typically involves several phases, including acute treatment, maintenance treatment, and long-term management. Here’s an overview of these phases:
• Acute treatment phase
• Maintenance phase
• Long-term management

Medication

Future Trends

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References

• https://www.ncbi.nlm.nih.gov/books/NBK558998/
• https://www.ncbi.nlm.nih.gov/books/NBK547001/