Bipolar Disorder

Overview

Definition

Bipolar Bipolar Nervous System: Histology disorder is a psychiatric illness that is characterized by fluctuating periods of elevated mood (mania/hypomania) and periods of low mood (depression).

• Mania: marked by severe symptoms, longer duration (≥ 1 week), and possible need for hospitalization Hospitalization The confinement of a patient in a hospital. Delirium
• Hypomania: less severe symptoms than with mania, duration (< 1 week) without need for hospitalization Hospitalization The confinement of a patient in a hospital. Delirium  
• Depressive episode: low mood, with lethargy Lethargy A general state of sluggishness, listless, or uninterested, with being tired, and having difficulty concentrating and doing simple tasks. It may be related to depression or drug addiction. Hyponatremia, hopelessness, and changes in appetite and sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep

Bipolar Bipolar Nervous System: Histology disorders are associated with impairments in social, occupational, and cognitive functioning.

Epidemiology

• Lifetime prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency: 1%–3% in adults
• Bipolar Bipolar Nervous System: Histology disorder I (≥ 1 episode of mania) affects both sexes with similar frequency.
• Bipolar Bipolar Nervous System: Histology II (≥ 1 episode of hypomania and depression) is slightly more frequent among women. 
• The disease manifests clinically in early adulthood at a mean age of 21 years.
• About 10%–15% of adolescents diagnosed with major depression develop bipolar Bipolar Nervous System: Histology disorder I.

Pathophysiology

The precise etiology of bipolar Bipolar Nervous System: Histology disorder is unknown, but a complex interaction of different factors is believed to be involved in the pathogenesis.

• Genetic predisposition:
  • ≥ ⅔ of cases have a family history Family History Adult Health Maintenance of the disorder.
  • Individuals with a 1st-degree relative with bipolar Bipolar Nervous System: Histology disorder: 5%–10% risk of developing the disease
  • Those with monozygotic co-twin affected by bipolar Bipolar Nervous System: Histology disorder: 40%–70% risk
• Biochemical and biologic influence:
  • Disruption of developmental processes affecting the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification networks controlling emotional behavior (prefrontal cortex and limbic structures)
  • A decrease in the amount of certain neurotransmitters (e.g., ↓ available norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS in depression) might contribute.
  • Abnormalities in the hypothalamic– pituitary Pituitary A small, unpaired gland situated in the sella turcica. It is connected to the hypothalamus by a short stalk which is called the infundibulum. Hormones: Overview and Types–adrenal– thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy axis are noted to be common.
  • Studies show elevation of peripheral inflammatory cytokine levels as compared with healthy individuals.
• Environmental:
  • Environmental factors can exacerbate the genetic and biologic defects in these individuals.
  • Factors include:
    • Abuse during childhood
    • Exposure to long-term stress
    • Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep deprivation
    • Substance use
    • Advanced paternal age  (↑ mutations in spermatogenesis Spermatogenesis The process of germ cell development in the male from the primordial germ cells, through spermatogonia; spermatocytes; spermatids; to the mature haploid spermatozoa. Gametogenesis) 
• Pharmacologic factors: Antidepressant Antidepressant Antidepressants encompass several drug classes and are used to treat individuals with depression, anxiety, and psychiatric conditions, as well as those with chronic pain and symptoms of menopause. Antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and many other drugs in a class of their own. Serotonin Reuptake Inhibitors and Similar Antidepressants use may precipitate bipolar Bipolar Nervous System: Histology and manic episodes in high-risk individuals.

Clinical Presentation

Clinical features

Bipolar Bipolar Nervous System: Histology disorder can present with:

• Mania
• Hypomania
• Depression
• Mixed features (meet criteria for both depressive and manic episodes simultaneously)

Major depression (55%) is usually the most common 1st lifetime episode, followed by mania (22%).

• Given the likelihood of presenting with depressive episodes 1st, it is important to inquire about prior episodes of mania.
• Additionally, criteria for at ≥ 1 manic (for bipolar Bipolar Nervous System: Histology I) or one hypomanic (for bipolar Bipolar Nervous System: Histology II) episode must be met MET Preoperative Care.

Mania

Mania is a period of elevated, expansive, or irritable mood Irritable mood Abnormal or excessive excitability with easily triggered anger, annoyance, or impatience. Oppositional Defiant Disorder for ≥ 1 week, with symptoms for most of nearly every day.

• Symptoms:
  • Distractibility
  • Impulsivity Impulsivity Attention Deficit Hyperactivity Disorder
    • Involvement in high-risk behavior or activities without thinking
    • Examples: buying sprees, multiple sexual encounters
  • Increased goal-directed activity or psychomotor agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus (plans many activities but unable to complete any tasks)
  • Decreased sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep (does not feel tired even after just a few hours of sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep)
  • Talkativeness
  • Grandiosity or increased self-esteem
  • Flight of ideas
• Cause significant decline in function:
  •  A manic episode is a medical emergency, given the risk to self and others.
  • Example: cannot perform assigned job, financial loss, violence/assault on others
• May have psychotic features (delusions, hallucinations Hallucinations Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders. Schizophrenia, disorganized thinking and behavior)
• Symptoms are not due to substance use or underlying medical conditions.

Hypomania

Hypomania is a period of elevated, expansive, or irritable mood Irritable mood Abnormal or excessive excitability with easily triggered anger, annoyance, or impatience. Oppositional Defiant Disorder for > 4 consecutive days but < 1 week.

• Symptoms similar to those for manic episode but less severe:
  • Distractibility
  • Impulsivity Impulsivity Attention Deficit Hyperactivity Disorder
  • Increased goal-directed activity or psychomotor agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus
  • Decreased sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep
  • Talkativeness
  • Grandiosity or increased self-esteem
  • Flight of ideas
• No significant decline in function, no need for hospitalization Hospitalization The confinement of a patient in a hospital. Delirium
• Change in mood is observable by others.
• No psychotic features
• Symptoms are not due to substance use or medical conditions.

Major depressive disorder Major depressive disorder Major depressive disorder (MDD), commonly called depression, is a unipolar mood disorder characterized by persistent low mood and loss of interest in association with somatic symptoms for a duration of ≥ 2 weeks. Major depressive disorder has the highest lifetime prevalence among all psychiatric disorders. Major Depressive Disorder (MDD)

• Period of depressed mood or loss of pleasure for ≥ 2 weeks
• Symptoms:
  • Depressed mood, all day, every day
  • Anhedonia Anhedonia Inability to experience pleasure due to impairment or dysfunction of normal psychological and neurobiological mechanisms. It is a symptom of many psychotic disorders (e.g., depressive disorder, major; and schizophrenia). Schizophrenia (reduced pleasure from previously enjoyable habits)
  • Appetite/weight changes (increase or decrease)
  • Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep disturbance (increase or decrease)
  • Psychomotor agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus or retardation (individual is anxious and moves a lot, or barely moves)
  • Loss of energy
  • Feeling worthless or excessively guilty
  • Trouble concentrating
  • Suicidal ideation Suicidal ideation A risk factor for suicide attempts and completions, it is the most common of all suicidal behavior, but only a minority of ideators engage in overt self-harm. Suicide and/or attempts
• Causes significant decline in function 
• Symptoms are not due to substance use or medical conditions.

Mnemonic

• DIG FAST is the mnemonic used to memorize manic episode symptoms:
  • Distractibility
  • Impulsivity
  • Grandiosity
  • Flight of ideas
  • Activity increase
  • S leep LEEP Diagnostic Procedures in Gynecology decrease
  • Talkativeness 
• SIGECAPS is the mnemonic used to memorize depression symptoms:
  • S leep LEEP Diagnostic Procedures in Gynecology
  • Interest decreased
  • Guilt or worthlessness
  • Energy decreased
  • Concentration difficulties
  • Appetite disturbance
  • Psychomotor agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus/retardation
  • Suicidal thoughts

Diagnosis

Diagnostic approach

• Screening Screening Preoperative Care (self-questionnaires and clinician-rated questionnaires) to classify depressive and manic mood symptoms, which includes:
  • Mood Disorder Questionnaire for manic episodes
  • Patient Health Questionnaire Patient health questionnaire A self-administered version of the primary care evaluation of mental disorders (prime-md), a diagnostic tool containing modules on multiple mental health disorders including anxiety, alcohol, eating, and somatoform modules. The patient health questionnaire (phq-9) is designed specifically for mood/depression scoring each of the 9 dsm-iv criteria based on the mood module from the original prime-md. The generalized anxiety disorder scale (gad-7) scores 7 common anxiety symptoms. Psychiatric Assessment (PHQ-9) for depressive episodes
• Assessment of suicide Suicide Suicide is one of the leading causes of death worldwide. Patients with chronic medical conditions or psychiatric disorders are at increased risk of suicidal ideation, attempt, and/or completion. The patient assessment of suicide risk is very important as it may help to prevent a serious suicide attempt, which may result in death. Suicide risk 
• Laboratory evaluation (used to rule out other causes):
  • Thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy function
  • Urine drug screen 
  • Vitamin B₁₂, vitamin D Vitamin D A vitamin that includes both cholecalciferols and ergocalciferols, which have the common effect of preventing or curing rickets in animals. It can also be viewed as a hormone since it can be formed in skin by action of ultraviolet rays upon the precursors, 7-dehydrocholesterol and ergosterol, and acts on vitamin D receptors to regulate calcium in opposition to parathyroid hormone. Fat-soluble Vitamins and their Deficiencies, folic acid levels 
• Imaging: CT and MRI of brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification to rule out organic causes
• Must rule out these other causes of manic episodes:
  • Medical causes of mania:
    • Neurologic disorders ( temporal lobe Temporal lobe Lower lateral part of the cerebral hemisphere responsible for auditory, olfactory, and semantic processing. It is located inferior to the lateral fissure and anterior to the occipital lobe. Cerebral Cortex: Anatomy seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures, multiple sclerosis Sclerosis A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. Wilms Tumor, viral encephalitis Viral encephalitis Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of togaviridae infections; herpesviridae infections; adenoviridae infections; flaviviridae infections; bunyaviridae infections; picornaviridae infections; paramyxoviridae infections; orthomyxoviridae infections; retroviridae infections; and arenaviridae infections. Encephalitis, and cerebral tumors)
    • Metabolic ( hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism, Cushing syndrome Cushing syndrome A condition caused by prolonged exposure to excess levels of cortisol (hydrocortisone) or other glucocorticoids from endogenous or exogenous sources. It is characterized by upper body obesity; osteoporosis; hypertension; diabetes mellitus; hirsutism; amenorrhea; and excess body fluid. Endogenous Cushing syndrome or spontaneous hypercortisolism is divided into two groups, those due to an excess of adrenocorticotropin and those that are acth-independent. Paraneoplastic Syndromes)
    • Neoplasms Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Bone Tumors
    • HIV HIV Anti-HIV Drugs infection
    • Systemic disorders (vitamin B₁₂ deficiency, carcinoid syndrome Carcinoid syndrome A symptom complex associated with carcinoid tumor and characterized by attacks of severe flushing of the skin, diarrheal watery stools, bronchoconstriction, sudden drops in blood pressure, edema, and ascites. The carcinoid tumors are usually located in the gastrointestinal tract and metastasize to the liver. Symptoms are caused by tumor secretion of serotonin, prostaglandins, and other biologically active substances. Cardiac manifestations constitute carcinoid heart disease. Carcinoid Tumors and Syndrome, uremia Uremia A clinical syndrome associated with the retention of renal waste products or uremic toxins in the blood. It is usually the result of renal insufficiency. Most uremic toxins are end products of protein or nitrogen catabolism, such as urea or creatinine. Severe uremia can lead to multiple organ dysfunctions with a constellation of symptoms. Acute Kidney Injury)
  • Medication/substance-induced mania:
    • Corticosteroids Corticosteroids Chorioretinitis
    • Sympathomimetics Sympathomimetics Sympathomimetic drugs, also known as adrenergic agonists, mimic the action of the stimulators (î±, β, or dopamine receptors) of the sympathetic autonomic nervous system. Sympathomimetic drugs are classified based on the type of receptors the drugs act on (some agents act on several receptors but 1 is predominate). Sympathomimetic Drugs
    • Bronchodilators Bronchodilators Asthma Drugs
    • Levodopa Levodopa The naturally occurring form of dihydroxyphenylalanine and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonian disorders and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. Parkinson’s Disease Drugs
    • Antidepressants
    • Dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS agonists
    • Cocaine Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Local Anesthetics
    • Phencyclidine
    • Alcohol

Types of bipolar Bipolar Nervous System: Histology disorders

Bipolar Bipolar Nervous System: Histology disorder can be classified into several subtypes, depending on the severity and the associated features in the symptoms and history:

• Bipolar Bipolar Nervous System: Histology I:
  • 1 manic episode in a lifetime is enough to make the diagnosis. 
  • Depressive episodes may present but are not required for diagnosis.
• Bipolar Bipolar Nervous System: Histology II:
  • ≥ 1 hypomanic episode
  • ≥ 1 MDD episode
  • No history of manic episodes
• Cyclothymic disorder:
  • Numerous periods of hypomania and depression within a distinct time frame, but symptoms do not meet the full criteria of hypomania and depression
  • Symptoms recur in ≥ 2 consecutive years, present ≥ ½ the time, and are not absent for > 2 consecutive months.
  • Cause distress or impaired function
• Substance/medication-induced bipolar Bipolar Nervous System: Histology disorder: Mood episode(s) occur soon after use or intake of substance/medication.
• Bipolar Bipolar Nervous System: Histology disorder due to another medical condition
• Other specified bipolar Bipolar Nervous System: Histology disorder: does not meet full criteria (e.g., short duration of symptoms)

In the diagnosis of bipolar Bipolar Nervous System: Histology disorder, mood specifiers can be used, such as:

• Rapid cycling:
  • Experience ≥ 4 mood episodes during a 12-month period
  • Episodes take place in any order.
• Psychotic features
• Mixed features
• Catatonia Catatonia A neuropsychiatric disorder characterized by one or more of the following essential features: immobility, mutism, negativism (active or passive refusal to follow commands), mannerisms, stereotypies, posturing, grimacing, excitement, echolalia, echopraxia, muscular rigidity, and stupor; sometimes punctuated by sudden violent outbursts, panic, or hallucinations. This condition may be associated with psychiatric illnesses (e.g., schizophrenia; mood disorders) or organic disorders (neuroleptic malignant syndrome; encephalitis, etc.). Major Depressive Disorder
• Anxious distress
• Melancholic features
• Peripartum onset
• Atypical features

Management

Principles of therapy

• Treatment of bipolar Bipolar Nervous System: Histology disorder begins with assessment of the individual’s ability to function and their need for hospitalization Hospitalization The confinement of a patient in a hospital. Delirium. 
• Treatment options for bipolar Bipolar Nervous System: Histology I and II are the same.
• Treatment is lifelong; options involve pharmacotherapy, behavioral therapy, and electroconvulsive therapy Electroconvulsive therapy Electrically induced convulsions primarily used in the treatment of severe affective disorders and schizophrenia. Major Depressive Disorder.
• Medication classes (antimanic drugs (drugs that reduce manic/hypomanic symptoms)):
  • Lithium Lithium An element in the alkali metals family. It has the atomic symbol li, atomic number 3, and atomic weight [6. 938; 6. 997]. Salts of lithium are used in treating bipolar disorder. Ebstein’s Anomaly:
    • Mood stabilizer with narrow therapeutic index Therapeutic Index An indicator of the benefits and risks of treatment. Dosage Calculation (monitoring needed)
    • About 80% of those with mania respond to lithium Lithium An element in the alkali metals family. It has the atomic symbol li, atomic number 3, and atomic weight [6. 938; 6. 997]. Salts of lithium are used in treating bipolar disorder. Ebstein’s Anomaly.
    • May be used as adjunct to treatment of major depression
  • 2nd-generation antipsychotics ( SGAs SGAs Second-generation antipsychotics (SGA) are also called atypical antipsychotics. Medications in this class include aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, iloperidone, lumateperone, lurasidone, olanzapine, paliperidone, pimavanserin, quetiapine, risperidone, and ziprasidone. Second-Generation Antipsychotics; e.g., quetiapine Quetiapine A dibenzothiazepine and antipsychotic agent that targets the serotonin 5-HT2 receptor; histamine h1 receptor, adrenergic alpha1 and alpha2 receptors, as well as the dopamine d1 receptor and dopamine D2 receptor. It is used in the treatment of schizophrenia; bipolar disorder and depressive disorder. Second-Generation Antipsychotics, aripiprazole Aripiprazole A piperazine and quinolone derivative that is used primarily as an antipsychotic agent. It is a partial agonist of serotonin receptor, 5-HT1a and dopamine D2 receptors, where it also functions as a postsynaptic antagonist, and an antagonist of serotonin receptor, 5-HT2a. It is used for the treatment of schizophrenia and bipolar disorder, and as an adjunct therapy for the treatment of depression. Second-Generation Antipsychotics)
  • Anticonvulsants:
    • Valproic acid Valproic acid A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of epilepsy and bipolar disorder. The mechanisms of its therapeutic actions are not well understood. It may act by increasing gamma-aminobutyric acid levels in the brain or by altering the properties of voltage-gated sodium channels. First-Generation Anticonvulsant Drugs: wider therapeutic index Therapeutic Index An indicator of the benefits and risks of treatment. Dosage Calculation than lithium Lithium An element in the alkali metals family. It has the atomic symbol li, atomic number 3, and atomic weight [6. 938; 6. 997]. Salts of lithium are used in treating bipolar disorder. Ebstein’s Anomaly
    • Carbamazepine Carbamazepine A dibenzazepine that acts as a sodium channel blocker. It is used as an anticonvulsant for the treatment of grand mal and psychomotor or focal seizures. It may also be used in the management of bipolar disorder, and has analgesic properties. First-Generation Anticonvulsant Drugs: induces hepatic enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes, which decrease levels of antipsychotics (so generally not combined with SGAs SGAs Second-generation antipsychotics (SGA) are also called atypical antipsychotics. Medications in this class include aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, iloperidone, lumateperone, lurasidone, olanzapine, paliperidone, pimavanserin, quetiapine, risperidone, and ziprasidone. Second-Generation Antipsychotics)
    • Lamotrigine Lamotrigine A phenyltriazine compound, sodium and calcium channel blocker that is used for the treatment of seizures and bipolar disorder. Second-Generation Anticonvulsant Drugs: indicated for maintenance treatment 
• Benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines:
  • Not used to treat bipolar Bipolar Nervous System: Histology disorders 
  • Adjunctive therapy in acute manic episodes to treat insomnia Insomnia Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. Insomnia, agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus, or anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder
• Monotherapy with antidepressants is generally avoided in bipolar Bipolar Nervous System: Histology disorder because of the risk of causing manic episodes.

Pharmacotherapy

• Acute severe mania:
  • Characteristics:
    • Suicidal or homicidal ideation or behavior
    • Psychotic features
    • Aggressiveness
    • Impaired judgment Judgment The process of discovering or asserting an objective or intrinsic relation between two objects or concepts; a faculty or power that enables a person to make judgments; the process of bringing to light and asserting the implicit meaning of a concept; a critical evaluation of a person or situation. Psychiatric Assessment (placing self or others in danger)  
  • Treatment:
    • Generally require hospitalization Hospitalization The confinement of a patient in a hospital. Delirium
    • Stop any agents that elevate mood, such as antidepressants or stimulants Stimulants Stimulants are used by the general public to increase alertness and energy, decrease fatigue, and promote mental focus. Stimulants have medical uses for individuals with ADHD and sleep disorders, and are also used in combination with analgesics in pain management. Stimulants.
    • Use lithium Lithium An element in the alkali metals family. It has the atomic symbol li, atomic number 3, and atomic weight [6. 938; 6. 997]. Salts of lithium are used in treating bipolar disorder. Ebstein’s Anomaly or valproic acid Valproic acid A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of epilepsy and bipolar disorder. The mechanisms of its therapeutic actions are not well understood. It may act by increasing gamma-aminobutyric acid levels in the brain or by altering the properties of voltage-gated sodium channels. First-Generation Anticonvulsant Drugs with antipsychotic Antipsychotic Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics.
  • Episode resistant to initial treatment:
    • Switch medications (if lithium Lithium An element in the alkali metals family. It has the atomic symbol li, atomic number 3, and atomic weight [6. 938; 6. 997]. Salts of lithium are used in treating bipolar disorder. Ebstein’s Anomaly is used, switch to valproic acid Valproic acid A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of epilepsy and bipolar disorder. The mechanisms of its therapeutic actions are not well understood. It may act by increasing gamma-aminobutyric acid levels in the brain or by altering the properties of voltage-gated sodium channels. First-Generation Anticonvulsant Drugs, or vice versa)
    • If no response, switch to a different kind of antipsychotic Antipsychotic Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics.
  • Treatment-refractory mania:
    • Consider electroconvulsive therapy Electroconvulsive therapy Electrically induced convulsions primarily used in the treatment of severe affective disorders and schizophrenia. Major Depressive Disorder if, after 4–6 medication combinations, there is still no response.
• Hypomania or mild to moderate mania:
  • Without suicidal or homicidal behavior, psychotic features, aggressiveness or judgment Judgment The process of discovering or asserting an objective or intrinsic relation between two objects or concepts; a faculty or power that enables a person to make judgments; the process of bringing to light and asserting the implicit meaning of a concept; a critical evaluation of a person or situation. Psychiatric Assessment endangering self or others
  • Treatment:
    • Monotherapy with antipsychotic Antipsychotic Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics or lithium Lithium An element in the alkali metals family. It has the atomic symbol li, atomic number 3, and atomic weight [6. 938; 6. 997]. Salts of lithium are used in treating bipolar disorder. Ebstein’s Anomaly
    • Valproic acid Valproic acid A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of epilepsy and bipolar disorder. The mechanisms of its therapeutic actions are not well understood. It may act by increasing gamma-aminobutyric acid levels in the brain or by altering the properties of voltage-gated sodium channels. First-Generation Anticonvulsant Drugs or carbamazepine Carbamazepine A dibenzazepine that acts as a sodium channel blocker. It is used as an anticonvulsant for the treatment of grand mal and psychomotor or focal seizures. It may also be used in the management of bipolar disorder, and has analgesic properties. First-Generation Anticonvulsant Drugs are alternatives.
  • Resistant to initial treatment: combination therapy after a trial of 3–5 monotherapy options
• Rapid cycling:
  • 1st-line: antipsychotic Antipsychotic Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics ( quetiapine Quetiapine A dibenzothiazepine and antipsychotic agent that targets the serotonin 5-HT2 receptor; histamine h1 receptor, adrenergic alpha1 and alpha2 receptors, as well as the dopamine d1 receptor and dopamine D2 receptor. It is used in the treatment of schizophrenia; bipolar disorder and depressive disorder. Second-Generation Antipsychotics)
  • Failed: Consider combination therapy ( lithium Lithium An element in the alkali metals family. It has the atomic symbol li, atomic number 3, and atomic weight [6. 938; 6. 997]. Salts of lithium are used in treating bipolar disorder. Ebstein’s Anomaly or valproic acid Valproic acid A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of epilepsy and bipolar disorder. The mechanisms of its therapeutic actions are not well understood. It may act by increasing gamma-aminobutyric acid levels in the brain or by altering the properties of voltage-gated sodium channels. First-Generation Anticonvulsant Drugs and an antipsychotic Antipsychotic Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics).
• Maintenance:
  • Continuous treatment is critical to avoid relapse Relapse Relapsing Fever. 
  • Goals:
    • ↓ Symptoms and risk of suicide Suicide Suicide is one of the leading causes of death worldwide. Patients with chronic medical conditions or psychiatric disorders are at increased risk of suicidal ideation, attempt, and/or completion. The patient assessment of suicide risk is very important as it may help to prevent a serious suicide attempt, which may result in death. Suicide
    • Prevent recurrence of new mood episodes.
    • Improve psychosocial functioning.
  • Recommendation is to use same regimen as used initially if the response was good
  • Combination therapy for partial response or recurrences

Precautions in pharmacotherapy

• Renal disease: Avoid lithium Lithium An element in the alkali metals family. It has the atomic symbol li, atomic number 3, and atomic weight [6. 938; 6. 997]. Salts of lithium are used in treating bipolar disorder. Ebstein’s Anomaly (↑ risk of lithium Lithium An element in the alkali metals family. It has the atomic symbol li, atomic number 3, and atomic weight [6. 938; 6. 997]. Salts of lithium are used in treating bipolar disorder. Ebstein’s Anomaly toxicity Toxicity Dosage Calculation).
• Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease: Avoid valproate Valproate A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of epilepsy and bipolar disorder. The mechanisms of its therapeutic actions are not well understood. It may act by increasing gamma-aminobutyric acid levels in the brain or by altering the properties of voltage-gated sodium channels. First-Generation Anticonvulsant Drugs.
• Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity: Avoid  quetiapine Quetiapine A dibenzothiazepine and antipsychotic agent that targets the serotonin 5-HT2 receptor; histamine h1 receptor, adrenergic alpha1 and alpha2 receptors, as well as the dopamine d1 receptor and dopamine D2 receptor. It is used in the treatment of schizophrenia; bipolar disorder and depressive disorder. Second-Generation Antipsychotics, olanzapine Olanzapine A benzodiazepine derivative that binds serotonin receptors; muscarinic receptors; histamine h1 receptors; adrenergic alpha-1 receptors; and dopamine receptors. It is an antipsychotic agent used in the treatment of schizophrenia; bipolar disorder; and major depressive disorder; it may also reduce nausea and vomiting in patients undergoing chemotherapy. Second-Generation Antipsychotics, and risperidone Risperidone A selective blocker of dopamine D2 receptors and serotonin 5-HT2 receptors that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of schizophrenia. Second-Generation Antipsychotics.
• Sensitivity to extrapyramidal symptoms Extrapyramidal Symptoms Ataxia-telangiectasia: Avoid aripiprazole Aripiprazole A piperazine and quinolone derivative that is used primarily as an antipsychotic agent. It is a partial agonist of serotonin receptor, 5-HT1a and dopamine D2 receptors, where it also functions as a postsynaptic antagonist, and an antagonist of serotonin receptor, 5-HT2a. It is used for the treatment of schizophrenia and bipolar disorder, and as an adjunct therapy for the treatment of depression. Second-Generation Antipsychotics and risperidone Risperidone A selective blocker of dopamine D2 receptors and serotonin 5-HT2 receptors that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of schizophrenia. Second-Generation Antipsychotics.
• In women of childbearing age: Avoid valproate Valproate A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of epilepsy and bipolar disorder. The mechanisms of its therapeutic actions are not well understood. It may act by increasing gamma-aminobutyric acid levels in the brain or by altering the properties of voltage-gated sodium channels. First-Generation Anticonvulsant Drugs (associated with neural tube Neural tube A tube of ectodermal tissue in an embryo that will give rise to the central nervous system, including the spinal cord and the brain. Lumen within the neural tube is called neural canal which gives rise to the central canal of the spinal cord and the ventricles of the brain. Gastrulation and Neurulation defects) and lithium Lithium An element in the alkali metals family. It has the atomic symbol li, atomic number 3, and atomic weight [6. 938; 6. 997]. Salts of lithium are used in treating bipolar disorder. Ebstein’s Anomaly (associated with Ebstein’s anomaly).

Psychotherapy Psychotherapy Psychotherapy is interpersonal treatment based on the understanding of psychological principles and mechanisms of mental disease. The treatment approach is often individualized, depending on the psychiatric condition(s) or circumstance. Psychotherapy

• Adjunct to pharmacotherapy
• The forms of psychotherapy Psychotherapy Psychotherapy is interpersonal treatment based on the understanding of psychological principles and mechanisms of mental disease. The treatment approach is often individualized, depending on the psychiatric condition(s) or circumstance. Psychotherapy include:
  • Psychologic counseling/ psychoeducation Psychoeducation Psychotherapy
  • CBT
  • Interpersonal and social rhythm therapy (IPSRT)
  • Family therapy Family therapy A form of group psychotherapy. It involves treatment of more than one member of the family simultaneously in the same session. Psychotherapy

Somatic therapies

• Electroconvulsive therapy Electroconvulsive therapy Electrically induced convulsions primarily used in the treatment of severe affective disorders and schizophrenia. Major Depressive Disorder (ECT):
  • Procedure done under general anesthesia General anesthesia Procedure in which patients are induced into an unconscious state through use of various medications so that they do not feel pain during surgery. Anesthesiology: History and Basic Concepts during which brief seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures are intentionally induced via small electric currents 
  • Releases neurotransmitters ( dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS, serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS, and norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS) and hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types ( prolactin Prolactin A lactogenic hormone secreted by the adenohypophysis. It is a polypeptide of approximately 23 kd. Besides its major action on lactation, in some species prolactin exerts effects on reproduction, maternal behavior, fat metabolism, immunomodulation and osmoregulation. Breasts: Anatomy, thyroid-stimulating hormone Thyroid-stimulating hormone A glycoprotein hormone secreted by the adenohypophysis. Thyrotropin stimulates thyroid gland by increasing the iodide transport, synthesis and release of thyroid hormones (thyroxine and triiodothyronine). Thyroid Hormones, and endorphins Endorphins One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. Receptors and Neurotransmitters of the CNS)
  • Usually indicated in cases of failure of multiple drug therapies or for bipolar Bipolar Nervous System: Histology cases with psychotic features or catatonia Catatonia A neuropsychiatric disorder characterized by one or more of the following essential features: immobility, mutism, negativism (active or passive refusal to follow commands), mannerisms, stereotypies, posturing, grimacing, excitement, echolalia, echopraxia, muscular rigidity, and stupor; sometimes punctuated by sudden violent outbursts, panic, or hallucinations. This condition may be associated with psychiatric illnesses (e.g., schizophrenia; mood disorders) or organic disorders (neuroleptic malignant syndrome; encephalitis, etc.). Major Depressive Disorder
  • Typical course usually has 6–12 sessions.
  • Side effects include the complications from the general anesthesia General anesthesia Procedure in which patients are induced into an unconscious state through use of various medications so that they do not feel pain during surgery. Anesthesiology: History and Basic Concepts as well as short-term memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment problems. 
• Transcranial magnetic stimulation Transcranial magnetic stimulation A technique that involves the use of electrical coils on the head to generate a brief magnetic field which reaches the cerebral cortex. It is coupled with electromyography response detection to assess cortical excitability by the threshold required to induce motor evoked potentials. This method is also used for brain mapping, to study neurophysiology, and as a substitute for electroconvulsive therapy for treating depression. Induction of seizures limits its clinical usage. Major Depressive Disorder (TMS):
  • Current passed through a metal coil (applied against the scalp) generates a magnetic field.
  • Short pulses of magnetic energy stimulate a specific region of the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification.
  • Unlike ECT, does not require anesthesia Anesthesia A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. Anesthesiology: History and Basic Concepts 
  • Efficacy noted in bipolar Bipolar Nervous System: Histology major depression and bipolar Bipolar Nervous System: Histology disorder with mixed features
  • Rate of TMS causing manic switch in bipolar Bipolar Nervous System: Histology major depression appears low.
  • Side effects include scalp pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways/discomfort and possible generalized tonic-clonic seizure

Differential Diagnosis

• Major depressive disorder Major depressive disorder Major depressive disorder (MDD), commonly called depression, is a unipolar mood disorder characterized by persistent low mood and loss of interest in association with somatic symptoms for a duration of ≥ 2 weeks. Major depressive disorder has the highest lifetime prevalence among all psychiatric disorders. Major Depressive Disorder (MDD): marked by depressed mood, sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep disturbance, anhedonia Anhedonia Inability to experience pleasure due to impairment or dysfunction of normal psychological and neurobiological mechanisms. It is a symptom of many psychotic disorders (e.g., depressive disorder, major; and schizophrenia). Schizophrenia, feelings of guilt or worthlessness, loss of energy, low concentration, weight or appetite changes, psychomotor retardation or agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus and suicidal ideation Suicidal ideation A risk factor for suicide attempts and completions, it is the most common of all suicidal behavior, but only a minority of ideators engage in overt self-harm. Suicide. These symptoms last for ≥ 2 weeks. Individuals with bipolar Bipolar Nervous System: Histology disorder are often likely to present with depressive symptoms, but careful history taking reveals past incidents of mania or hypomania. Individuals with bipolar Bipolar Nervous System: Histology disorder are more likely to have poor response to antidepressant Antidepressant Antidepressants encompass several drug classes and are used to treat individuals with depression, anxiety, and psychiatric conditions, as well as those with chronic pain and symptoms of menopause. Antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and many other drugs in a class of their own. Serotonin Reuptake Inhibitors and Similar Antidepressants monotherapy, greater risk of hospitalizations/ suicide Suicide Suicide is one of the leading causes of death worldwide. Patients with chronic medical conditions or psychiatric disorders are at increased risk of suicidal ideation, attempt, and/or completion. The patient assessment of suicide risk is very important as it may help to prevent a serious suicide attempt, which may result in death. Suicide attempts, family history Family History Adult Health Maintenance of bipolar Bipolar Nervous System: Histology disorder, and higher rates of comorbid substance use disorders, anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder disorders, and personality disorders Personality Disorders A major deviation from normal patterns of behavior. Cluster A Personality Disorders. 
• Personality disorders Personality Disorders A major deviation from normal patterns of behavior. Cluster A Personality Disorders: cluster of mental diseases that involve semipermanent patterns of thoughts and behavior that can be harmful and obstinate. Individuals with personality disorders Personality Disorders A major deviation from normal patterns of behavior. Cluster A Personality Disorders have difficulty handling everyday stresses and issues and their behavior can lead to serious issues with relationships and work. Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas of bipolar Bipolar Nervous System: Histology disorder is often complicated because of comorbid personality disorders Personality Disorders A major deviation from normal patterns of behavior. Cluster A Personality Disorders. 
• Cyclothymia: milder form of bipolar Bipolar Nervous System: Histology II disorder. Cyclothymia is marked by chronic episodes of hypomania and mild depression for a period of at ≥ 2 years. Neither the hypomanic episodes nor the depressive episodes are severe enough to meet criteria for bipolar Bipolar Nervous System: Histology disorder or major depression. Mood stabilizers are 1st-line therapy for pharmacologic treatment. Lifelong psychosocial therapy is also recommended because of the long-term nature of this disorder.