Bipolar disorder

Bipolar disorder is a psychiatric condition characterized by episodes of mania (or hypomania) and major depression, interspersed with periods of normal mood and functioning. Men and women are equally affected, and there is a strong genetic component to the disease. During manic episodes, patients may experience elevated mood, talkativeness, racing thoughts, and psychosis, which may endanger themselves or others. Depressive episodes are characterized by sadness, anhedonia, and hopelessness. Although episodes of mania or depression can occur at any time, they are especially triggered by environmental factors, such as lack of sleep or psychosocial stress. Manic episodes are treated acutely with lithium, antipsychotics, and benzodiazepines. Lithium is also commonly used for long-term treatment, as is valproic acid.

• Sex: ♀ = ♂ ^[1]
• Age of onset ^[2]
  • The average age of onset is 20 years
  • The frequency of depressive and manic episodes increases with age.
• Lifetime prevalence
  • General population: 1–3%
  • First-degree relative with bipolar disorder: up to 10%
  • Monozygotic twin: 40–70%

Patients with bipolar disorder have a very high risk of suicide.

Epidemiological data refers to the US, unless otherwise specified.

• Multifactorial origin
  • Strong genetic component → increased risk if first-degree relative is affected (see “Epidemiology” above) ^[3]
  • ↑ Paternal age → ↑ mutations during spermatogenesis → ↑ risk of bipolar disorder in offspring ^[4]
• Triggers
  • Psychosocial stress
  • Medications (e.g., dexamethasone)
  • Childhood traumatic experiences
  • Sleep disturbances
  • Physical illness

General

Bipolar disorder is characterized by alternating episodes of mania (often also hypomania) and major depression, in between which individuals may be asymptomatic. See “DSM-5 diagnostic criteria for bipolar disorder” for details. ^[5]

• Manic/hypomanic episode
  • Characterized by an elevated mood
  • Symptoms include:
    • Intense prolonged happiness (e.g., for several days)
    • Irritability
    • Overconfidence, risky behavior (e.g., overspending money)
    • Decreased need for sleep
    • Hypersexuality
    • Psychotic features (only during manic episodes)
• Major depressive episode
  • Characterized by a depressed mood
  • Symptoms include:
    • Anhedonia
    • Fatigue, sleep disturbances
    • Frequent reports of pain, e.g., headache or stomach ache
    • Lack of interest in activities that were previously enjoyed
    • Feelings of worthlessness or guilt
    • Suicidal ideation

DIGFAST for features of mania: Distractibility, Irresponsibility, Grandiosity, Flight of ideas, Activity increase, Sleep deficit, and Talkativeness.

SIGECAPS for features of depression: Sleep (insomnia or hypersomnia), Interest loss (anhedonia), Guilt (low self-esteem), Energy (low energy or fatigue), Concentration (poor concentration or difficulty making decisions), Appetite (decreased appetite or overeating), Psychomotor agitation or retardation, and Suicidal ideation.

Types of bipolar disorder ^[6]

• Bipolar I disorder: at least one episode of mania. Major depressive or hypomanic episodes usually occur but are not required for diagnosis.
• Bipolar II disorder: at least one episode of hypomania and one major depressive episode; no previous episodes of mania (distinguishing feature from bipolar I)

In contrast to bipolar II disorder, a history of major depressive episodes is not required for the diagnosis of bipolar I disorder.

In children and adolescents

A sudden change in mood or activity of a child or adolescent that differs greatly from their normal behavior may be a sign of bipolar disorder. Symptoms of bipolar disorder should be differentiated from mood swings, which are normal for puberty.

• Changes during manic episode may include:
  • Sleeping only for a few hours but not feeling tired
  • Difficulty staying focused in school
  • Increased interest in risky activities (e.g., dangerous sports without proper training)
• Changes during depressive episode may include:
  • Sleeping more than usual (e.g., more than 12 hours several days in a row)
  • Lack of interest in activities that were previously enjoyed
  • Feelings of doing everything wrong

Rapid cycling ^[6]

• Patients affected by rapid cycling have 4 or more episodes of depression, mania, or hypomania occurring in a single year.

Cyclothymia ^[6]

• Persistent instability of mood involving numerous periods of depressive symptoms and periods of hypomanic symptoms
• Symptoms are not sufficiently severe or persistent enough to diagnose bipolar disorder (symptoms never meet the criteria for a major depressive or hypomanic episode)
• Symptoms last at least 2 years, are present at least half of the time, and are never absent for more than 2 months at a time.

Substance/medication-induced bipolar and related disorder ^[6]

• Elevated, disinhibited, or irritable mood with/without depressed mood or anhedonia that develops during or soon after substance intoxication or withdrawal, or after exposure to a medication
• Common precipitants
  • Alcohol
  • Phencyclidine
  • Amphetamine
  • Cocaine
  • Benzodiazepines
  • Glucocorticoids (e.g., dexamethasone)

Approach ^[7][8]

The diagnosis is clinical and based on the DSM-5 criteria for bipolar disorder. Patients presenting with features of an acute episode should prompt a psychiatry consult and, depending on the severity of the episode, an urgent referral for management.

Suspected bipolar disorder ^[5][7][8]

• Suspect bipolar disorder in patients presenting with current or previous features of mania/hypomania and/or major depression.
• Consider using screening tools ^[5][7]
  • Mood Disorder Questionnaire for manic episodes
  • Patient Health Questionnaire-9 (PHQ-9) for depressive episodes
• Identify associated features that support the diagnosis, including:
  • Suicide attempt
  • Onset at an early age
  • First-degree relatives with bipolar disorder
• Obtain a detailed clinical history and physical examination; request laboratory studies based on clinical suspicion.
  • Rule out differential diagnoses, including:
    • Organic conditions, e.g., hyperthyroidism, hypothyroidism, frontotemporal dementia
    • Psychiatric conditions, e.g., schizophrenia, delusional disorders
  • Identify coexisting psychiatric conditions and comorbidities that may affect decisions regarding pharmacotherapy.
• Assess the risk of self-injury and consult psychiatry early for a specialized evaluation.

Patients with known bipolar disorder ^[7][9]

• Symptoms suggest an acute episode
  • Assess for suicidal ideation.
  • Identify potential substance misuse as the trigger for the acute episode.
  • Obtain urgent psychiatry consult for management.
• Follow-up visits or visits not related to bipolar disorder
  • Ask about frequency and severity of acute episodes, symptom control, and medication history
  • Screen for related medical comorbidities (e.g., migraine, metabolic syndrome, type 2 diabetes mellitus). ^[7][9]

Patients with bipolar disorder have the highest suicide rate among patients with affective disorders. All patients with suspected or confirmed bipolar disorder should be assessed promptly for suicide risk (especially during acute episodes) and evaluated by a psychiatrist. ^[5]

Patients with bipolar disorder are often misdiagnosed with major depressive disorder because the first presentation is usually a major depressive episode. ^[7]

Diagnostic studies ^[7][8]

Studies help rule out differential diagnoses and detect conditions that may affect management. A complete history and physical examination should guide the requested studies.

• Blood
  • CBC: may detect anemia ^[7]
  • BMP, liver chemistries: to establish a baseline before long-term pharmacological treatment
  • Thyroid function tests: to rule out thyroid disease
  • Additional studies based on the suspected underlying condition (e.g., evaluation for syphilis or frontotemporal dementia)
  • Monitoring studies depend on medications (e.g., serum levels of lithium or valproate, liver chemistries; see also “Overview of antipsychotics”).
• Urine
  • Urinalysis: may identify urinary tract infections
  • Urine toxicology screen: to rule out acute intoxication (e.g., with amphetamines)
  • Pregnancy test: Pregnancy will affect treatment decisions.
• ECG: To identify QT interval prolongation and other heart conditions that may be aggravated by lithium, valproic acid, and antipsychotics

Always do a urine drug screening in patients presenting with mania.

DSM-5 diagnostic criteria for bipolar disorder ^[9]

• The DSM-5 diagnostic criteria are used to identify episodes of mania, hypomania, and major depression.
  • Bipolar I disorder: ≥ 1 confirmed episode of mania
  • Bipolar II disorder: ≥ 1 confirmed episode of hypomania AND ≥ 1 major depressive episode AND absence of any manic episodes

In contrast to bipolar II disorder, a history of major depressive episodes is not required for the diagnosis of bipolar I disorder.

Manic and hypomanic episodes

A key difference between mania and hypomania is the intensity of the symptoms. Symptoms of mania are much more intense than those of hypomania, result in significant dysfunction, and manic patients often require hospitalization.

If psychotic symptoms are present, the episode is by definition manic, not hypomanic.

Major depressive episodes

Substance/medication-induced bipolar and related disorder

Bipolar and related disorder due to another medical condition

Bipolar and related disorder due to another medical condition is a mood disorder that is diagnosed when a persistent period of abnormally elevated, expansive, or irritable mood and abnormally increased activity or energy is attributable to another medical condition. Possible underlying conditions include:

• Endocrine disorders, e.g., hypercortisolism (Cushing disease)
• Autoimmune disorders, e.g., multiple sclerosis
• Neurological disorders, e.g., stroke, traumatic brain injury, delirium

Other

• Catatonia
• Acute anxiety

The differential diagnoses listed here are not exhaustive.

General principles ^[7][8][11]

• Consult psychiatry before starting treatment.
• Goals
  • Acute treatment: resolution of mania and psychosis (if present) in order to prevent harm to the patient and/or others
  • Maintenance therapy: prevention of manic episodes, reduction of suicide risk, improvement in social functioning
• Effective treatment combines pharmacotherapy with psychological interventions (e.g., cognitive behavioral therapy).

Mood stabilizers are a type of drug used as part of the treatment and prevention of episodes of acute mania, hypomania, and depression.

Acute management for mania, hypomania, and depressive episodes ^[8][11][12]

• Initial steps
  • Reduce external stimuli.
  • Assess symptom severity and for suicidal ideation to determine the appropriate level of care.
• Disposition: Often, patients can be managed by a specialist in ambulatory settings; indications for admission are listed below.
  • Immediate risk of harm to themselves or others
  • Significant psychiatric or medical comorbidities
  • No response to ambulatory treatment
• Management of agitation
  • Use rapid-acting intramuscular atypical antipsychotics (e.g., olanzapine, aripiprazole) or benzodiazepines (e.g., lorazepam).
  • See “Pharmacotherapy” in “Approach to the agitated or violent patient” for dosages.

Antipsychotics are the preferred initial therapy in agitated patients because of their rapid onset of action.

Patients with suicidal ideation should be admitted immediately for emergency management and monitoring by a specialist.

Acute mania is a psychiatric emergency that requires immediate management.

Lithium has a narrow therapeutic index and doses should be individualized according to serum levels and clinical response; an overdose may result in life-threatening lithium toxicity. Lithium is contraindicated in patients with renal dysfunction. ^[7]

Long-term maintenance treatment ^{[5][8][11][12]}

Maintenance treatment of bipolar disorder combines pharmacotherapy with nonpharmacological interventions. Most patients need lifelong maintenance therapy to prevent relapses.

• Indications: Consider for all patients, particularly those with a history of one or more manic episodes.
• Nonpharmacological interventions: an essential part of long-term management associated with better outcomes ^[15]
• Pharmacotherapy: Consider continuing the drug(s) that resolved the acute manic or depressive episode. ^[11];
  • Commonly used agents
    • Lithium (preferred): Individualize the dose according to clinical response and serum levels.
    • Valproic acid; , lamotrigine , quetiapine ^[16]
  • Alternative agents: aripiprazole, olanzapine, carbamazepine, oxcarbazepine
  • Refractory or severe bipolar episodes
    • Combination therapy with a mood stabilizer (e.g., lithium or valproic acid)
    • PLUS atypical antipsychotics (e.g., quetiapine, olanzapine, aripiprazole)
  • Severe depression or predominantly depressive bipolar II disorder: Antidepressants may be started after initiating mood stabilizers. ^[8]

Avoid prescribing antidepressants to patients with bipolar disorder before initiating therapy with mood stabilizers, as antidepressants can precipitate a manic episode. ^[11]

Lithium is the only maintenance drug shown to lower the risk of suicide. ^[8]