Bipolar Disorder

Essentials of Diagnosis

• Episodic mood shifts into mania, major depression, hypomania, and mixed states

• Bipolar I is diagnosed in individuals who have manic episodes

• Bipolar II is diagnosed in individuals who experience hypomanic episodes without frank mania

General Considerations

• Manic episodes

  • Begin abruptly and may be triggered by life stresses

  • Last days to months—generally shorter than depressive episodes

• Cyclothymia

  • Chronic mood disturbances with episodes of subsyndromal depression and hypomania

  • Symptoms are milder than those in a manic or depressive episode, but have at least a 2-year duration

  • Symptoms occasionally escalate to a full-blown manic or depressive episode, warranting a diagnosis of bipolar I or II

Symptoms and Signs

• Manic episodes

  • Mood ranging from euphoria to irritability

  • Over-involvement in life activities

  • Flight of ideas with distractibility

  • Sleep disruption, little need for sleep

  • Racing thoughts

  • Behaviors may initially attract others

  • Irritability, mood lability, aggression, and grandiosity usually lead to problems in relationships

  • Excessive spending, resignation from a job, hasty marriage or divorce, sexual acting out, or exhibitionism may occur

  • Atypical episodes involve gross delusions, paranoid ideations, and auditory hallucinations

  • Patients with four or more discrete episodes of a mood disturbance in 1 year have "rapid cycling"

• Most depressions

  • Lowered mood, varying from mild sadness to intense feelings of guilt, worthlessness, and hopelessness

  • Difficulty in thinking, including inability to concentrate, ruminations, and lack of decisiveness

  • Loss of interest, with diminished involvement in work and recreation

  • Somatic complaints such as

    • Headache

    • Disrupted, lessened, or excessive sleep

    • Loss of energy

    • Change in appetite

  • Anxiety

• Some severe depressions

  • Psychomotor retardation or agitation

  • Delusions of a hypochondriacal or persecutory nature

  • Withdrawal from activities

  • Physical symptoms of major severity, eg,

    • Anorexia

    • Insomnia

    • Reduced sexual drive

    • Weight loss

    • Various somatic complaints

  • Suicidal ideation

Differential Diagnosis

• Schizophrenia and other psychotic disorders

• Intoxication with stimulants

• Major depressive episode

• Hypothyroidism

• Persistent depressive disorder (dysthymia)

Laboratory Tests

• Consider thyroid-stimulating hormone

• Consider toxicology screen

Medications

• Antipsychotics

  • Initial treatment for acute manic symptoms includes

    • Olanzapine, 5–20 mg orally

    • Risperidone, 2–3 mg orally

    • Aripiprazole, 15–30 mg orally

    • A benzodiazepine (eg, clonazepam) may be used in conjunction with these agents, if indicated

  • When behavioral control is immediately necessary, the following may be used until symptoms subside

    • Olanzapine, 2.5–10 mg intramuscularly or

    • Haloperidol, 5–10 mg orally or intramuscularly

  • The dosage of the antipsychotic may be gradually reduced after lithium or another mood stabilizer is started

  • Maintenance treatments for bipolar disorder to prevent subsequent cycles of mania and depression include

    • Olanzapine

    • Quetiapine

    • Ziprasidone

    • Aripiprazole

    • Risperidone (the long-acting injectable)

• Valproic acid helps acute manic or hypomanic symptoms

  • First-line treatment for mania

  • Dosage: Start at 750 mg/day orally, then titrate to achieve therapeutic serum levels

  • Oral loading in acutely manic bipolar patients in an inpatient setting (initiated at a dosage of 20 mg/kg/day) can safely achieve serum therapeutic levels in 2–3 days

  • Gastrointestinal symptoms and weight gain are the main side effects

• Lithium is used for maintenance and manic episodes

  • Common starting dose: 300–900 mg daily, with trough blood levels measured after 4–5 days of treatment

  • Significantly decreases the frequency and severity of both manic and depressive attacks

  • Bipolar disease can be managed long-term with lithium alone in many patients, but some will require continued or intermittent use of an antipsychotic or lamotrigine to help prevent depressive episodes

• Carbamazepine is used in the treatment of bipolar patients who cannot be satisfactorily treated with lithium (nonresponsive, excessive side effects, or rapid cycling)

  • Dosage: Start at 400–600 mg orally daily and is increased slowly to therapeutic levels

  • Can be effective in conjunction with lithium, although there have been reports of reversible neurotoxicity with the combination

• Oxcarbazepine

  • A derivative of carbamazepine

  • May have efficacy in acute mania

  • Appears to be safer than carbamazepine due to its lower risk of hepatotoxicity and fewer drug interactions but may impose a higher risk of hyponatremia

• Lamotrigine is used for the maintenance treatment of bipolar disorder

  • Dosage: Start at 25–50 mg/day orally and titrate upward slowly to decrease the likelihood of rash

  • Slower titration and a lower total dose are indicated for patients taking valproic acid

• Depression

  • See Depression

Follow-Up

• Lithium levels should be measured 5–7 days after initiation and after dose changes, then monthly to bimonthly early in treatment, and every 6–12 months in stable patients

• Thyroid and kidney function should be monitored every 4–6 months in patients taking lithium

• Liver biochemical tests and complete blood count must be monitored in patients taking valproic acid or carbamazepine

• Weight, fasting blood sugar, and lipids must be monitored in patients taking most atypical antipsychotics

Complications

• Suicide (see Depression)

• Drug–drug interactions complicate therapy with all agents—careful review of concomitant medications is needed

• Lithium toxicity occurs at serum levels > 2 mEq/L (see Lithium Toxicity)

• Long-term lithium use can cause cogwheel rigidity and other extrapyramidal signs

Prognosis

• Good prognosis with adequate treatment

• Breakthrough manic or depressive episodes are common, even with adherence to maintenance treatments, although maintenance therapy lessens the risk of recurrent episodes

• Compliance with lithium is adversely affected by the loss of some hypomanic experiences valued by the patient

When to Refer

• When diagnosis is in question or when standard management strategies are ineffective

• Irrational behavior or when there is a question of suicidiality

When to Admit

• Depressed patients who are at risk for self-harm or suicide

• Manic patients whose judgment is sufficiently impaired to make them a risk to themselves or others