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Bipolar I Disorder
Wendy K. Marsh, MD, MSc
image BASICS
  • Bipolar I (BP-I) is an episodic mood disorder of at least one manic or mixed (mania and depression) episode that causes marked impairment, psychosis, and/or hospitalization, major depressive, episodes are not required, but usually occur.
  • Symptoms are not caused by a substance (e.g., drug), a general medical condition, or a medication.
Geriatric Considerations
New onset in older patients (>50 years of age) requires a workup for organic or chemically induced pathology.
Pediatric Considerations
Diagnosis less well defined, more rapid cycling, and mixed states. Depression often presents as irritable mood. There is an overlap with symptoms of attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD).
Pregnancy Considerations
  • Potential teratogenic effects of commonly used medications (e.g., valproic acid)
  • Postpartum caries risk of severe acute episode with psychosis and/or infanticidal ideation.
  • Onset usually between 15 and 30 years of age
  • More common in separated/widowed/divorced persons
  • 1.0-1.6% lifetime prevalence
  • Equal among men and women (manic episodes more common in men; depressive episodes more common in women)
  • Equal among races; however, clinicians tend to diagnose schizoaffective in African Americans with BP-I.
Genetic predisposition and major life stressors can trigger initial and subsequent episodes:
  • Dysregulation of biogenic amines or neurotransmitters (particularly serotonin, norepinephrine, and dopamine)
  • MRI findings suggest abnormalities in prefrontal cortical areas, striatum, and amygdala that predate illness onset (1)[C].
  • Monozygotic twin concordance 40-70%
  • Dizygotic twin concordance 5-25%
  • 50% have at least one parent with a mood disorder
  • First-degree relatives are 7 times more likely to develop BP-I than the general population.
Genetics, major life stressors (especially loss of parent or spouse), or substance abuse
Treatment adherence and education can help to prevent relapses.
Substance abuse (60%), ADHD, anxiety disorders, and eating disorders
  • The diagnosis of BP-I requires at least one manic or mixed episode (simultaneous mania and depression). Although a depressive episode is not necessary for the diagnosis, 80-90% of people with BP-I also experience depression.
  • Manic episode, DSM-5 criteria (2)
    • Distinct period of abnormally and persistently elevated, expansive, or irritable mood lasting plus increased activity or energy for at least 1 week (or any duration if hospitalization is necessary)
    • During the period of mood disturbance, three or more of the “DIG FAST” symptoms must persist (four if the mood is only irritable) and must be present to a significant degree.
      • Distractibility
      • Insomnia, decreased need for sleep
      • Grandiosity or inflated self-esteem
      • Flight of ideas or racing thoughts
      • Agitation or increase in goal-directed activity
      • Speech-pressured/more talkative than usual
      • Taking risks: excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g., financial or sexual)
    • Mixed specifier: when three or more symptoms of opposite mood pole are present during primary mood episode, For example, mania with mixed features (of depression).
  • Mental status exam in acute mania
    • General appearance: bright clothing, excessive makeup, disorganized or discombobulated, psychomotor agitation
    • Speech: pressured, difficult to interrupt
    • Mood/affect: euphoria, irritability/expansive, labile
    • Thought process: flight of ideas (streams of thought occur to patient at rapid rate), easily distracted
    • Thought content: grandiosity, paranoia, hyperreligious
    • Perceptual abnormalities: 3/4 of manic patients experience delusions, grandiose, or paranoia.
    • Suicidal/homicidal ideation: Irritability or delusions may lead to aggression toward self or others; suicidal ideation is common with mixed episode.
    • Insight/judgment: poor/impaired
  • See “Bipolar II Disorder” for an example of a mental status exam in depression.
  • With mixed episodes, patients may exhibit a combination of manic and depressive mental states.
  • Other psychiatric considerations: unipolar depression ± psychotic features, schizophrenia, schizoaffective disorder, personality disorders (particularly antisocial, borderline, histrionic, and narcissistic), ADD ± hyperactivity, substance-induced mood disorder
  • Medical considerations: epilepsy (e.g., temporal lobe), brain tumor, infection (e.g., AIDS, syphilis), stroke, endocrine (e.g., thyroid) disease, multiple sclerosis
  • In children, consider ADHD and ODD.
  • BP-I is a clinical diagnosis.
  • The Mood Disorder Questionnaire is a self-assessment screen for bipolar disorders (sensitivity 73%, specificity 90%) (3).
  • Patient Health Questionnaire-9 helps to determine the presence and severity of a depressive episode.
Initial Tests (lab, imaging)
  • Drug/alcohol screen with each presentation
  • Dementia workup if new onset in seniors
  • Consider brain imaging (CT, MRI) with initial onset of mania to rule out organic cause (e.g., tumor, infection, or stroke), especially with onset in elderly and if psychosis is present.
Diagnostic Procedures/Other
Consider EEG if presentation suggests temporal lobe epilepsy (hyperreligiosity, hypergraphia).
  • Ensure safety.
  • Psychotherapy (e.g., cognitive-behavioral therapy, social rhythm therapy)
  • Stress reduction
  • Patient and family education
  • Psychotherapy for depression (e.g., cognitive-behavioral therapy, social rhythm, interpersonal) in conjunction with medications
  • Regular daily schedule, exercise, a healthy diet, and sobriety
First Line
  • Treatment mood stabilizer(s) or other psychotropic medications. When combining, use different classes (e.g., an atypical antipsychotic and/or an antiseizure medication and/or lithium).
  • Lithium (Lithobid, Eskalith, generic): dosing: 600 to 1,200 mg/day divided BID-QID; start 600 to 900 mg/day divided BID-TID, titrate based on blood levels. Warning: caution in kidney and heart disease; use can lead to diabetes insipidus or thyroid disease. Caution with diuretics or ACE inhibitors; dehydration can lead to toxicity (seizures, encephalopathy, arrhythmias). Pregnancy Category D (Ebstein anomaly). Monitor: Check ECG >40 years, TSH,

    BUN, creatine, electrolytes at baseline and every 6 months; check level 5 to 7 days after initiation or dose change, then every 2 weeks × 3, then every 3 months (goal: 0.8 to 1.2 mmol/L).
  • Antiseizure medications
    • Divalproex sodium, valproic acid (Depakote, Depakene, generic): dosing: start 250 to 500 mg BID-TID; maximum 60 mg/kg/day. Black box warnings: hepatotoxicity, pancreatitis, thrombocytopenia, pregnancy Category D. Monitor CBC and LFTs at baseline and every 6 months; check level 5 days after initiation and dose changes (goal: 50 to 125 µg/mL).
    • Carbamazepine (Equetro, Tegretol, generic): dosing: 800 to 1,200 mg/day PO divided BID-QID; start 100 to 200 mg PO BID and titrate to lowest effective dose. Warning: Do not use with TCA or within 14 days of an MAOI. Caution in kidney/heart disease; risk of aplastic anemia/agranulocytosis, enzyme inducer; pregnancy Category D. Monitor CBC and LFTs at baseline and every 3 to 6 months; check level 4 to 5 days after initiation and dose changes (goal: 4 to 12 µg/mL).
    • Lamotrigine (Lamictal, generic): dosing: 200 to 400 mg/day; start 25 mg/day for 2 weeks, then 50 mg/day for 2 weeks, then 100 mg/day for 1 week, then 150 mg/day. (Note: Use different dosing if adjunct to valproate). Warning: Titrate slowly (risk of Stevens-Johnson syndrome); caution with kidney/liver/heart disease; pregnancy Category C
    • Oxcarbazepine (Trileptal) dosing: 300 mg PO QD. Titrate to 1,800 to 2,400/day max.
  • Atypical antipsychotics
    • Side effects: orthostatic hypotension, metabolic side effects (glucose and lipid dysregulation, weight gain), tardive dyskinesia, neuroleptic malignant syndrome (NMS), prolactinemia (except Abilify), increased risk of death in elderly with dementia-related psychosis, pregnancy Category C
    • Monitor LFTs, lipids, glucose at baseline, 3 months, and annually; check for extrapyramidal symptoms (EPS) with Abnormal Involuntary Movement Scale (AIMS) and assess weight (with abdominal circumference) at baseline, at 4, 8, and 12 weeks, and then every 3 to 6 months; monitor for orthostatic hypotension 3 to 5 days after starting or changing dose.
    • Risperidone (Risperdal, Risperdal Consta, generic): dosing: 1 to 6 mg/day divided QD-QID. IM preparation available (q2wk)
    • Olanzapine (Zyprexa, Zydis, generic): dosing: 5-20 mg/day; most likely to cause metabolic side effects (weight gain, diabetes)
    • Quetiapine (Seroquel, Seroquel XR, generic): dosing: in mania, 200 to 400 mg BID; in bipolar depression, 50 to 300 mg QHS. XR dosing 50 to 400 mg QHS
    • Aripiprazole (Abilify): dosing: 15 to 30 mg/day; less likely to cause metabolic side effects
    • Ziprasidone (Geodon): dosing: 40 to 80 mg BID; less likely to cause metabolic side effects. Caution: QTc prolongation (>500 ms) has been associated with use (0.06%). Consider ECG at baseline.
    • Asenapine: dosing: 5 to 10 mg sublingual BID
    • Lurasidone: dosing: 20 to 60 mg/day. FDA-approved for depression
    • Cariprazine:dosing: 1.5 to 6 mg/day. Start 1.5 mg
Second Line
  • Antidepressants (in addition to mood stabilizers) have mixed evidence to support use.
  • Benzodiazepines (for acute agitation with mania, associated anxiety)
  • Sleep medications
  • Refer to psychiatry, depends on knowledge level of the doctor, stability of patient.
  • Patients benefit from a multidisciplinary team, including a primary care physician, psychiatrist, and therapist.
  • Electroconvulsive therapy can be helpful in acute or treatment-resistant mania and depression.
  • Modest evidence supports transcranial magnetic stimulation, vagus nerve stimulation, ketamine infusion, sleep deprivation, and hormone therapy (e.g., thyroid) in bipolar depression.
Admit if dangerous to self or others.
Admission Criteria/Initial Stabilization
To admit involuntarily, the patient must have a psychiatric diagnosis (e.g., BP-I) and present a danger to self or others or the mental disease must be inhibiting the person from obtaining basic needs (e.g., food, clothing).
Alert staff to potentially dangerous or agitated patients. Acute suicidal threats need continuous observation.
Discharge Criteria
Determined by safety
  • Regularly scheduled visits support adherence with treatment.
  • Frequent communication among primary care doctor, psychiatrist, and therapist
Patient Monitoring
Mood charts are helpful to monitor symptoms.
  • National Alliance on Mental Illness (NAMI): http://www.nami.org/
  • National Institutes of Mental Health (NIMH): http://www.nimh.nih.gov/index.shtml
  • Frequency and severity of episodes are related to medication adherence, consistency with therapy, quality of sleep, and support systems (4)[B].
  • 40-50% of patients experience another manic episode within 2 years of first episode.
  • 25-50% attempt suicide and 15% die by suicide.
  • Substance abuse, unemployment, psychosis, depression, and male gender are associated with a worse prognosis.
1. Fornito A, Yücel M, Wood SJ, et al. Anterior cingulate cortex abnormalities associated with a first psychotic episode in bipolar disorder. Br J Psychiatry. 2009;194(5):426-433.
2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013.
3. Hirshfeld RM. Validation of the mood disorder questionnaire. Bipolar Depression Bulletin. 2004.
4. Depp CA, Moore DJ, Patterson TL, et al. Psychosocial interventions and medication adherence in bipolar disorder. Dialogues Clin Neurosci. 2008;10(2):239-250.
Additional Reading
  • Agency for Healthcare Research and Quality. Antipsychotic medicines for treating schizophrenia and bipolar disorder: a review of the research for adults and caregivers. In: Comparative Effectiveness Review Summary Guides for Consumers. Rockville, MD: Agency for Healthcare Research and Quality; 2013.
  • American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry. 2002;159(4)(Suppl):1-50.
  • Licht RW. A new BALANCE in bipolar I disorder. Lancet. 2010;375(9712):350-352.
  • Perlis RH, Brown E, Baker RW, et al. Clinical features of bipolar depression versus major depressive disorder in large multicenter trials. Am J Psychiatry. 2006;163(2):225-231.
See Also
Algorithm: Depressive Episode, Major
  • F31.9 Bipolar disorder, unspecified
  • F31.10 Bipolar disorder, current episode manic without psychotic features, unspecified
  • F31.30 Bipolar disord, crnt epsd depress, mild or mod severt, unsp
Clinical Pearls
  • BP-I is characterized by at least one manic or mixed episode that causes marked impairment, major depressive episodes usually occur, but are not necessary.
  • 25-50% of BP-I patients attempt suicide and 15% die by suicide.
  • There is no known way to prevent BP-I, but treatment adherence and education helps reduce further episodes.
  • Goal of treatment is to decrease the intensity, length, and frequency of episodes as well as greater mood stability between episodes.