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Bipolar II Disorder
Wendy K. Marsh, MD, MSc
image BASICS
DESCRIPTION
Bipolar II (BP-II) is a mood disorder characterized by at least one episode of major depression (with or without psychosis) and at least one episode of hypomania, a nonsevere mood elevation.
Geriatric Considerations
New onset in older patients (>50 years) requires a workup for organic or chemically induced pathology.
Pediatric Considerations
  • Overlap with symptoms of attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD)
  • Depression often presents as irritable mood.
Pregnancy Considerations
  • Counsel women of childbearing age about potentially teratogenic effects of commonly used medications (e.g., valproic acid).
  • Postpartum caries risk of severe acute episode with psychosis and/or infanticidal ideation.
EPIDEMIOLOGY
More common in women
Prevalence
0.5-1.1% lifetime prevalence
ETIOLOGY AND PATHOPHYSIOLOGY
  • Dysregulation of biogenic amines or neurotransmitters (particularly serotonin, norepinephrine, and dopamine)
  • Genetics
  • Major life stressors increase risk of episode onset.
Genetics
Heritability estimate: >77%
GENERAL PREVENTION
No way to prevent the onset of BP-II, but treatment adherence and education can help to prevent further episodes.
COMMONLY ASSOCIATED CONDITIONS
Substance abuse or dependence, ADHD, anxiety disorders, and eating disorders
image DIAGNOSIS
  • DSM-5 criteria: one hypomanic episode and at least one major depressive episode. The symptoms cause unequivocal change in functioning noticed by others but not severe enough to cause marked impairment (1)[C].
  • Hypomania is a distinct period of persistently elevated, expansive, or irritable mood, different from usual euthymic mood, including increase in activity or energy lasting at least 4 days:
    • The episode must include at least three of the “DIG FAST” symptoms plus increased energy below (four if the mood is only irritable):
      • Distractibility
      • Insomnia, decreased need for sleep
      • Grandiosity or inflated self-esteem
      • Flight of ideas or racing thoughts
      • Agitation or increase in goal-directed activity (socially, at work or school, or sexually)
      • Speech-pressured/more talkative than usual
      • Taking risks: excessive involvement in pleasurable activities that have high potential for painful consequences (e.g., sexual or financial)
  • Major depression
    • Depressed mood or diminished interest and four or more of the “SIG E CAPS” symptoms are present during the same 2-week period:
      • Sleep disturbance (e.g., trouble falling asleep, early-morning awakening)
      • Interest: loss or anhedonia
      • Guilt (or feelings of worthlessness)
      • Energy, loss of
      • Concentration, loss of
      • Appetite changes, increase or decrease
      • Psychomotor changes (retardation or agitation)
      • Suicidal/homicidal thoughts
    • Rapid cycling is ≥4 mood episodes in 12 months (major depression or hypomania).
    • Mixed specifier: When three or more symptoms of opposite mood pole are present during primary mood episode, for example, hypomania with mixed features (of depression)
  • Note: If symptoms have ever met criteria for a full manic episode or hospitalization was necessary secondary to manic/mixed symptoms or psychosis was present, then the diagnosis is BP-I.
PHYSICAL EXAM
  • Mental status exam in hypomania
    • General appearance: usually appropriately dressed, with psychomotor agitation
    • Speech: may be pressured, talkative, difficult to interrupt
    • Mood/affect: euphoria, irritability/congruent, or expansive
    • Thought process: may be easily distracted, difficulty concentrating on one task
    • Thought content: usually positive, with “big” plans
    • Perceptual abnormalities: none
    • Suicidal/homicidal ideation: low incidence of homicidal or suicidal ideation
    • Insight/judgment: usually stable/may be impaired by their distractibility
  • Mental status exam in acute depression
    • General appearance: unkempt, psychomotor retardation, poor eye contact
    • Speech: low, soft, monotone
    • Mood/affect: sad, depressed/congruent, flat
    • Thought process: ruminating thoughts, generalized slowing
    • Thought content: preoccupied with negative or nihilistic ideas
    • Perceptual abnormalities: 15% of depressed patients experience hallucinations or delusions.
    • Suicidal/homicidal ideation: Suicidal ideation is very common.
    • Insight/judgment: often impaired
DIFFERENTIAL DIAGNOSIS
  • Other psychiatric considerations
    • BP-I disorder, unipolar depression, personality disorders (particularly borderline, antisocial, and narcissistic), ADD with 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
DIAGNOSTIC TESTS & INTERPRETATION
  • BP-II is a clinical diagnosis.
  • Mood Disorder Questionnaire, self-assessment screen for BP, sensitivity 73%, specificity 90% (2)[B]
  • Hypomania Checklist-32 distinguishes between BP-II and unipolar depression (sensitivity 80%, specificity 51%) (3)[B].
  • Patient Health Questionnaire-9 helps to determine the presence and severity of depression.
Initial Tests (lab, imaging)
  • Rule out organic causes of mood disorder during initial episode.
  • Drug/alcohol screen is prudent with each presentation.
  • Dementia workup if new onset in seniors
  • With initial presentation: Consider CBC, chem 7, TSH, LFTs, ANA, RPR, HIV, and ESR.
  • Consider brain imaging (CT, MRI) with initial onset of hypomania to rule out organic cause, especially with onset in the elderly.
image TREATMENT
  • Ensure safety.
  • Medication management
  • Psychotherapy (e.g., cognitive-behavioral therapy [CBT], social rhythm therapy, interpersonal therapy)
  • Stress reduction
  • Patient and family education
  • Refer to psychiatrist.
GENERAL MEASURES
  • Psychotherapy (e.g., CBT, social rhythm, interpersonal, family focused) in conjunction with medications
  • Regular daily schedule, exercise, a healthy diet, and sobriety have been shown to help.
MEDICATION
  • Less research has been conducted on the appropriate treatment of BP-II, but current consensus is to treat with the same medications as BP-I.
  • Antidepressant medications must be used with caution during depressive episodes, because they may increase risk of hypomania or increase cycling (less common than with BP-I).
P.125

First Line
  • When combining mood stabilizers, consider adding 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, titrate based on blood levels:
    • Caution in kidney or heart disease; use can lead to diabetes insipidus, thyroid disease; caution in sodium-depleted patients (diuretics, ACE inhibitors); dehydration can lead to toxicity, which may cause seizures, encephalopathic syndrome, arrhythmias; pregnancy Category D (Ebstein anomaly with 1st-trimester use)
    • Monitor electrocardiogram in patients >40 years, TSH, BUN, creatinine, electrolytes at baseline and q6mo; check level 5 to 7 days after initiation or dose change, then q1-2wk × 3, then q3mo (goal: 0.8 to 1.2 mmol/L).
  • Anticonvulsants
    • Valproic acid, divalproex sodium: dosing: Start 250 to 500 mg BID-TID, max 60 mg/kg/day. Warning: hepatotoxicity, pancreatitis, thrombocytopenia, pregnancy Category D (neural tube defects). Monitor CBC, LFTs at baseline and q6mo; check valproic acid level 5 days after initiation and dose changes (goal: 50 to 125 µm/mL).
    • Carbamazepine: dosing: 800 to 1,200 mg/day PO divided BID-QID, start 100 to 200 mg PO BID and titrate to lowest effective dose. Do not use with tricyclic antidepressants or within 14 days of monoamine oxidase inhibitor; caution with kidney or heart disease, may cause aplastic anemia/agranulocytosis. Monitor CBC, LFTs at baseline and q3-6mo; check level 4 to 5 days after initiation and dose changes (goal: 4 to 12 µm/mL).
    • Lamotrigine: treats depression only. Dosing: 200 mg/day start 25 mg for 2 weeks, then 50 mg for 2 weeks, then 100 mg for 1 week. (Note: different dosing if adjunct to valproate) Selected warnings: Titrate slowly (risk of Stevens-Johnson syndrome); caution with kidney, liver, or heart impairment. Monitor patient to monitor for rash.
  • Atypical antipsychotics (AAs)
    • Side effects of AAs: orthostatic hypotension, negative metabolic side effects (effect glucose and lipid regulation, weight gain), tardive dyskinesia, neuroleptic malignant syndrome, prolactinemia increased risk of mortality in elderly with dementia-related psychosis, pregnancy Category C
    • Monitor LFTs, lipids, glucose at baseline, 3 months, and annually; check for extrapyramidal symptoms with Abnormal Involuntary Movement Scale (AIMS) and assess weight (with abdominal circumference) at baseline, then 4, 8, and 12 weeks, then q3-6mo; monitor for orthostatic hypotension 3 to 5 days after starting or changing dose.
    • Antimanic is a presumed class effect.
    • Aripiprazole: dosing: 15 mg/day, max 30 mg/day, less likely to cause metabolic side effects
    • Olanzapine: dosing: 5 to 20 mg/day, most likely AA to cause metabolic side effects (weight gain, diabetes mellitus)
    • Quetiapine: dosing: hypomania 200 to 400 mg BID; depression: 50 to 300 mg QHS
    • Risperidone: dosing: 1 to 6 mg/day QD-BID; generic and q2wk IM preparations available
    • Ziprasidone: dosing: 40 to 80 mg BID take with food. Less likely to cause metabolic side effects. Warning: QTc prolongation (>500 ms): consider baseline ECG.
    • 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 better data in BP-II than BP-I.
  • Sleep medications
ISSUES FOR REFERRAL
Patients benefit from care by a multidisciplinary team, including a primary care physician, therapist, and psychiatrist.
ADDITIONAL THERAPIES
  • Electroconvulsive therapy for severe or treatment-resistant depression or mood elevation
  • Modest evidence exists to support transcranial magnetic stimulation, vagal nerve stimulation, ketamine infusion, sleep deprivation, and hormone therapy (e.g., thyroid) in bipolar depression.
INPATIENT CONSIDERATIONS
If hospitalized for mood elevation symptoms, then diagnosis is mania and bipolar I. May be hospitalized for depression and be bipolar II
Admission Criteria/Initial Stabilization
To admit patients (> 18 years) to a psychiatric unit involuntarily, they must have a psychiatric diagnosis and present a danger to themselves or others, or their mental disease must be inhibiting them from providing their basic needs (e.g., food, clothing, shelter).
Nursing
Acute suicidal threats require close observation.
Discharge Criteria
Determined by safety
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
  • Regularly scheduled visits support treatment adherence.
  • Frequent communication between primary care doctor, psychiatrist, and therapist ensures comprehensive care.
Patient Monitoring
Mood charts are helpful adjuncts to care.
PATIENT EDUCATION
  • Support groups for patients and families are recommended.
  • National Alliance on Mental Illness: http://www.nami.org/
PROGNOSIS
  • Frequency and severity of problematic episodes are related to medication adherence, consistency with psychotherapy, sleep, support systems, regularity of daily activities, and social history.
  • Substance abuse, unemployment, persistent depression, and male gender are associated with a worse prognosis.
  • Although data are limited, evidence indicates that patients with BP-II may be at greater risk of both attempting and completing suicide than with BP-I and unipolar depression.
REFERENCES
1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013.
2. Hirshfeld RM. Validation of the mood disorder questionnaire. Bipolar Depression Bulletin; 2004.
3. Angst J, Adolfsson R, Benazzi F, et al. The HCL-32: towards a self-assessment tool for hypomanic symptoms in outpatients. J Affect Disord. 2005;88(2):217-233.
Additional Reading
  • American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry. 2002;159(4 Suppl):1-50.
  • Benazzi F. A prediction rule for diagnosing hypomania. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(2):317-322.
  • Benazzi F. Bipolar disorder—focus on bipolar II disorder and mixed depression. Lancet. 2007; 369(9565):935-945.
  • 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
Codes
ICD10
F31.81 Bipolar II disorder
Clinical Pearls
  • BP-II is characterized by at least one episode of major depression and one episode of hypomania.
  • Patients may not recognize symptoms and or decline treatment during a hypomanic episode; they may enjoy the elevated mood and productivity.
  • Patients with BP-II are at great risk of both attempting and completing suicide.