Bipolar II Disorder – Causes, Symptoms, Diagnosis, Treatment and Ongoing care

Basics

Description

Bipolar II (BP-2) is a mood disorder characterized by at least 1 episode of major depression and at least 1 episode of hypomania, a milder form of mania.

Geriatric Considerations

New onset in older patients (>50) requires a workup for organic or chemically induced pathology.

Pediatric Considerations

  • Large 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., lithium, valproic acid).
  • Symptoms may be exacerbated in the postpartum period.

Epidemiology

More common in women

Prevalence

0.5–1.1% lifetime prevalence

Risk Factors

Genetics

Heritability estimate: >77%

General Prevention

There is no way to prevent the onset of BP-2, but treatment adherence and education can help to prevent further episodes.

Pathophysiology

Dysregulation of biogenic amines or neurotransmitters (particularly serotonin, norepinephrine, and dopamine)

Etiology

  • Genetics
  • Major life stressors (especially loss of parent or spouse)

Commonly Associated Conditions

Substance abuse or dependence, ADHD, anxiety disorders, and eating disorders

Diagnosis

  • DSM-IV-TR criteria: Patient must experience at least 1 hypomanic episode and at least 1 major depressive episode. The symptoms have caused some distress or impairment in social, occupational, or other areas of functioning. There can be no history of full manic or mixed episodes.
  • Hypomania is a distinct period of persistently elevated, expansive, or irritable mood, different from usual nondepressed mood, lasting at least 4 days:
    • The episode must include at least 3 of the “DIG FAST” symptoms below (4 if the mood is only irritable):
      • Distractibility
      • Insomnia, decreased need for sleep
      • Grandiosity or inflated self-esteem
      • Flight of ideas or subjective experience that thoughts are racing
      • 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)
    • The symptoms are not severe enough to cause marked impairment in functioning or hospitalization, and there is no associated psychosis as with BP-1.
  • Major depression:
    • Depressed mood or diminished interest and 4 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
    • BP-2 with rapid cycling is diagnosed when a patient experiences at least 4 episodes of a mood disturbance in a 12-month period (either major depression or hypomania).
  • Signs, symptoms, and history seen more often in BP-2 than in unipolar depression (1):
    • Agitation, hyperphagia, hypersomnia, melancholia, psychomotor retardation, suicidal ideation/planning, increased frequency of depressive episodes, younger age of onset, family history of bipolar disorder, subsyndromal hypomanic symptoms (especially overactivity) (2)
  • 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 changes to bipolar I disorder (BP-1).

History

Collateral information makes diagnostics more complete and is often necessary for a clear history.

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 1 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

Diagnostic Tests & Interpretation

  • BP-2 is a clinical diagnosis.
  • Mood disorder questionnaire, self-assessment screen for BP, sensitivity 73%, specificity 90% (3)
  • Hypomania checklist-32 distinguishes between BP-2 and unipolar depression (sensitivity 80%, specificity 51%) (4)
  • Patient health questionnaire-9 helps to determine the presence and severity of depression.

Lab

  • 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 (e.g., thyroid-stimulating hormone [TSH], rapid plasma reagin [RPR], B12, brain imaging).

Initial lab tests

With initial presentation: Consider complete blood count (CBC), chem 7, TSH, liver function tests (LFTs), antinuclear antibody, RPR, HIV, erythrocyte sedimentation rate

Imaging

Consider brain imaging (computed tomography, magnetic resonance imaging) with initial onset of hypomania to rule out organic cause (e.g., tumor, infection, stroke), especially with onset in elderly.

Differential Diagnosis

  • Other psychiatric considerations:
    • Bipolar 1 disorder, unipolar depression, personality disorders (particularly borderline, antisocial, and narcissistic), attention deficit disorder +/- 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.

Treatment

  • Ensure safety
  • Medication management
  • Psychotherapy (e.g., cognitive behavioral therapy [CBT], social rhythm therapy)
  • Stress reduction
  • Patient and family education

Medication

  • Less research has been conducted on the appropriate treatment of BP-2, but current consensus is to treat with the same medications as BP-1.
  • Antidepressant medications must be used with caution during depressive episodes, as they may precipitate hypomanic episodes (less common than with BP-1).

First Line

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  • American Psychological Association guidelines state lithium or lamotrigine as first-line treatment for bipolar depression.
  • Treatment may consist of 1–4. 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 600–1200 mg/day divided b.i.d.–q.i.d., titrate based on blood levels:
    • Selected warnings: Caution in kidney or heart disease; use can lead to diabetes insipidus, thyroid disease; caution sodium-depleted patients (diuretics, angiotensin-converting enzyme inhibitors); dehydration can lead to toxicity, which may cause seizures, encephalopathic syndrome, arrhythmias, pregnancy category D (Ebstein anomaly with 1st trimeter use)
    • Monitor: Check electrocardiogram (EKG) >40 y, TSH, blood urea nitrogen, creatinine, lytes at baseline and q6 months; check level 5 days after initiation or dose change, then q1–2 wk × 3, then q2–3 mo (goal: 0.8–1.2 mmol/L)
  • Antiseizure medications:
    • Valproic acid, divalproex sodium (Depakene, Depakote, generic): Dosing: Start 250–500 mg b.i.d.–t.i.d., max 60 mg/kg/day. Selected warnings: Hepatotoxicity, pancreatitis, thrombocytopenia, pregnancy category D (neural tube defects). Monitor: CBC, LFTs at baseline and q6 mo; check valproic acid level 5 days after initiation and dose changes (goal: 50–125 mcg/mL).
    • Carbamazepine (Carbatrol, Equetro, Tegretol, generic): Dosing: 800–1200 mg/day p.o. div b.i.d.–q.i.d., start 100–200 mg p.o. b.i.d. and titrate to lowest effective dose. Selected warnings: Do not use with tricyclic antidepressants or within 14 d of monoamine oxidase inhibitor; caution with kidney or heart disease, may cause aplastic anemia/agranulocytosis, pregnancy category D. Monitor: CBC, LFTs at baseline and q3–6 mo; check level 4–5d after initiation and dose changes (goal: 4–12 mcg/mL).
    • Lamotrigine (Lamictal): Dosing: 200 mg a day, start 25 mg × 2 wk, then 50 mg × 2 wk, then 100 mg × 1 wk (Note: Different dosing if adjunct to valproate). Selected warnings: Titrate slowly (risk of Stevens-Johnson syndrome); caution with kidney, liver, or heart impairment; pregnancy category C. Monitor: Patient to monitor for rash.
    • Oxcarbmazepine (Trileptal), gabapentin (Neurontin), and topiramate (Topamax) are also used in BP but are not Food and Drug Administration (FDA)-approved.
  • 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 (except Abilify), 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 AIMS and assess weight (with abdominal circumference) at baseline, then 4, 8, and 12 weeks, then q3–6 m; monitor for orthostatic hypotension 3–5 days after starting or changing dose
    • Aripiprazole (Abilify) Dosing: 15 mg/day, max 30 mg/day, less likely to cause metabolic side effects
    • Olanzapine (Zyprexa, Zydis): Dosing: 5–20 mg/day, most likely AA to cause metabolic side effects (weight gain, diabetes mellitus)
    • Symbyax (olanzapine + fluoxetine): Dosing: 6/25 mg, FDA-approved for bipolar depression
    • Quetiapine (Seroquel): Dosing: Hypomania 200–400 mg b.i.d. Depression 50–300 mg q.h.s. Caution: Cataracts, sedation.
    • Risperidone (Risperdal): Dosing: 1–6 mg/day every day-b.i.d. Generic and q2 wk IM preparations available.
    • Ziprasidone (Geodon): Dosing: 40–80 mg b.i.d. Less likely to cause metabolic side effects, Warnings: QTc prolongation (>500 msec) has been associated with use (0.06%), consider EKG at baseline.

Second Line

  • Antidepressants (in addition to mood stabilizers)
  • Benzodiazepines (for acute agitation, anxiety)
  • Sleep medications

Additional Treatment

General Measures

  • Psychotherapy (e.g., CBT, social rhythm therapy) in conjunction with medications is key.
  • Regular exercise, a healthy diet, and sobriety have shown to help prevent worsening of symptoms.

Issues for Referral

  • Experience and comfort level of physician
  • Stability of patient
  • Patients may benefit from care by a multidisciplinary team, including a primary care physician and a psychiatrist.

Additional Therapies

  • Electroconvulsive therapy with severe depression (may precipitate hypomania)
  • Light therapy if there is seasonal component to depressive episodes (may precipitate hypomania)

In-Patient Considerations

If hypomanic symptoms are severe enough to necessitate hospitalization, the patient automatically meets criteria for mania and BP-1.

Initial Stabilization

  • Medications for stabilization with acute depression
  • Safety plan reviewed and safe environment assured

Admission Criteria

To admit a patient (>18) to a psychiatric unit involuntarily, they must have a psychiatric diagnosis (e.g., major depression) 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, and/or shelter).

Nursing

Acute suicidal threats need closer observation.

Discharge Criteria

Determined by safety

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
  • 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 sex are associated with a worse prognosis.
  • Although data are limited, evidence indicates that patients with BP-2 may be at greater risk of both attempting and completing suicide than with BP-1 and unipolar depression.

References

1. 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;163:225–31.

2. Benazzi F. A prediction rule for diagnosing hypomania. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33:317–22.

3. Hirshfeld RM. Validation of the Mood Disorder Questionnaire. Bipolar Depression Bulletin. 2004.

4. 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;88:217–33.

Additional Reading

Benazzi F. Bipolar disorder–focus on bipolar II disorder and mixed depression. Lancet. 2007;369:935–45.

Benazzi F. Bipolar II disorder: epidemiology, diagnosis and management. CNS Drugs. 2007;21:727–40.

Edvardsen J, Torgersen S, Røysamb E, et al. Heritability of bipolar spectrum disorders. Unity or heterogeneity? J Affect Disord. 2007.

See Also (Topic, Algorithm, Electronic Media Element)

Algorithm: Depression, Adult

Codes

ICD9

296.89 Other manic-depressive psychosis

Snomed

83225003 Bipolar II disorder (disorder)

Clinical Pearls

  • BP-2 is characterized by at least 1 episode of major depression and 1 episode of hypomania.
  • Patients are often resistant to treatment during a hypomanic episode, as they enjoy the elevated mood and productivity.
  • Evidence indicates that patients with BP-2 may be at greater risk of both attempting and completing suicide than with BP-1 and unipolar depression.

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