Bipolar Disorder

Diagnosis of Bipolar Disorder

  • Requires a period of increased activity, with an abnormally elevated, expansive, or irritable mood
  • Along with 3 or more of:
    – Grandiosity or euphoria
    – Decreased need for sleep
    – Pressure to keep talking
    – Flight of ideas or racing thoughts
    – Distractibility
    – Psychomotor agitation
    – Engaging in unrestrained buying sprees, sexual activity, substance use, etc.

Pitfalls of Diagnosis

  • Only one manic episode required for diagnosis of bipolar (depressed episode not necessary)
  • Ask patients presenting with depression about symptoms of mania
  • Can use the Mood Disorder Questionnaire ( during depressed or manic phase to assist with diagnosis


Types of Bipolar Disorders

  1. Bipolar I — Full manic episodes (at least 1 week duration)
  2. Bipolar II — Hypomanic episodes (at least 4 days duration) - The essential feature of bipolar II disorder is a clinical course that is characterized by the occurrence of one or more major depressive episodes (criterion A) accompanied by at least one hypomanic episode (criterion B).
    • Hypomania is a mood state characterized by persistent disinhibition and pervasive elevated (euphoric) or irritable mood but generally less severe than full mania
  3. Cyclothymia - Cyclothymia is characterized by dysthymia with periods of hypomania
  4. Unspecified Bipolar Disorder (was Bipolar Disorder NOS in DSM-IV)




Bipolar Depression

  • Major depression + Hx of hypomanic episode.


  • Although there are 10 FDA-approved agents for acute mania, only quetiapine and a combination of olanzapine and fluoxetine are FDA-approved for bipolar depression.
  • While some evidence shows that antidepressants may reduce the risk of recurrent depression in patients with bipolar disorder, they also appear to increase the risk of a switch to a hypomanic or manic episode


  • The exact etiology of bipolar disorder is unknown, although the risk for disease is thought to be influenced by several genes. Family and twin studies substantiate the importance of genetic factors influencing a person's risk for bipolar disorder, with environmental stressors or triggers being likely to contribute to the phenotypic expression of the underlying mood disorder


  • Primary Care Evaluation of Mental Disorders (PRIME-MD)
  • Patient Health Questionnaire (PHQ-9)
  • Mood Disorder Questionnaire (MDQ)
  • Composite International Diagnostic Interview (CIDI)
  • Bipolarity Index
  • Young Mania Rating Scale (YMRS)
  • CBC
  • TFTs
  • serum vitamin D
  • toxicology screen
  • fasting lipid profile
  • fasting glucose
  • MRI brain


Need for Treatment

  • Untreated mood swings tend to accelerate and become rapid cycling (known as “kindling”)
  • To prevent suicide
  • To prevent patient’s embarrassment and disruption of lives (many patients will remember manic actions)

Mood Stabilizers (Used for Bipolar I, II, & Cyclothymia)

  • Lithium
    • FDA-approved for mania
    • Usual dose 300 mg three or four times a day
    • Usually works in 9-10 days
  • Anticonvulsants
    • Valproic acid (FDA-approved for mania)
    • Carbamazepine(FDA-approved for mania)
    • Lamotrigine (NOT FDA-approved for acute mania)
    • Oxcarbazepine (FDA-approved for mania)
    • (NOT phenytoin, phenobarbital, or gabapentin)
  • Antipsychotic:
    • Risperidone (FDA-approved for mania)
    • Quetiapine (FDA-approved for mania)
    • Olanzapine (FDA-approved for mania)
    • Aripiprazole (FDA-approved for mania)


  • Usual dose:
    • 300 mg three or four times a day, Maximum 1800 mg/day
    • Usually works in 9-10 days
  • Pharmacology: 
    • Excreted by kidney unchanged by body
    • Works in 80% of Bipolar I cases
    • May prevent depressive swings, but not as effective for treating them; may need to add antidepressant
    • Lithium is less effective in:
      – Rapid cycling bipolar illness
      – Poorly compliant patients
    • Rapid discontinuation can cause relapse
    • Lithium is dialyzable if patient is toxic
  • Side Effects of Lithium
    • Fine tremor
    • Contraindicated in pregnancy
      – (Ebstein’s anomaly in 1st trimester)
    • Increased urination
    • If toxic:
      – Nausea & vomiting
      – Diarrhea
      – Ataxia
      – Coma & death
  • Lithium Levels
    • Must check 5 days after starting or changing dose
    • Seek to maintain 0.8-1.0 mEq/L levels to prevent relapse (acute mania may require levels of 1.2)
  • Lithium Monitoring
    • Long-term effects on thyroid (reversible) and kidney (irreversible).
      • Check TSH & CMP prior to starting and every 6-12 months
    • Avoid dehydration and diuretics, careful with NSAIDs (ibuprofen, naproxen, etc.)
    • ECG for patients over age 40 (can rarely cause junctional rhythm)


Valproic Acid (Depakote)

  • Is most frequently prescribed mood stabilizer
  • May be more effective for rapid cycling bipolar disorders (> 4 swings per year)
  • Loading dose: 10 mg/Lb/day
    – Ex: 150 lb. man = 1500 mg per day = 500 mg 3 times/day
  • Usually start at 1/2 to 2/3 daily dose as outpatient

  • Divalproex sodium : 20 mg/kg orally (extended-release) once daily initially, increase according to response and serum drug level, maximum 60 mg/kg/day

Side Effects

  • GI upset— take with food
  • Liver dyscrasias — check liver panels
  • Occasional sedation
  • Usually well tolerated
  • Levels available—therapeutic levels between 50-100 mcg/mL


Carbamazepine (Tegretol)

  • May also be more effective for rapid cycling bipolar disorders
  • Dose:
    • 200-800 mg/day orally (extended-release) initially given in 2 divided doses
  • Side Effects:
    • May cause blood dyscrasias — must check CBC
  • Levels available — want levels between 8-12 mcg/mL

Lamotrigine (Lamictal)

  • Dose: 200 mg PO qd
    • Start: 25 mg PO qd x2wk, then 50 mg PO qd x2wk, then 100 mg PO qd x1wk;
    • Max: 200 mg/day
    • Info: taper dose over 2wk to D/C
  • Use:
    • Bipolar depression (Has anti-depression effects)
  • Side Effect:
    • Rash in 5%; may progress to Stevens-Johnson syndrome

Atypical antipsychotics

Risperidone : 1 mg orally once daily initially, increase according to response, maximum 6 mg/day or
Olanzapine (Zyprexa): 5 mg orally once daily initially, increase according to response, maximum 20 mg/day or
Quetiapine (Seroquel) : 50 mg orally (immediate-release) once daily initially, increase according to response, maximum 800 mg/day given in 2-3 divided doses or
Aripiprazole (Abilify): 15 mg orally once daily initially, increase according to response, maximum 30 mg/day or
Ziprasidone (Geodon) : 40 mg orally twice daily initially, increase according to response, maximum 160 mg/day or
Asenapine : 5-10 mg sublingually twice daily, maximum 20 mg/day or
Paliperidone : 3 mg orally once daily initially, increase according to response, maximum 12 mg/day

  • Benefits/Uses:
    • Antidepressant effects; also effective in mania
    • Can use lower doses for bipolar than psychosis
  • Side Effects:
    • Weight gain, lipid/glucose abnormalities