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Bipolar Disorder
Aka: Bipolar Disorder, Bipolar Depression, Bipolar I Disorder, Bipolar II Disorder, Mania, Manic Depression, Manic Disorder, Hypomania, Cyclothymia, Cyclothymic Disorder
- See Also
- Mania Diagnosis
- Hypomania Diagnosis
- Mania Secondary Causes
- Epidemiology
- Bipolar Incidence: 1% of adults (United States)
- Gender predisposition: Men and women equally affected
- Age of onset: Early adulthood to mid-40s
- Affective disorder Family History confers risk
- One parent with affective disorder: 27%
- Two parents with affective disorder: 50-75%
- Pathophysiology
- Related to noradrenergic system (Norepinephrine)
- Types
- Bipolar I Disorder
- Manic or mixed episode
- Psychosis may be present
- Major Depression may be present
- Bipolar II Disorder
- Recurrent Major Depression
- Hypomanic episodes that do not meet criteria for Mania Diagnosis
- Cyclothymic Disorder (Cyclothymia)
- Depressive symptoms that do not meet criteria for Major Depression
- Hypomanic episodes that do not meet criteria for Mania Diagnosis
- History
- Impaired social functioning
- Multiple divorces
- Legal or financial problems
- Recurrent job loss
- Recurrent Major Depression
- Typically onset by age 13 years
- May present as Seasonal Affective Disorder
- Failed response to at least three Antidepressants
- Atypical Depression
- Hypersomnia
- Pathologic guilt
- Attempted Suicide
- Drug Abuse or Alcohol Abuse
- Manic symptoms
- Mania or Hypomania episodes
- Psychosis
- Agitation or mania caused by Antidepressant, Corticosteroid or other medication
- Family History
- Bipolar Disorder
- Multiple relatives with Major Depression or Anxiety Disorder
- Multiple relatives with Suicidality, incarceration, Drug Abuse or Alcohol Abuse
- Symptoms: Adults
- Maintains several days with reduced sleep and without feeling tired
- Frequent mood swings (or mood lability) or periods of intense goal orientation
- Racing thoughts interfere with sleep onset
- Sleep disruptions trigger mania or Hypomania
- Seasonal changes in spring and fall
- Jet Lag on time zone changes
- Shift work or child care
- Associated symptoms
- Irritability
- Impulsivity
- Irrationality
- Symptoms: Children
- Present with irritability, sadness and Insomnia (euphoria is typically absent)
- Differential Diagnosis
- See Mania Secondary Causes
- Personality Disorder
- Recurrent Major Depression
- Schizophrenia
- Obsessive-Compulsive Disorder
- Diagnosis
- See Mania Diagnosis
- Labs: Consider for evaluation of secondary causes
- Highest yield tests
- Thyroid Function Tests (Thyroid Stimulating Hormone)
- Serum or Urine Drug Screen
- Urinalysis
- Older patients to evaluate for Urinary Tract Infection
- Sexually Transmitted Diseases
- Syphilis Serology (e.g. RPR)
- HIV Test
- Hepatitis C
- Rare causes
- Heavy metal levels
- Labs: Consider for baseline labs prior to starting medications
- Complete Blood Count
- Chemistry panel with Renal Function tests
- Serum Sodium
- Serum Creatinine
- Serum Glucose
- Liver Function Tests
- Serum Prolactin
- Urine Pregnancy Test
- Electrocardiogram (for baseline QT Interval)
- Diagnostics: Consider if suggested by history or examination
- Head MRI
- Electroencephalogram (EEG)
- Management: General
- Continue mood stabilizers indefinately due to high relapse rate
- Consult psychiatry for comanagement
- Discuss Teratogenicity of medications with women of child bearing age
- Reliable Contraception is critical
- Do not use Antidepressants as monotherapy for mania, mixed disorder or Bipolar Disorder
- High risk of triggering manic episode
- Avoid medications that are more likely to trigger or exacerbate mania
- Avoid Trazodone
- Avoid Tricyclic Antidepressants
- Avoid SNRIs (e.g. Venlafaxine or Duloxetine)
- Employ behavioral management as a first line therapy
- Cognitive Behavioral Therapy
- Caregiver Support
- Manage comorbidity
- Alcohol Abuse
- Tobacco Abuse
- Drug Abuse
- Patients and their family should be aware of early warning signs of relapse
- Sleep disturbance
- Agitation
- Increased goal oriented activity
- Disrupted routine
- Management: Acute
- Acute Mania
- Hospitalize due to high risk of self harm or Suicidality
- Therapy goals
- Adequate sleep
- Reduce psychotic symptoms
- Medication protocol
- Start mood stabilizer (see below)
- Lithium (preferred) or
- Valproate
- Start adjunctive therapy (see below)
- Indicated while mood stabilizer (esp. Lithium) reaches steady state over days
- Atypical Antipsychotic (e.g. Olanzapine, Quetiaprine) or Haloperidol
- Benzodiazepines (e.g. Lorazepam)
- Acute Hypomania
- Medication management is similar to acute mania
- Observe for major depressive episode immediately following acute Hypomania episode
- Assess for functional capacity
- Decision making
- Compliance with treatment
- Acute Major Depression
- Hospitalize for Suicidality or Homicidal Thoughts
- Psychotherapy
- First-line therapies
- Primary mood stabilizers are both effective for Major Depression
- Lithium (preferred)
- Valproate
- Other anticonvulsants effective for Major Depression
- Lamotrigine or Lamictal (preferred)
- Requires 6 weeks to titrate to level (due to Steven's Johnson Syndrome risk)
- Carbamazepine or Tegretol
- Topiramate
- Atypical Antipsychotics effective for Major Depression
- Quetiapine or Seroquel (preferred)
- Risk of weight gain, Glucose Intolerance, and Extrapyramidal Side Effects
- Olanzapine (Zyprexa)
- Second-line therapies
- Add only to first line agents if effect is incomplete
- Do not use standard Antidepressants without mood stabilizers
- These agents do not increase efficacy over mood stabilizers alone
- Avoid Tricyclic Antidepressants, Trazodone, or Venlafaxine which can trigger manic episodes
- Selective Serotonin Reuptake Inhibitors
- Bupropion
- Refractory Cases
- Consider switching mood stabilizer
- Consider combining 2-3 mood stabilizers
- Consider Electroconvulsive Therapy
- Management: Mood Stabilizer Selection
- Mood stabilizer options
- First-line agents
- Lithium (preferred)
- Suicide is 3 fold less likely with Lithium than Valproate
- Starting dose may be up to 300 mg twice daily
- Titrate dose every 2-3 days as tolerated to effect and serum Lithium level of 0.6 to 1.5 mEq/L
- Target dose: 900 to 1800 mg orally daily
- Valproate
- Loading dose in acute mania: 15-20 mg/kg
- Starting dose without load: 500 to 750 mg/day in divided dosing
- Titrate every 2-3 days as tolerated to serum Valproic Acid level of 50 to 125 mcg/ml
- Target dose: 200 to 1600 mg daily
- Alternative mood stabilizers (consider for specific indications)
- Carbamazepine (Tegretol)
- Starting dose 200 mg twice daily
- Therapeutic range for biopolar: 4-12 mcg/ml
- Available as long acting agent (Equetro)
- Oxcarbazepine
- Consider instead of Carbamazepine
- Similar efficacy with fewer adverse effects
- Lamotrigine (Lamictal)
- Starting dose 25 mg daily
- Effective as mood stabilizer and Antidepressant
- No blood monitoring needed
- Rash develops in 10% of patients (Risk of Steven's Johnson)
- Requires slow titration over at least 6 weeks to effective dose
- Titrate Lamotrigine slowly (2 week increments)
- Do not exceed 100 mg when combined with Valproate
- Specific agent indications
- Classic mania or Hypomania (Euphoric mood)
- Lithium (preferred) or
- Valproate
- Mixed episode or rapid cycling
- Valproate (preferred) or
- Carbamazepine
- Combinations in refractory cases
- Lithium with Lamotrigine OR Valproate
- Valproate with Lithium OR Lamotrigine
- Management: Adjunctive Medications
- Adjunctive medications: Benzodiazepine
- Examples: Lorazepam, Clonazepam
- Indications for Benzodiazepine
- Mania or Hypomania with Insomnia or Agitation
- Psychosis refractory to Antipsychotic
- Alternatives
- Consider Gabapentin for anxiety
- Adjunctive medications: Antipsychotics
- Precautions
- Monitor for Extrapyramidal Side Effects (e.g. Tardive Dyskinesia)
- Atypical Antipsychotic agents have specific lab monitoring guidelines
- Antipsychotic indications
- Psychosis
- Consider Electroconvulsive Therapy
- Mania with Insomnia or Agitation
- Despite Benzodiazepine
- Acute mania episode
- Antipsychotic use may increase Lithium or Valproate efficacy
- Agents (low doses are often effective in mania)
- Risperidone (Risperdal) 2-4 mg per day
- Olanzapine (Zyprexa) 10-15 mg per day
- Lurasidone (Latuda) 20 mg orally daily (may advance gradually to 60 mg daily)
- Quetiapine 400-800 mg per day
- Mood stabilizers have improved efficacy when used with Quetiapine
- Yatham (2009) Bipolar Disord 11(3):225-55 [PubMed]
- Avoid Antipsychotics with lower efficacy in Bipolar Disorder
- Avoid Aripiprazole (Abilify)
- Avoid Ziprasidone (Geodon)
- Adjunctive medications: Antidepressants
- See Acute Depression Management above
- First-line agents
- Mood Stabilizers (Lithium, Valproate)
- Second-line agents (used only in combination with mood stabilizers)
- Selective Seotonin Reuptake Inhibitors (SSRIs) or Bupropion
- Risk of precipitating mania (do not use as montherapy)
- Avoid Tricyclic Antidepressants, Trazodone, or Venlafaxine which can trigger manic episodes
- Avoid Paroxetine (Paxil) as it is less effective in Bipolar Disorder
- May taper off 6-8 weeks after full bipolar remission (restart as needed)
- Other adjunctive measures
- Omega-3 Fatty Acid Supplements
- References
- (2015) Presc Lett 22(1): 4
- (1997) Am Fam Physician 55(4):1447-9 [PubMed]
- Docherty (1996) J Clin Psychiat 57(suppl 12A):1-89 [PubMed]
- McIntyre (2004) Can Fam Physician 50:388-94 [PubMed]
- Manning (2010) J Clin Psychiatry 12(suppl 1): 17-22 [PubMed]
- Price (2012) Am Fam Physician 85(5): 483-93 [PubMed]
- Werder (1995) Am Fam Physician 51(5):1126-36 [PubMed]