Bipolar Disorder

DIG FAST

Distrabtability

Irresponsibility and erratic, uninhibited behavior

Grandiosity

Flight of ideas

Activity increased with weight loss and increased libido

Sleep is decreased

Talkativeness

Need at least 3 of the symptoms for at least 1 week

Target symptoms for bipolar disorder (mania)

1. At least ONE manic episode

- A major depressive episode may occur, but is NOT required.

2. Manic Episode Criteria:

- A distinct period of abnormally elevated, expansive, or irritable mood AND increased energy/activity lasting ≥1 week OR any duration if hospitalization is required

- PLUS ≥3 symptoms (or ≥4 if mood only irritable): DIG FAST

3. Marked functional impairment not due to substances or medical illness

DSM-5 criteria for bipolar I disorder

1. Same symptoms as mania but different severity.

2. Mood disturbance lasting ≥4 consecutive days

3. Symptoms: Same DIG FAST list (≥3 or ≥4 if irritable)

DSM-5 criteria for hypomania

2

Patients should be counseled on using ___ forms of birth control while on mood stabilizers (Lithium, Valproate)

Benzodiazepines

- Clonazepam and Lorazepam studied

Adjunctive therapy in the treatment of bipolar disorder that can help with insomnia and anxiety; only to be used short-term; can be combined with an antipsychotic

NONE (for the majority of patients)

- increases the rate of cycling

What is the role of antidepressants in bipolar disorder management?

2-4 weeks

Rapid medication discontinuation can increase the risk of relapse. Medications should be tapered over ____ weeks

Lithium

The first psychiatric mediation used that is found in natural spring water and mineral deposits.

- administered in salt form

- reduces suicidal thinking

classic manic episodes

- less effective in rapid cycling and mixed BPD

Lithium (Eskalith, Lithobid) works best for ____

renally

- follows body water

- can be dialyzed in OD

Lithium (Eskalith, Lithobid) is 95% ____ excreted.

Ebstein's Anomaly (first trimester): displacement of the tricuspid valve

Lithium (Eskalith, Lithobid) can cause ____ in the first trimester. Do not use in pregnancy.

Acute phase: 0.6-1.2 mEq/L

Maintenance: 0.6-1.0 mEq/L

Serum lithium level for Lithium (Eskalith, Lithobid)

sodium

- don't abruptly change salt intake when stabilized on a maintenance regimen of Lithium

Monitor ____ intake when on Lithium (Eskalith, Lithobid)

1. GI disturbances

- Food or milk helps

2. Polyuria, polydipsia (70%)

3. Tremor (hand)

4. Sedation

5. Headache

6. Confusion, decreased memory and concentration (transient)

7. Muscle weakness

8. Lethargy

9. Dry mouth

10. Leukocytosis (not transient)

SEs of Lithium (Eskalith, Lithobid) seen early in treatment

1. Fine hand tremor (50%)

- treat with beta blockers

2. Weight gain (20%)

3. Leukocytosis

4. Goiter, hypothyroidism

- may develop after years; more likely in women

- mostly irreversible

5. EKG changes

6. Neurologic

7. Dermatologic (40%)

8. Decreased libido

9. Metallic taste

10. Urinary incontinence

11. Late nephrogenic diabetes insipidous

SEs of Lithium (Eskalith, Lithobid) seen in maintenance treatment

1. Diarrhea

2. Severe n/v

3. Coarse hand tremor, hyperreflexia

4. Drowsiness, lethargy, confusion, CNS irritability

5. Muscular weakness, lack of coordination, ataxia

6. Blurred vision, dry mouth

7. Large output of dilute urine

8. Slurred speech

9. CV: arrhythmias, hypotension

10. Seizures, coma, death

**Patients appear drunk

Symptoms of Lithium (Eskalith, Lithobid) toxicity

1. Lavage for acute ingestion

2. Correct/maintain fluid and electrolyte balance

3. Monitor cardiac and respiratory function

4. Seizure precaution

5. Monitor Lithium concentration (Q3-4 hours)

6. Dialysis

- intermittently dialyze if blood levels are >3.5 mEq/L

Treatment of extreme Lithium (Eskalith, Lithobid) toxicity

1. NSAIDs: decrease renal function and increase serum concentrations of lithium

2. Thiazide and Potassium-sparing diuretics: increase serum lithium

3. ACE inhibitors/ARBs: increase serum lithium

4. Sodium chloride/sodium bicarbonate: decrease serum lithium

- inversely related to lithium concentrations

5. Antipsychotics: increased risk of neurotoxicity

Lithium (Eskalith, Lithobid) drug interactions

1. Take with food or milk

2. Discontinue medication and notify physician if signs of toxicity occur

3. May cause drowsiness; caution while driving

4. Maintain adequate fluid and salt intake, especially in situations of dehydration

Lithium (Eskalith, Lithobid) counseling points

Lithium (Eskalith, Lithobid)

What is the only dialyzable psychotropic?

1. Hepatotoxicity

2. Teratogenicity

3. Pancreatitis

Other warnings:

- Thrombocytopenia (10% of patients)

- Hyperammonemia (especially with Topiramate)

List the boxed warnings of Valproic acid (Depakote, Depakene)

Topiramate

Patients are at an increased risk of hyperammonemia if they are taking Valproic acid with _____

50-125 mcg/ml

The therapeutic range for valproic acid in acute bipolar treatment

50-100 mcg/ml

The therapeutic range for valproic acid for epilepsy treatment

Valproic acid

Which mood stabilizer is usually preferred in patients with comorbid disorders (migraines, substance abuse, anxiety, panic disorder) and mixed features (mania + depression)?

1. Neurologic: ataxia, dizziness, drowsiness, tremor

2. GI: n/v

- give with food to minimize

3. Hematologic: thrombocytopenia; prolonged bleeding

4. Hepatologic: transient increase in LFTs

5. Dermatologic: rash, alopecia, hair changes

6. Weight gain

AEs of VPA

PCOS

- patients who already have PCOS should use caution with VPA (use is usually avoided)

VPA increases the risk of ____

spina bifida (boxed warning)

Valproic acid is pregnancy category D (X for migraine prophylaxis). It can cause _____ in the first trimester and it can lead to lower IQ and increased risk for autism.

Pregnancy prevention is in place (2 birth control methods)

Do not offer Valproic acid to women of childbearing age unless there is ___ in place.

Aspirin and oral anticoagulants

Valproic acid is highly protein-bound. ____ can displace VPA.

50%

Decrease the dose of Lamotrigine by ___% if taken with Valproic acid

Carbamazepine (Tegretol, Carbatrol, Equetro)

Third-line agent for bipolar disorder

1. Aplastic anemia and agranulocytosis

2. Serious dermatologic reactions

- increased risk with HLA-B1502 or HLA-A 3101

- can progress to SKS or TEN

- genetic testing should be done before starting in Asian, Native American, and Indian patients

Boxed warnings of Carbamazepine (Tegretol, Carbatrol, Equetro)

1. Neurologic (60%): drowsiness, dizziness, diplopia

2. GI (15%)

3. Dermatologic: rash, photosensitivity

4. Hematologic: agranulocytosis, aplastic anemia

5. Hyponatremia (rare SIADH)

6. Transient increase in LFTs

7. Caution in pregnancy and breastfeeding

Carbamazepine (Tegretol, Carbatrol, Equetro) SEs

Maintenance treatment of bipolar disorder

- NOT used in acute mania because it should not be titrated rapidly; rapid titration can cause SJS/TEN

What is the role of Lamotrigine (Lamictal) in bipolar disorder?

1. Valproic acid doubles Lamotrigine blood levels

- decrease lamotrigine dose by 50%

2. Enzyme-inducing antiepileptic drugs: Carbamazepine, Phenytoin, Phenobarbital, and Primidone decrease Lamotrigine concentrations by 40%

3. Oral estrogen-containing contraceptives and Rifampin decrease lamotrigine concentrations by 25-50%

- switch to progestin-only birth control or take the estrogen-containing oral contraceptive continuously (skip placebo week)

Lamotrigine (Lamictal) drug interactions

Expert Consensus Guidelines have changed to include atypicals as first-line agents.

- Most are FDA-approved as monotherapy or adjunct to Lithium or Valproate (adjunctive therapy results in faster and better remission rates)

What is the place in therapy for Atypical Antipsychotics?

1. Symbyax (Fluoxetine/Olanzapine)

2. Seroquel XR (Quetiapine)

3. Latuda (Lurasidone)

4. Vraylar (Cariprazine)

5. Caplyta (Lumateperone)

FDA-approved medications for bipolar depression