ILE 10 - Comprehensive Study Guide for Bipolar Disorder and Medications

Bipolar I mood states

Hypomania

Mania

Depression

5 medications (4 mood stabilizers) that treat Bipolar I disorder

Lithium

Valproate

Carbamazepine

Oxcarbazepine

Antipsychotics

Bipolar II mood states

Hypomania

Depression

2 mood stabilizers that treat Bipolar II disorder

Lithium

Lamotrigine

Hypomania

Shorter time period (days)

No medication needed

No hospitalization

Does not cause social or occupational dysfunction

No psychosis

Mania

Longer time period (weeks)

Medication treatment needed

Often requires hospitalization

Causes social and occupational dysfunction

Often involves psychosis

Rapid cycling

Four or more mood episodes in the course of one year

Rapid cycling mood stabilizers/medications

Valproic acid

Carbamazepine

Antipsychotics

Possible symptoms of mania

Decreased need for sleep (3 hours or less)

Decreased appetite

Inflated self esteem

Delusional grandiosity

Euphoria or irritability

Rapid, pressured, or loud speech

Flight of ideas

Increase in risk taking activities like spending, sex, and increased motor activity

Psychosis

Symptoms of depression

Decrease or increase sleep

Decreased interest

Increase in guilt over things outside of your control

Decreased energy

Decreased concentration

Decrease or increase in appetite

Increase in psychomotor agitation or psychomotor depression

Suicidal thinking

Kindling theory

The more episodes of mania/depression that you have, the more that you will have in the future. This is why it is important to control symptoms early so that it does not lead to rapid cycling

Risk factors for developing bipolar disorder

Family history (genetics)

Head trauma

Perinatal insult

Stress

Environment-seasonal changes in mood

Nutrition - caused by a decrease in fatty acids and amino acids

Genetic risk of developing bipolar disorder: First degree relatives

5-10% risk of bipolar disorder

Genetic risk of developing bipolar disorder: Monozygotic twins

60-80% risk of bipolar disorder

Genetic risk of developing bipolar disorder: Dizygotic twins

14-20% risk of bipolar disorder

Why is it so difficult to treat bipolar disorder?

69% of individuals with bipolar disorder are initially misdiagnosed. It takes approximately 10 years to get a correct diagnosis. This time spent cycling into different moods leads to rapid cycling which is more difficult to control.

Goal of treating bipolar disorder

Prophylaxis to prevent future mood episodes

Non-pharm treatment of bipolar disorder

Patients should get adequate sleep, adequate nutrition, and exercise

Lithium carbonate similarity to sodium chloride (table salt)

Both NaCl and LiCo3 are elements, and the body recognizes them both as salt - the body doesn't differentiate between them.

What happens to lithium blood levels when sodium chloride is decreased?

When sodium chloride in the body declines, the body recognizes lithium as salt and hangs on to it, often leading to lithium toxicity, because lithium has a narrow therapeutic range

Situations where a patient might have a decreased sodium level

Dehydration, flu (vomiting, diarrhea), hyponatremia, low salt diet, taking a diuretic

Lithium uses

Mania

Depression

Suicide

Therapeutic range for lithium

0.8-1.2 mEq/L

Mild lithium toxicity (>1.5-2) symptoms

Drowsiness

Decreased concentration

Unsteady gait

Hand tremors

Diarrhea

Moderate lithium toxicity (2-3) symptoms

Speech difficulties

Muscle weakness

Ataxia

Blurred vision

Tinnitus

Confusion

Nausea

Vomiting

Incontinence

Severe lithium toxicity (>3) symptoms

Seizures

Deep tendon reflexes

CV collapse

Coma

Death

Severe lithium toxicity (>3) treatment

dialysis

Teratogenic effect with lithium

Ebstein's anomaly

Lithium side effects that are dose related

Nausea

Vomiting

Diarrhea

Tremor

Agitation

Confusion

Polydipsia

Polyuria

3 non-dose related side affects for lithium

Renal scarring

Thyroid scarring

Leukocytosis

ECG changes

Rash

Weight gain

Why should lithium be given as a single daily dose (if tolerated)

Renal damage is worse in individuals that take lithium multiple times daily

third degree heart block

CV condition that lithium should be avoided in

Acne

Dermatologic effect is seen most frequently with lithium

Lithium toxicity

Interaction that occurs when lithium and NSAIDs are used together

Sulindac and aspirin

Nonsteroidals that do not cause interaction with lithium

Drug interactions that can cause lithium toxicity

Lithium plus ACEi or ARB

Lithium plus NSAID (except sulindac, aspirin)

Lithium plus a diuretic (except Lasix)

Lithium plus methylxanthine (example: theophylline or caffeine)

Lithium plus metronidazole

12 hours

Lithium dose trough level timing

Steven johnson syndrome (SJS)

Mortality 5-15%

Difference in SJS and TEN is the amount of skin detachment and mortality

Epidermal detachment is between 10 and 30% in SJS

Toxic epidermal necrolysis (TEN)

Mortality 30-35%

Difference in TEN and SJS is the amount of skin detachment and mortality

Epidermal detachment is >30% in TEN

Drug reaction with eosinophilic and systemic symptoms (DRESS)

Mortality 10%

Specific, severe reaction defined by a widespread and long lasting papulopustular or erythematous skin eruption often progressing to exfoliative dermatitis with fever, lymphadenopathy, and visceral involvement (hepatitis, pneumonitis, myocarditis, pericarditis, nephritis). Eosinophilia occurs in 90% and mononucleosis in 40% of cases

Valproic acid, carbamazepine, oxcarbazepine, and lamotrigine

Medications used for bipolar disorder that cause SJS, TEN, and DRESS

2 situations that valproic acid works for

Mania

Rapid cycling

Situation that valproic acid does NOT work for

Depression

Less GI irritation

Divalproex sodium preferred over valproic acid

50-125 mcg/mL

Therapeutic level of valproic acid

Neural tube defect

teratogenic effect seen with VPA

Thrombocytopenia

hematologic effect that is most often seen with valproic acid

Lab values for valproic acid

ALT and AST for liver function

Amylase and lipase for pancreatitis

doubles, half

Valproic acid __________ the AUC of lamotrigine, so the lamotrigine dose needs to be cut in __________

DDI between valproic acid and phenytoin

Valproic acid may cause an initial decrease in total phenytoin levels, while free levels remain unaltered. Drug levels may normalize after several weeks. Phenytoin may double valproic acid clearance

Carbamazepine use

Mania and rapid cycling

8-12 mcg/mL

Therapeutic level of carbamazepine

Carbamazepine teratogenic effect

Neural tube defect

Two major DDIs with carbamazepine

It causes a decrease in oral contraceptive leaving them ineffective

Decrease antipsychotic levels down to zero

Benefit of using oxcarbazepine over carbamazepine

Decreased risk of SJS, TEN, and DRESS

Decrease in DDI

No autoinduction

Less risk for agranulocytosis

Similar efficacy

Lamotrigine use

Depression only

Lamotrigine BBW

Life threatening rash

Avoid causing SJS

Reason for lamotrigine having such a slow titration schedule

Lamotrigine dose with valproic acid

Lamotrigine should not be used at a dose greater than 100 mg daily

Lamotrigine + oral contraceptive DDI

Oral contraceptives decrease the lamotrigine blood level

Bipolar mania antipsychotics

Aripiprazole

Asenapine

Cariprazine

Olanzapine

Quetiapine

Risperidone

Ziprasidone

Chlorpromazine

Bipolar depression antipsychotics

Cariprazine

Olanzapine-fluoxetine

Lurasidone

Lumateperone

Quetiapine

Acute mania treatment combo

Antipsychotic, benzodiazepine and a mood stabilizer

Why avoid giving antidepressants for BPAD I disorder

Antidepressants can cause individuals with BPAD I to become manic. It flips them from a depressed to a manic episode

Young mania ration scale (YMRS)

Most commonly used mania rating scale