Bipolar Disorder

Question 1

What is bipolar disorder?

Answer 1

a serious brain disorder characterized by extreme alterations in mood, energy level, and thought processes, with a reduced capacity to function “normally” in daily life; associated with HIGH RATES OF MEDICATION NON-ADHERENCE

Question 2

What medications may produce manic-like symptoms?

Answer 2

-antidepressants= TCAs, MAOIs, SSRIs
-anxiolytics= buspirone, benzodiazepines
-stimulants= cocaine, MPH, AMP, ephedrine, pseudoephedrine
-endocrine= corticosteroids, thyroid supplements, androgens
-others: levodopa, EtOH, bronchodilators

Question 3

Describe Bipolar I Disorder

Answer 3

at least 1 manic episode- if a patient has a manic episode (even if the have hypomanic/depression episodes) it is considered B1D

Question 4

Describe Bipolar II Disorder

Answer 4

at least 1 hypomanic/depressive episode, but if pt has a manic episode then they would be categorized as B1D

Question 5

What are the goals of treatment of Bipolar Disorder?

Answer 5

-eliminate mood episode/remission of symptoms
-mood stabilization; recurrence/relapse prevention
-return to baseline psychosocial functioning
-maximize adherence
-educate patient, family, caregivers
-treat comorbid substance use and use disorders
-avoid stressors or substances that precipitate an acute episode

Question 6

What are the potential pharmacological treatment options for Bipolar Disorder?

Answer 6

-lithium
-valproic acid
-carbamazepine
-lamotrigine
-antipsychotics

Question 7

MOA: Lithium (Li)

Answer 7

increases 5HT (serotonin) function, reduces dopamine function, and enhances GABA and normalizes levels

Question 8

What are the benefits of using Lithium in Bipolar Disorder?

Answer 8

BAP GUIDELINES: the most effective treatment preventing relapse and hospital admissions in Bipolar I Disorder
alleviates mania and provides prophylaxis against both manic and depressive episodes. anti-suicidal effects also seen and benefits for impulsivity

Question 9

What is the Black Box Warning of Lithium?

Answer 9

lithium toxicity is closely related to serum lithium concentrations and can occur at doses close to therapeutic concentrations

Question 10

What is the dosing of Lithium?

Answer 10

600-1800mg/day in 1-3 divided doses
AVOID IN SEVERE RENAL IMPAIRMENT

Question 11

What are the baseline monitoring parameters before treatment with Lithium?

Answer 11

-ECG (especially if age >50 or if history of CV disease)
-blood pressure
-thyroid function
-parathyroid hormone/calcium
-CBC
-BMP
-pregnancy status

Question 12

What is the reasoning for monitoring ECG while on lithium?

Answer 12

sick sinus syndrome, BRADYCARDIA, unmask Brugada syndrome, AV block

Question 13

What is the reasoning of monitoring thyroid function while on lithium?

Answer 13

lithium can precipitate hypothyroidism

Question 14

What is the reasoning for monitoring CBC while on lithium?

Answer 14

risk of leukocytosis (75-100% may have it to some degree)

Question 15

What is the reasoning for monitoring BMP while on lithium?

Answer 15

Na+ (hyponatremia) and kidney function (risk of nephrogenic diabetes insipidus)

Question 16

When would serum lithium levels be monitored in bipolar patients?

Answer 16

4-5 days after initiation at ~12 hours post dose

Question 17

What is the treatment of lithium toxicity?

Answer 17

*a medical emergency; rapid, aggressive treatment is needed to reduce risk of suffering permanent neurologic damage *
if mild= hold dose, if severe (any Li level >6 or chronic use Li level >4)= hemodialysis

Question 18

What are the risk factors for lithium toxicity?

Answer 18

-sodium restriction
-dehydration
-vomiting
-diarrhea
-fever
-heavy exercise
-large quantities of caffeine or alcohol
-pregnancy & delivery

Question 19

What are the adverse effects of lithium?

Answer 19

-tremor (high incidence): can be reduced with slow titration
-cognitive problems: agitation/confusion/mental dullness
-nausea/vomiting/diarrhea
-dermatologic: rashes
-weight gain
-polyuria/excessive thirst

Question 20

What are the drug interactions of lithium?

Answer 20

-diuretics
-NSAIDs
-renin angiotensin system antagonists (ACEI or ARBs)

Question 21

What is the reasoning for discouraging the use of lithium during pregnancy?

Answer 21

lithium can cause epsteins anomaly when used in the first trimester and causes neonatal toxicity

Question 22

What is the indication of Valproic Acid in Bipolar Disorder?

Answer 22

acute mania & maintenance

Question 23

With what condition may valproic acid be specifically useful with?

Answer 23

comorbid substance use disorder

Question 24

What are the black box warnings of Valproic Acid?

Answer 24

-hepatoxicity, hepatic failure
-pancreatitis
-contraindicated in mitochondrial disorders/urea cycle disorders
-fetal risk

Question 25

What are the monitoring parameters for Valproic Acid?

Answer 25

-CBC -LFTs -pregnancy test -drug levels (50-125 mccg/mL) which are obtained at steady state

Question 26

What are the adverse effects of Valproic Acid?

Answer 26

-sedation, N/V/D, dizziness -tremor -PCOS (10% risk) -increased AST/ALT -hyperammonemia and/or hyperammonemic encephalopathy

Question 27

What are the drug interactions of Valproic Acid?

Answer 27

topiramate due to increased risk of hyperammonemic encephalopathy

Question 28

Why is Valproic Acid contraindicated in women in child-bearing age?

Answer 28

teratogenic (BBW)= malformations, developmental delays, autism

Question 29

What is the indication of Carbamazepine?

Answer 29

acute mania and mixed episodes *NOT A FIRST LINE OPTION- COMBO THERAPY*

Question 30

Which drug induce auto-induction metabolism?

Answer 30

carbamazepine

Question 31

What are the black box warnings of Carbamazepine?

Answer 31

-SJS/TEN: genetic testing for HLA-B*15:02 -aplastic anemia and agraulocytosis

Question 32

What are the special dosing recommendations for Carbamazepine?

Answer 32

-slow titration to minimize neurological adverse effects -close monitoring around dosing adjustments or dosage conversions

Question 33

What is the target drug plasma level of Carbamazepine?

Answer 33

4-12 mcg/mL

Question 34

What are the adverse effects of Carbamazepine?

Answer 34

-dizziness, diplopia, ataxia, drowsiness, confusion -cardiac conduction abnormalities= tachycardia, bradyarrhythmia, AV block -SIADH/hyponatremia

Question 35

What are the drug interactions of Carbamazapine?

Answer 35

-hormonal contraceptives= decreased efficacy -lamotrigine= enhances the adverse/toxic effects of LTG

Question 36

What are the recommendations for pregnant patients while on Carbamazepine?

Answer 36

folic acid supplementation

Question 37

What is the indication of Lamotrigine?

Answer 37

maintenance therapy of BPD or bipolar depression (off label) *NOT EFFECTIVE FOR MANIA*

Question 38

What are the black box warnings of Lamotrigine?

Answer 38

SJS/TEN *do not exceed recommended dose titrations*

Question 39

What drugs titration must be restarted if >5 half lives of dosing have been missed?

Answer 39

Lamotrigine

Question 40

What are the adverse effects of lamotrigine?

Answer 40

-headache -diplopia -ataxia, somnolence -blurred vision -N/V/D -considered a class 1B antiarrhythmic at therapeutically relevant drug concentrations -benign rash

Question 41

What are the drug interactions of Lamotrigine?

Answer 41

-valproic acid (decreases clearance of LTG) -carbamazepine, phenytoin, primidone, phenobarbital (increase clearance of LTG) -oral contraceptives (increased clearance of LTG)

Question 42

What drug is cautioned to be used in children <16 yo due to serious rash?

Answer 42

Lamotrigine

Question 43

What is the place of second generation antipsychotics in the treatment of bipolar disorder?

Answer 43

first line as monotherapy or in combination in acute mania

Question 44

What is the first line treatment for mania?

Answer 44

mood stabilizers or atypical antipsychotics

Question 45

What drugs may be used for depressive episodes in BPD?

Answer 45

-mood stabilizers: lithium, lamotrigine -atypical antipsychotics: quetiapine, lurasidone (recommended in children), olanzapine, cariprazine

Question 46

What is the recommendation of antidepressant use in BPD?

Answer 46

avoid use due to precipitation of mania, especially avoid TCA due to high risk of switch rates

Question 47

What drugs are recommended maintenance treatment?

Answer 47

lithium, valproic acid, lamotrigine, quetiapine