Ott Pharmacotherapy of Bipolar Disorder

Question 1

Why is bipolar disorder often misdiagnosed?

Answer 1

Depression is the mood pole that is experienced most often in bipolar disorder, often people are diagnosed with depression instead

Question 2

Comorbidities associated with bipolar disorder

Answer 2

-Alcohol and substance use common (50-60%)
-Anxiety disorders are common comorbidities and can significantly impact remission of mood episodes if left untreated or inadequately treated

Question 3

How is bipolar 1 disorder defined?

Answer 3

1 or more manic episodes

Question 4

How is bipolar 2 disorder defined?

Answer 4

Hypomanic episodes generally lasting 4 days or more

Question 5

Lithium clinical pearls

Answer 5

-Associated with decrease in suicidality
-Narrow therapeutic index medication
-Some differences in lithium content, but use 1:1 conversion between liquid and tablet

Question 6

Lithium dosing for acute treatment

Answer 6

0.9-1.2 mEq/L

Question 7

Lithium dosing for maintenance therapy

Answer 7

0.6-0.9 mEq/L

Question 8

Lithium dosing that leads to toxicity

Answer 8

1.5 - >30 mEq/L

Question 9

How is lithium dosing monitored?

Answer 9

Draw trough serum concentration 72 hours after dose initiation, 12 hours after last dose

Question 10

Symptoms of lithium toxicity

Answer 10

-GI upset
-Ataxia
-Coarse hand tremor
-Altered mental status
-Seizure
-Lethargy
-Confusion
-Agitation

Question 11

Lithium side effects

Answer 11

-Fine hand tremor
-Hypothyroidism
-Polyuria
-Polydipsia
-Acne
-Dry mouth
-Weight gain
-ECG changes

Question 12

Teratogenic effects of lithium

Answer 12

-Cardiac structure abnormality (Ebstein’s anomaly)
-Avoid in first trimester - use with caution in second and third trimester

Question 13

Lithium monitoring parameters

Answer 13

-SCr, BUN (almost entirely renally excreted)
-Urine specific gravity
-Na, K, Ca
-ECG (especially if age is over 40 or other risk factors)
-Thyroid function - TSH, T4
-Parathyroid hormone
-CBC with differential
-Weight
-Pregnancy test

Question 14

Lithium drug interactions

Answer 14

-Decreased lithium renal clearance (increase in lithium levels) - ACEi, ARBs, thiazide diuretics, NSAIDs, dehydration
-Increased Li renal clearance (decreased Li levels) - caffeine, osmotic diuretics, +/- loop diuretics
-Increased Li excretion (decreased Li levels) - sodium bicarbonate, high Na intake
-Toxicity related to Na depletion - thiazide diuretics

Question 15

Valproate clinical pearls

Answer 15

-Extended release form is ~10-15% less bioavailable than delayed release dosage form
-1:1 conversion, expect lower serum concentration with ER dosage form - usually not clinically significant
-Valproic acid syrup and capsule sprinkle form have a higher risk for GI ulcerations (usually esophageal)
-serum levels 80-125 mcg/ml associated with most efficacy in mania, obtain level at least 96 hours after first dose or dose increase

Question 16

Valproate adverse effects

Answer 16

-Unsafe in any trimester of pregnancy - obtain baseline pregnancy test
-Polycystic ovarian syndrome occurs in up to 50% of women
-GI - anorexia, N/V/D, dyspepsia, ulceration
-Thrombocytopenia, platelet dysfunction
-Teratogenic - neural tube defects, enduring negative effects on IQ of offspring
-Increased appetite - weight gain (~6-8kg)
-Hyperammonemia

Question 17

Valproate monitoring

Answer 17

-Baseline - pregnancy test, LFTs, CBC w/differential
-Serum concentration
-Serum ammonia if suspect hyperammonemia; routine ammonia monitoring is not necessary

Question 18

Valproate drug interactions

Answer 18

-Significant concern with combination use with lamotrigine - increased lamotrigine serum concentrations and increased risk of Stevens-Johnson syndrome

Question 19

Carbamazepine side effects

Answer 19

Thrombocytopenia/hematogenic effects

Question 20

Oxcarbazepine clinical pearls

Answer 20

-CYP450 3A4 inducer
-Hyponatremia

Question 21

Lamotrigine clinical pearls

Answer 21

-First line treatment for depressive symptoms
-NOT useful for acute treatment or for manic episodes

Question 22

Topiramate clinical pearls

Answer 22

-May cause weight loss
-Heat intolerance/hypohidrosis
-Metabolic acidosis and kidney stones
-Possible teratogen - cardiac structural defects

Question 23

Antipsychotic clinical peals

Answer 23

-Atypical antipsychotics may be used as monotherapy or can be used combo with other mood stabilizers (usually valproate or lithium)
-All monitoring parameters for metabolic syndrome and movement side effects apply when used for bipolar disorder

Question 24

Treatment considerations

Answer 24

-Mood stabilizer treatment is long-term and considered to be maintenance treatment to reduce time to subsequent mood episodes
-Suicide attempt risk is high in both poles of bipolar disorder - monitor closely, use lithium cautiously

Question 25

Which drugs to treat bipolar disorder are known as possible teratogens

Answer 25

-Lithium
-Valproic acid
-Carbamazepine
-Topiramate

Question 26

How are antidepressants used to treat bipolar disorder?

Answer 26

-Need to have maintenance mood stabilizer therapy in combination with antidepressant therapy
-Will use serotonergic antidepressants to treat anxiety
-Prefer to use mood stabilizers that target the depressive pole - lamotrigine, lithium, lurasidone, quetiapine