Pharmacotherapy of Bipolar Disorder Dr. Ott

Question 1

Clinical Factors

Answer 1

Depression is the mood pole that is experienced most often in bipolar disorder. - can lead to misdiagnosis
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 2

Bipolar I disorder classification

Answer 2

> or equal to 1 manic episodes, depressive episodes have occurred
generally lasting a week or longer

Question 3

Bipolar II disorder classification

Answer 3

Major depressive and hypomanic episodes
episodes lasting 4 or more days

Question 4

Target symptoms

Answer 4

Mood : euphoria, depression, hostility, irritability

Cognitive/perceptual: Flight of ideas, racing thoughts, delusions

Activity/behavior: pressured speech, impulsivity, insomnia, aggression

Question 5

Pharmacotherapy overview

Answer 5

1st line: usually lithium or valproic acid

Question 6

Lithium use and dosing

Answer 6

Associated with decrease in suicidality - but it does have a narrow therapeutic index so overdose is easy to occur

Some difference in lithium content but use 1:1 conversion from IR to CR -EXAM Q

Question 7

Lithium monitoring and adverse events

Answer 7

Narrow therapeutics index: around 1.5mEq/L levels is getting close to toxicity/overdose

SE: fine hand tremor, hypothyroidism, polyuria, polydipsia, acne, dry mouth, weight gain

Toxicity: GI, ataxia, coarse hand tremor, altered mental status, seizure, lethargy, confusion, agitation

Teratogenic: Avoid in 1st trimester - use with caution in 2nd and 3rd trimester, Cardiac structural abnormality (ebstein’s anomaly)

Question 8

Valproate (valproic acid)

Answer 8

Available in several dosage forms risk for med errors
- extended release dosafe form is - 10-15% less bioavailable than delayed released dosage form

1:1 conversion, expect lower serum concentration with the ER dosage form - usually ot clinically significant

Valproic acid syrup (IR) and capsule sprinkle form - high risk for GI ulcerations

Serum levels 80-125 mcg/ml associated with most efficacy in mania, obtain level at least 96 hours after first dose or dose increase - EXAM Q

Question 9

Lithium monitoring

Answer 9

Laboratory monitoring
SCr, BUN, Na,K,Ca, Thyroid function, weight, pregnancy test

Drug interactions
increase lithium levels: ACEi, ARBs, Thiazide diuretics, NSAIDS, dehydration
Decrease lithium levels: caffeine, osmotic diuretics, +/- loop diuretics, sodium bicarbonate, high NA intake

toxicity related to Na depletion - thiazide diuretics

Question 10

Valproate Adverse effects

Answer 10

Unsafe in any trimester of pregnancy - always get pregnancy test at baseline
Polycystic ovarian syndrome occurs in up to 50% of women

SE: GI- (anorexia, N/V/D,dyspepsia, ulceration), increased appetite- weight gain (6-8kg), thrombocytopenia, platelet dysfunction, teratogenic- neural tube defects, enduring negative effects on IQ of offspring, Hyperammonemia

Question 11

Valproate monitoring

Answer 11

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

Drug interactions: significant concern with combination use with lamotrigine - increased lamotrigine serum concentration increases risk of stevens johnson syndrome

Question 12

Other mood stabilizers

Answer 12

Carbamazepine - thrombocytopenia/ hematologic effects

Oxcarbazepine: CYP450 3A4 inducer, associated with hyponatremia

Topiramate: may cause weight loss, heat intolerance, metabolic acidosis and kidney stones, possible teratogen- cardiac structural defects in fetus

Question 13

Lamotrigine

Answer 13

Lamictal
1st line treatment for depressive symptoms
not useful for acute treatment or manic episodes

Question 14

Antipsychotics in bipolar disorder - pearls

Answer 14

Atypical antipsychotics may be used as monotherapy or can be used 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 15

Treatment considerations

Answer 15

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 16

Treatment in pregnancy

Answer 16

Atypial antipsychotics are first line choice in pregnancy
Lithium, valproic acid, carbamazepine and topiramate are known or possible teratogens

Question 17

Antidepressants in bipolar disorder

Answer 17

Prefer to use mood stabilizers that tarfet the depressive pole: Lamotrigine, lithium, lurasidone, quetiapine

Use of antidepressants is linked with a switch to mania: need to have maintenance mood stabilizer therapy in combination with antidepressant therapy

Anxiety disorders are a common comorbhidity in bipolar disorder: will use serotonergic antidepressants to treat anxiety