PHRM845-FINAL EXAM

Question 1

What two things must a patient have to be diagnosed with bipolar disorder?

Answer 1

Mania and depression

Question 2

Lifetime prevalence of bipolar disorder

Answer 2

2.4%

Question 3

Clinical factors of bipolar disorder

Answer 3

Disease course
-Age at onset (late adolescents/early adulthood)
-Episodic course with episodes lasting a few weeks to several months
-Acceleration of cycle frequency is common as illness progresses
-Depression is the mood pole that is experienced most often in bipolar disorder–can lead to misdiagnosis

Question 4

Comorbidities of bipolar disorder

Answer 4

-Alcohol and substance use is common (50-60%)
-2-3x higher mortality rate than general population
-Anxiety disorders are common comorbidities and can significantly impact remission of mood episodes if left untreated or inadequately treated

Question 5

What is mania?

Answer 5

-Abnormally and persistently elevated, expansive, or irritable mood
-Grandiosity, flight of ideas, distractibility, pressured speech, decreased need for sleep, agitation, excessive involvement in pleasure activities
-Hospitalization is generally required
-Severe episode may involve psychosis
-Change in sleep pattern often initiates episode

Question 6

What is hypomania?

Answer 6

-Less severe form of mania, hospitalization not often required
-Elevated, expansive, or irritable mood symptoms
-Inflated self-esteem, decreased need for sleep, distractibility
-No psychotic features
-Appear like type A (fly around to various types of projects)

Question 7

What is rapid-cycling?

Answer 7

-Characterized by four or more mood episodes in 1 year
-Not based on mood changes in a day

Question 8

Bipolar I classification

Answer 8

At least 1 manic episode, depressive or hypomanic episode may have occurred; manic episodes generally last at least 1 week

**Pt experiences at least 1 manic episode

Question 9

Bipolar II classification

Answer 9

Major depressive and hypomanic episodes; hypomanic episodes generally last at least 4 days

*No manic episodes

Question 10

Does bipolar mixed with depression matter for classification?

Answer 10

NO; just based on if the patient had a manic episode

Question 11

What is mixed features of bipolar disorder?

Answer 11

It is a clinical conundrum that is confusing

Question 12

What medication works best for mixed features of bipolar disorder?

Answer 12

Valproate

Question 13

Target symptoms of mood for bipolar disorder

Answer 13

-Euphoria/elation/happiness
-Depression
-Lability
-Irritability
-Hostility
-Dissatisfaction

Question 14

Target symptoms of cognitive/perceptual

Answer 14

-Flight of ideas
-Racing thoughts
-Grandiosity
-Delusions
-Hallucinations
-Ideas of reference
-Fragmented thoughts

**DOES NOT INCLUDE DISORDERED THINKING

Question 15

Target symptoms of activity/behavior

Answer 15

-Pressured speech
-Impulsivity
-Insomnia
-Aggression/outbursts/violence
-Increased sexual dysfunction
-Panic

Question 16

Pharmacotherapy overview for bipolar disorder

Answer 16

-Mood stabilizers are the foundation of acute and maintenance treatment
-First line: usually lithium or valproic acid (atypical antipsychotics can also be used as first line, as monotherapy, or in combination with lithium or valproic acid)
-Many pts will take polytherapy with mood stabilizers

Question 17

What are the mood stabilizing agents?

Answer 17

-Lithium
-Valproic acid
-Carbamazepine
-Oxcarbazepine
-Lamotrigine
-Topiramate

Question 18

What are the antipsychotic agents?

Answer 18

Atypical antipsychotics are FDA-approved for acute and/or maintenance bipolar disorder with or without psychosis

Question 19

Lithium use and dosage forms

Answer 19

-Good for classic mania and for pts with suicidal ideation
-Decreases number and severity of episodes in bipolar disorder
-Associated with decrease in suicidality—lithium has a narrow therapeutic index, so it can be fatal in OD. Evaluate if the pt has a suicidal plan and if so, if it involved OD via pill ingestion
-It comes in a citrate liquid (IR) and carbonate tablets/capsules (IR or CR)
-Some difference in the lithium content, but use 1:1 conversion!

Question 20

Lithium monitoring and adverse events

Answer 20

-Narrow therapeutic index: toxicity is above 1.2-1.5 mEq/L and we must think about renal function
-Toxicities: GI, ataxia, coarse hand tremor, altered mental status, seizure, lethargy, confusion, agitation
-SE: fine hand tremor, hypothyroidism (stopping med will NOT stop this; clear SE of lithium–treat with levothyroxine), polyuria, polydipsia, acne, dry mouth, weight gain, ECG changes
-Teratogenic: Avoid in 1st trimester, use with caution in 2nd and 3rd trimester (distributed based on volume; must increase lithium dose during pregnancy)
~Happens a lot less often than previously thought
~Have preg planning convo
~Corrected by surgery if unplanned

Question 21

Lithium lab monitoring

Answer 21

-SCr, BUN (almost entirely renally excreted)
-Urine specific gravity
-Na, K, Ca
-ECG
-Thyroid function test-TSH and T4
-Parathyroid
-CBC with differential
-Weight
-Pregnancy test
**RENALLY CLEARED AND TIED TO SODIUM
**Need pts to be consistent with fluid and sodium intake

Question 22

Lithium drug interactions

Answer 22

-Decreased lithium renal clearance which increases lithium levels from ACEi, ARBs, thiazide diuretics, NSAIDs, and dehydration
**Use acetaminophen (tylenol) if needed

-Increased Li renal clearance which decreases Li levels with caffeine, osmotic diuretics, and loop diuretics

-Increased Li excretion (decreases lithium levels) with sodium bicarbonate and high Na intake
-Toxicity related to Na depletion from thiazide diuretics

Question 23

Valproate (valproic acid, divalproex)
-Dosage forms
-Dosing

Answer 23

-ER dosage form is ~10-15% less bioavailable than delayed release dosage form
~1:1 conversion, expect lower serum concentration with the ER dosage form (usually not clinically significant)

-Valproic acid syrup (IR) and capsule sprinkle form-higher risk for GI ulcerations (usually esophageal)

-Usual initial dose is 1000 mg given as a nighttime dose or split into 2 divided doses
~Serum levels 80-125 mcg/ml are associated with most efficacy in mania; obtain level at least 96 hours (4 days) after first dose or dose increase

Question 24

Valproic acid adverse effects

Answer 24

-Unsafe in ANY trimester of pregnancy–obtain baseline pregnancy test
-PCOS occurs in up to 50% of women who take valproic acid
~Assess for menstrual cycle changes or hirsutism
~May treat with metformin
~Refer to endocrinologist
-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: 6-8 kg)
-Hyperammonemia

Question 25

Valproate lab monitoring

Answer 25

-Baseline pregnancy test, LFTs, CBC with differential
-serum concentration
-Serum ammonia-if suspect hyperammonemia (routine ammonia monitoring is not necessary)

Question 26

Valproate drug interactions

Answer 26

-Significant concern with combination use with lamotrigine–increased lamotrigine serum concentrations increase the risk of SJS

Question 27

Carbamazepine

Answer 27

-Considered 2nd or 3rd line
-Known teratogen
-Induces nearly all CYP450 enzymes
-Serum concentration not well correlated to efficacy in bipolar disorder
-Associated with thrombocytopenia/hematologic effects

Question 28

Oxcarbazepine

Answer 28

-Considered 2nd or 3rd line
-May be used as adjunctive therapy
-CYP450 3A4 inducer (NO auto induction)
-Associated with hyponatremia, but less hematologic effects compared to carbamazepine

Question 29

Lamotrigine

Answer 29

-1st line tx for DEPRESSIVE sx in bipolar disorder
*Not useful for acute treatment or for manic episodes
-Slow dose titration due to SJS

Question 30

Topiramate

Answer 30

-Clinically used as adjunctive tx
-Limited efficacy as a mood stabilizer in placebo-controlled studies
-Slow dose titration to avoid cognitive deficits (dope-amax)
-May cause weight loss
-Heat intolerance/hypo hidrosis
-Metabolic acidosis and kidney stones
-Possible teratogen–cardiac structural defects
-DRESS warning

Question 31

Antipsychotics in bipolar disorder

Answer 31

**Clinically, it is okay to use them as monotherapy
**Think about quetiapine and lurasidone specifically
-Atypical antipsychotics (except brexpiprazole, clozapine, iloperidone, and paliperidone) are FDA-approved for acute and/or maintenance tx (manic/mixed episodes) with and without psychosis

Question 32

Antipsychotics in bipolar disorder (clinical pearls)

Answer 32

-Atypical antipsychotics may be used as monotherapy or can be used in combination with other mood stabilizers (usually valproate or lithium)
-Antipsychotic polytherapy is not appropriate in most cases for psychiatric illnesses
-All monitoring parameters for metabolic syndrome and movement side effects apply when used for bipolar disorder
-Can use lithium + antipsychotic, lithium + valproate, or valproate + antipsychotic
**Can NOT use 2 antipsychotics together

Question 33

Treatment considerations

Answer 33

-Mood stabilizer tx is long-term and considered to be maintenance tx to reduce time to subsequent mood episodes **Keeps pt from rapid cycling
-Tx is limited by tolerability to meds and med adherence
-Suicide attempt risk is high in both poles of bipolar disorder–monitor closely and use lithium cautiously
**More pts die from bipolar/schizophrenia than depression

Question 34

Combination tx

Answer 34

-Drug regimens in psychiatry is as much an art as a science (may result in difficult regimens)
-Combo often designed based on pt response, drug interactions, and adverse effects
-Lithium and valproate can be used together and can also be used with an antipsychotic

Question 35

Tx in pregnancy

Answer 35

-Lithium, valproic acid, carbamazepine, and topiramate are known or possible teratogens
-Atypical antipsychotics, besides olanzapine and clozapine, are often used in pregnancy because they are thought to have less evidence of teratogenic effect

Question 36

Antidepressants in bipolar disorder

Answer 36

-Depression is experienced most often
-Use of antidepressants is linked with a switch to mania
~Questionable efficacy of antidepressants for depression in bipolar disorder
~Need to have maintenance mood stabilizer tx in combo with antidepressant tx

-Anxiety disorders are a common comorbidity in bipolar disorder: will use serotonergic antidepressants to tx anxiety