PHRM845-FINAL EXAM Flashcards
Pharmacotherapy of bipolar disorder
What two things must a patient have to be diagnosed with bipolar disorder?
Mania and depression
Lifetime prevalence of bipolar disorder
2.4%
Clinical factors of bipolar disorder
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
Comorbidities of bipolar disorder
-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
What is mania?
-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
What is hypomania?
-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)
What is rapid-cycling?
-Characterized by four or more mood episodes in 1 year
-Not based on mood changes in a day
Bipolar I classification
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
Bipolar II classification
Major depressive and hypomanic episodes; hypomanic episodes generally last at least 4 days
*No manic episodes
Does bipolar mixed with depression matter for classification?
NO; just based on if the patient had a manic episode
What is mixed features of bipolar disorder?
It is a clinical conundrum that is confusing
What medication works best for mixed features of bipolar disorder?
Valproate
Target symptoms of mood for bipolar disorder
-Euphoria/elation/happiness
-Depression
-Lability
-Irritability
-Hostility
-Dissatisfaction
Target symptoms of cognitive/perceptual
-Flight of ideas
-Racing thoughts
-Grandiosity
-Delusions
-Hallucinations
-Ideas of reference
-Fragmented thoughts
**DOES NOT INCLUDE DISORDERED THINKING
Target symptoms of activity/behavior
-Pressured speech
-Impulsivity
-Insomnia
-Aggression/outbursts/violence
-Increased sexual dysfunction
-Panic
Pharmacotherapy overview for bipolar disorder
-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
What are the mood stabilizing agents?
-Lithium
-Valproic acid
-Carbamazepine
-Oxcarbazepine
-Lamotrigine
-Topiramate
What are the antipsychotic agents?
Atypical antipsychotics are FDA-approved for acute and/or maintenance bipolar disorder with or without psychosis
Lithium use and dosage forms
-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!
Lithium monitoring and adverse events
-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
Lithium lab monitoring
-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
Lithium drug interactions
-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
Valproate (valproic acid, divalproex)
-Dosage forms
-Dosing
-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
Valproic acid adverse effects
-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
Valproate lab monitoring
-Baseline pregnancy test, LFTs, CBC with differential
-serum concentration
-Serum ammonia-if suspect hyperammonemia (routine ammonia monitoring is not necessary)
Valproate drug interactions
-Significant concern with combination use with lamotrigine–increased lamotrigine serum concentrations increase the risk of SJS
Carbamazepine
-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
Oxcarbazepine
-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
Lamotrigine
-1st line tx for DEPRESSIVE sx in bipolar disorder
*Not useful for acute treatment or for manic episodes
-Slow dose titration due to SJS
Topiramate
-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
Antipsychotics in bipolar disorder
**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
Antipsychotics in bipolar disorder (clinical pearls)
-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
Treatment considerations
-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
Combination tx
-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
Tx in pregnancy
-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
Antidepressants in bipolar disorder
-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
