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Neurology > Bipolar Disorder > Flashcards

Bipolar Disorder Flashcards

1
Q

What are the excitatory neurotransmitters?

A
  • Norepinephrine
  • Dopamine
  • Glutamine
  • Aspartate
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2
Q

What are the inhibitory neurotransmitters?

A
  • Serotonin
  • GABA
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3
Q

Kindling effect

A

Acceleration of episode frequency and treatment resistance with inadequate treatment

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4
Q

Manic episode (Bipolar I disorder)

A

Criteria have met for at least one manic episode

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5
Q

Major Depressive Episode (Bipolar II disorder)

A
  • Criteria have been met for at least one hypomanic episode AND at least one major depressive episode
  • NO manic episode
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6
Q

What is the diagnostic criteria of a manic episode?

A
  • Abnormally and persistently elevated, expansive, or irritable mood with increased goal-directed activity/energy lasting at least 1 week and present most of the day, nearly every day
  • Symptoms occur for at least one week
  • Mood disturbances is severe enough to cause impairment in occupational or social functioning
  • 3 or more of the symptoms must occur
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7
Q

What are the presentations of a manic episode?

A
  • Grandiosity
  • Decreased sleep
  • Pressured sleep
  • Racing thoughts
  • Distracted
  • Increased activity or pscyhomotor agitation
  • Involvement in activities with serious consequences
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8
Q

What are the diagnostic criteria of a hypomanic episode?

A
  • Abnormally and persistently elevated, expansive, or irritable mood with increased goal-directed activity/energy lasting at least 4 consecutive days and present most of the day, nearly every day
  • Associated with an unequivocal change in functioning that is uncharacteristic of the individual when not symptomatic
  • The disturbance in mood and the change in functioning are observable by others
  • The episode is NOT severe enough to cause marked impairment in social or occupational functioning or to necessitate hospitalization
  • 3 or more of the symptoms must be present
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9
Q

What are the diagnostic criteria of a depressive episode?

A
  • Five or more of the symptoms during the same 2- week period and represent change from previous functioning
  • At least one symptoms is depressed mood or loss of interest
  • The symptoms cause clinically signified distress or impairment in social, occupational, or other important areas of functioning
  • Major depressive episode is NOT required for a diagnosis of bipolar I disorder
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10
Q

Lithium

A
  • Bipolar disorder, maintenance therapy, suicidality benefit
  • Manic, depressive, mixed episodes
  • First-line as monotherapy and combination therapy for maintenance therapy and acute manic, hypomanic, depressive, and mixed episodes
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11
Q

What are the mechanisms of Lithium?

A

Unknown but current hypothesis:
* Inhibits second messenger systems (inostol, adenylate cyclase, G protein) which dampens neurotransmission
* Enhanced GABA and serotonin transmission
* Increases neurogenesis and neuroprotection

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12
Q

What is the dosing of Lithium?

A
  • Initial: 300-900 mg/day
  • Maintenance: 900-1200 mg/day
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13
Q

What is the onset of effect of Lithium?

A
  • Mania: 7-14 days
  • Depression: 6-8 weeks
  • 300 mg of oral formulations if lithium = 8.12 mEq
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14
Q

How is lithium eliminated?

A

Renally

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15
Q

What is the box warning of lithium?

A

Lithium toxicity

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16
Q

Symptoms of mild toxicity of lithium

A

Hand tremor, GI, fatigue

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17
Q

Symptoms of modertate lithium toxicity

A

Course hand tremor, confusion, slurred speech, unsteady gait

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18
Q

Symptoms of severe lithium toxicity

A

Seizures, stupor, coma, arrhythmia

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19
Q

What are some key points of lithium?

A
  • After steady state (approx. 5 days)
  • Obtain 12-hour levels for monitoring (trough)
  • Linear dose to level response
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20
Q

What are the baseline labs for lithium?

A
  • Renal panel (BUN, SCr, electrolytes)
  • Thyroid function status
  • Pregnancy test (as indicated)
  • ECG for patients > 40 days old or underlying cardiac risk factors
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21
Q

What are some monitoring parameters of lithium?

A
  • Li+ levels 5-7 days after dose adjustments
  • Li+ levels for 1 month
  • Li+ levels every 6 month
  • BUN, SCr, electrolytes every 6-12 months
  • Thyroid function status every 6-12 months
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22
Q

What are some side effects of lithium?

A
  • GI
  • Tremor/fatigue
  • Polyuria/polydipsia
  • Weight gain
  • Dermatologic
  • Leukocytosis
  • Hypothyroidism
  • Diabetes
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23
Q

What are some drugs that increase lithium levels?

A
  • NSAIDs
  • Thiazide diuretics
  • ACEis/ARBs
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24
Q

What are drugs decrease Li levels?

A
  • Theophylline
  • Potassium-sparing diuretics
  • Caffeine
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25
Q

Divalproex

A
  • Bipolar mania, maintenance therapy
  • First line therapy as monotherapy and combination therapy for manic, hypomanic, and mixed episode
  • Preferred agent for mixed episodes
  • May be beneficial in rapid cycling
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26
Q

What is the mechanism of Divalproex?

A
  • Mechanism not understood
  • Enhanced GABA
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27
Q

What is the dosing of Divalproex?

A
  • Can be weight-based or fixed dose
  • Start: 25 mg/kg/day
  • Start: 500-1000 mg HS and increase by 250-500 mg every 1-3 days
  • Target dose: 1500-2000 mg/day
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28
Q

How do you monitor Divalproex?

A
  • Trough levels
  • After steady state (approx. 3-5 days)
    • Once daily ER formulations: 18-24 hours post-dose
    • Twice daily DR formulation: ~12 hours post-dose
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29
Q

What is the therapeutic range of divalproex?

A

50-125 mg/L

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30
Q

What are the levels of divalproex and its effects?

A
  • 75-100 mg/L: Ataxia, sedation, lethargy, fatigue
  • 100-175 mg/L: Tremor
  • > 175: Stupor or coma
31
Q

What are the boxed warnings of divalproex?

A
  • Hepatotoxicity (usually during the 6 months)
  • Fetal risk
  • Pancreatitis
32
Q

What are some contraindications of divalproex?

A
  • Hepatic disease or severe hepatic impairment
  • Urea cycle disorders
33
Q

What are some common side effects of divalproex?

A
  • Nausea/vomiting
  • Weight gain
  • Alopecia
  • Sedation
  • Tremor
  • Fatigue
34
Q

What are some serious side effects of divalproex?

A
  • Hepatic failure
  • Thrombocytopenia (decrease Plt)
  • Pancreatitis
  • Hyperammonemai (increase NH3)–treat w/ levocarnitine
35
Q

What are some baseline labs of divalproex?

A
  • CBC with platelets
  • LFTs (hepatic function)
  • Pregnancy test
36
Q

What are some ongoing labs for divalproex?

A
  • Valproate level 3-5 days after dose adjustments
  • Valproate level every 6-12 months
  • CBC every 6-12 months
  • LFTs every 6-12 months
  • NH3 if symptomatic or suspicion
37
Q

What are some drugs that increase valproate levels?

A
  • Aspirin
  • Warfarin
  • Risperidone
  • Fluoxetine
38
Q

What are some drugs that decrease valproate levels?

A
  • Carbamazepine
  • Carbapenems
  • Rifampin
39
Q

Lamotrigine

A
  • Bipolar depression, maintenance therapy
  • First line as monotherapy and combination therapy for depressive episodes
40
Q

What is the mechanism of Lamotrigine?

A
  • Exact mechanism not well understood
  • Sodium channel blockade, decrease glutamate
41
Q

What happens if patients misses more than 5 days of lamotrigine?

A

Restart titration

42
Q

What are some common side effects of lamotrigine?

A
  • Nausea/vomiting
  • Rash
  • Somnolence/fatigue
43
Q

What are some serious side effects of lamotrigine?

A
  • Stevens-Johnson Syndrome and toxic epidermal necrolysis (TEN)
  • Angioedema
  • Multi-organ failure
44
Q

What is the boxed warning of lamotrigine?

A

Life-threatening rashes (SJS and TEN)

45
Q

What are the baseline labs of lamotrigine?

A
  • BUN, SCr
  • LFTs
46
Q

What are the ongoing labs of lamotrigine?

A
  • BUN, SCr every 6-12 months
  • LFTs every 6-12 months
47
Q

Carbamazepine

A
  • Bipolar disorder, mania, or mixed episodes
  • Second-line as monotherapy and combination therapy for manic, hypomanic, and mixed episodes
48
Q

What is the dosing of carbamazepine?

A
  • Initial: 400 mg/day (divided BID)
    Increase by 200 mg/day q5-7 days
  • Usual dose: 600-1200 mg/day
49
Q

What are the therapeutic levels of carbamazepine?

A

4-12 mg/L

50
Q

What are the carbamazepine’s levels and its effect?

A
  • > 8 mg/L: Nausea, vomiting, headache, dizziness, blurred, vision
  • > 40 mg/dL: Apnea, dystonia, coma
51
Q

What is the boxed warning of carbamazepine?

A
  • Serious dermatologic reactions and HLA-B 1501 allele
  • Aplastic anemia & agranulocytosis
52
Q

What are some contraindications of carbamazepine?

A
  • Bone marrow depression
  • Concurrent MAOI use
  • Concurrent NNRTI
  • Hepatic failure
53
Q

What are the warnings of carbamazepine?

A
  • Avoid if history of hepatic porphyria
  • Increased suicidality
  • Teratogenicity
  • Potential for withdrawal seizure if discontinued abruptly
  • Hyponatremia
54
Q

What are the common side effects of carbamazepine?

A
  • Nauea/vomiting
  • Blurred vision
  • Dizziness
  • Somnelence
55
Q

What are some serious side effects of carbamazepine?

A
  • Stevens-Johnsons Syndrome
  • Toxic Epidermal Necrolysis
  • Anemia
  • Agranulocytosis
  • Hepatic failure
56
Q

What is the baseline monitoring of carbamazepine?

A
  • HLA-B 1502 allele patients of Asian descent (risk of fatal rash)
  • CBC
  • LFTs
  • BUN, SCr, electrolyte
  • Pregnancy test
57
Q

What are the ongoing monitoring labs of carbamazepine?

A
  • Carbamazepine level 5 days after dose adjustments
  • Carbamazepine level every 6-12 months
  • CBC every 6-12 months
  • BUN, SCr, electrolytes every 6-12 months
58
Q

What are drugs that increase of carbamazepine level?

A

Phenobarbital

59
Q

What are the CYP metabolism of carbamazepine?

A

Induces CYP1A2, 2C19, 2C8, 2C9, 3A4, P-gp
-decrease oral hormonal contraceptives, theophylline, warfarin, and itself (auto-inducers)

60
Q

What are some patient counseling of carbamazepine?

A
  • Stopping medication abruptly may lead to adverse effect
  • Adequate trial duration: 2-3 weeks
61
Q

What is the 1st line monotherapy of acute mania?

A
  • Lithium
  • Divalproex
  • Risperidone
  • Quetiapine
  • Aripiprazole
  • Ziprasidone
  • Asenapine
  • Paliperidone
62
Q

What is the 2nd line adjunctive therapy for acute mania?

A

With lithium or divalproex:
* Risperidone
* Quetiapine
* Olanzapine
* Aripiprazole
* Asenapine

63
Q

What is the 2nd line monotherapy of acute mania?

A
  • Carbamazepine
  • ECT
  • Haloperidol
64
Q

What is the 2nd line adjunctive therapy of acute mania?

A

Lithium and divalproex

65
Q

What is the 3rd line monotherapy of acute mania?

A
  • Chlorpromazine
  • Clozapine
  • Oxcarbazepine
  • Tamoxifen
  • Cariprazine
66
Q

What is the 3rd line combination therapy of acute mania?

A
  • Lithium or divalproex and haloperidol
  • Lithium and carbamazepine
  • Adjunctive tamoxifen
67
Q

What monotherapy is not recommended for acute mania?

A
  • Gabapentin
  • Topiramate
  • Lamotrigine
  • Verapamil
  • Tiagabine
68
Q

What are the combination therapy that is not recommended for acute mania?

A
  • Risperidone and carbamazepine
  • Olanzepine and carbamazepine
69
Q

What is the 1st line monotherapy for acute depression?

A
  • Lithium
  • Lamotrigine
  • Quetiapine
70
Q

What is the 1st line combination therapy of acute depression?

A
  • Lithium or divalproex and SSRI
  • Olanzapine and SSRI
  • Lithium and divalproex
  • Lithium or divalproex and bupropion
71
Q

What is the 2nd line monotherapy of acute depression?

A
  • Divalproex
  • Lurasidone
72
Q

What is the 2nd line combination therapy of acute depression?

A
  • Quetiapine and SSRI
  • Adjunctive modafinil
  • Lithium or divalproex and lamotrigine
  • Lithium or divalproex and lurasidone
73
Q

What is the third line monotherapy of acute depression?

A
  • Carbamazepine
  • Olanzepine
  • ECT

Neurology (21 decks)

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