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Neurologic & Psych > EXAM 5 Bipolar disorder Therapy Surbaugh > Flashcards

EXAM 5 Bipolar disorder Therapy Surbaugh Flashcards

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1
Q

When is a patient diagnosed with Bipolar I disorder?

A

after ONE manic episode, not explained by any other disorder

average age onset is 18y

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2
Q

When is a patient diagnosed with Bipolar II disorder?

A

at least ONE hypomanic episode and at least ONE depressive episode

-often mid 20s, and more lifetime episodes
-mixed episodes and rapid cycling (rapid change from manic to depressive episodes)

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3
Q

When is a patient diagnosed with Cyclothymic Disorder?

A

Fluctuation between depressive and hypomanic
episodes for two years (1 year if adolescent)

-they don’t meet the full criteria for manic, hypomanic, or major depressive disorder

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4
Q

What is rapid cycling?

A

4 separate mood episodes in the previous 12 months, full remission for at least 2 months in between

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5
Q

What are catatonic features?

A

if the patient has 3 or more catatonic features during an episode

-staring
-mutism (don’t talk)
-negativism

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6
Q

A patient was diagnosed with bipolar II (at least one HYPOMANIC and one DEPRESSIVE episode). The patient has now experienced a MANIC episode. What is the diagnosis?

A

It switched from Bipolar II to Bipolar I due to having ONE MANIC episode now

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7
Q

What is considered Mania?

A

-period of at least 1 week (if hospitalized it is automatically Mania?)
-their mood is elevated, expansive, irritable, they have more energy

minimum of 3 of those symptoms (if the mood is irritable we need 4)

-Grandiosity or inflated sense of self (self-confidence)
-Decreased need for sleep !!!
-Increased quantity of speech or pressured speech
-Flight of ideas or racing thoughts
-Easily distracted – work, social, school
-Increased goal-directed activity
-Engaging in activities that can be detrimental – spending spree, increased sexual activity

-they are not functioning, may need hospitalization
-not caused by drugs

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8
Q

What is Hypomania, difference to Mania

A

abnormally elevated, expansive, irritable for at least 4 consecutive days

-same symptoms as seen with mania
-not severe, hospitalization is NOT required (not a threat to others or to self, still able to work)

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9
Q

What are conditions that look like bipolar episodes that should be ruled out?

A

-CNS disorders: like stroke
-Infections
-Electrolyte or metabolite abnormalities
-Endocrine or hormonal dysregulation: low thyroid levels

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10
Q

Meds that induce Manic episodes

A

-Alcohol
-drug withdrawal
-Antidepressants - can flip patients into mania !!! which ones ???
-Dopamine or NE augmenting agents (more dopamine)
-Hallucinogens, Cannabis
-Stimulants
-Steroids !!!
-Thyroid preparations?
-Xanthanines
-Non-Rx weight loss agents and decongestants
-herbal products

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11
Q

Pathophysiology of Bipolar disorder

A

not fully understood

-DA, NE, and 5-HT are involved
-GABA deficiency or excess Glutamate (both excitatory effects) can change DA and NE activity

-HPA axis dysregulation: cortisol release - mania, Hypothyroidism is linked to rapid cycling

-sleep can lead to depressive or manic episodes

-second messenger systems

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12
Q

Clinical Presentation - Manic or Hypomania

A

DIGFAST

Distractibility
Irritable
Grandiose (self-esteem)
Fast ideas
Activity is increased
Sleep is decreases
Talkativeness

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13
Q

First-line options for Mania

A

-Lithium
-Valproic acid
-Second-Gen antipsychotics

-might use Benzos short-term if they need sleep, anxious features, agitation (Lorazepam)

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14
Q

A patient was diagnosed with depression and started on an SSRI. At her follow-up visit, she presented with manic symptoms. Which drug change is appropriate?

A

Taper the antidepressant, it can make Bipolar I (ONE manic episode) worse

Antidepressants should not be used as monotherapy for Bipolar disorder

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15
Q

First-line options - Combotherapy

A

Combo therapy is often used
-Lithium + Benz (+AP) - short-term
-VPA + Benz (+AP) - short-term
-SGA + Benz
Alternative: Carbamazepine then Oxcarbamzepine, has to be titrated to therapeutic level though

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16
Q

Second-line options - Combotherapy

A

3 drug combo (she has not seen one started with 3 at once, may be added if 2 don’t work)

Lithium + Antiseizure (depakote) + AP
Antiseizure + Antiseizure + AP

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17
Q

Third line options

A

ECT (electrotherapy) + Clozapine

Clozapine is an effective antipsychotic, but it is a REMS drug and needs lab monitoring and close follow-up

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18
Q

Which drug may be a good choice for acute manic episodes?

A

Second Gen Antipsychotics - they work faster

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19
Q

Hypomania First-Line treatment

A

Monotherapy

-Lithium
-VPA
-SGA
-Carbamazepine

Adjunctive options:
-Benzo: Lorazepam, Clonazepam (for sleep)
-Oxcarbazepine

-may optimize dose before going to second line

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20
Q

Hypomania Second-Line treatment

A

-Lithium + Antiseizure
-Lithium + SGA

-Antiseizure + Antiseizure
-Antiseizure + SGA

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21
Q

Bipolar Depressive episode - First-Line

A

L drugs

Lithium (1st)
Lamotrigine

SGA:
-Lurasidone (1st)
-Lumateperone
-Quetiapine (1st)
-Olanzapine-Fluoxetine

-use antipsychotics if psychotic features are present
-avoid antidepressant monotherapy - add a mood stabilizer, alone it can flip them into mania !!!

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22
Q

MOA Lithium

A

not fully understood
-decreases 5-HT reuptake
-increases 5-HT receptor sensitivity

-inhibits DA synthesis
-decreases DA receptor sensitivity

-enhances GABA activity

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23
Q

Goal concentration for Lithium

A

acute mania: 0.8 - 1.2 mEq/L

for maintenance: 0.6-1.0 mEq/L

if able, use once-daily dosing

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24
Q

Lithium dosing for Bipolar disorder

A

600-900 mg/day

-if they are having a manic episode - closer to 900 if the kidney function is OK

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25
Q

When do patients see the effect of Lithium?

A

for Mania- 6-10 days (not ideal for an acute manic episode)

for Depression: a week

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26
Q

When should Lithium be checked?

A

5 days after starting or changing the dose

-may check earlier if signs of toxicity, increase in creatinine levels, elderly patients

-measure the trough

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27
Q

Which kinetic order does Lithium follow?

A

Linear kinetics

on average 300 mg will raise levels by 0.3 mEq/L

600 mg/daily - we expect levels of 0.6 mEq/L
when increased to 900 mg/d -> 0.9 mEq/L

if they were on 600 mg/d and the level were 0.4 mEq/L and we double the dose to 1200 mg/d we expect the levels to double to 0.8 mEq/L

28
Q

What reduces Lithium clearance and increases the risk for toxicity?

A

-dehydration
-Na depletion
-cardiac or renal dysfunction

Counsel: Keep sodium levels consistent (especially when on a diet), drink enough

29
Q

Side effects of Lithium

A

Dermatologic:
-Acne
-Psoriasis
-Alopecia (could be caused by low thyroid, so check)

CV:
-QT prolongation (rare)

CNS:
-Benign tremor - consider propranolol

GI: worst at peak concentrations (1-2h post-dose)
-N/V/D ,abdominal pain

Urinary:
Polyuria, AKI (acute toxicity) and CKD

Endocrine:
-Hypothyroidism: alter T3 and T4 release
-Hyperparathyroidism: check Ca2+ and PTH if needed
-weight gain

30
Q

At what Lithium levels do we expect severe toxicity?

A

2 - 2.5 mEq/L: moderate to severe
confusion, dysarthria (difficulty speaking), nystagmus (uncontrolled eye movements), hyperreflexia, ataxia

> 3 mEq/L: severe
seizure, coma, myoclonus, hypertonicity, rigidity

31
Q

What interventions are considered at levels above 4 or 2.5 with neurologic symptoms?

A

IV fluids or hemodialysis to clear the drug out of the system

32
Q

Lithium DDI

A

Increases Lithium level:
-NSAIDs (also Aspirin)
-ACEi and ARBs
-Thiazide diuretic, loops

Decrease Lithium level:
-Theophylline
-Caffeine (if they drink coffee they should keep it consistent)

others that increase Lithium levels: antipsychotics, metronidazole, methyldopa,
phenytoin, and non-DHP CCB

33
Q

Which labs should be checked before starting Lithium?

A

-Baseline renal function
-Baseline CBC
-Baseline ECG (due to QTc)
-Pregnancy
-Thyroid level

34
Q

A patient has presented with tremor. Her lithium level was 0.8 two weeks ago. She had N/V/D from a stomach bug. What is your advice?

A

-get a lab and check if it is high
-cut be increased due to diarrhea and vomiting (dehydration)
-recommend hydration, if she cant keep it down -> go to the ER (IV fluid)

35
Q

Role of Valproic acid

A

-Anti-kindling properties
-LEAST effective in acute depression (go with Lamotrigine for bipolar depression)

-MOA: not fully understood
increases GABA concentration, prevents reuptake and breakdown, normalizes Ca2+ and Na+ levels

36
Q

VPA Goal concentration

A

Goal concentration: 50-125 mcg/ml

need to be at the upper end to treat manic symptoms (especially in the acute phase)

37
Q

When do patients see the effect of VPA?

A

after 3 days with a loading dose

faster than Lithium (6-10 days)

38
Q

BBW of VPA

A

-hepatic failure and pancreatitis

CONTRAINDICATED in:
-hepatic dysfunction
-Pregnancy

39
Q

Valproic Acid DDI

A

-Lamotrigine: VPA increases Lamotrigine: titrate VPA slower !!!

-Carbapenem: reduce VPA levlels
-Phenytoin
-Ritonavir: increases clearance of VPA
-Warfarin: increased risk for bleeding

40
Q

ADE for VPA

A

-Rash: SJS, TEN, DRESS !!!
-Alopecia

-Weight gain
-Hyperammonemia
-Thrombocytopenia !!!
-GI: N/V/D, constipation
-Neurological: Ataxia, diplopia, dizziness, sedation, tremor
-Pancreatitis!!!
-Hepatoxic !!! -> BBW

41
Q

Which labs to monitor for VPA

A

-CBC
-LFT
-Renal function
-Pregnancy test

-Ammonia levels: if concern for hyperammonemia
-check weight

get VPA levels after 3-5 days or a dose change

42
Q

Which drug may be used in acute mania?

A

Carbamazepine
also for mixed epsiodes biopolar I disorder

43
Q

What is the Goal concentration for Carbamaezpeine?

A

4-12 mcg/L

-monitoring not needed

44
Q

Carbamazepine dosing

A

100-400 mg/d
often divided: 200 mg BID
max dose: 1600 mg/d

titrate slowly

45
Q

How long does it take to see the effect?

A

7 days in mania

46
Q

When to check Carbamazepine levels?

A

after 4 weeks -> assess for dose adjustments

47
Q

What is the BBW for Caramazepine?

A

-SJS, TEN (increased risk with HLA-B*1502)
-aplastic anemia and agranulyctosis

48
Q

What are the signs of toxicity(side effects with Carbamazepine?

A

-Hyponatremia (SIADH)
-GI- N/V, constipation, dry mouth
-Neurological: Ataxia, dizziness

49
Q

At what levels do we see the toxicity of Carbamazepine?

A

greater than 12 mcg/ml

ataxia and nystagmus (uncontrolled eye movements)

-greater than 40 mcg/ml -> seizure, coma

50
Q

Carbamazepine DDIs

A

CYP 3A4, 2D6, 2C9 inducer
-autoinducer
-makes oral contraceptives less effective

-Cimetidine, fluoxetine, ketoconazole, nefadozone inhbitis its metabolism -> increase levels

-don’t give Carbamazepine and Clozapine together (risk for agranulocytosis)

51
Q

Role of Lamotrigine

A

-Maintenance of bipolar I (not acute mania!!!)
-acute bipolar depression

-has anti-kindling properties, decreases rapid cycling and mixed episodes

52
Q

How is Lamotrigine dosed?

A

-must TITRATE due to risk for RASH

any break of more than 3-5 days requires retritration

first 2 weeks: 25 mg/d
next 2 weeks: 50 mg/d
Week 5: 100 mg/d
Week 6: 200 mg/d

with VPA, start lower (since it increases Lamotrigine) from 12.5 to 100 mg/d
with CYP inducer (decreases levels): start higher
from 50 to 300 mg/d

53
Q

BBW for Lamotrigine

A

SJS/TEN
higher risk if not titrated correctly or at a younger age (<13y)

54
Q

ADE for Lamotrigine

A

-agranulocytosis, aplastic anemia, neutropenia, pancytopenia,

-N/V/D

-ataxia, dizziness, sedation, aseptic meningitis

55
Q

Role of SGA

A

-Acute mania or adjunctive acute mania (SGAs work faster)
-Maintenance therapy
-some can be used in bipolar depression

MOA: dopamine and 5-HT blocking

56
Q

Which SGAs are approved for bipolar depression?

A

-Cariprazine
-Lumateperone
-Lurasidone
-Quietiapine

57
Q

What is the BBW for SGAs?

A

increased mortality in elderly patients with dementia-related symptoms

58
Q

ADE of SGA

A

higher risk for metabolic dysfunction:
-Hyperlipidemia
-diabetes
-weight gain

there are specific ADEs for the specific SGA

First-gens:
EPS side effects

59
Q

Which labs should be checked for SGA?

A

Baseline:
-BMI
-waist circumference
-BP
-fasting Glucose (A1c)
-fasting lipid profile

Annually:
-BMI
-waist circumference
-BP
-fasting glucose

60
Q

What are treatment options for acute mania in pregnant women?

A

-Antipsychotics (SGA) - quick onset and low risk for teratogenicity
-divide doses of mood stabilizers (once-daily dosing can lead to spikes in pregnancy)
-get levels regularly since the body metabolism of pregnant is different
-ECT

-avoid benzos if possible (withdrawal of the baby)

61
Q

Which drugs should be avoided during pregnancy?

A

-Lithium during the first trimester: Esptein’s anomaly and Floppy baby syndrome

-VPA (if not able to avoid, supplement with folate 4 mg)
-> fetal VPA syndrome, cognitive dysfunction, neural tube defects

-Carbamazepine (consider folate 4 mg supplement if not able to avoid)
->spina bifida, developmental delays, and low IQ

-Lamotrigine is favorable !!!

62
Q

Which antipsychotics are safe for breastfeeding?

A

-VPA
-Carbamazepine

Contraindicated:
-Lithium (monitor for hyperthermia if used)
-Lamotrigine (risk for SJS)

63
Q

Which mood stabilizers are cleared through the kidneys?

A

-Lithium
-Valproic acid

64
Q

Which drug used for bipolar disorder is hepatoxic?

A

VPA

65
Q

Which drugs are approved for children with bipolar disorder?

A

-Lithium XR and IR for >7 years
-SGA including aripiprazole, risperidone, lurasidone >10 y and many more
-antidepressant with a mood stabilizer (lithium, VPA, carbamazepine)

-Lamotrigine is not FDA approved but it is often used due to minimal weight gain

66
Q

Drugs for acute mania

A

-Lithium
-VPA (least effective in depression)
-Carbamazepine

67
Q

Lamotrigine is effective for…

A

depression and maintenance therapy
-not effective for acute mania

Neurologic & Psych (37 decks)

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