EXAM 5 Bipolar disorder Therapy Surbaugh

Question 1

When is a patient diagnosed with Bipolar I disorder?

Answer 1

after ONE manic episode, not explained by any other disorder

average age onset is 18y

Question 2

When is a patient diagnosed with Bipolar II disorder?

Answer 2

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)

Question 3

When is a patient diagnosed with Cyclothymic Disorder?

Answer 3

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

Question 4

What is rapid cycling?

Answer 4

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

Question 5

What are catatonic features?

Answer 5

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

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

Question 6

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?

Answer 6

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

Question 7

What is considered Mania?

Answer 7

-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

Question 8

What is Hypomania, difference to Mania

Answer 8

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)

Question 9

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

Answer 9

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

Question 10

Meds that induce Manic episodes

Answer 10

-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

Question 11

Pathophysiology of Bipolar disorder

Answer 11

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

Question 12

Clinical Presentation - Manic or Hypomania

Answer 12

DIGFAST

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

Question 13

First-line options for Mania

Answer 13

-Lithium
-Valproic acid
-Second-Gen antipsychotics

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

Question 14

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?

Answer 14

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

Antidepressants should not be used as monotherapy for Bipolar disorder

Question 15

First-line options - Combotherapy

Answer 15

Chemotherapy 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

Question 16

Second-line options - Combotherapy

Answer 16

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

Question 17

Third line options

Answer 17

ECT (electrotherapy) + Clozapine

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

Question 18

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

Answer 18

Second Gen Antipsychotics - they work faster

Question 19

Hypomania First-Line treatment

Answer 19

Monotherapy

-Lithium
-VPA
-SGA
-Carbamazepine

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

-may optimize dose before going to second line

Question 20

Hypomania Second-Line treatment

Answer 20

-Lithium + Antiseizure
-Lithium + SGA

-Antiseizure + Antiseizure
-Antiseizure + SGA

Question 21

Bipolar Depressive episode - First-Line

Answer 21

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 !!!

Question 22

MOA Lithium

Answer 22

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

-inhibits DA synthesis
-decreases DA receptor sensitivity

-enhances GABA activity

Question 23

Goal concentration for Lithium

Answer 23

acute mania: 0.8 - 1.2 mEq/L

for maintenance: 0.6-1.0 mEq/L

if able, use once-daily dosing

Question 24

Lithium dosing for Bipolar disorder

Answer 24

600-900 mg/day

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

Question 25

When do patients see the effect of Lithium?

Answer 25

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

for Depression: a week

Question 26

When should Lithium be checked?

Answer 26

5 days after starting or changing the dose

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

-measure the trough

Question 27

Which kinetic order does Lithium follow?

Answer 27

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

Question 28

What reduces Lithium clearance and increases the risk for toxicity?

Answer 28

-dehydration
-Na depletion
-cardiac or renal dysfunction

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

Question 29

Side effects of Lithium

Answer 29

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

Question 30

At what Lithium levels do we expect severe toxicity?

Answer 30

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

Question 31

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

Answer 31

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

Question 32

Lithium DDI

Answer 32

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: antipsychotics, metronidazole, methyldopa,
phenytoin, and non-DHP CCB

Question 33

Which labs should be checked before starting Lithium?

Answer 33

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

Question 34

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?

Answer 34

-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)

Question 35

Role of Valproic acid

Answer 35

-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

Question 36

VPA Goal concentration

Answer 36

Goal concentration: 50-125 mcg/ml

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

Question 37

When do patients see the effect of VPA?

Answer 37

after 3 days with a loading dose

faster than Lithium (6-10 days)

Question 38

BBW of VPA

Answer 38

-hepatic failure and pancreatitis

CONTRAINDICATED in:
-hepatic dysfunction
-Pregnancy

Question 39

Valproic Acid DDI

Answer 39

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

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

Question 40

ADE for VPA

Answer 40

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

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

Question 41

Which labs to monitor

Answer 41

-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

Question 42

Which drug may be used in acute mania?

Answer 42

Carbamazepine
also for mixed epsiodes biopolar I disorder

Question 43

What is the Goal concentration for Carbamaezpeine?

Answer 43

4-12 mcg/L

-monitoring not needed

Question 44

Carbamazepine dosing

Answer 44

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

titrate slowly

Question 45

How long does it take to see the effect?

Answer 45

7 days in mania

Question 46

When to check Carbamazepine levels?

Answer 46

after 4 weeks -> assess for dose adjustments

Question 47

What is the BBW for Caramazepine?

Answer 47

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

Question 48

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

Answer 48

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

Question 49

At what levels do we see the toxicity of Carbamazepine?

Answer 49

greater than 12 mcg/ml

ataxia and nystagmus (uncontrolled eye movements)

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

Question 50

Carbamazepine DDIs

Answer 50

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)

Question 51

Role of Lamotrigine

Answer 51

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