Bipolar Tx (acute)

what are some goals of therapy

• relieve acute symptoms

• prevent suicide

• maintain good function

• med adherence

• max efficacy with minimal side effects

• improve QOL

main pharm therapies (classes)

1. lithium

2. anticonvulsants

3. antipsychotics

non-pharm therapies

• improve sleep

• psychotherapy

• ECT

• bright light therapy

• exercise, stress reduction

• rTMS

what do mood stabilizers focus on treating 

• treat both mania and reduce depressive symptoms

MOA of lithium

enhances neuronal proliferation and plasticity of several neurotransmitters

FDA indications of lithium

acute mania, bipolar maintenance, acute BP depression

true or false: lithium is metabolized

false

what is a key lab to look at when on lithium

RFT

what is the target lithium concentration

0.6-1.5 mEq/L

what is the dosing for acute mania

0.8-1.2 mEq/Lw

what is dosing of lithium for maintenance

0.6-1.0 mEq/L

dosing for acute mania is slightly (higher/lower) than the dose for maintenance 

higher 

how long does it take lithium to start working

~10-14 days or about a month for full, optimal results

contraindications to lithium

• unstable or severe cardiac or renal disease

• severe dehydration 

• severe sodium depletion 

• lithium toxicity (BBW) 

true or false: lithium has a narrow therapeutic index

true

risk factors for lithium toxicity

• >50 years

• renal insufficiency

• dehydration, NVD

• sodium restriction/loss

acute ADR of lithium

• GI upset

• fine hand tremor

chronic ADR of lithium

• dermatologic

  • acne/psoriasis activation

• CV

  • ECG changes

  • >50 y.o with prior cardiac disease

• weight gain

• hypothyroidism 

• polyuria/polydipsia

• leukocytosis (usually reversible)

during the ____ trimester, the teratogenic effects are the highest risk 

1st

what trimester can the baby have cardiac malformations such as ebstein’s anomaly

1st trimester

what might a baby have with lithium exposure during 2nd/3rd trimester

• floppy baby syndrome

• neonatal toxicity

• hypothyroidism

lithium monitoring 

• ECG

• TSH

• Serum e-

• RFT

• CBC w/ differential 

• pregnancy 

what drugs increase lithium concentrations

• NSAIDs

• ACEi/ARBs

• Thiazide

what decreases lithium concentrations

theophylline or caffeine

when sodium levels are down, lithium is ____ and when sodium levels are up, lithium levels are ____

up, down

counseling with lithium

• take with food

• 1-2 weeks onset of action

• maintain adequate level of hydration

MOA of valproic acid

regulates GABA synthesis, release, and uptake; normalizes sodium and calcium channels

FDA indications of valproic acid

acute mania or mixed episodes

• maintenance therapy

what is the loading dose of IR valproic acid

20 mg/kg/day

what is the loading dose of ER valproic acid

25 mg/kg/day

target serum levels of valproic acid

50-125 mcg/mL

max dose of valproic acid

60 mg/kg/day

loading dose of valproic acid provides faster symptom control but more _____ side effects

GI

what are the BBW of valproic acid

• hepatic failure

• pancreatitis

• tertogenic effects

contraindication for valproic acid

hepatic disease

what is a big teratogenic effect of valproic acid

spina bifida

ADR of valproic acid

GI upset

mild hand tremor

thrombocytopenia

sedation

increased LFTs

alopecia

weight gain

hyperammonemia 

monitoring for valproic acid 

• drug level

• CBC w/ differential 

• LFTs

• pregnancy 

• ammonia

drug interactions with valproic acid

• lamotrigine

• phenytoin

• warfarin

if VPA must be used, supplement with ____ and keep VPA level ______mcg/mg

folate 4mg/day , 70

VPA is DOC for

rapid cyclers

FDA indication of carbamazepine

acute mania or mixed episodes

generally reserved for tx resistant cases that have failed Li and VPA

carbamazepine is an 

auto-inducer

BBW of carbamazepine

serious dermatologic rxns and HLA-B *1502 allele

aplastic anemia and agranulocytosis

contraindication for carbamazepine

bone marrow suppression

ADR of carbamazepine

• GI upset

• hyponatremia

• ataxia

• dizziness

• drowsiness

therapeutic range of carbamazepine for bipolar/ seizure

4-12 mcg/mL

when serum levels of carbamazepine are >12 mcg/mL, what do you see

nystagmus, ataxia

when serum levels of carbamazepine are >15 mcg/mL, what do you see

diplopia, cardiac conduction changes, anti-cholinergic effects

when serum levels of carbamazepine are >40 mcg/mL, what do you see

seizures, coma

monitoring for carbamazepine

• serum drug level

• CBC w/ differential

• renal function

• serum e- 

• LFTs

• pregnancy

• HLA-B*1502 

Drug interactions with carbamzpeine

• clozapine

• hormonal contraceptives

• warfarin/DOACs

• lurasidone

• CYP3A4 inhibitors/ inducers

• CYP 3A4 and 1A2 substrates

time of efficacy with carbamazepine

7 days

grapefruit juice can increase levels with this medication

carbamazepine