Bipolar Disorder: Mood Stabilizers and treatment choices Flashcards
Mood stabilizers used in bipolar disorder
Lithium
Anticonvulsants
-VPA (Valproic acid, valproate, divalproex)
-Carbamazepine (tegretol)
-Lamotrigine (lamictal)
Atypical Antipsychotics
Lithium
MOA: not fully known
effective in manic epi and in maintenance of recurrence
monotherapy or in combo
reduce suicide
Lithium dosing
600-900mg/day
2-3 divided doses
inc 300-600mg every 1-5 days based on response/tolerability
Lithium therapeutic index
Acute tx: 0.8-1.2
Maint tx: 0.6-1
Draw trough 12 hrs post dose
Lithium AE Acute
GI
sedation
fine tremor
polyurea
polydipsia
take with food to help
Lithium AE chronic
weight gain
hair loss
acne
tremor
sedation
decreased cognition
incoordination
hypothyroid (6-18 mo after start)
Lithium monitor
thyroid
renal
plasma calcium
plasma lithium
urinalysis
CBC
weight
Mild lithium toxicity
> 1.5
nausea
diarrhea
blurred vision
marked tremor
vertigo
confusion
Moderate lithium toxicity
> 2.5
severe neuro complications
seizures
coma
cardia dysrhythmia
permanent neuro impairment
Severe lithium toxicity
> 3.5
potentially lethal
lithium toxicity risk inc
high dose
dehydration
renal impairment
drug interactions
lithium toxicity tx
hold dose, IV normal saline, supportive care
if severe: hemodialysis, lavage if not absorbed
Lithium Pharmacokinetics
clearance, elimination, half life, steady state
clearance dec:
NSAID
ACEI
diuretic
clearance inc:
methylxanthines: caffeine, theophylline
Elimination: 100% renal
Half life 18-36 hrs
Steady state: 3-5 days
Valproic acid
MOA: not well known
- prob inhibit VSSC, boost GABA
used for acute mania and mixed states and maintenance
monotherapy or combo
more efficacious than lithium for rapid cycling
Valproic acid dosing
500-750mg/day
inc 250-500mg every 1-3 days
weight based loading dose for rapid control
therapeutic level for mania 50-125 mcg/ml
VPA black box
Liver and pancreatic effects
avoid CrCl <30
fetal toxicities
VPA side effects
hair loss
wt gain
sedation
GI
dizzy
Thrombocytopenia (dose dependent)
VPA side effects women
menstrual disturbances
PCOS
hyperandrogenism
VPA monitoring
CBC
LFT
pregnancy
ammonia (if sx for hyperammonemia)
VPA pharmacokinetics
bound, metabolism, half life, peak
protein bound (80-90%)
predominantly hepatic metabolism
half life 9-19 hrs
time to peak: 4 hrs
ER: 4-17
DR: 2
Carbamazepine
MOA: inhibit VSSC, enhanced GABA
Tx acute mania and maintenance
Carbamazepine dosing
initial: 100-400 mg/day
inc 200mg/day every 1-4 days
usual dose: 600-1200mg/day
Max 1600mg/day
Carbamazepine side effects
Common, serious, black box
Common:
GI, rash, sedation, anticholinergic, dizzy, transient LFT inc
Serious:
diplopia, hyponatremia, birth defects
Black box:
SJS
aplastic anemia
agranulocytosis
Carbamazepine monitoring
baseline and periodic:
CBC
Fe
liver
renal
urinalysis
sodium
ophthalmic exam including intraocular pressure
rash
suicidal ideation
consider asian: HLA for SJS
Carbamazepine pharmacokinetics
binding, interaction, half life
Protein binding 75-90%
CYP450
- Inducer of 3A4, 1A2, 2C19
-metabolized via 3A4
Autoinduction—>shorter half life over time (3-5 wks)
half life
25-65 hrs—>12-17 hrs
Lamotrigine
MOA: block VSSC, reduce glutamate
bipolar depression and maintenance
preferred in bipolar depression
mono or combo
Lamotrigine dosing
titrate slowly to minimize rash
dosing depends on concomitant rx
Lamotrigine side effects
sx and black box
Sedation
headache
dizzy
ataxia
nausea
black box
Skin: usually non serious and self limiting
but: Can be SJS/TEN
titrate slowly
Lamotrigine risk factors for serious AE
rapid titration
higher initial dosing
younger age
history of rash
Lamotrigine pharmacokinetics
absorption, bioavailability, binding, half life, metabolism
Absorption: ~97.6%, rapid and complete
Bioavailability: 98%
Protein binding: ~55%
Half-life: 25-33 hours (may change depending on concomitant therapy)
Metabolism: hepatic and renal
○ >75% via glucuronidation
Lamotrigine drug interactions
○ Valproic acid inhibits metabolism and can double serum lamotrigine levels
○ Carbamazepine and phenytoin can induce metabolism and decrease lamotrigine levels
○ Estrogen derivatives (including hormonal contraceptives) induce lamotrigine metabolism
Atypical Antipsychotics possible MOA
5HT2A receptor antagonism
D2 antagonism
5HT1A partial agonism
D2 partial agonism
Atypical Antipsychotics addition of 5HT2A receptor antagonism vs 1st gen
dec EPS and hyperprolactinemia
Atypical Antipsychotics D2 partial agonism
balance between silent antagonism and full stimulation
Atypical Antipsychotics for bipolar depression
FDA indicated for bipolar depression
Quetiapine
300mg/day
Lurasidone (latuda)
20-120mg/day
Olanzapine-fluoxetine (Symbyax)
6/25-12/50mg/day
Atypical Antipsychotics for bipolar mania/mixed
Most are approved/FDA indicated
Quetiapine
risperidone
olanzapine
ziprasidone
aripiprazole
asenapine
Atypical Antipsychotics side effects
weight gain
GI sx
renal toxicity
hematological effects
Overall tx AE: wt gain
many
olanzapine
clozapine
risperidone
quetiapine
divalproex
lithium
asenapine (long term)
aripiprazole (long term)
Overall tx AE: Gi symptoms
Lithium
Divalproex
Overall tx AE: Renal toxicity
Lithium
Overall tx AE: hematological effects
Carbamazepine (leukopenia)
Clozapine (Agranulocytosis)
- REMS program to monitor
Overall tx AE: cardiovascular effects
Lithium (QT)
Antipsychotics (arrhythmia, QT)
- risperidone
-olanzapine
-ziprasidone
-asenapine
clozapine
Overall tx AE: endocrine
Lithium (thyroid, parathyroid)
divalproex (PCOS, menorrhea, hyperandrogen)
antipsychotics (hyperprolactinemia)
-risperidone
-amisulpride
-paliperidone
Overall tx AE: cognition
antipsychotics
lithium
anticonvulsants
- except lamotrigine
Overall tx AE: sedation
divalproex
atypical antipsychotics
- quetiapine
-clozapine
-olanzapine
Overall tx AE: neurological effects/EPS
lithium (tremor)
divalproex (tremor)
Antipsychotics (EPS)
-1st gen>2nd gen
- poss in higher dose 2nd gen
—-especially risperidone, aripiprazole, cariprazine, ziprasidone, lurasidone
atypical antipsychotics
- NMS
Overall tx AE: derm
lamotrigine
carbamazepine
divalproex
lithium (many)
Overall tx AE: metabolic syndrome
most
-clozapine and olanzapine
next
-high dose quetiapine
-risperidone
next
-aripiprazole
-ziprasidone
- asenapine
-lurasidone
CANMAT acute mgmt of mania
1st line
-Monotherapy: lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, cariprazine
- Combo: lithium or divalproex AND quetiapine or aripiprazole, or risperidone or asenapine
2nd line
- olanzapine, carbamazepine, ziprasidone, haloperidol, olanzapine + lithium/divalproex, lithium +divalproex, ECT
3rd line
- mult rx
CANMAT acute mgmt of Bipolar 1 Depression
1st line
- quetiapine, lurasidone +lithium/divalproex
- lithium, lamotrigine, lurasidone, lamotrigine adjunctive
2nd line
- SSRI/buproprion adjunctive, cariprazine
- divalproex, symbyax, ECT
CANMAT acute mgmt of Bipolar 2 depression
1st line:
-quetiapine
2nd line
- multiple rx
3rd line
- multiple rx
CANMAT maintenance therapy
1st line
- lithium, quetiapine, divalproex, lamotrigine, quetiapine + lithium/divalproex
- asenapine, aripiprazole, aripiprazole + lithium/divalproex, aripiprazole once monthly
2nd line
- olanzapine, risperidone long acting injectible
-mult others
3rd line
- mult rx
Not recc
- perphenazine, tricyclics
