Epilepsy

should no mental retard eff on child

but need to rule out meningitis

PHAR 3412 / 3414

Lee Chui Ping, Pharm.D., BCPS, BCPP
School of Pharmacy
Faculty of Medicine, CUHK

Objectives

one drug fail--> use another mechanism

Be familiar with definition and etiology of

seizure disorders
Understand the general clinical presentation
of seizure disorders
Discuss the use of phenytoin, valproate,
carbamazepine and the newer agents in
epilepsy




Side effects
Drug interactions
Monitoring
2

References

Nadkarni S, LaJoie J, Devinsky O. Current treatments of

epilepsy. Neurology. 2005 Jun 28;64(12 Suppl 3):S2-11.
Ziemba KS, O'Carroll CB, Drazkowski JF, et al. Do
antiepileptic drugs increase the risk of suicidality in adult
patients with epilepsy?: a critically appraised topic.
Neurologist. 2010 Sep;16(5):325-8.
Brodie MJ and Kwan P. Staged approach to epilepsy
management. Neurology 2002;58 (Suppl 5):S2-8

Outline

Definitions & Etiology

Diagnosis & Classification
Treatment





Endpoints
Available agents & indications
Individual agents
Important treatment issues

Status Epilepticus
4

Definition

seizure vs epilepsy

Seizure (Epileptic seizure)



Sx
clinical menifestation

Clinical manifestation from an abnormal and

excessive discharge of a set of neurons in the
brain. many dz condition can trigger it
Consists of sudden and transitory abnormal
phenomena that may include alterations of

Consciousness a lot , loss

Motor shut or chronic contraction
Sensory ahllucination, voices
Autonomic, or psychic events perceived by the patient or
observer.

Definition

Epilepsy


Disorder of brain characterized by

Eg. Multiple epileptic seizures due to multiple different causes in

the same patient would not be considered to be epilepsy. get Tx or not ?

The neurobiologic, cognitive, psychological and social diff

consequence of this condition (Fisher, 2005)
consideration

Some other authorities require the presence of at least

2 unprovoked seizure attacks to be considered
epilepsy
at least 2 seizure to called epilepsy (not valid now, old def)

Convulsion


persistent , generate seizure

an enduring predisposition to generate epileptic seizures, and



disease

"FIT"

Intense muscular movement associated with a

muscular Sx ass seizure
seizure
6

Etiology of seizures: (age dependent)

Perinatal: brain injury, infection, and congenital

anomaly
Infancy and childhood: febrile, idiopathic, infection,
trauma, and congenital malformation kid fever brain damage
Adolescence: idiopathic, trauma
Young adults: trauma, drugs, metabolic, neoplasm,
idiopathic
Middle age: neoplasm, drugs (alcohol), trauma,
vascular disease
Elderly: vascular disease, neoplasm, and trauma
get older --> vascular related
7

Outline

Definitions & Etiology

Diagnosis & Classification
Treatment





Endpoints
Available agents & indications
Individual agents
Important treatment issues

Status Epilepticus
8

History taking: Onset, duration & characteristics of a seizure

feel diff prior attack ?

how long ?
--> need those description
Diagnosis / may need witness as pt X consious

Physical exam &

other
investigations to
identify underlying
cause
alcohol

Classification
of seizure
type

First attack:
stimulant ? Treat or not?
Laboratory/
Consider EEG
Electroencephalog
evidence &
ram (EEG) / CT/
individual
MRI
factors

description
medical Hx
EEG

Recurrent:
Drug treatment

nowadays, even 1st attack may be treated

if hi chance recurent
(look at pt factor, EEG )
--> classify

need general idea

Classification
Generalized Seizures

both side of brain

TONIC-CLONIC SEIZURES (GRAND MAL

seizures)


Brief or no aura, EEG diffusely abnormal. Begin

with loss of consciousness.
Tonic (sTiff) muscle spasms followed by a period of
bilateral, repetitive clonic (twitChing) movements.
After the clonic phase, patient becomes conscious
but remain lethargic and may be confused. after regain
Tongue biting and other potential injuries, cyanosis,
or altered respiratory pattern, bladder and bowel
incontinence may occur
purple face ?
incontinence --> embarrasing

calm
side lay
10
remove danger
observe record Sx

Generalized Seizures

diff to spot, thought as loss of attention

less vigorous in presentation

ABSENCE


no facial expression, loss of attention

Staring spells fine motor movements;

associated with characteristic 3/sec spike and
wave activity on EEG
No aura, very short (<15 sec) duration; no postictal confusion or somnolence.
Part of several epilepsy syndromes and mixed
seizure disorders

11

Generalized Seizures

MYOCLONIC


Rhythmic quick jerking of extremities, part of

juvenile myoclonic epilepsy syndrome

ATONIC


sudden loss of muscle tone --> drop

drop attacks, often happens in younger children

with neurologic damage

12

Classification
Partial Seizures

SIMPLE PARTIAL


Motor movements without impaired

consciousness

Various motor, sensory, or psychic manifestations may

occur

Localized in a single cerebral hemisphere or

position of a hemisphere
limited Sx

13

usually read the chart

just say partial ,, as similar Tx

Classification
Partial Seizures (cont.)

COMPLEX PARTIAL


bigger area in one side of brain --> impaired

consiousness

Starring and/or motor movements with impaired

consciousness
fast flash back
Usually preceded by an aura (subjective symptoms
including unpleasant taste, auditory hallucination, etc.)
Result from spread of focal discharges to involve a larger
area.
Inappropriate behavior (automatism) such as lip smacking,
picking at clothing, or aimless wandering.
A period of brief postictal lethargy or confusion is common

like day dreaming

doing repeated mild movement involuntary
tremor

14

Classification
one side, spread to both side
Tx as partial as started as partial

PARTIAL SEIZURES WITH SECONDARY

GENERALIZATION


Begin focally and then spread to involve both

brain hemispheres
Once generalized, seizure presents no different
than primary generalized tonic-clonic seizures

Treatment would be the same as partial seizures

15

Outline

Definitions & Etiology

Diagnosis & Classification
Treatment





Endpoints
Available agents & indications
Individual agents
Important treatment issues

Status Epilepticus
16

Treatment

predisposing factor?

Non-pharmacological


Avoidance of potential seizure precipitants (stress,

sleep deprivation, or ingestion of excessive
caffeine or alcohol)
Patients should be advised to avoid any activities
that seem to precipitate seizures
Kid
Ketogenic Diet (low carbohydrate, low protein, more than
adult
high fat diet) no rice, focus calories in high fat diff to tolerate

butter, heavy whipping cream, mayonnaise, and oils

Vagus nerve stimulation (for treatment of

intractable partial seizures.)
17

Pharmacologic therapy (AED)

General considerations

60-70 % tx by first drug

~ 60% of patients are successfully treated

with the first or second AED


Responding to first AED is the best predictor of

--> long term prognosis
long-term prognosis

Response to AED



Seizure frequency 5/mo --> 2/mo = improve, but not at goal (0)
Presence & severity of dose-related toxicity

Optimal use of AED is essential to quality patient

care

need to consider pt preference : combination ? tolerate SE ?

if OK with 2attack / mo --> then leave it
balance seizure freq and SE
18

no driving license if seizure

Hx unless safe long time with doctor allow

1st --> 2nd --> 3rd

try to stick on one drug

Pharmacologic therapy (AED)

15 drugs can use
General considerations ~consider
: type ,past med Hx, SE , DDI

trial and error

Initial adverse effects


esp initial SE at first

Sedation, dizziness, ataxia, headache and

nausea are common during initial treatment with
AED. SE--> on/ off drug himself --> not compliant --> high risk
The effects can be managed by reducing the dose
by 25 to 50% and wait for 2 weeks for tolerance to
tolerate SE then resume titration up
develop

Then can resume gradual titration

19

Therapeutic endpoints

Choice of drugs





Type of seizure
Side effect profile
Drug interactions
Previous drug experience

trial, X re try if fail

Titration of doses to achieve seizure control

is mainstay of therapy

20

AED Regulatory Status in Hong Kong

commonly use

Add-on +
Monotherapy

Established

New

Phenobarbital
Phenytoin
Carbamazepine 1st line
Valproate
Lamotrigine

Gabapentin
Oxcarbazepine
Topiramate
Levetiracetam
Pregabalin
Lacosamide (Vimpat)
Retigabine (Trobalt)

Add-on only

Clobazam
Clonazepam
Vigabatrin
Tiagabine*
Zonisamide*

can add on benzo

same SE in the use of bipolar

* not available in Hong Kong

CBZ 1st line

Treatment options
Partial

GTC

Absence

Atonic/
myoclonic

Carbamazepine

Clobazam

3 (m)

Clonazepam

1-2

4 (m)

Lorazepam

Ethosuximide
Gabapentin

unique
2

Pregabalin

Lacosamide

Lamotrigine

Levetiracetam

3 (m)

Oxcarbazepine

Phenytoin

3 (m)

1 only

4 (m)

LennoxGastaut
syndrome

1 typo
XX

Retigabine

Valproate acid

Topiramate

Status
Epilepticus

Diazepam

Infantile
Spasms

1
3
1
1

1- 1st line
2- 2nd line
3- some effect
4- adjunctive

22

X test MOA in Tx part, but pharmacology

neurologist know it, choose drugs based on MOA

fail Na blocking
use Ca blocking

Lason W et al.
Pharmacological Reports
2011; 63:271-92
23

gene test
SIADH
neutropenia

Carbamazepine
inducer
Dosage and Administration

May be considered a drug of choice for

partial seizure
Initiate gradually to avoid side effects


100mg twice a day, increase by 100-200mg every

1-2 weeks

Blood levels


Trough: 21 50 mmol/L (5-12 mcg/ml)

*Valproate increases concentration CBZ 10-11
epoxide (active metabolite)
may normal level of CBZ but CBZ toxicity with VPA
VPA inhibit microsomal epoxide hydrolase

24

Case Study 1

IDENTIFYING the CAUSE

A 54 year old male (hostel resident) is

admitted to the hospital for stroke
PMH:


Hypertension

Depression

Adalat retard
Sertraline 100mg PO QD

Generalized tonic clonic seizure

Carbamazepine 200mg PO BD

25

Case Study 1

During hospitalization, he developed high

fever and pneumonia
Resistant strain of S. pneumo


Antibiotic was to be prescribed

Next day, patient developed significant

muscle twitching, profuse sweating, spiking
fever, and tremor
What is this patient experiencing?

diff to identify actual cause

relapse?
infection ?
problem angle ; what could be the cause
antibiotic ?

26

Case Study 1

Linezolid is a reversible MAO-I serious infection

Use with TCAs, SSRIs, carbamazepine and
any serotonergic agents may induce
serotonergic syndrome danger
D/C sertraline immediately; as no argent need
D/C carbamazepine immediately? Yes,

Should not abruptly D/C AED --> seizure

use other drug to cover the

seizure risk (benzo, VPA,
penytoin)

CBZ structure similar t o TCA

also CI with MAOI
27

Oxcarbazepine (Trileptal)
better tolerated, less DDI
still SIADH

Chemically and structurally similar to

carbamazepine; similar mechanism of action
Monotherapy or adjunctive therapy in
treatment of partial seizures in adults
Inhibits CYP 2C19 & induces 3A4


May ______________________________________________
reduce the potency of oral contraceptives

Major side effects



Cognitive symptoms: psychomotor slowing,

difficult concentration
Hyponatremia
28

Phenytoin

Widely studied AED and one of the oldest

Pharmacokinetics








Dose-dependent (Michaelis-Menten or capacitylimited) pharmacokinetics

Clinically effective range: 40 - 80 mol/L
Remember: Levels may not always reflect side
effects or efficacy! just idea for further increase
if great control / SE, X increase even space
Enzyme inducer
Causes mild elevation in LFT (esp. alkaline
phosphatase, GGT)
if AP increase is mild, monitor only
29

dun care which CYP CBZ and phenytoin induce,

considered as induce all

Phenytoin
ADR

GI upset (common)
Sedation
qHS
Cardiac side effects (sinus bradycardia, shortened
PR intervals)(rare)
Gingival hyperplasia cosmetic concern common, dose dependent





Common and troublesome, occurrence and severity related

to the dose/serum concentration of phenytoin (40-50% of
treated patients).
Oral hygiene programs appear to effectively eliminate local
irritants and maintains oral hygiene (but cant reverse the
hyperplasia) reduce inflammation but not curative
Dosage reduction or alternative agent
Surgical gingivectomy
_____________________
30

Phenytoin

May need to supplement with





Vitamin D (interferes with vit D metabolism)

Calcium
Folic acid (?) for preg, higher dose enough to protect fetus

but increase Cl of phenytoin --> lower efficacy

Be careful in patients with low albumin level

weak elderly malnourished

31

Phenytoin
Toxicity

Serum level of 60-120 mol/L



Nystagmus

Serum level >120 mol/L



Ataxia, lethargy, vertigo, decreased mental

capacity very gerneral --> if these Sx occur, need to make sure not phenytoin
toxicity

Management



Drug discontinuation
Supportive care if needed

32

Phenytoin
Dosing & administration

Irritating
 Avoid IM & IV in small veins
Poor solubility in water & at neutral pH
use NS


Requires slow infusion in glucose free solutions to avoid precipitation
 Fosphenytoin: water-soluble prodrug of phenytoin not in HK
useful IM inj > iV infusion
Oral loading dose:
fast cure

15-20mg/kg, based on phenytoin serum level

 Administer oral loading dose in 3 divided doses (2 hrs in-between)
to GI side effects
Maintenance dose
 300mg/d nocte


33

Valproate (Epilim EC, Chrono)

Effective for a wide spectrum of seizures

Dosing: Initiate at 125-200mg twice daily


Teratogenicity (probably highest risk among

most agents)


Epilim Chrono: once or twice daily dosing

Eg. Neural tube defects

Therapeutic range:


not best choice for preg

** children controled by VPA
grow up --> preg age ?

Trough: 350 to 700 mol/L

34

Ethosuximide

Used primarily for absence seizures

Well absorbed from the GI tract, long half-life
allowing once daily dosing
Initiate at a dose of 15-20mg/kg/day, increase
by 250mg every 10-14 days as necessary to
control seizures

35

Ethosuximide
GISE

ADR: Most frequent side effects include

abdominal discomfort, fatigue, anorexia,
nightmares and dizziness
GI side effects can be minimized by taking
ETX with meals
Phenytoin, carbamazepine and phenobarbital
may increase hepatic metabolism of ETX,
thus lowering its level

36

Lamotrigine

Effective as monotherapy and adjunct

therapy for treatment of partial and
generalized seizures
diff kind
Also useful in absence seizures useful for mixed types
Initiate with slow upward dosage titration to
minimize early sedative effects and reduce
the likelihood of skin rash

37

Newer treatments

Gabapentin (Neurontin)
Vigabatrin (Sabril) visual view
Levetiracetam (Keppra)
Topiramate (Topamax)
Pregabalin (Lyrica)

Lacosamide (Vimpat)
Retigabine (Trobalt)

38

Newer treatments

In pts with highly refractory epilepsy, a > 50%

seizure reduction was seen in 30-50% of pts
All are indicated for adjunctive treatment of
partial seizures
X ocmplete cure
not eff in all pt
long trial and error

39

keep monotherapy if possible --> prevent DDI And SE

Comparison of new anticonvulsants

t1/2

Elimination

Side effects
Behavioral changes, Wt gain
Behavioral changes; maybe
some psychosis & hallucination.
Somnolence & weakness
Hyponatremia, rash, nausea

most renal

Drug
interactions
-

Gabapentin
Levetiracetam

6
7

Renal 100%
Renal 60%,
hydrolysis 34%

Oxcarbazepine

2 (active
metabolite
12.5)
6

Hepatic 70%

Renal mostly

dizziness, somnolence, dry mouth, _

edema, thinking abnormalities

19

Renal 55%

Vigabatrin

5-7

Renal

Lacosamide

13 (active
metabolite 1523)
6-10

Renal mostly;
2C19 substrate

Language impairment, ?
Cognitive impairment, weight loss,
kidney stones, metabolic acidosis
Amnesia; blurred vision; blueyellow color blindness; vision or
other vision changes; eye pain
>10%: dizziness, headache,
nausea, diplopia
>10%: dizziness, somnolence,
fatigue
Urinary retention in 5%
~9% reported confusion new

Pregabalin
Topiramate

Retigabine

high dose to half renal

affect OC
part liver

Renal

ensure good renal Fx

go for renal drugs to avoid DDI if polypharmacy

+ (CBZ &
phenytoin)
-

agents: may :::

cognitive impariement
behaviorl problem

Pharmacokinetic Interactions
Affects

Affected by

other AEDs

other AEDs

AED

Metabolism

Gabapentin

Not metabolised

Lamotrigine

Glucuronidation

Levetiracetam

Nonhepatic hydrolysis

Oxcarbazepine

Glucuronidation/CYP

Pregabalin

Not metabolised

Topiramate

CYP/glucuronidation

Vigabatrin

Not metabolised

Lacosamide

Not metabolised

Retigabine

Not metabolised

newer agent

41

Patsalos PN et al Epilepsia 2002;43:365-85.

VPA affect gluconidation process

Newer treatments
Drug interactions

Topiramate:




May efficacy of oral contraceptives 1/2 liver

May phenytoin and valproic acid level
Carbamazepine, phenytoin and valproic acid:
decrease topiramate level

Phenytoin decreases topiramate levels by 48%

42

Outline

Definitions & Etiology

Diagnosis & Classification
Treatment





Endpoints
Available agents & indications
Individual agents
Important treatment issues

Status Epilepticus
43

Serum drug concentrations

Dosage


Correlation between dose and resulting steady

state concentration is generally poor

Clinical response



poor correlation
individual variation

most important

Seizure frequency & side effects

Patients often differ dramatically in response to
drug concentrations
Seizure type & other clinical variables influence
control
44

When to measure serum drug

concentrations

check if pt taking drug be raise dose

Uncontrolled seizures despite high doses

Seizure recurrence in a previously controlled
patient
Intoxication documentation
Assessment of compliance
CBZ
Potentially significant drug interactions affect other drugs
efficacy ?
When precise dosage changes are required
albumin, water level, preg

45

Inadequate seizure control

The dose of the first-line drug should be

increased to maximal tolerated dose until



the seizures are controlled or

side effects preclude further increases in the dose

If seizures are still not controlled,



common

Another first-line AED or a second-line AED

can be added

When adding a second agent,



Continue to administer first AED

maximize ,, add 1st or 2nd line
** continuing 1st drug at first, then titrate down

46

No abrupt switch ************

Inadequate seizure control (cont.)

The first drug should be gradually withdrawn



to reduce the risk of drug interactions and other

adverse effects
But what if there were significant seizure reduction
with 1st agent?

Regimens of two or more AEDs are generally

used for the treatment of seizures only after two
or more first-line agent given as monotherapy
had been ineffective 1st drug --> 2ng --> 3rd drug --> combination



Consider the drug-drug interactions!

Consider mechanism of actions
47

Lason W et al.
Pharmacological Reports
2011; 63:271-92
48

Duration of therapy and discontinuation

of AEDs often patient question

AED therapy may be successfully withdrawn

from some patients after a seizure-free period
of 2 to 5 years not only criteria
AEDs should be withdrawn slowly



Decrease by 25% every 2 to 4 weeks

If a patient receives multiple drugs, each drug
withdraw one by one
should be withdrawn separately
Too rapid withdrawal may result in status
epilepticus.
49

Duration of therapy and discontinuation

of AEDs (Cont.)

Risk factors possibly predicting seizure

recurrence following AED withdrawal





<2 years of seizure-free before withdrawal

onset of seizure after age 12
>2 yrs before seizure controlled
large number of seizures (>30) before control or
total of >100 seizures
organic neurologic disorder or moderate to severe
mental retardation structural problem
X take off
50

Duration of therapy and discontinuation

of AEDs (Cont.)

Risk factors possibly predicting seizure recurrence

following AED withdrawal (cont.)




History of atypical febrile or absence seizures

A combination of seizure types
Abnormal EEG persisting throughout treatment

51

AED withdrawal can be considered

if

seizure free for 2 to 5 years,

a history of a single type of partial seizure or
primary GTC seizures,
a normal neurologic exam and normal IQ,
and
an EEG that has been normalized with
treatment

52

Seizure control during pregnancy

VPA worst

Almost all anticonvulsants have a weak teratogenic

effect


if not >2 yr seizure free,, continue as benefit > risk

Monotherapy at the lowest effective dose is

advisable
use one agent !!
Use of multiple drugs increases risk to > 10%
Advise to continue anticonvulsants


Risk ~ 6%

baseline risk for normal preg --> 3%

Withdrawal seizure may be deleterious to fetus & mother

Folic acid supplements recommended

4mg / day (locally use 5mg /day no matter what)
very high dose
water soluble, easily excreted
53

NEVER say no risk to baby

Folic acid

LAMO lower preg risk

4mg/d for high risk drugs eg. VPA, phenytoin

Reduce the risk of congenital neural tube
malformation, in patients without epilepsy
Does not reliably reduce the teratogenic
effects of AEDs
better than nothing

for VPA,, need to plan for switch b4 preg

can be seizure free 2 yr ? no high risk recurrence? get off
hopefully safest to have not med
if really need VPA,, keep VPA .... although teratogenic risk
but if indicated for migraine, bipolar ..... can stop
54
seizure ,, need to keep if cant off or swift -----> need patient to know the risk and benefit
its the patient to decide finally

Anticonvulsant medications and Risk

of Suicide

Analysis of clinical trials showed twice the

risk compared to placebo
Cohort studies try to compare among agents
Still not confirm yet due to many confounding
factors
Yr 2008: FDA warning label for
anticonvulsant use & increased risk for
suicidal thoughts and behavior based on
meta-analyses
not very high risk
but with report
X know is it drug induced

not confirm

55

Risk of suicide (from package insert)

Proposed neurobiological mechanisms (still

unclear)





Forced normalization
Folate deficiency
Enhanced GABA neurotransmission
History of affective disorders
56

Case Study 2

HK is a 34 y/o patient who has been

maintained on carbamazepine 400mg PO BD
for the past 2 yrs. She has simple partial
seizures and has been seizure free for the
past 4 yrs. She inquires whether she could
get off the drug. How would you respond?
Yes based on these info
need to look at EEG during Tx ( normal during Tx?)
no structural problem ?
MUST have physician permit to D/C

57

Case Study 2

The physician decided that HK can go for a

trial of tapering off of carbamazepine.
Unfortunately, she develops stratus
epilepticus and presents to the emergency
room.
Which of the following drugs is best to use
first?

58

Case Study 2

Diazepam
Lorazepam
Phenytoin
Valproate

prefer for status

P & V use after the benzo

59

Outline

Definitions & Etiology

Diagnosis & Classification
Treatment





Endpoints
Available agents & indications
Individual agents
Important treatment issues

Status Epilepticus
60

Status Epilepticus

Recurrent seizures without an intervening

period of consciousness before the next
seizure
or any seizure lasting for more than
30minutes, whether or not consciousness is
impaired
arbitary def,, can be lowered
Complications:


Hypoxic brain damage, brain infarction, acute

renal & hepatic failure, etc
61

Status Epilepticus

Place the patient in a safe place so that the

risk of injury is minimal
Lie in semi-prone position when possible
Avoid putting anything in the mouth while the
patient is fitting; protect the airway by
inserting a plastic pharyngeal airway if patient
remains unconscious

62

Treatment

Ensure ventilation
Position on side to prevent aspiration
Terminate current seizure activity
IV rapid-acting anticonvulsant


Lorazepam

2-4mg IV dose
Diazepam

5mg/min IV dose

63

Treatment (cont.)

Following the lorazepam or diazepam,

 Phenytoin




Give I.V. bolus of 15-20 mg/kg slowly (no more than 50

mg per minute) and then 5 mg/kg/day

IV sodium valproate 400mg q6h can be given

If the seizures have not stopped within 5 minutes,
repeat 10 mg of I.V. diazepam.

64

Case study 3

37 y/o male with partial seizure onset 4 years

ago


PMH: depression
Current meds



EEG: abnormal activities in temporal lobe

in range

Carbamazepine 600mg BD (level: 41 mmol/L)

Citalopram 20mg PO QD

Follow up for depression today and tells you

that he still has seizures 3-6 x/ month
ensure compliance
seizure nature (triggers ? how to terminate? )
can use benzo suppository ..... not convenient

stress?

65

Case study 3

What questions will you ask the patient?

What would you suggest for management at

patients next neurology visit?
A.
B.
C.
D.

Suggest switching to another drug (2 tgt, then taper off)

Suggest increasing dose of carbamazepine too severe now
cannot go very
not recommended
Suggest adding another drug
further
keep 1 drug
Further monitoring with no medication changes
needed X
66

Case study 3

Patient crossed taper to lamotrigine 25mg PO

QD at next visit per your intervention
While decreasing the dose of carbamazepine (at
1000mg/d), seizure worsens to 2 times in the
think CBZ not working as 6x /mo, but its working
first week ifpreviously
worsen so quickly when off ---> means CBZ working, need stay
What should be done now?
A.
B.

C.

D.

Keep monitoring, keep current dosage

Further increase the dose of lamotrigine and taper off
carbamazepine
Further increase the dose of lamotrigine and keep
current dose of carbamazepine
Keep current regimen, add valproate
67

X decrease CBZ when worsening

Case study 3

CBZ can induce meta of LAMO

if increase CBZ, LAMO need to increase too

1 month later: Patient was titrate to lamotrigine

200mg QD and carbamazepine 400mg BD inducer to
LAMO
Seizure frequency same as before drug change
What should be done next?
A.
B.
C.

D.

Increase dose of lamotrigine / carbamazepine

Add 3rd agent
Switch both lamotrigine & carbamazepine to
levetiracetam
Switch both lamotrigine to levetiracetam and maintain
carbamazepine
at least maintain CBZ ,, may be LAMO X work --> switch LAMO

Whats next?

68

The End

69