SEIZURES AND EPILEPSY 3 Flashcards
GOALS OF THERAPY
Individualized goals of therapy
Ideal: Complete seizure freedom
Reduce frequency of seizures (1/3 of patients)
Balance between seizure control and adverse
effects of antiseizure medications
Improve quality of life
Treatment goals to be reviewed at follow up
NON-PHARMACOLOGICAL
Avoid individual precipitants
Sleep deprivation
Avoid drug abuse e.g. cocaine, amphetamines
Minimize alcohol intake
Patient to consult pharmacist or health care provider when
starting or stopping any complementary and alternative
medicine (CAM) products e.g. herbal supplements
Seizure precautions, examples
Driving restrictions
Avoid heights, power tools to avoid accidental injury
Bathing, swimming, caring for young children precautions
Ketogenic diet
- High fat diet, no carbohydrate, and adequate protein diet.
no carbohydrate diet, so there is no glucose and the body will use the fat as a source of energy instead. That the liver will switch the fats into fatty acids. And fatty acids gets metabolized to ketone bodies. And actually they found out the ketone, ketone bodies can be used by the brain as a source and alternative source of energy.
Controls seuizres
ketogenic diet had proven effective also in status epilepticus
Vagus Nerve Stimulation: : Providing electrical impulses through the vagal nerve. And it’s proven useful in some cases of intractable epilepsy, select resistant drug resistant epilepsy
Epilepsy surgery: focal epilepsyy and drug resistant (eh/ remove temporal lobe of brain)
Cannabis: there’s some conflicting evidence in term of using recreational cannabis to control seizures. Actually, one of the ingredients in cannabis, cannabidiol, this I actually have proven in clinical trials to be effective in controlling seizures.
PRINCIPLES OF THERAPY
decisiion to treat
Not all seizures need to be treated
To treat or not to treat after the first seizure
Questions to ask:
Did an external precipitant cause the seizure?
Can precipitants be avoided?
Will seizure recur? . Two unprovoked seizure separated by more than 24 h, correct? Or one unprovoked seizure, and the risk of seizure is increased more than 60%. If you see any EEG abnormalities, we say this patient is at high risk of seizure
EEG abnormalities
Presence of a remote cause of increase risk
Neurological examination
How disabling are the seizures?
Risk/benefit ratio for ASM therapy
Treat if
The patient experienced 2 or more unprovoked
seizures
The patient experienced a seizure and provoked
from some acquired causes such as stroke,
meningitis, brain injury
Initiation of Antiseizure Medication (ASM) therapy
Start with one first line agent
Start with fraction of the target dose and titrate up
(exceptions phenytoin and phenobarbital)
Allow adequate time to assess the efficacy unless toxicity,
severe adverse drug reaction
If seizures were not controlled, check:
if the selected ASM is effective in the patient’s seizure type
if the ASM dose was sufficient
if the patient was adherent
for any drug interactions
DOSE TITRATION
Slow titration might alleviate ADRs
Carbamazepine nausea, vomiting, drowsiness
Topiramate cognitive impairment
Lamotrigine rash
Gabapentin CNS adverse effects
Slower titration is recommended when lamotrigine given
with valproic acid: valproic acid is a liver microsomal enzyme inhibition, inhibitor. It inhibits the metabolism of lamotrigine. And so the exposure to lamotrigine is way higher, like you need to be way slower
Some agents can be given at target dose with no titration
Phenytoin, phenobarbital, levetiracetam
PRINCIPLES OF THERAPY
If monotherapy fails
Try another first line agent before adding second
agent
Why?
Less adverse reactions
Less drug interactions
Less cost
Better adherence
And, similar efficacy and tolerability
If monotherapy still fails (after 2-3 agents being
tried)
Add a second agent
Consider synergy in mechanism and antagonism
for adverse ractions if possible
~ 30% will need polytherapy
~ 10 % refractory to all ASMs
ASM Switch
Titrate up the new agent faster than titrating down the
old agent (dose change every 3-5 half-lives)
Preferable to titrate to full dose before tapering the old
agent
Monitor for worsening seizure control or adverse
reactions during switch
In case of life-threatening adverse reactions, the old
agent should be stopped immediately and the new
agent should be fast titrated
When to stop?
Consider if patient has been seizure free for
two or more years (non-acquired)
6-12 months (acquired cases such as stroke and
meningitis)
Pros: less cost, no adverse reactions, less life style
restrictions
Cons: risk of relapse, status epilepticus, harm, loss of
driving privileges
Seizure recurrence is highest in the first year after ASM
withdrawal
How to stop?
SLOW taper is recommended (months – e.g. decrease
by 25% every 2-4 weeks)
If patient on more than one ASM:
Taper ASMs separately
Least beneficial or most toxic ASMs to be withdrawn
first
Seizure precautions e.g. driving avoidance should be
followed during withdrawal
If seizures recur, restart therapy, could be indefinite
COUNSELLING AND MONITORING
Stress on adherence
Efficacy
ADRs and Toxicity
Short-term ADRs
Long-term ADRs
Major ADRs
Labs
CBC, LFTs (lytes) at baseline
Repeat 4-8 weeks after starting drug then every year
May be done more frequently in symptomatic patients
Drug interactions
GENERIC SUBSTITUTION
Controversy about generic substitution and link to poor
seizure control
American Epilepsy Society Position Statement (2016):
Drug formulation substitution reduces cost but does not
compromise efficacy
Patient counseling is very important
patient needs to be aware that this change might not change the efficacy, but you never know what will happen. And patient might have increased risk for seizures or something like that, need to be monitored frequently if they’re switching from one generic to another
FACTORS GUIDING THERAPY
Seizure type/epilepsy syndrome
Drug pharmacokinetics
Drug interactions: DOAC abs contraindicated
Adverse effects profile
Cost and drug coverage
Patient’s comorbidities
Patient’s age, sex, life style
Effect on pregnancy and lactation
Patient preferences
Convenience of dosing e.g. once vs twice daily
SPECIAL POPULATION
Contraception
Contraception
Decreased Effectiveness of OCs by enzyme-inducing ASMs
Options
Use high-dose estrogen OCs (> 50ug estrogen) – not available
anymore in Canada
Use back-up method of contraception
Consider non-interacting ASMs
Estrogens might reduce the concentration of lamotrigine
So that’s important to monitor lamotrigine level if the patient starts on an oral contraceptive.
Decrease liver enzyme ASML phenytoin, phenobarb, primidone, carbamazepine, topirmate high dose
they decrease the effectiveness of oral contraceptives because it increases metabolism of those hormones
Pregnancy
A balance needs to be achieved between seizure
control and minimizing the risk to fetus
Effects of Seizures:
Seizures in 1st trimester increase risk of malformations
Seizures (especially tonic-clonic) increase the risk of
maternal and fetal hypoxia
Pregnancy reduces ASMs levels (esp. in 3rd trimester)
Potential for non-adherence
Risk of malformation doubles with ASM (4-6 vs. 2-
3%)
No ASM is absolutely safe
Valproic acid is the least favorable among ASMs
Pregabalin: Concern about causing major birth defect
following exposure in the first trimester (6 vs 2%)
anti-seizure meds double the risk of malformation as well
seizures, especially the tonic clonic, the red one increase the risk for maternal and fetal hypoxia.
Lamotrigine can cause breakthru seizures cuz pregancy in Vd increases and drug will distribute further
- In addition, hormones can increase lamotrigine metabolism
- You measure a steady-state level prior to pregnancy If it’s planned
- monitor that every trimester, targer the dose
- If unplanned preg, do a level to see therapeutic conc
importantly, after the patient delivers the baby, their metabolism will go back to normal very quickly within days. This means if the patient was on humungous those lamotrigine after delivery, this Lamotrigine dose has to go down quickly
Pregnancy
Management principles
If patient was controlled on an agent before pregnancy,
continuing same agent preferred
Exceptions: valproic acid
Monotherapy is preferred
TDM is recommended to maintain lowest effective dose
and to account for PK changes e.g. lamotrigine
Avoid triggers e.g. sleep deprivation
Stress on compliance
Avoid smoking, alcohol and illicit drugs
Multivitamins, folic acid (1 mg
The one that’s big no, is valproic acid is the least favorable among anti-seizure meds given the evidence that actually causes lots of malformation.
IF CHILD-BEARING DONT USE VALPROIC ACID
