Transcript AED Selection

AED Selection
Megan Selvitelli, MD
May 14, 2007
Paroxysmal Event
Is it a seizure?
If no, determine and treat underlying cause
 Adults
 Nonepileptogenic
seizures
 TIA
 Migraine
 Syncope
 TGA
 Episodic Dyscontrol
 Meniere’s disease
 Kids
 Breath-holding spells
 Parasomnias
 Tics, Chorea,
Dystonia
 Nonepileptogenic
seizures
Paroxysmal Event
 If event is a seizure, should you treat it
with AEDs?
 No,
if situational seizures
 Yes, if >2/5 risk factors for recurrent
seizures OR if status epilepticus (see
status protocol for meds)
Paroxysmal Event
Situational seizures which do NOT require
treatment long-term
 1st Febrile seizure
 Reflex seizures
 Eclampsia
 Electrolyte
abnormalities
 Head trauma
 Alcohol withdrawal
seizures
 Benzo withdrawal
seizures
 Seizures due to
recreational drug
use
 Seizures due to
antidepressants
Paroxysmal Event
Seizures which should be treated
 If 2 or more of following risk factors
present, 100% probability of second
seizure in 2 years
 Structural
lesion
 Abnormal EEG
 Partial seizure
 Positive family history of seizure
 Post-ictal paralysis
Paroxysmal Event
Is seizure part of epilepsy syndrome?
 If yes, choose AED according to
epilepsy syndrome
 Juvenile
myoclonic epilepsy: VPA, LMT,
LEV, TPM, ZNS
 Childhood absence: Ethosuximide, VPA
 If no, categorize the seizure type(s)
present in your patient
Paroxysmal Event
What is seizure type(s)?
 Partial
 Focal
 Complex
Partial
 Focal with Secondary Generalization
 Primary Generalized
Choosing AED
 Difficulties with interpreting AED trial studies
 Most with either comparison to older AEDs, placebo or
differential doses




No direct comparisons between newer AEDs
Only need to show noninferiority of newer AED compared to old
Frequently assessed as add-on therapy in patients with
refractory partial seizures, less information on patients with
primary generalized seizure, new onset seizures, epilepsy
syndromes
Often variable is time to first seizure, rather than clinically
meaningful information such as number of seizures with one
year of therapy
Choosing AED
 Use med list for seizure type
 Eliminate AEDs with contraindications in your
patient, either due to other medical conditions
or concomitant medications which interfere
with AEDs
 Consider choosing AED which may treat
other symptoms your patient experiences
Choosing an AED
 Other variables include:
 Simple
dosing schedule and monitoring
 Cost
 Formulations
(IV form if needed, oral forms
if dysphagia, IM if refuses meds)
 Recall that 2/3 of patients will become
seizure-free with first or second AED
Focal Seizure AEDs
Primary Generalized Seizure
AEDs
If insufficient control with 1st AED:
 And no side effects, increase dose of 1st
AED
 If side effects or insufficient control,
substitute another AED
If insufficient control,
 Add on second AED
 Monitor seizure control with seizure
calendar
For patients with difficult to
control seizures
 Use meds which haven’t been tried yet
 Stay with “winners” and drop “losers”
 DON’T change meds if they are
effective and no side effects
 Remember:
 #AEDs
 significantly #side effects
 Paradoxical reaction

#AEDs #seizures
For patients with difficult to
control seizures
 Goals of therapy
 Best seizure control
 Least side effects
 Consider alternative therapies
 Vagal nerve stimulator
 Ketogenic diet
 Surgery




Lesionectomy
Temporal lobectomy
Corpus callosotomy
Hemispherectomy
Management of AED side effects
 Rashes
 Hormonal
 Bone health
 Cosmetic effects
 Idiosyncratic reactions
Rash AED Side Effects
 If rash hurts, stop AED
 If serious rash (eosinophilia, fever,
lymphadenopathy, myalgia, exfoliation),
discontinue AED
 If rash itches, give Benadryl and lower
dose of AED, later titrate up dose
 Look for other causes of rashes
 Viral,
Lyme, contact dermatitis
Hormonal AED Side Effects
 OCPs
 Decreased effectiveness if used with CBZ, OXC,
PB, PRM, LTG, high dose TPM
 Use higher dose OCPs to maintain effectiveness
and consider other forms of birth control
 Pregnancy
 Risk of teratogenicity w/VPA, PB, PRM, PHT, CBZ
 Ask about pregnancy goals and switch to less
teratogenic AED 6 months before conception, if
possible
 Increased clearance of AEDs during pregnancy,
thus ideally check AED levels monthly
Bone Health AED Side Effects
 Increased risk of osteopenia with P450 enzyme
inducers  active Vit Dsecondary
hypoparathyroidismincreased bone turnover &
↓BMD
 CBZ,PB,PHT,PRM,OXC
 VPA causes osteomalacia through effect on
osteoblasts
 Prophylactic treatment Calcium 1200 mg BID and Vit
D 400 IU daily
 DEXA scan after two years of therapy with enzyme
inducers and q2-4 years





If abnormal scan, do endocrine eval
Increase Calcium to 600 mg TID and Vit D 800 IU qd
Increase physical activity
Decrease soda consumption
Stop smoking
Cosmetic Side Effects of AEDs
 Phenytoin
 Coarsening
of facial features, gingival
hyperplasia, acne, hirsutism
 Valproic acid
 Hair
loss
 Primidone and Phenobarbital
 Frozen
shoulder, Dupuytren’s contractures
Idiosyncratic Side Effects of AEDs
 Anorexia/Weight loss: TPM, ZNS
 Weight gain: VPA (up to 50% through
hyperinsulinemia), GBP, PGB
 Anhidrosis and Renal Stone: TPM, ZNS
 Hyponatremia: CBZ, OXC
 Peripheral neuropathy: PHT
All AEDs may cause…
 Sedation, lethargy
 Encephalopathy
 Cerebellar syndrome
 Dipoplia
 Paradoxical increase in seizures
 Headache
Conclusion
 Is paroxysmal event a seizure?
 Does seizure need to be treated?
 Is seizure part of a seizure syndrome?
 What type of seizure(s) are present?
 What contraindications prohibit choosing a
particular AED?
 What co-morbidities may be treated by AED?
 What is simplest dosing schedule and
monitoring?
 Manage effectiveness and side effects of
AEDs
Cases
 24 year old female presents with a spell
of nausea, followed by confusion and
automatisms. She is sexually active
and using OCPs.
Cases
 60 year old man with recent CVA,
hypertension, hyperlipidemia, obesity,
and depression presents with a new
focal motor seizure
Cases
 15 year old boy who develops
generalized tonic clonic seizures upon
awakening. He has a history of
absence seizures as a child.
Cases
 45 year old woman with a history of
migraines, GTC, and s/p hysterectomy,
seeing you regarding side effects of her
phenytoin, including facial hair and
osteoporosis. She wishes to change
meds.
Cases
 35 year old man with a history of alcohol
and IVDA abuse, HIV, and liver disease
who presents with “shaking all over,
foaming at the mouth, and eyes rolled
back”
References




Glauser T, Ben-Menachem E, Bourgeois B et al. ILAE treatment guidelines: Evidencebased analysis of antiepileptic drug efficacy and effectiveness as initial monotherapy for
epileptic seizures and syndromes. Epilepsia 47(7): 1094-1120.
AAN Practice Guidelines: April 2004. Efficacy and tolerability of the new antiepileptic drugs:
I, Treatment of new onset epilepsy and II: Treatment of medically refractory epilepsy.
Brown TR and Holmes GL. Handbook of Epilepsy. Philadelphia: Lippincott, Williams and
Wilkins. 2003.
Sheth RD. Metabolic concerns associated with antiepileptic medications. Neurology
63(S4):S24-9, 2004.