Treatment

DEPENDS on the underlying cause

• Metabolic : correction• Structural abnormality: seizure control + consider

surgeryTumorVascular

• Idiopathic : seizure control

Diagnosis and Classification of seizure disorder

choose Anti-epileptic drug of choice

Main Goal: Adequate seizure control

monitoring of response (seizure-free) and side effects

therapeutic monitoring

drug interactions

Principles of Treatment• Individualized treatment• Selection of specific drug for initial therapy is based on specific clinical

seizure type• Monotherapy is preferred• Dose is increased gradually• Enough time for steady state to be reached must be allowed• Prompt substitution when serious adverse reaction develops • If poor seizure control-gradually withdraw first drug while replacing with

second drug of choice for seizure type (should not be stopped abruptly)• Treatment failures may be due to poor compliance or misdiagnosis• Continue treatment to achieve minimum seizure-free period of 3-5

years

Katzung Basic and Clinical Pharmacology, 9th ed.The Treatment of Epilepsy, 3rd ed.

Absence seizures• Ethosuximide is the drug

of choice for typical absence seizure

• Valproic Acid is the drug of choice for atypical absence seizure

• used only when treatment tolerance or failure appear with Ethosuximide

• Wide spectrum AED

Katzung Basic and Clinical Pharmacology, 9th ed.The Treatment of Epilepsy, 3rd ed.

Anti Epileptic Drug Glutamate Antagonist

GABA agonist

Na channel blocker

Ca channel blocker

Phenobarbital *

Phenytoin *

Carbamazepine *

Valproic Acid * *

Gabapentin *

Topiramate * * * *

Oxcarbazepine * *

Ethosuximide *

Lamotrigine * *

Ethosuximide • Primary indication: First-line or adjunctive therapy of generalized absence

seizures• Mechanisms of action: Inhibition of neuronal T-type calcium channels in the

thalamus (Type III AED)• Usual preparations: Capsules: 250 mg; syrup: 250 mg/5 mL• Usual dosages: Initial: 250 mg (adults); 10–15 mg/kg/day (children)• Maintenance: 750–1500 mg/day (adults); 15–40 mg/kg/day (children)• Dosing frequency: 2–3 times/day• Significant drug interactions:

– Ethosuximide levels are reduced by co-medication with carbamazepine, phenytoin, phenobarbital and rifampicin.

– Valproic acid may exert synergistic effects with ethosuximide in patients refractory to either drug given alone, and may have variable and inconsistent effects on ethosuximide levels. Serum valproic acid levels may be decreased by ethosuximide. Ethosuximide levels are increased by isoniazid

Katzung Basic and Clinical Pharmacology, 9th ed.The Treatment of Epilepsy, 3rd ed.

• Serum level monitoring: usually optimized based on clinical and EEG response.

• Main advantages: Well-established treatment for absence epilepsy without the risk of hepatic toxicity carried by valproic acid

• Main disadvantages: Adverse effects common. Unlike valproic acid, ethosuximide does not protect against generalized tonic–clonic seizures

• Common/important adverse effects: Gastrointestinal symptoms, drowsiness, ataxia, diplopia, headache, dizziness, hiccoughs, sedation, behavioural disturbances, acute psychotic reactions, extrapyramidal symptoms, blood dyscrasias, rash, lupus-like syndrome, other severe idiosyncratic reactions

Katzung Basic and Clinical Pharmacology, 9th ed.The Treatment of Epilepsy, 3rd ed.

Valproic Acid• Primary indications: First line for atypical absence seizures. First-line

therapy of idiopathic generalized epilepsies. First-line or adjunctive therapy of cryptogenic or symptomatic generalized epilepsies. Valuable but not generally first-line therapy for partialseizures

• Mechanisms of action: Increases brain GABA activity by increasing activity of glutamic acid decarboxylase, inhibition of GABA transaminase, inhibition of succinic semialdehyde dehydrogenase

• Usual dosages: Initial: 400–500 mg/day (adults); 15 mg/kg/day (children)• Maintenance: 500–2500 mg/day (adults); 20–40 mg/day (children under 20

kg); 20–30 mg/kg/day (children over 20 kg)• Dosing frequency: 2-3 times a day• Serum level monitoring: Dosage usually can be adjusted on the basis of

clinical response, but monitoring serum valproic acid levels may be useful in selected cases

Katzung Basic and Clinical Pharmacology, 9th ed.The Treatment of Epilepsy, 3rd ed.

• Significant drug interactions : Enzyme-inducing drugs and imipenem antibiotics reduce serum valproic acid levels. Felbamate, stiripentol, isoniazid and other drugs may increase valproic acid levels. Valproic acid inhibits the metabolism of a number of drugs, most notably phenobarbital, lamotrigine and rufinamide. Valproic acid displaces phenytoin from plasma protein binding sites and may inhibit phenytoin metabolism at the same time

• Common/important adverse effects: Tremor, sedation, asthenia, encephalopathy, extrapyramidal symptoms, nausea, vomiting, hyperammonaemia, weight gain, polycystic ovary syndrome, hair loss, platelet and coagulation disorders, liver toxicity, pancreatitis, teratogenic effects (including spina bifi da)

• Main advantages: Unsurpassed effi cacy in most generalized epilepsy syndromes. Broadspectrum efficacy in different seizure types

• Main disadvantages: Weight gain, severe liver toxicity (particularly in children), teratogenicity

Katzung Basic and Clinical Pharmacology, 9th ed.The Treatment of Epilepsy, 3rd ed.

Other Modalities

• Surgical Management– surgical excision of epileptic foci in simple and

complex partial epilepsies that have not responded to intensive and prolonged medical therapy may be beneficial for some

• Regulation of Physical and Mental Activity– precipitating factors needs to be modified and

stressed to the patient – moderate amount of physical exercise can also be

advised– psychosocial difficulties needs to be identified and

addressed early The Treatment of Epilepsy, 3rd ed.

• Ketogenic Diet– biochemical alteration both in the blood and in the

brain– possible GABA-mimetic effects of ketosis given the

structural similarities of GABA, -hydroybutyrate and acetoacetate

Vagal Nerve Stimulation– vagal stimulation produces its effects are unclear and

it is done through attachment of electrodes to the vagus nerve at the left carotid bifurcation

The Treatment of Epilepsy, 3rd ed.

Management

American Academy of Neurology Guidelines on CESSATION OF TREATMENT

• Stopping the treatment may be considered when:

– The patient has been seizure-free for 2 to 5 years– The patient has a single type of seizure– The patient has no abnormalities on neurologic

examination and has a normal IQ– The patient’s electroencephalogram (EEG) has become

normal