Juvenile Myoclonic Epilepsy

Medications
First-Line Treatment
Valproic Acid
Consider lamotrigine or levetiracetam if
valproic acid is unsuitable or not tolerated
First-Line Treatment
Valproic Acid 400–3000 mg
• Mechanism of Action:
Enhancement of GABA-mediated inhibition
Reduce high-frequency firing of neurons by
blocking voltage-gated sodium and calcium
channels
First-Line Treatment
Valproic Acid
• Adverse Effects
x Development of major congenital malformations
and adverse cognitive outcome
x Neurologic: Ataxia, Sedation, Tremor
x Systemic: Hepatotoxicity, Thrombocytopenia,
Gastrointestinal irritation, Weight gain, Transient
alopecia, Hyperammonemia
First-Line Treatment
Lamotrigine 100–400 mg
- Worsening of myoclonic seizures and GTCS at
higher doses
• Mechanism of Action:
 Stabilizes presynaptic neuronal membranes by
blocking voltage sensitive Na channels,
subsequently inhibiting the release of excitatory
amino acid neurotransmitters (e.g. glutamate,
aspartate) which are involved in the
generation and spread of epileptic seizures
First-Line Treatment
Lamotrigine
• Adverse Effects
x Neurologic: Dizziness, Diplopia, Sedation, Ataxia,
Headache
x Systemic: Skin rash, Stevens-Johnson,
syndrome
First-Line Treatment
Levetiracetam 500–3000 mg
- an alternative to VPA due to its low incidence of
endocrine and metabolic adverse effects
- Less efficacious in controlling absence seizures
• Mechanism of Action:
Binds to synaptic proteins which modulate
neurotransmitter release
Partial inhibition of N-type Ca currents and reducing
the release of Ca from intraneuronal stores
Modifies synaptic release of GABA and
glutamate
First-Line Treatment
Levetiracetam
• Adverse Effects
x Neurologic: Sedation, Fatigue, Incoordination,
Mood changes
x Systemic: Anemia, Leukopenia
Adjunctive Treatment
 Lamotrigine, levetiracetam, topiramate
 If ineffective or not tolerated consider
clobazam or clonazepam
Adjunctive Treatment
Valproic Acid and Lamotrigine
Synergistic effect

Adverse Effect: Severe skin rash

Adjunctive Treatment
Lamotrigine and Clonazepam
Clonazepam is a useful adjunct for myoclonus
Used in combination with lamotrigine to avoid
lamotrigine's myoclonic effects
Adjunctive Treatment
Clonazepam 4–8 mg
Mechanism of Action:
facilitate GABAergic transmission
in the brain by a direct effect on
benzodiazepine receptors
Adverse Effects:
x Neurologic: Ataxia, sedation,
lethargy
x Systemic: Anorexia
Adjunctive Treatment
Topiramate 100–400 mg
- able to control GTCS and myoclonic jerks
- increase in frequency of absence seizures
Mechanism of Action:
Blocks voltage-dependent Na channels
Augments γ-aminobutyric acid (GABA) at GABAA
receptors
Adverse Effects:
x Neurologic: Psychomotor slowing, Sedation,
Speech or language problems, Fatigue,
Paresthesias
x Systemic: Renal stones, Glaucoma, Weight
loss, Hypohidrosis
Adjunctive Treatment
Clobazam 10–40 mg
- long been used in the treatment of generalized
epilepsy
Mechanism of Action:
It allosterically binds to the benzodiazepine site of
the γ-aminobutyric acid type A (GABAA) receptor
w/in the CNS, thereby enhancing its inhibitory
effects.
Adverse Effects:
x Neurologic: Fatigue, Sedation, Ataxia,
Aggression, Insomnia
x Systemic: Constipation, anorexia, skin
rash
Contraindicated Drugs
xPhenytoin
xCarbamazepine
xOxcarbazepine
xGabapentin
xPregabalin
xTiagabine
xVigabatrin