All anti epileptic their dose side effects and indications
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Antiepileptic Drugs (AEDs) - Complete Reference
Based on Adams and Victor's Principles of Neurology, 12th Edition
Overview
AEDs are classified into First Generation (older, pre-1990s), Second Generation (1990s-2000s), and Third Generation (2000s-present). The goal is seizure freedom with minimal adverse effects. About 70% of patients are fully controlled; ~25% partially. Monotherapy is always tried first.
Drug Tables
Dosing Reference
| Drug | Trade Name | Adult Dose (mg/day) | Children (mg/kg/day) | Half-life (h) | Therapeutic Level (µg/mL) |
|---|---|---|---|---|---|
| Valproic acid | Depakote | 1,000-3,000 | 30-60 | 6-15 | 50-100 |
| Phenytoin | Dilantin | 300-400 | 4-7 | 12-36 | 10-20 |
| Carbamazepine | Tegretol | 600-1,200 | 20-30 | 14-25 | 4-12 |
| Oxcarbazepine | Trileptal | 900-2,400 | 10-40 | 1-5 | - |
| Eslicarbazepine | Aptiom | 400-1,200 | - | 13-20 | - |
| Phenobarbital | Luminal | 90-200 | 3-5 (8 in infants) | 40-120 | 15-40 |
| Lamotrigine | Lamictal | 300-500 | 0.5 | 15-60 | 2-7 |
| Levetiracetam | Keppra | 500-3,000 | 20-60 | 6-8 | - |
| Topiramate | Topamax | 200-400 | 3-9 | 20-30 | - |
| Gabapentin | Neurontin | 900-3,600 | 25-35 | 5-7 | - |
| Pregabalin | Lyrica | 150-600 | - | 6-7 | - |
| Zonisamide | Zonegran | 200-400 | 4-8 | 50-70 | - |
| Lacosamide | Vimpat | 200-400 | - | 13 | - |
| Ethosuximide | Zarontin | 500-1,500 | 20-40 | 30-60 | 40-100 |
| Clonazepam | Klonopin | 1-20 | 0.05-0.2 | 18-50 | - |
| Clobazam | Onfi | 10-40 | 0.25-1 | 36-42 | - |
| Vigabatrin | Sabril | 1,000-3,000 | 50-150 | 5-8 | - |
| Rufinamide | Banzel | 1,600-3,200 | 10-45 | 6-10 | - |
| Perampanel | Fycompa | 4-12 | - | 70-110 | - |
| Brivaracetam | Briviact | 50-200 | - | 9 | - |
| Cenobamate | Xcopri | 100-400 | - | 50-60 | - |
Individual Drug Profiles
1. Phenytoin (Dilantin)
Mechanism: Sodium channel blocker (prolongs inactivation state)
Indications:
- Focal (partial) seizures
- Generalized tonic-clonic (GTC) seizures
- Status epilepticus (IV form - fosphenytoin preferred)
- Post-neurosurgical seizure prophylaxis
Dose: 300-400 mg/day (adults); 4-7 mg/kg/day (children)
- Therapeutic level: 10-20 µg/mL
- Zero-order (saturable) kinetics - small dose changes cause large level changes
Side effects:
- Dose-related: Nystagmus, diplopia, ataxia, cognitive dulling, sedation
- Chronic: Gingival hyperplasia, hirsutism, coarsening of facial features, peripheral neuropathy, osteomalacia (vitamin D deficiency), folate deficiency, megaloblastic anemia
- Idiosyncratic: Steven-Johnson syndrome (SJS), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), hepatotoxicity
- Teratogenic: Fetal hydantoin syndrome (craniofacial defects, digit/nail hypoplasia, growth retardation)
- IV: Hypotension, cardiac arrhythmia, purple glove syndrome
2. Carbamazepine (Tegretol)
Mechanism: Sodium channel blocker
Indications:
- Focal seizures (drug of choice)
- GTC seizures
- Trigeminal neuralgia (first-line)
- Bipolar disorder (mood stabilizer)
Dose: 600-1,200 mg/day; 20-30 mg/kg/day (children)
- Therapeutic level: 4-12 µg/mL
- Auto-induces its own metabolism
Side effects:
- Dose-related: Diplopia, ataxia, nausea, sedation
- Idiosyncratic: Aplastic anemia, agranulocytosis (rare but serious), SJS/TEN (especially in HLA-B*1502 carriers - Asian populations)
- Hyponatremia (SIADH-like effect)
- Hepatotoxicity
- Teratogenic: Neural tube defects
- Note: Active epoxide metabolite can accumulate and cause toxicity (inhibited by valproate)
3. Valproic Acid / Valproate (Depakote)
Mechanism: Multiple - sodium channel blockade, GABA enhancement, calcium channel (T-type) blockade
Indications:
- Broadest spectrum AED - effective in nearly all seizure types
- GTC seizures
- Absence seizures
- Myoclonic seizures (juvenile myoclonic epilepsy - drug of choice)
- Focal seizures
- Lennox-Gastaut syndrome
- Bipolar disorder, migraine prophylaxis
Dose: 1,000-3,000 mg/day; 30-60 mg/kg/day (children)
- Therapeutic level: 50-100 µg/mL
Side effects:
- Common: Weight gain, hair loss (alopecia), tremor, GI upset, nausea
- Serious: Hepatotoxicity (especially in children <2 years on polytherapy - can be fatal), pancreatitis, thrombocytopenia, platelet dysfunction
- Teratogenic: Highest teratogenic risk among AEDs - neural tube defects (spina bifida, 1-2%), cardiac defects, cognitive impairment in offspring; avoid in women of childbearing age if possible
- Inhibits hepatic enzymes - raises levels of phenobarbital, lamotrigine
4. Lamotrigine (Lamictal)
Mechanism: Sodium channel blocker; also inhibits glutamate release
Indications:
- Focal seizures
- GTC seizures
- Absence seizures
- Lennox-Gastaut syndrome
- Bipolar disorder (mood stabilizer)
- Relatively safe in pregnancy (among AEDs)
Dose: 300-500 mg/day adults
- Must titrate SLOWLY to avoid rash
- Dose halved when added to valproate (valproate inhibits lamotrigine metabolism)
- Dose doubled when added to enzyme inducers (carbamazepine, phenytoin)
Side effects:
- Rash - most important; 10% incidence; can progress to SJS/TEN (especially with rapid titration or with valproate co-administration)
- Diplopia, dizziness, headache, tremor
- Relatively well-tolerated cognitively
- Insomnia, irritability
5. Levetiracetam (Keppra)
Mechanism: Binds synaptic vesicle protein SV2A - unique mechanism; modulates neurotransmitter release
Indications:
- Focal seizures (adjunctive)
- GTC seizures
- Myoclonic seizures (juvenile myoclonic epilepsy)
- Status epilepticus (IV available)
- Widely used due to minimal drug interactions
Dose: 500-3,000 mg/day; 20-60 mg/kg/day (children)
Side effects:
- Behavioral/psychiatric: Irritability, aggression, mood changes, depression, psychosis ("Keppra rage") - most clinically significant
- Sedation, dizziness, headache
- Renally excreted - adjust in renal impairment
- Minimal drug interactions (does not affect liver enzymes)
- Relatively safe in pregnancy
6. Phenobarbital (Luminal)
Mechanism: Enhances GABA-A receptor (prolongs Cl⁻ channel opening duration)
Indications:
- Focal and GTC seizures
- Status epilepticus (IV)
- Neonatal seizures (drug of choice in neonates)
- Febrile seizures (prophylaxis, though less used now)
Dose: 90-200 mg/day (adults); 3-5 mg/kg/day (children); 8 mg/kg/day (infants)
- Therapeutic level: 15-40 µg/mL
- Long half-life allows once-daily dosing
Side effects:
- Sedation, cognitive impairment, depression (limits use)
- Tolerance/dependence
- In children: Paradoxical hyperactivity
- Osteomalacia (enzyme induction increases vitamin D catabolism)
- Teratogenic
- Enzyme inducer - lowers levels of many drugs
- Withdrawal can precipitate seizures
7. Ethosuximide (Zarontin)
Mechanism: T-type calcium channel blocker in thalamic neurons
Indications:
- Absence seizures ONLY (drug of choice for pure absence without GTC)
- Not effective for GTC or focal seizures
Dose: 500-1,500 mg/day; 20-40 mg/kg/day (children)
- Therapeutic level: 40-100 µg/mL
Side effects:
- GI upset (nausea, vomiting) - take with food
- Drowsiness, headache, dizziness
- Rarely: SJS, blood dyscrasias, lupus-like syndrome
8. Topiramate (Topamax)
Mechanism: Sodium channel blockade, GABA enhancement, AMPA/kainate receptor antagonism, carbonic anhydrase inhibition
Indications:
- Focal seizures
- GTC seizures (generalized)
- Lennox-Gastaut syndrome
- Migraine prophylaxis
- Weight loss (off-label)
Dose: 200-400 mg/day; 3-9 mg/kg/day (children)
Side effects:
- Cognitive impairment ("Dopamax") - word-finding difficulty, memory problems
- Weight loss (unique among AEDs)
- Kidney stones (carbonic anhydrase inhibition - alkaline urine, citrate reduction)
- Metabolic acidosis
- Glaucoma (acute angle closure)
- Oligohidrosis (decreased sweating) with hyperthermia
- Teratogenic (oral clefts)
- Paresthesias (perioral, limbs)
9. Gabapentin (Neurontin)
Mechanism: Binds α2δ subunit of voltage-gated calcium channels (reduces calcium influx and neurotransmitter release)
Indications:
- Focal seizures (adjunctive)
- Neuropathic pain (postherpetic neuralgia, diabetic neuropathy)
- Restless legs syndrome
- Anxiety (off-label)
Dose: 900-3,600 mg/day (divided TID - short half-life)
Side effects:
- Sedation, dizziness, ataxia
- Weight gain
- Peripheral edema
- Relatively benign profile
- No drug interactions (renally excreted unchanged)
10. Pregabalin (Lyrica)
Mechanism: Same as gabapentin (α2δ calcium channel subunit); more potent and predictable absorption
Indications:
- Focal seizures (adjunctive)
- Neuropathic pain (diabetic neuropathy, postherpetic neuralgia, central neuropathic pain)
- Fibromyalgia
- Generalized anxiety disorder
Dose: 150-600 mg/day (BID-TID dosing)
Side effects:
- Sedation, dizziness, weight gain
- Peripheral edema
- Potential for misuse/dependence
- Schedule V controlled substance (USA)
11. Oxcarbazepine (Trileptal)
Mechanism: Sodium channel blocker (prodrug - active metabolite MHD/eslicarbazepine)
Indications:
- Focal seizures (first-line)
- GTC seizures
- Less drug interactions than carbamazepine
Dose: 900-2,400 mg/day; 10-40 mg/kg/day (children)
Side effects:
- Hyponatremia (more common than with carbamazepine - up to 30%)
- Dizziness, diplopia, ataxia, nausea
- Rash (cross-reactivity with carbamazepine ~25%)
- Less bone marrow suppression risk than carbamazepine
12. Zonisamide (Zonegran)
Mechanism: Sodium and T-type calcium channel blockade; carbonic anhydrase inhibition
Indications:
- Focal seizures (adjunctive)
- Generalized seizures
- Myoclonic seizures
- Parkinson's disease (off-label)
Dose: 200-400 mg/day (once daily due to long half-life ~50-70h)
Side effects:
- Cognitive slowing, word-finding difficulty
- Kidney stones (carbonic anhydrase inhibition)
- Oligohidrosis with hyperthermia (especially in children)
- Weight loss
- Metabolic acidosis
13. Lacosamide (Vimpat)
Mechanism: Enhances slow inactivation of sodium channels (unique mechanism); modulates CRMP-2
Indications:
- Focal seizures (monotherapy and adjunctive)
- GTC seizures (generalized)
- Increasingly used in status epilepticus (IV)
Dose: 200-400 mg/day (BID)
Side effects:
- Dizziness, diplopia, headache, nausea
- PR interval prolongation (use caution in cardiac conduction disease)
- Minimal drug interactions
- Well-tolerated cognitively
14. Clonazepam (Klonopin)
Mechanism: Enhances GABA-A receptor (increases frequency of Cl⁻ channel opening) - benzodiazepine
Indications:
- Myoclonic seizures
- Absence seizures
- Infantile spasms
- Atonic seizures (Lennox-Gastaut)
- Anxiety disorders
Dose: 1-20 mg/day; 0.05-0.2 mg/kg/day (children)
Side effects:
- Sedation, tolerance (develops over weeks-months - limits long-term AED use)
- Ataxia, cognitive impairment
- Dependence, withdrawal seizures on abrupt discontinuation
- Hypersalivation (especially in children)
15. Vigabatrin (Sabril)
Mechanism: Irreversible GABA-transaminase inhibitor - raises GABA levels
Indications:
- Infantile spasms (West syndrome) - drug of choice (especially tuberous sclerosis)
- Focal seizures refractory to other drugs
- Available through restricted REMS program (USA)
Dose: 1,000-3,000 mg/day; 50-150 mg/kg/day (children)
Side effects:
- Permanent visual field defects (concentric constriction in up to 30-40%) - major limiting toxicity; requires regular ophthalmology monitoring
- Sedation, weight gain
- Behavioral changes in children
- MRI abnormalities in infants (signal changes in basal ganglia/thalamus - usually reversible)
16. Clobazam (Onfi)
Mechanism: 1,5-benzodiazepine (different structure from other benzodiazepines); GABA-A enhancer
Indications:
- Lennox-Gastaut syndrome (adjunctive)
- Drug-resistant focal seizures
- Dravet syndrome
Dose: 10-40 mg/day; 0.25-1 mg/kg/day (children)
Side effects:
- Sedation (less than other benzodiazepines)
- Drooling, constipation, URI
- Tolerance develops, though slower than other benzodiazepines
- Behavioral changes
17. Perampanel (Fycompa)
Mechanism: First-in-class AMPA glutamate receptor antagonist (post-synaptic)
Indications:
- Focal seizures (adjunctive)
- GTC seizures (generalized, adjunctive)
Dose: 4-12 mg/day (once daily at bedtime - very long half-life ~70-110h)
Side effects:
- Dizziness, somnolence, ataxia
- Serious psychiatric effects: Irritability, aggression, hostility, suicidal ideation - black box warning
- Weight gain
18. Brivaracetam (Briviact)
Mechanism: High-affinity SV2A binding (similar to levetiracetam but ~10x higher affinity; also has sodium channel effects)
Indications:
- Focal seizures (adjunctive; ages 4+)
- May work when levetiracetam has failed
Dose: 50-200 mg/day (BID)
Side effects:
- Sedation, dizziness
- Fewer psychiatric side effects than levetiracetam
- IV formulation available
19. Cenobamate (Xcopri)
Mechanism: Sodium channel (slow inactivation) + positive allosteric modulator of GABA-A receptor (at a different site than benzodiazepines)
Indications:
- Focal seizures (adults) - one of the most effective newer AEDs; high rates of seizure freedom in refractory focal epilepsy
Dose: 100-400 mg/day (once daily, slow titration over months)
Side effects:
- Dizziness, somnolence, headache
- DRESS syndrome risk (requires slow titration to minimize)
- Diplopia, fatigue
- Drug interactions (CYP inducer/inhibitor)
20. Rufinamide (Banzel)
Mechanism: Sodium channel modulation (prolongs inactivation)
Indications:
- Lennox-Gastaut syndrome (adjunctive)
Dose: 1,600-3,200 mg/day (BID); 10-45 mg/kg/day (children)
Side effects:
- Nausea, vomiting, headache, dizziness, fatigue
- Shortened QT interval (caution in familial short QT syndrome)
Seizure Type - Drug Choice Summary
| Seizure Type | First Line | Second Line | Third Line |
|---|---|---|---|
| Focal (partial) | Carbamazepine, Levetiracetam, Lamotrigine, Oxcarbazepine | Valproate, Lacosamide, Topiramate | Gabapentin, Phenytoin, Zonisamide |
| GTC (generalized) | Valproate, Lamotrigine, Levetiracetam | Carbamazepine, Topiramate, Oxcarbazepine | Phenytoin, Phenobarbital |
| Absence | Ethosuximide (pure absence), Valproate | Lamotrigine | Topiramate, Levetiracetam |
| Myoclonic | Valproate, Levetiracetam | Clonazepam, Lamotrigine | Topiramate, Zonisamide |
| Atonic/drop attacks (Lennox-Gastaut) | Valproate, Clobazam | Topiramate, Lamotrigine, Rufinamide | Levetiracetam |
| Infantile spasms | Vigabatrin (tuberous sclerosis), ACTH | Valproate | Clonazepam |
| Status epilepticus | Lorazepam/diazepam (acute) then Fosphenytoin/Levetiracetam/Valproate IV | Phenobarbital IV | Midazolam/Propofol infusion |
| Juvenile myoclonic epilepsy | Valproate, Levetiracetam | Lamotrigine | Topiramate, Clonazepam |
Key Clinical Pearls
Drug interactions to know:
- Valproate raises lamotrigine levels (halve lamotrigine dose) and phenobarbital levels
- Enzyme inducers (carbamazepine, phenytoin, phenobarbital) lower levels of each other and many other drugs (oral contraceptives, warfarin, etc.)
- Valproate inhibits carbamazepine epoxide hydrolase - causes epoxide buildup and toxicity
Teratogenicity ranking (avoid if possible in pregnancy):
- Valproate > Phenytoin/Phenobarbital/Carbamazepine > Topiramate > Lamotrigine/Levetiracetam (safer)
- All AEDs should be given with folic acid supplementation in women of childbearing age
Drugs safe in renal failure (hepatically metabolized): Valproate, phenytoin, carbamazepine
Drugs requiring renal dose adjustment: Levetiracetam, gabapentin, pregabalin, topiramate
SJS/DRESS risk drugs: Carbamazepine (especially HLA-B*1502+), phenytoin, lamotrigine (with rapid titration), cenobamate (without slow titration)
Weight effects:
- Weight gain: Valproate, gabapentin, pregabalin, vigabatrin
- Weight neutral/loss: Topiramate, zonisamide, lamotrigine
Sources: Adams and Victor's Principles of Neurology, 12th Edition; Bradley and Daroff's Neurology in Clinical Practice; Harriet Lane Handbook, 23rd Edition
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