What are the treatment options and dosage guidelines for epilepsy?

Seizure and Epilepsy Treatment Guidelines

For the treatment of epilepsy, monotherapy with standard antiepileptic drugs (carbamazepine, phenobarbital, phenytoin, or valproic acid) should be offered as first-line treatment, with drug selection based on seizure type, patient characteristics, and side effect profiles. 1

Pathophysiology and Causes

• Epilepsy is a neurological disorder characterized by recurrent unprovoked seizures due to abnormal excessive or synchronous neuronal activity in the brain 2
• Seizures result from an imbalance between excitatory and inhibitory neurotransmission, leading to hypersynchronous neuronal discharges 3
• Causes include:
  • Genetic factors (channelopathies, metabolic disorders)
  • Structural abnormalities (trauma, stroke, tumors, malformations)
  • Infections (meningitis, encephalitis)
  • Metabolic disturbances (hypoglycemia, hyponatremia)
  • Unknown etiology (idiopathic) 3

Symptoms

• Focal seizures (originating in one hemisphere):
  • Simple focal: preserved consciousness with motor, sensory, autonomic, or psychic symptoms
  • Complex focal: impaired consciousness, automatisms
  • Secondary generalized: progression to bilateral tonic-clonic activity 3
• Generalized seizures (involving both hemispheres):
  • Tonic-clonic: convulsions with loss of consciousness
  • Absence: brief lapses in awareness
  • Myoclonic: sudden brief muscle jerks
  • Atonic: sudden loss of muscle tone 3

Diagnosis

• Clinical diagnosis based on detailed seizure history from patient and witnesses 1
• Non-specialist healthcare providers can be trained to recognize and diagnose convulsive epilepsy 1
• Electroencephalography (EEG) and neuroimaging should not be used routinely in non-specialized settings but should be done in specialized facilities when needed for etiological diagnosis 1
• Differential diagnosis includes pseudoseizures, syncope, migraine, cerebrovascular events, movement disorders, and sleep disorders 3

Differential Diagnosis

• Psychogenic non-epileptic seizures: stress-related episodes without EEG changes
• Syncope: transient loss of consciousness due to cerebral hypoperfusion
• Migraine: especially with aura or basilar-type
• Transient ischemic attacks: focal neurological symptoms
• Movement disorders: tics, tremors, dystonias
• Sleep disorders: parasomnias, cataplexy 3

Treatment Guidelines

Acute Seizure Management

1. Without IV access:

   • Administer rectal diazepam (avoid IM diazepam due to erratic absorption)
   • Consider IM phenobarbital when rectal diazepam is not possible 1

2. With IV access:

   • Administer IV benzodiazepine (lorazepam preferred over diazepam)
   • For sustained control or continuing seizures, administer IV phenobarbital or phenytoin 1

3. Refractory status epilepticus:

   • Consider IV valproate (30 mg/kg) or levetiracetam (30 mg/kg) if seizures continue after benzodiazepines and phenytoin 1
   • Both valproate and levetiracetam show similar efficacy (68-73%) in refractory status epilepticus 1

Chronic Epilepsy Management

First-line Treatment Options

1. For focal seizures:

   • Carbamazepine is preferred for partial onset seizures 1
   • Initial dose: 200 mg twice daily for adults and children >12 years; 100 mg twice daily for children 6-12 years; 10-20 mg/kg/day for children <6 years 4
   • Maintenance dose: 800-1200 mg daily for adults; 400-800 mg daily for children 6-12 years; below 35 mg/kg/day for children <6 years 4

2. For generalized seizures:

   • Valproic acid is the preferred first-line treatment 1, 5
   • Avoid valproic acid in women of childbearing potential 1

3. Alternative options:

   • Lamotrigine and levetiracetam show better tolerability profiles compared to other AEDs 5
   • Levetiracetam dosing: Target dose of 3000 mg/day for adults or 60 mg/kg/day for children, given in 2 divided doses 6

Treatment Principles

• Monotherapy is preferred over polytherapy to minimize side effects 1
• Do not prescribe AEDs after a first unprovoked seizure unless high risk for recurrence 1
• Consider discontinuation after 2 seizure-free years, taking into account clinical, social, and personal factors 1
• For women with epilepsy:
  • Use monotherapy at minimum effective dose
  • Avoid valproic acid if possible
  • Prescribe folic acid supplementation 1
• For people with intellectual disability and epilepsy:
  • Consider valproic acid or carbamazepine instead of phenytoin or phenobarbital due to lower risk of behavioral adverse effects 1

Special Considerations

• Status epilepticus: IV benzodiazepines followed by phenytoin/fosphenytoin, valproate, or levetiracetam 1
• Febrile seizures: Follow local standards for fever management; observe for 24 hours; consider prophylactic intermittent diazepam only for recurrent or prolonged complex febrile seizures 1
• Drug selection based on comorbidities:
  • Psychiatric disorders: Avoid levetiracetam 2
  • Obesity: Consider topiramate or zonisamide which may cause weight loss 7
  • History of drug-induced rash: Consider valproate, gabapentin, topiramate, tiagabine, or levetiracetam 7
  • Cognitive concerns: Consider gabapentin, tiagabine, lamotrigine, oxcarbazepine, or levetiracetam 7

Common Adverse Effects

• Drowsiness/fatigue
• Headache or migraine
• Gastrointestinal disturbances
• Dizziness/faintness
• Rash or skin disorders 5

Treatment Pitfalls and Caveats

• Avoid polytherapy when possible to minimize adverse effects and drug interactions 1
• Monitor for specific drug-related adverse effects:
  • Carbamazepine: hyponatremia, osteoporosis
  • Phenytoin: gingival hyperplasia, hirsutism
  • Topiramate: acute angle closure glaucoma, cognitive impairment
  • Valproate: weight gain, hair loss, teratogenicity 7
• If seizures persist after trials of two appropriate AEDs, consider referral to an epilepsy center for evaluation of surgical options 3
• Enzyme-inducing AEDs (carbamazepine, phenytoin) may worsen comorbid conditions and interact with other medications 2