How do you diagnose and treat epilepsy with medications?

Diagnosis and Treatment of Epilepsy

Diagnosis of Epilepsy

Epilepsy is diagnosed clinically after two or more unprovoked seizures, though treatment may be initiated after a single unprovoked seizure in high-risk patients. 1

When to Diagnose Epilepsy

• Two unprovoked seizures occurring at least 24 hours apart establishes the diagnosis of epilepsy 2
• Single unprovoked seizure warrants diagnosis and treatment consideration when:
  • History of prior brain insult or structural lesion on MRI 3
  • Epileptiform abnormalities on EEG 3
  • Seizure occurred during sleep 4
  • Patient occupation makes even one additional seizure devastating (e.g., commercial driver, pilot) 3

Clinical Recognition

• Non-specialist healthcare providers can be trained to recognize and diagnose convulsive epilepsy through appropriate training programs 1
• Diagnosis is based on seizure type classification (focal vs. generalized) which determines the brain region of origin and guides treatment 3, 2
• Approximately 10% of the population will have at least one seizure during their lifetime, but this does not constitute epilepsy 3, 2

Role of Diagnostic Testing

• EEG and neuroimaging should NOT be used routinely for diagnosis in non-specialized healthcare settings, particularly in low- and middle-income countries 1
• When required for etiological diagnosis, EEG and neuroimaging should be performed in specialized facilities with adequate expertise for interpretation 1
• MRI is preferred over CT for identifying structural lesions that increase recurrence risk 3

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Medication Treatment: Who Should Be Treated

Antiepileptic drugs should NOT be routinely prescribed after a first unprovoked seizure, but ARE indicated for epilepsy (two or more unprovoked seizures). 1

Clear Indications for Starting Medication

• Two or more unprovoked seizures (definitive epilepsy diagnosis) 1
• Single unprovoked seizure with high recurrence risk (structural lesion, epileptiform EEG, or brain insult history) 4, 3
• Seizure freedom is achieved in approximately 60-70% of patients with appropriate medication 4, 5

When NOT to Start Medication

• After a first unprovoked seizure in low-risk patients (normal EEG, normal MRI, no brain insult history) 1
• Provoked seizures (acute illness, metabolic disturbance, drug intoxication) should be treated by addressing the underlying cause, not with antiepileptic drugs 3

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First-Line Medication Selection

For Focal (Partial) Epilepsy

Carbamazepine or lamotrigine are first-line monotherapy options, with levetiracetam as an alternative if no psychiatric history exists. 6, 4, 7

• Carbamazepine should be preferentially offered to children and adults with partial onset seizures when available 1
• Oxcarbazepine and lamotrigine have demonstrated efficacy equal to older agents with better tolerability 7
• Levetiracetam (30 mg/kg) is effective but should be avoided in patients with psychiatric disorders due to behavioral side effects 6, 8, 4
• Phenobarbital should be offered as first-line when cost is the primary constraint, given its low acquisition costs 1, 6

For Generalized Epilepsy

Valproate is the preferred agent for generalized epilepsy, but must be avoided in women of childbearing potential. 1, 3

• Valproate demonstrates superior efficacy for generalized seizures but carries teratogenic risks 1, 9, 3
• Lamotrigine or topiramate are alternatives for generalized epilepsy 3, 7
• Levetiracetam has equal efficacy to valproate (73% vs 68%) for some generalized seizure types 6

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Monotherapy Principles

All patients should be started on monotherapy with a single antiepileptic drug at the minimum effective dose. 1

• Standard antiepileptic drugs (carbamazepine, phenobarbital, phenytoin, valproic acid) all have similar efficacy for convulsive epilepsy 1
• Approximately 60-70% of patients achieve lasting seizure remission with the first or second medication trial 3, 5
• If two adequate trials of monotherapy fail, the patient should be referred to an epilepsy center for consideration of surgery or other options 3

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Special Populations

Women of Childbearing Potential

Valproic acid must be avoided if possible; all women on antiepileptic drugs should take folic acid 5 mg daily. 1, 6

• Antiepileptic drug monotherapy at minimum effective dose is essential to minimize teratogenic risk 1
• Polytherapy should be avoided in women of childbearing potential 1
• Standard breastfeeding recommendations remain appropriate for phenobarbital, phenytoin, carbamazepine, and valproic acid 1

Patients with Psychiatric Comorbidities

Levetiracetam should be avoided in patients with depression, anxiety, or behavioral disorders due to risk of aggression, agitation, and psychotic symptoms. 8, 4

• 25-50% of epilepsy patients have psychiatric comorbidities including mood, anxiety, and attention deficit disorders 4
• Carbamazepine or lamotrigine are preferred alternatives in this population 4, 7

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When to Discontinue Medication

Discontinuation of antiepileptic drugs should be considered after 2 seizure-free years, with shared decision-making involving the patient and family. 1

• The decision must consider relevant clinical, social, and personal factors 1
• Approximately two-thirds of adults with new-onset epilepsy will achieve lasting remission on or off drugs 5

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Critical Pitfalls to Avoid

• Do not start antiepileptic drugs after a single low-risk seizure 1
• Do not use enzyme-inducing agents (carbamazepine, phenytoin) in patients with cardiovascular disease, as they worsen hyperlipidemia and accelerate osteoporosis 4
• Do not use valproate in women of childbearing potential unless absolutely necessary 1, 6
• Do not continue adding medications indefinitely—refer for epilepsy surgery evaluation after two failed medication trials 3
• Do not confuse provoked seizures with epilepsy—provoked seizures do not require chronic antiepileptic drug therapy 3