For how long should anti-epileptic (AED) medication be continued in a patient presented with a probable seizure?

Duration of Antiepileptic Drug Therapy After a Probable First Seizure

For a patient presenting with a probable first unprovoked seizure, antiepileptic drugs (AEDs) should generally NOT be routinely initiated, and if treatment is started, it should be discontinued after 24 consecutive months of seizure freedom. 1, 2

Initial Treatment Decision

The World Health Organization explicitly recommends against routine prescription of antiepileptic drugs after a first unprovoked seizure in both adults and children. 2 This represents the clearest guideline-level recommendation and should frame your decision-making.

Key considerations for the initial decision:

• Recurrence risk is moderate but treatment doesn't improve long-term outcomes: Approximately one-third to one-half of patients will have a recurrent seizure within 5 years, even with normal MRI and EEG 2
• Treatment reduces short-term recurrence but not 5-year outcomes: The number needed to treat to prevent a single recurrence within 2 years is 14 patients, and treatment does not appear to affect long-term outcomes at 5 years 2
• The default approach should be observation with neurology follow-up, not immediate treatment 2

If treatment IS initiated (against guideline recommendations):

The American College of Emergency Physicians suggests this decision should be made in coordination with neurology, particularly if there is a remote history of brain injury 1

Duration of Treatment When AEDs Are Started

For patients who remain seizure-free:

If a patient is seizure-free for 24 consecutive months after resolution of any structural lesions on imaging, consideration should be given to tapering and stopping antiepileptic drugs. 1 This recommendation comes from the Infectious Diseases Society of America and provides the most specific timeline.

Evidence supporting withdrawal after extended seizure freedom:

• Approximately 70% of patients remain seizure-free at 2 years after AED discontinuation 3
• In adults, the probability of remaining seizure-free ranges from 39-74% at 1 year and 35-57% at 2 years after withdrawal 4
• The relapse risk is highest in the first 6-12 months after withdrawal and decreases thereafter 4

Critical Caveats and Risk Factors

Factors favoring LONGER treatment duration (or not withdrawing):

• Adolescent-onset epilepsy 4
• Partial seizures 4
• Underlying neurological condition 4
• Abnormal EEG at time of withdrawal 4
• Age ≥40 years, history of alcoholism, hyperglycemia, or Glasgow Coma Scale <15 2

Factors favoring withdrawal after 24 months:

• Childhood-onset epilepsy 4
• Idiopathic generalized epilepsy 4
• Normal EEG in children 4

Important Warnings

Avoid phenytoin for long-term use:

Phenytoin should not be used long-term due to negative cognitive effects and poor side effect profile. 1 The American Academy of Neurology notes that prophylactic antiepileptic drugs may negatively affect specific cognitive domains even when global functional outcomes appear unchanged. 1

Risk of treatment failure after relapse:

In approximately 20% of individuals whose seizures relapse following AED withdrawal, re-institution of pharmacological therapy may not readily restore seizure control. 5 This is a critical consideration when counseling patients about withdrawal.

Teratogenic considerations:

Valproate should be avoided in women of childbearing potential if possible. 2

Practical Algorithm

1. First unprovoked seizure with normal MRI/EEG: Do NOT start AEDs routinely 2
2. If AEDs are started (patient preference, high-risk features, or neurology recommendation): Continue for minimum 24 months seizure-free 1
3. At 24 months seizure-free: Assess risk factors and discuss withdrawal 1, 4
4. If withdrawing: Taper gradually, with highest relapse risk in first 6 months 4
5. Monitor closely during first year post-withdrawal: 85% of early recurrences occur within 6 hours of a trigger event 2