Should a child with a history of rare, uncertain episodes resembling seizures, occurring approximately every 12-18 months, with only three incidents, be tapered off levetiracetam (Keppra) under close medical supervision?

Discontinuation of Levetiracetam in Uncertain Seizure History

This child should be tapered off levetiracetam under close medical supervision, as the episodes were rare, uncertain in nature, and prophylactic antiepileptic therapy is not indicated for infrequent or questionable seizure activity.

Rationale for Discontinuation

The clinical scenario describes only three episodes over several years (every 12-18 months) with diagnostic uncertainty about whether these were true seizures. This presentation does not meet criteria for epilepsy requiring chronic antiepileptic therapy.

Key Principles from Guidelines

• The American Academy of Pediatrics explicitly recommends against continuous anticonvulsant prophylaxis for children with simple febrile seizures, stating that potential toxicities clearly outweigh minimal risks 1

• Even for confirmed simple febrile seizures with known recurrence risk, the harm-benefit analysis clearly favors no treatment, as recurrent simple febrile seizures cause no harm and do not warrant prophylactic treatment 1

• The American Academy of Pediatrics states that simple febrile seizures cause no decline in IQ, academic performance, neurocognitive function, behavioral abnormalities, or structural brain damage 1

Application to This Case

Given that this child's episodes are:

• Extremely rare (only 3 episodes over multiple years)
• Diagnostically uncertain (unclear if they were true seizures)
• Non-recurrent in recent history (occurring only every 12-18 months)

The indication for continuous antiepileptic therapy is even weaker than for confirmed simple febrile seizures, where prophylaxis is already contraindicated 1.

Risks of Continuing Levetiracetam

Behavioral and Psychiatric Side Effects

• Behavioral abnormalities occur frequently with levetiracetam in pediatric patients, including irritability (6.3% vs 2.4% placebo), aggression, and conduct disorders (11.4% vs 3.6% placebo) 2

• Non-psychotic mood disorders including depression, mood swings, and tearfulness occur in 12.7% of levetiracetam-treated patients compared to 8.3% of placebo patients 2

• A systematic review demonstrated a statistically significant relative risk of 2.18 for behavioral side-effects with levetiracetam versus placebo, with aggression, hostility, and nervousness reported most commonly 3

• Acute psychosis has been reported in children taking levetiracetam, with dramatic improvement within days of discontinuation or dose reduction 4

Other Adverse Effects

• Somnolence requiring dose reduction occurs in 7% of levetiracetam-treated patients 2

• Rare but serious adverse effects include refractory hypokalemia that resolves upon medication discontinuation 5

Safe Tapering Approach

Withdrawal Protocol

• Antiepileptic drugs, including levetiracetam, should be withdrawn gradually to minimize the potential of increased seizure frequency 2

• The FDA label explicitly warns against abrupt discontinuation 2

Practical Tapering Strategy

While specific tapering schedules are not provided in the guidelines, a reasonable approach based on general antiepileptic withdrawal principles would be:

• Reduce the dose by 25% every 1-2 weeks over 4-8 weeks total
• Monitor closely for any seizure activity during the taper
• Educate caregivers about seizure recognition and first aid management 1

Monitoring During and After Discontinuation

What to Watch For

• Any seizure-like activity should be documented carefully, including duration, characteristics, and associated fever or illness 1

• If true seizures occur during or after taper, neurological consultation should be requested for prolonged seizures, repetitive focal seizures, or abnormal neurological exam 1

Parent Education

• Educate caregivers about the benign nature of infrequent seizure-like episodes and practical home management 1

• Provide clear instructions on when to seek emergency care (seizures lasting >5 minutes, multiple seizures in 24 hours, or focal neurological deficits) 1

• Reassure that even if true epilepsy were present, the risk of developing long-term complications is extremely low, and brief observation off medication is reasonable given the diagnostic uncertainty 1

Important Caveats

When NOT to Discontinue

Do not taper levetiracetam without further evaluation if:

• The child has documented epilepsy on EEG
• There are underlying neurological abnormalities or developmental delays 1
• Seizures have been clearly witnessed and documented as true epileptic events
• There is a family history of epilepsy combined with other risk factors 1

Need for Diagnostic Clarification

• If diagnostic uncertainty persists and seizure-like episodes recur after discontinuation, consider neurological consultation and possible EEG monitoring rather than empiric long-term antiepileptic therapy 1

• MRI with diffusion-weighted imaging is the most sensitive modality for detecting underlying structural abnormalities if indicated by clinical features 1