Is it safe to restart Keppra (levetiracetam) in a patient with a history of seizure disorders who previously discontinued it due to side effects?

Restarting Keppra (Levetiracetam) After Prior Discontinuation

Direct Answer

Yes, Keppra can be safely restarted in most patients with seizure disorders who previously discontinued it due to side effects, but this decision requires careful assessment of the specific adverse effects that led to discontinuation and the patient's psychiatric history. 1, 2

Critical Risk Assessment Before Restarting

High-Risk Patients Who May Not Be Candidates for Restart

• Patients with prior psychiatric disorders (schizoaffective disorder, depression, bipolar disorder) who developed behavioral symptoms on Keppra face significantly elevated risk of recurrence 2, 3
• History of suicidal ideation or behavior while on levetiracetam represents a contraindication to restart, as these patients constitute a specific high-vulnerability subgroup 3
• Prior psychotic symptoms (auditory hallucinations, delusional behavior) on Keppra should generally preclude restart 1
• Severe aggression or hostility requiring discontinuation suggests the patient may not tolerate rechallenge 1, 2

Lower-Risk Scenarios Where Restart Is Reasonable

• Mild somnolence or fatigue that resolved after discontinuation can often be managed with slower titration or lower dosing 1
• Gastrointestinal side effects (diarrhea, nausea) are typically dose-dependent and may be avoided with modified dosing 1
• Asthenia or dizziness occurring predominantly in the first 4 weeks may not recur with rechallenge, as these effects often diminish with continued exposure 1

Evidence-Based Restart Protocol

Step 1: Document the Original Adverse Event

• Identify the specific adverse effect that led to discontinuation (behavioral vs. somatic) 1
• Determine timing of onset (early titration period vs. late-emerging symptoms) 1
• Assess severity (dose reduction vs. complete discontinuation required) 1

Step 2: Screen for Psychiatric Risk Factors

Do NOT restart if the patient has: 2, 3

• Active suicidal ideation or recent suicide attempt
• Uncontrolled psychiatric disorder (especially schizoaffective disorder, severe depression)
• History of traumatic brain injury with psychiatric sequelae
• Active substance use disorder

Proceed with extreme caution if the patient has: 3

• Prior psychiatric disorder (even if currently stable)
• Structural brain abnormality
• History of substance use disorder (in remission)

Step 3: Implement Modified Dosing Strategy

• Start at lower dose than previously used (e.g., 250-500 mg twice daily rather than 750 mg twice daily) 1
• Titrate more slowly than standard protocols to minimize behavioral emergence 1
• Monitor closely during first 4 weeks when behavioral symptoms most commonly emerge 1

Step 4: Establish Monitoring Plan

Weekly monitoring for first month: 1, 2

• Behavioral changes (irritability, aggression, mood swings)
• Depressive symptoms or suicidal thoughts
• Somnolence or cognitive impairment
• Gastrointestinal tolerance

Monthly monitoring thereafter with specific questioning about psychiatric symptoms at each visit 3

Alternative Considerations

When Keppra Should NOT Be Restarted

If the original discontinuation was due to: 1, 2, 3

• Psychotic symptoms (hallucinations, delusions)
• Suicidal ideation or attempt
• Severe aggression requiring intervention
• Hepatic failure or pancreatitis (rare but serious)

Consider alternative antiepileptic drugs instead: 4

• Valproate (avoid in women of childbearing potential due to teratogenicity)
• Lamotrigine (requires slow titration but better psychiatric profile)
• Lacosamide (similar mechanism to levetiracetam but different side effect profile)

When Restart Is Most Appropriate

• Previous side effects were mild and dose-dependent 1
• Patient has no psychiatric history and prior adverse effects were somatic (fatigue, dizziness) 1
• Seizures are inadequately controlled on alternative medications and benefits outweigh risks 3
• Patient successfully tolerated levetiracetam previously for extended period before late-emerging side effects 5

Critical Pitfalls to Avoid

• Do not restart at the same dose that caused problems previously - always start lower and titrate more slowly 1
• Do not assume behavioral side effects won't recur - they often emerge beyond initial titration period and may be more severe on rechallenge 2
• Do not restart without psychiatric consultation in patients with prior psychiatric history who developed behavioral symptoms 3
• Do not ignore early warning signs - irritability and mood changes often precede more severe behavioral disturbances 1, 2

Gradual Withdrawal Requirement

If restart fails and discontinuation is again necessary: 1

• Taper gradually to minimize seizure risk
• Antiepileptic drugs, including levetiracetam, should be withdrawn gradually to minimize potential of increased seizure frequency
• Abrupt discontinuation increases risk of breakthrough seizures or status epilepticus