When should I increase a patient's anti-seizure medication dose or add another medication to their regimen?

When to Increase or Add Anti-Seizure Medications

Anti-seizure medication should be increased or a second medication added when a patient continues to have seizures despite being on an optimized dose of their first medication, with priority given to achieving seizure freedom while minimizing adverse effects. 1, 2

Indications for Medication Adjustment

• Persistent seizures despite adherence to the first anti-seizure medication at an adequate dose 2, 3
• Breakthrough seizures after a period of seizure control 4
• Seizures that continue despite reaching therapeutic blood levels of the medication (when applicable) 1
• Status epilepticus or acute repetitive seizures not responding to initial treatment 1
• Intolerable side effects at current dose requiring a change in medication strategy 5

Step-by-Step Approach to Medication Adjustment

1. Evaluate Current Medication Efficacy and Adherence

• Confirm medication adherence through patient interview and, if possible, blood level monitoring 1
• Verify the patient is on an appropriate dose for their weight, age, and renal/hepatic function 6, 7
• Rule out potential triggers for breakthrough seizures (sleep deprivation, alcohol, drug interactions) 4

2. Optimize First Medication Before Adding Another

• Increase the dose of the first medication to the maximum tolerated dose before adding a second agent 2, 5
• For most anti-seizure medications, dose increases should be done gradually (typically every 1-2 weeks) to minimize side effects 6, 7
• Target doses that achieve therapeutic blood levels when applicable (e.g., phenytoin, valproate) 1

3. When to Add a Second Medication

• Add a second medication when seizures persist despite reaching the maximum tolerated dose of the first medication 8, 3
• Consider adding a second medication immediately in cases of status epilepticus refractory to benzodiazepines 1
• In refractory status epilepticus, fosphenytoin, levetiracetam, or valproate are equally effective options (45-47% efficacy) 1

4. Selecting the Second Medication

• Choose a medication with a different mechanism of action from the first drug 8, 9
• Consider potential drug interactions when selecting combinations 1, 8
• Effective combinations based on clinical evidence include:
  • Levetiracetam with sodium channel blockers (lacosamide, lamotrigine) 8
  • Lamotrigine with valproate 8
  • Carbamazepine with gabapentin or levetiracetam 8

Important Considerations

• Up to 70% of patients with epilepsy can achieve seizure freedom with optimized medication therapy 2
• Approximately 30% of patients have drug-resistant epilepsy requiring more complex management 2, 9
• Most patients can be controlled on a single anti-seizure medication, but some require combination therapy 2
• When adding a second medication, introduce it gradually while maintaining the first medication, then reassess efficacy 8

Common Pitfalls to Avoid

• Increasing medication too rapidly, leading to avoidable side effects 5
• Failing to consider age-related or disease-related changes in drug metabolism 7, 5
• Combining medications with similar mechanisms of action, which may increase toxicity without improving efficacy 8
• Premature use of polytherapy before optimizing monotherapy 5
• Continuing ineffective high-dose regimens or combinations without reassessing the risk-benefit ratio 5
• Overlooking potential drug interactions that may reduce efficacy or increase toxicity 1, 8