What are the adjuvant (add-on) antiepileptics?

Adjuvant Antiepileptic Drugs

For patients requiring add-on therapy for epilepsy, levetiracetam is the preferred adjuvant antiepileptic drug due to its favorable efficacy, minimal side effect profile, and lack of enzyme-inducing properties. 1

First-Line Monotherapy vs. Adjuvant Therapy

When initial monotherapy with standard antiepileptic drugs (carbamazepine, phenobarbital, phenytoin, or valproic acid) fails to control seizures adequately, adjuvant therapy becomes necessary. The choice of adjuvant antiepileptic drug should be guided by:

• Seizure type
• Patient characteristics
• Potential drug interactions
• Side effect profile
• Comorbidities

Preferred Adjuvant Antiepileptic Drugs

Levetiracetam

• First choice adjuvant due to:
  • Non-enzyme-inducing properties
  • Minimal drug interactions
  • Good tolerability profile
  • Efficacy across multiple seizure types
  • Available in IV formulation for emergency use 1
• Dosing: 500-3000 mg/day divided into two doses
• Potential side effects: Somnolence, irritability, behavioral changes 2

Lamotrigine

• Effective broad-spectrum adjuvant therapy
• Advantages:
  • Good tolerability profile
  • Minimal cognitive effects
  • Suitable for women of childbearing potential 3
• Requires slow titration to minimize risk of serious rash
• Dosing: Starting at 25 mg daily, gradually increasing to 200-400 mg/day 4

Topiramate

• Indicated as adjunctive therapy for:
  • Partial onset seizures
  • Primary generalized tonic-clonic seizures
  • Seizures associated with Lennox-Gastaut syndrome 5
• Advantages: Weight loss potential in obese patients 6
• Disadvantages: Cognitive side effects, risk of kidney stones, acute angle closure glaucoma 6

Valproic Acid

• Effective broad-spectrum adjuvant therapy
• Particularly effective for refractory status epilepticus (88% seizure control) 1
• Disadvantages:
  • Should be avoided in women of childbearing potential
  • Risk of hepatotoxicity and thrombocytopenia 1
  • Drug interactions

Zonisamide

• Effective for both partial and generalized seizures
• Long half-life allows once-daily dosing
• High long-term retention rate (55.1% at 6 years) 7
• Disadvantages: Somnolence, rash, gastrointestinal problems

Eslicarbazepine

• Newer adjuvant option for partial-onset seizures
• Demonstrated efficacy in clinical trials with 800-1200 mg/day dosing 8
• Less enzyme-inducing than older carbamazepine derivatives

Special Considerations

Brain Tumor Patients

For patients with brain tumors and seizures, non-enzyme-inducing antiepileptic drugs (NEIAEDs) are strongly preferred:

• Levetiracetam is the first choice
• Lamotrigine is an alternative option
• Avoid enzyme-inducing AEDs (phenytoin, phenobarbital, carbamazepine) due to interactions with chemotherapy 1

Status Epilepticus

For refractory status epilepticus after benzodiazepine failure:

1. Valproate: 20-30 mg/kg IV (88% success rate)
2. Levetiracetam: 30-60 mg/kg IV (44-73% success rate)
3. Phenytoin/Fosphenytoin: 18-20 mg/kg IV (56% success rate)
4. Propofol or Barbiturates for highly refractory cases 1

Women of Childbearing Potential

• Lamotrigine or Levetiracetam are preferred
• Avoid valproic acid due to teratogenic effects
• Folic acid supplementation is essential 3

Practical Approach to Adjuvant Selection

1. Assess seizure control with current monotherapy
2. Choose adjuvant based on seizure type:
   • For partial seizures: Levetiracetam, lamotrigine, topiramate, eslicarbazepine
   • For generalized seizures: Levetiracetam, lamotrigine, zonisamide
3. Consider comorbidities:
   • Obesity: Consider topiramate or zonisamide (weight loss potential)
   • Cognitive concerns: Prefer levetiracetam or lamotrigine
   • History of rash: Avoid lamotrigine, consider levetiracetam
4. Check for drug interactions with current medications
5. Start low and titrate slowly to minimize side effects

Common Pitfalls to Avoid

• Polytherapy with similar mechanisms of action: Combining multiple sodium channel blockers may increase toxicity without additional benefit
• Ignoring enzyme-inducing properties: EIAEDs can reduce efficacy of many medications including chemotherapy and oral contraceptives
• Rapid titration: Especially with lamotrigine, can lead to serious rash
• Overlooking side effect profiles: Match AED choice to patient characteristics to improve adherence and quality of life

By carefully selecting the appropriate adjuvant antiepileptic drug based on seizure type, patient characteristics, and potential interactions, clinicians can optimize seizure control while minimizing adverse effects and improving quality of life.