From the Guidelines
For breakthrough seizures while on Topamax (topiramate) and seeking an alternative to Keppra (levetiracetam), I would recommend considering Valproate as an effective add-on antiepileptic drug (AED) with a different mechanism of action. Valproate works by enhancing the activity of gamma-aminobutyric acid (GABA), a neurotransmitter that inhibits neuronal excitability, which complements topiramate's multiple mechanisms of action, including blocking voltage-dependent sodium channels, augmenting the activity of GABA at the GABA_A receptors, and antagonizing the AMPA/kainate subtype of the glutamate receptor 1. Typical dosing of valproate starts at 20 to 30 mg/kg at a rate of 40 mg/min, with common side effects including dizziness, thrombocytopenia, liver toxicity, and hyperammonemia 1. Other good options with different mechanisms include Lamictal (lamotrigine), which modulates sodium channels and inhibits glutamate release, or Briviact (brivaracetam), which has a similar mechanism to levetiracetam but with potentially fewer behavioral side effects. The choice should be individualized based on seizure type, comorbidities, potential drug interactions, and side effect profile, with valproate being a viable option due to its efficacy and relatively favorable side effect profile compared to other alternatives like phenytoin or fosphenytoin, as demonstrated in studies where valproate was shown to be at least as effective as phenytoin for refractory status epilepticus, with potentially fewer adverse effects 1. Any medication change should be done gradually under medical supervision to minimize breakthrough seizures during transition. Key considerations for valproate include monitoring for signs of liver toxicity and thrombocytopenia, as well as adjusting the dose based on serum levels and clinical response, as recommended by guidelines that endorse valproate for both emergent treatment of seizures and refractory status epilepticus based on high-level evidence 1.
From the Research
Alternative AEDs to Supplement Topamax
To find an alternative AED to supplement Topamax (topiramate) besides Keppra (levetiracetam) for breakthrough seizures with a different mechanism, we can consider the following options:
- Lamotrigine: According to 2, lamotrigine is as effective as valproate for treating generalized tonic-clonic, tonic, and clonic seizures.
- Zonisamide: As mentioned in 3, zonisamide met the criteria for non-inferiority compared to lamotrigine in the primary intention-to-treat analysis of time to 12-month remission.
- Valproate: Although valproate is often used as a first-line treatment, it can be considered as an alternative to supplement Topamax, especially for generalized seizures, as shown in 2 and 3.
Mechanism of Action
These AEDs have different mechanisms of action:
- Lamotrigine: Blocks sodium channels and inhibits glutamate release 4.
- Zonisamide: Blocks sodium and calcium channels, and inhibits glutamate release 3.
- Valproate: Multiple mechanisms, including blocking sodium channels and inhibiting glutamate release 2.
Efficacy and Safety
The efficacy and safety of these AEDs have been evaluated in various studies:
- Lamotrigine: Shown to be effective in treating focal and generalized seizures, with a relatively favorable safety profile 4, 2.
- Zonisamide: Demonstrated efficacy in treating focal seizures, but with a higher risk of adverse reactions compared to lamotrigine 3.
- Valproate: Effective in treating generalized seizures, but with a higher risk of adverse reactions and teratogenicity compared to other AEDs 2, 3.