TABLE 3.
Experimental and clinical evidence for synergistic (supra-additive) two-drug combinations of antiseizure medications. For references see Deckers et al. (2000), Kaminski et al. (2009), Blaszczyk et al. (2018), and Verrotti et al. (2020a,b). “?” indicates that no data were found. Only few data are available on the combinations of more than two antiseizure medications (not shown here).
| Drug combination | Synergistic antiseizure effect in animal models | Presumed synergistic antiseizure effect in patients with epilepsy a | Pharmacokinetic interactions |
|---|---|---|---|
| Carbamazepine + lacosamide | + | ? | No |
| Carbamazepine + phenytoin | ? | + | Yes |
| Carbamazepine + valproate | No (only additive) | + | Yes |
| Carbamazepine + vigabatrin | ? | + | Minor |
| Gabapentin + tiagabine | + | ? | No |
| Gabapentin + lacosamide | + | ? | No |
| Gabapentin + carbamazepine | + | ? | Yes |
| Gabapentin + oxcarbazepine | + | ? | Yes |
| Gabapentin + phenytoin | + | ? | Yes |
| Gabapentin + valproate | + | ? | No |
| Lamotrigine + valproate | + | + | No |
| Lamotrigine + phenobarbital | + | + | Yes |
| Lamotrigine + lacosamide | + | + | No |
| Levetiracetam + lacosamide | + | + | No |
| Levetiracetam + valproate | + | ? | No |
| Levetiracetam + clonazepam | + | ? | No |
| Levetiracetam + phenobarbital | + | ? | ? |
| Levetiracetam + topiramate | + | ? | No |
| Phenytoin + phenobarbital | + | + | Yes |
| Stiripentol + carbamazepine | + | ? | Yes |
| Topiramate + felbamate | + | ? | No |
| Topiramate + gabapentin | + | ? | No |
| Topiramate + lamotrigine | + | + | No |
| Topiramate + oxcarbazepine | + | ? | No |
| Topiramate + lacosamide | + | No (only additive) | No |
| Valproate + phenytoin | + | ? | Yes |
| Valproate + ethosuximide | No (only additive) | + | Yes |
a
Note that the combination of lamotrigine with valproate is the only synergistic combination with sufficient clinical evidence (see text).