TABLE 4.
Antiepileptogenic and/or disease-modifying effects of selected drugs or drug combinations in chronic rat models of epilepsy and post-traumatic epilepsy prevention trials in humans. Note that, except for VX-605, all drugs shown here are in clinical use for other indications. Drug effect is indicated by + = effective; +/-, inconsistent data (+), retrospective clinical data or data from small trials; ? = no data available (or found by literature review using Pubmed). For detailed data and references see Löscher (2020) and Löscher and Klein (2021a). Abbreviations: COX, cyclooxygenase; NE, not effective; PTZ, pentylenetetrazole; TBI, traumatic brain injury; TLE, temporal lobe epilepsy.
| Drug (administered after brain insult) | Electrical (amygdala) kindling model of TLE | Post-SE models of TLE | Post-TBI models of acquired epilepsy | Post-traumatic epilepsy in patients | ||||
|---|---|---|---|---|---|---|---|---|
| Retardation of kindling acquisition during treatment | Disease-modification (modification of kindling upon continued stimulations after drug withdrawal) | Prevention of epilepsy | Disease-modification | Prevention of epilepsy | Disease-modification | Prevention of epilepsy | Disease-modification | |
| Carbamazepine | NE | NE | NE | + | ? | NE | NE | ? |
| Phenytoin | NE | NE | NE | + | ? | Negative effect? | NE | Negative effect? |
| Phenobarbital | + | + | NE | +/- | ? | Negative effect? | NE | ? |
| Valproate | + | + | NE | + | ? | + | NE | NE |
| Levetiracetam | + | + | NE | +/- | ? | + | (+) | (+) |
| Magnesium sulfate | ? | ? | ? | ? | ? | + | NE | NE |
| Statins (e.g., atorvastatin) | + a | ? | ? | + | ? | + | + | + |
| Phenytoin + phenobarbital | ? | ? | ? | ? | ? | ? | NE | NE |
| Gabapentin | ? | ? | ? | + | ? | + | ? | ? |
| COX inhibitors | + | ? | +/- | +/- | ? | + | ? | ? |
| Anakinra | + | ? | NE b | + b | ? | + | ? | ? |
| Losartan | + | ? | + | + | + | + | ? | ? |
| Isofluran | ? | ? | + | + | ? | + | ? | ? |
| Rapamycin | ? | ? | NE c | NE c | + | + | ? | ? |
| Anakinra and VX-605 | ? | ? | NE | + | ? | ? | ? | ? |
| Levetiracetam + topiramate | ? | ? | + | + | ? | ? | ? | ? |
| Levetiracetam + topiramate + gabapentin | ? | ? | + | + | ? | ? | ? | ? |
| Levetiracetam + ceftriaxone + atorvastatin | ? | ? | + | + | ? | ? | ? | ? |
PTZ kindling.
Administered together with VX-765 (a specific non-peptide inhibitor of IL-1β cleavage and release).
When sufficiently long withdrawal after termination of treatment (see Löscher, 2020).