Drug | Model (Induction of SE) | SE duration (Limited by) | Beginning of Prophylactic Treatment with Test Drug | Duration of Prophylactic Treatment | Consequences of Prophylactic Drug Treatment | Reference | |||||
---|---|---|---|---|---|---|---|---|---|---|---|
Latency to SRS | Incidence of SRS | Frequency, Severity, or Duration of SRS | Neurodegeneration | Behavioral Alterations (Psychopathology) | Impairment of Learning and Memory | ||||||
Carbamazepine | Kainate | Not limited | 1 day after SE | 56 days | N.D. | N.E. | ↓ | ↓ (Hippocampus) | N.D. | N.D. | Capella and Lemos, 2002 |
Carbamazepine | Pilocarpine (in hippocampus) | 3 h (thiopental) | 1 h after 3 h SE | 4 days | N.D. | N.D. | N.D. | ↓ (CA1, CA3, hilus) | N.D. | ↓ | Cunha et al., 2009 |
Carisbamate | Lithium-pilocarpine | 1 h (diazepam in controls) | 1 h after SE onset | 7 day | Increased | ↓ (motor SRS) | ↓ | ↓ (CA1, PC, EC, amygdala, thalamus) | N.D. | N.D. | François et al., 2005 (A) |
Diazepam* | Amygdala stimulation | Not limited in controls | 2 or 3 h after SE onset | Second dose 6 h later | N.D. | ↓ | ↓ | ↓ (Hippocampus) | N.D. | N.D. | Pitkänen et al., 2005* |
Diazepam | Pilocarpine (in hippocampus) | 3 h (thiopental) | 1 h after 3 h SE | 4 days | N.D. | N.D. | N.D. | ↓ (CA1, CA3, hilus) | N.D. | ↓ | Cunha et al., 2009 |
Fluorofelbamate* | Perforant path stimulation | Not limited in controls | 10 or 40 min after onset of stimulation | 1 dose | N.D. | N.E. | ↓ | N.D. | N.D. | N.D. | Mazarati et al., 2002* |
Gabapentin | Kainate (P35) | Not limited | 1 day after SE | 10 days | N.D. | N.D. | N.D. | ↓ (Hippocampus) | N.E. | N.E. | Cilio et al., 2001 |
Lamotrigine | Perforant path stimulation | 2 h after end of PPS (diazepam) | 1 h after SE onset | 2 weeks | N.D. | N.D. | N.D. | ↓ (CA3, hilus) | N.D. | N.E. | Halonen et al., 2001b |
Lamotrigine | Amygdala stimulation | Not limited in controls | 2 h after SE onset | 11 weeks | N.D. | N.E. | N.E. | N.E. | N.D. | N.D. | Nissinen et al., 2004 |
Levetiracetam | Pilocarpine | 30 min (diazepam) | 30 min after SE onset | 21 days | N.D. | N.E. | N.D. | ↓(Hippocampus) | N.D. | N.D. | Klitgaard et al., 2001 (A) |
Levetiracetam | Perforant path stimulation (PPS) | Not limited in controls | 1, 3, and 6 h after 30 min of PPS stimulation | 29 days | N.D. | N.E. | ↓ | N.D. | N.D. | N.D. | Mazarati et al., 2003 (A) |
Levetiracetam | Amygdala stimulation | 4 h (by diazepam) in exp. 2 | 24 h after onset of stimulation (exp. 1) or 4 h after SE onset (exp. 2) | 5–8 weeks | N.D. | N.E. | N.E. | N.E. | N.E. | N.E. | Brandt et al., 2007 |
Levetiracetam | Lithium-pilocarpine | Not limited | 24 h after SE onset | 2 weeks | N.D. | N.E. | N.D. | ↓ (CA1, CA3, hilus) | N.D. | N.E. | Zhou et al., 2007 |
Phenobarbital | Kainate (P35) | Not limited | 1 day after SE | 97 days | N.D. | N.E. | N.E. | N.E. | Worsened | Worsened | Mikati et al., 1994 |
Phenobarbital | Kainate (P35) | Not limited | 1 day after SE | 40 days | N.D. | N.E. | N.E. | N.E. | N.D. | N.E. | Bolanos et al., 1998 |
Phenobarbital* | Hippocampal stimulation | Not limited in controls | 1, 2 or 4 h after SE onset | 1 dose | N.D. | ↓ (Only for the 1 h after SE onset group) | N.D. | N.D. | N.D. | N.D. | Prasad et al., 2002* |
Phenobarbital | Lithium-Pilocarpine | 90 min (diazepam plus phenobarbital) | 90 min after SE onset | 2 weeks | Increased | N.E. | ↓ | N.E. (?) | N.E. | N.D. | Brandt et al., 2010 |
Phenytoin | Hippocampal stimulation | Not limited | 1, 2, or 4 h after SE onset | 1 dose | N.D. | N.E. | N.D. | N.D. | N.D. | N.D. | Prasad et al., 2002 |
Phenytoin | Pilocarpine (in hippocampus) | 3 h (thiopental) | 1 h after 3 h SE | 4 days | N.D. | N.D. | N.D. | ↓ (CA1, CA3, hilus) | N.D. | ↓ | Cunha et al., 2009 |
Pregabalin* | Lithium-pilocarpine | 2 h (diazepam) | 20 min after pilocarpine | 55 days | Increased | N.D. | N.D. | ↓ (PC, EC) | N.D. | N.D. | André et al., 2003* |
Retigabine | Kainate | 1.5 h (diazepam) | 1.5, 2.5 and 3.5 h after SE onset | 3 doses | N.D. | N.D. | N.D. | N.E. | N.D. | N.D. | Ebert et al., 2002 |
Topiramate | Hippocampal stimulation | 140 min (termination of stimulation) | 140 min after onset of stimulation | 1 dose | N.D. | N.D. | N.D. | ↓ (CA1, CA3, hilus) | N.D. | N.D. | Niebauer and Gruenthal, 1999 |
Topiramate | Lithium-pilocarpine | Not limited | 24 h after SE | 28 days | N.D. | N.D. | N.D. | ↓ (Hippocampus) | N.D. | ↓ | Cha et al., 2002 |
Topiramate | Pilocarpine | 1 h (diazepam) | 1 h after SE onset | 4 days | N.D. | ↓ (3–6 months after SE) | N.D. | ↓ (CA1) | N.D. | N.D. | DeLorenzo et al., 2002 (A) |
Topiramate | Lithium-pilocarpine | 1 h (diazepam) in controls) | 1 h after SE onset | 7 days | N.E. | N.E. | N.E. | ↓ (CA1, CA3) | N.D. | N.D. | Rigoulot et al., 2004 |
Topiramate (plus diazepam) | Lithium-pilocarpine | 1 h (diazepam) in controls | Topiramate at SE onset, diazepam 2 h after SE onset | 7 days | N.E. | N.E. | N.E. | ↓ (CA1, hilus) | N.D. | N.D. | François et al., 2006 |
Topiramate* | Lithium-pilocarpine (in P15 or P28 rats) | In controls atropine after 70 min SE | 20, 40, or 70 min after pilocarpine (together with atropine) | 1 dose | N.D. | ↓ (P15>P28) | ↓ | N.D. | N.D. | N.D. | Suchomelova et al., 2006* |
Topiramate | Pilocarpine | 2 h (diazepam) in controls | 40 min after SE onset | N.D. | N.D. | N.D. | ↓ (CA1, CA3) | N.D. | ↓ | Frisch et al., 2007 | |
Topiramate | Lithium-pilocarpine | 2 h (pentobarbital) | 1 h after 2 h SE | 6 weeks | N.D. | N.D. | N.D. | N.E. (Hippocampus) | N.D. | (↓) | Shatskikh et al., 2009 |
Valproate | Kainate (P35) | Not limited | 1 day after SE | 40 days | N.D. | ↓ (During taper) | ↓ (During taper) | ↓ (CA1) | ↓ | ↓ | Bolanos et al., 1998 |
Valproate | Pilocarpine | 30 min (diazepam) | 30 min after SE onset | 21 days | N.D. | N.E. | N.D. | N.E. | N.D. | N.D. | Klitgaard et al., 2001 (A) |
Valproate | Amygdala stimulation | 4 h (diazepam) | 4 h after SE onset | 4 weeks | N.D. | N.E. | N.E. | ↓ (Hippocampus and hilus) | ↓ | N.E. | Brandt et al., 2006 |
Valproate | Kainate | Not limited in controls | 5 h after SE onset | 1–5 weeks | N.D. | N.D. | N.D. | N.E. (Hippocampus and hilus) | N.D. | ↓ | Jessberger et al., 2007 |
Vigabatrin* | Lithium-pilocarpine | Not limited in controls | 10 min after pilocarpine | 45 days | N.E. | N.E. | N.E. | ↓ (CA1, CA3 and hilus) | N.D. | N.D. | André et al., 2001* |
Vigabatrin | Amygdala stimulation | Not limited | 2 days after SE | 10 weeks | N.E. | N.E. | N.E. | N.E. | N.D. | N.E. | Halonen et al., 2001a |
↵↓, A prophylactic (beneficial) effect; *, studies in which treatment effects were due to initial insult modification (i.e., reduction of SE duration or severity) rather than an antiepileptogenic effect (see text for discussion); (A), studies that are available only as abstracts.
EC, entorhinal cortex; N.D., not determined; N.E., no effect; P, postnatal day; PC, piriform cortex; PPS, perforant path stimulation; SRS, spontaneous recurrent seizures.