TABLE 2

Prophylactic effects of treatment with clinically used antiepileptic drugs on the long-term consequences of SE in rats

Only studies in which treatment started after onset of SE are included. If studies were performed in immature rats, this is indicated in the Model column.

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
Drug	Model (Induction of SE)	SE duration (Limited by)	Beginning of Prophylactic Treatment with Test Drug	Duration of Prophylactic Treatment	Latency to SRS	Incidence of SRS	Frequency, Severity, or Duration of SRS	Neurodegeneration	Behavioral Alterations (Psychopathology)	Impairment of Learning and Memory	Reference
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.