Table 3.
Studies of antidepressant administration in animal models of seizures and epilepsy
| Model | Species | Drug | Dose (mg kg–1) | Study protocol | Seizure outcome measures | Reference |
|---|---|---|---|---|---|---|
| Antidepressants were found to be proconvulsant | ||||||
| PTZ | Mouse | CIT | 25, 50 | Injection 30 min prior to sz test | Behavioural threshold | Payandemehr et al. (2012)* |
| PTZ | Rat | FLX | 10 | Injection 1 h prior to sz test | Severity | Zienowicz et al. (2005) |
| PTZ | Rat | FLX | 10 | Sz tested after 21 days admin. | Behavioural threshold | Ferrero et al. (2005) |
| PTZ | Rat | VEN | 75–100 | Injection 30 min prior to sz test | Severity and latency | Santos et al. (2002) |
| Lidocaine | Mouse | DES, MAP | 5–20 | Sz tested 2–5 after 5 days admin. | Severity, threshold, frequency | Arai et al. (2003)* |
| Lidocaine | Mouse | CIT | 10 | Injection 30 min prior to sz test | Frequency | Arai et al. (2003)* |
| Pilocarpine | Mouse | CIT, REB, BUP | 15,30,20–40 | Injection 30 min prior to sz test | Behavioural threshold | Vermoesen et al. (2011)* |
| Flurothyl | Mouse | SRT, BUP | 40,40 | Injection 30 min prior to sz test | Latency | Ahern et al. (2006)* |
| Flurothyl | Mouse | REB | 20 | Sz tested after 21 days admin. | Latency | Ahern et al. (2006)* |
| Antidepressants were found to be anticonvulsant | ||||||
| MES | Mouse | BUP | 15–30 | Injection 30 min prior to sz | Behavioural threshold | Tutka et al. (2004)* |
| PTZ | Zebrafish | CIT, REB, BUP | 10–300 μM | Injection 1 min prior to sz | Behavioural threshold | Vermoesen et al. (2011)* |
| PTZ | Mouse | REB, BUP | 5–10, 10–40 | Injection 30 min prior to sz test | Behavioural threshold | Vermoesen et al. (2011)* |
| PTZ | Mouse | FLX | 20 | Injection 60 min prior to sz test | Survival | Kecskemeti et al. (2005)* |
| PTZ | Mouse | FLX | 1–20 | Injection 30 min prior to sz test | Behavioural threshold, latency | Ugale et al. (2004) |
| PTZ | Mouse | CIT | 0.5, 1 | Injection 30 min prior to sz test | Behavioural threshold | Payandemehr et al. (2012)* |
| PTZ | Rat | VEN | 25–50 | Injection 30 min prior to sz test | Severity and latency | Santos et al. (2002) |
| Pilocarpine | Zebrafish | CIT | 10–300 μM | Injection 1 min prior to sz test | Behavioural threshold | Vermoesen et al. (2011)* |
| Pilocarpine | Rat | FLX | 20 | Once epileptic, drug admin for 5 days, sz assessed for 72 h | SRS | Hernandez et al. (2002) |
| Pilocarpine | Rat | FLX | 20 | Once epileptic, drug admin for 10 days, sz assessed for 7 days | Behavioural threshold | Mazarati et al. (2008)* |
| Flurothyl | Mouse | REB | 20 | Sz tested after 21 days admin. | Latency | Ahern et al. (2006)* |
| Focal pilocarpine | Rat | CIT | 1 μM | Sz tested over 4 h drug infusion | Severity | Clinckers et al. (2004) |
| Focal bicuculline | Rat | FLX | 5–20 | Injection 1 h prior to sz test | Frequency, severity | Prendiville and Gale (1993) |
| Focal bicuculline | Rat | FLX | 1.75–7 nM | Injection 15 min prior to sz test | Behavioural threshold | Pasini et al. (1992) |
| Picrotoxin | Mouse | FLX | 20 | Injection 65 min prior to sz test | Latency | Pericic et al. (2005)* |
| Picrotoxin | Mouse | FLX | 20 | Sz tested after 5 days admin. | Latency | Pericic et al. (2005)* |
| KA | Mouse | CIT | 10 | Sz tested after 7 days admin. | Severity | Jaako et al. (2011) |
| KA | Rat | CIT, REB | 15, 20–30 | Once epileptic, drug admin for 4 days and sz assessed | Frequency, cumulative duration | Vermoesen et al. (2012)* |
| MES | Mouse | VEN | 12.5, 25 | Injection 30 min prior to sz test | Convulsive threshold | Borowicz et al. (2011)* |
| MES | Mouse | VEN | 12.5, 25 | Sz tested after 14 days admin. | Convulsive threshold | Borowicz et al. (2011)* |
| MES | Mouse | FLX | 10 | Injection 60 min prior to sz test | Hind limb extension threshold | Raju et al. (1999)* |
| Ear shock | Mouse | FLX | 15–25 | Injection 30 min prior to sz test | Hind limb extension threshold | Borowicz et al. (2006)* |
| Hippocampal kindling | Rat | FLX | 10 nmol | Injection 15 min prior to sz test | Electrical threshold | Wada et al. (1993) |
| Hippocampal kindling | Rat | FLX | 10 | Sz tested after 21 days admin., 7 days wait, one injection | Electrical threshold∧ | Wada et al. (1995)* |
| Amygdala kindling | Cat | FLX | 2–10 | Injection 1–49 h prior to sz test | Electrical threshold | Siegal and Murphy (1979) |
| GEPR-3 and GEPR-9 | Rat | FLX | 30 | Injection 1–5 h prior to sz test | Severity | Dailey et al. (1992)* |
| GEPR-3 and GEPR-9 | Rat | FLX | 7–20 | Sz tested every 7 days over 28 days admin. | Behavioural threshold | Dailey et al. (1992)* |
| GEPR-9 | Rat | FLX | 15 | Injection 1 h prior to sz test | Severity and latency, behavioural | Yan et al. (1994) |
| El mice | Mouse | CIT | 0.01, 0.02, 0.04%# | Sz tested after 14 days admin. | Behavioural threshold | Kabuto et al. (1994b) |
| El mice | Mouse | FLX | 10 | Sz tested after 3 or 7 days admin. | Behavioural threshold | Richman and Heinrichs (2007) |
| Antidepressants resulted in no change | ||||||
| PTZ, KA | Mouse | BUP | 5–50 | Injection 30 min prior to sz test | Number of convulsions | Tutka et al. (2004)* |
| PTZ, LH | Rat | FLX | 10 | Injection 1 h prior to sz test | Behavioural threshold | Ferrero et al. (2005)* |
| PTZ, pilocarpine | Mouse | CIT, REB, BUP | various | Injection 30 min prior to sz test | Behavioural threshold | Vermoesen et al. (2011)* |
| PTZ | Mouse | FLX | 20 | Injection 60 min prior to sz test | Latency | Kecskemeti et al. (2005)* |
| PTZ | Rat | FLX | 2.5–20 | Injection 30 min prior to sz test | Latency and severity | Ceyhan et al. (2005) |
| Lidocaine | Mouse | DES, MAP | 20 | Sz tested 5–9 after 5 days admin. | Frequency | Arai et al. (2003)* |
| Lidocaine | Mouse | CIT | 10–20 | Sz tested after 5 days admin. | Frequency, threshold | Arai et al. (2003)* |
| Pilocarpine | Zebrafish | REB, BUP | 10–100 | Injection 1 min prior to sz test | Behavioural threshold | Vermoesen et al. (2011)* |
| Pilocarpine | Rat | FLX | 20 | Once epileptic, drug admin for 10 days, sz assessed for 7 days | Seizure frequency | Mazarati et al. (2008)* |
| Flurothyl | Mouse | VEN, REB | 20–40,20 | Injection 30 min prior to sz test | Latency | Ahern et al. (2006)* |
| Flurothyl | Mouse | VEN, BUP, SRT | 20–40,40,40 | Sz tested after 21 days admin. | Latency to first seizure | Ahern et al. (2006)* |
| KA | Mouse | FLX | 10–50 | Injection 30 min prior to sz test | Severity and duration | Jin et al. (2009) |
| KA | Rat | CIT, REB | 5–10, 10 | Once epileptic, drug admin for 4 days and sz assessed | Severity and duration | Vermoesen et al. (2012)* |
| MES | Mouse | FLX | 10 | Sz tested after 21 days admin. | Hind limb extension threshold | Raju et al. (1999)* |
| Ear shock | Mouse | FLX | 10 | Injection 30 min prior to sz test | Hind limb extension threshold | Borowicz et al. (2006)* |
| Ear shock | Mouse | FLX | 7.5–20 | Sz tested after 14 days admin. | Hind limb extension threshold | Borowicz et al. (2007) |
| Hippocampal kindling | Rat | FLX | 10 | Injection 2 h prior to sz test | Threshold and duration | Wada et al. (1999) |
| Hippocampal kindling | Rat | FLX | 1,10 | Injection 1 h prior to sz test | Electrical threshold | Wada et al. (1995)* |
| EEG | Rat | FLV, CLV | 10–30 | Drugs infused and seizures assessed at 10 min intervals | Epileptic activity on EEG | Krijzer et al. (1984) |
| GEPR-3 | Rat | FLX | 3.5, 7.2, 14.1 nmol | Injection 15 min prior to sz test | Severity and latency | Statnick et al. (1996) |
| GEPR-9 | Rat | FLX | 15 | Injection 2 h prior to sz test | Severity and latency | Browning et al. (1997) |
| El mice | Mouse | CIT | 80 | Sz tested after 14 days admin. | Behavioural threshold | Kabuto et al. (1994a) |
*
Study is repeated within the table; #dietary supplement; ∧no difference after 4 weeks.
ADT, afterdischarge threshold; BUP, bupropion; CIT, citalopram; CLV, clovoxamine; DES, desipramine; FLV, fluvoxamine; FLX, fluoxetine; GEPR, genetically epilepsy prone rats; h, hour; KA, kainic acid; LH, learned helplessness; MAP, maprotiline; min, minute; PAR, paroxetine; SRS, spontaneous recurrent seizures (as recorded on EEG); sz, seizure; VEN, venlafaxine.