(15) Grosso et al., 2007 | Retrospective | Focal epilepsy (30): - Probably symptomatic (12); - Symptomatic (18); West syndrome (17): - Cryptogenic (7); - Symptomatic (10); Lennox-Gastaut (2); Myoclonic-astatic(2); Eyelid myoclonia (2); Dravet syndrome (3); Early myoclonic Encephalopathy (6); Unclassifiable (19) | 81 F = 36; M = 45 | < 4 y Mean = 27 m (2 - 46 m) | 5 - 10 mg/kg/bid, ↑ weeky 62 mg/kg/day, Mean LEV Daily dose = 41 mg/kg (25 - 62 mg/kg/day) | 9 | SF = 10 (12%) ↓> 50% = 14 (30%) ↓21%-50%= 18 (22%), ↓<20 (unchanged) = 24 (30%), ↑> 50% comparison baseline = 15 (18%) | After 12 months follow-up: 9 (19%) | Drowsiness (45%), Nervousness (36%) Cognitive disturbances (29%) Loss of appetite (14%), Sleep disturbances (7%), Vomiting (4%) | Mean = 4 (1 - 10)/ mean = 2 (1 - 3); [Valproate (41%), Phenobarbital (31%), Carbamazepine (27%) Vigabatrin (26%) Topiramate (22%), Clonazepam (20%) Lamotrigine (9%), Oxcarbazepine (7%) Chlormethyldiazepam (6%) ACTH (10%)] |
(2) Opp et al., 2005 | Retrospective | Epilepsy syndrome: -Focal 191 (67.0%); -Generalized 49 (17.2%); -Focal and generalized signs 45 (15.8%) | 285, F = 128, M = 137, ND = 20 | Mean: 9.9 y Ranging: 0-17 | Maximum dose 47.7±21.8 mg/kg/day | ≥ 12 | SF = 13 (6.2%), ↓≥ 50% = 39 (18.7%), ↓< 50% no significant change = 136 (65.1%), Increase of >100% = 14 (6.7%), Not evaluated = 7 (3.3%) | 70 (33.5%) of the 209 patients at the last visi | - Somnolence/fatigue 52 ( 18.2), -Somnolence only initially 16 (5.6), -Sleeping disturbance 9 (3.1), -Behavioral changes 44 (15.4): Aggression 30 (10.5), Altered mood 8 (2.8), - Loss of appetite 10 (3.5), -Vomiting 6 (2.1), -Tremor 6 (2.1), -Cognitive disturbance 5 (1.8), - Severe side effects: - Hemorrhagic colitis 1 (0.4), - Apneas 1 (0.4) | 6.8 (ranging 0 - 20) AED on average and only 31 patients (11.0%), The most prevalent co-medication was valproic acid (VPA) in 133 patients (47.7%), followed by lamotrigine in 44 patients (15.8%) and oxcarbazepine in 43 patients (15.4%) |
(12) Lagae et al., 2003 | Open-label add-on trial | - Partial and generalized seizures -Lennox Gastaut syndrome = 5pts, Identifiable lesions on MRI = 8 pts-Mild or severe mental retardation = all 21 pts | 21, F = 11, M = 10 | 11 months and 14 years, old, (mean age = 5y) | 10 mg/kg/day, increased every 4th day by 10 mg/kg up to a maximum of 60 mg/kg/day | 12 w | SF = 1 (4.76%), ↓> 50% = 10 (47%), ↓< 10% (unchanged) = 8 (38.1) | no data | -Headache = 1, -Increased somnolence = 2, -Behavioral changes = 1, - Incr. alertness = 4 | - Valproic acid, - Vigabatrine, - Lamotrigine, - Benzodiazepine, -Topiramate, -Gabapentin, -Carbamazepine, -Tiagabine , -Phenobarbital-phenytoin |
(17) Stuelpnagel, 2007 | Prospective add-on trial | - Different severe epilepsy syndromes, - Focal epilepsy 79 (61.2%): Symptomatic 64 (81%), Cryptogenic 15 (19%), - Generalized epilepsy 36 (27.9%): symptomatic 19(52.8%), Cryptogenic 9 (25%), Idiopathic 8 (22.2%), -Unclassified epilepsy 14 (10.9%) | 129, F = 46, M = 83 | (Mean age=10.6y) 6 m-39 ys 9 ms | Maximum LEV dosage was 39.8 mg/kg/day (ranging 6 - 70 mg/kg/day) | 3 y in 35 responders pts | SF = 5(3. 9%), ↓≥ 50% = 35(27.1%) ↓< 50% = 8, - ↑seizure = 1 | 29 (22.5%); after 3 years follow-up | The rate of side effects = 39.8%, The most common side effects: -Fatigue (12.5%); -Aggressiveness (7.8%) , -Gastrointestinal disorders (13.3%) | -Valproic acid= 57 (44.2%), -Oxcarbazepine= 29 (22.5%), -Clobazam =24 (18.6%), -Lamotrigine= 20 (15.5%), -Other= 75 (58.1%) |
(10) Callenbach et al., 2008 | Prospective multi-center, open-label, add-on | -Seizure type (%), -Simple partial seizures, 2 (6.1), -Complex partial seizures, 19 (57.6), -Partial onset with secondary generalization 10 (30.3), -Generalized tonic-clonic, 2 (6.1) -Tonic 4 (12.1), -Atonic 1 (3.0), -Clonic 0, -Myoclonic 4 (12.1), -Absences 6 (18.2), -Unclassified seizures 1 (3.0); -Epilepsy syndrome No. (%): Symptomatic localization-related epilepsy not further defined 11 (33.3). Cryptogenic localization-related epilepsy 8 (24.2) Juvenile absence epilepsy 1 (3.0); Idiopathic generalized epilepsy not further defined. 2 (6.1)Epilepsy with myoclonic-astatic seizures 1 (3.0), Symptomatic generalized epilepsy not further, defined 8 (24.2); Epilepsy undetermined whether focal or generalized 1 (3.0), Not known 1 (3.0) | 33, F = 16 (48.5); M = 17 (51.5) | 4 - 16 y | 10 mg/kg/day was increased with 2 week up to a maximum dose of 60 mg/kg/day | 26 w | SF = 9(27%), ↓> 50% = 17 (51.5%), Unchanged = 4, ↑seizure = 4 | 23 (69.7%) after 26 weeks | Most common complaints were hyperactivity, (48.5%), somnolence (36.4%), irritability (33.3%) and aggressive behavior (27.3%) | Valproic acid (45.5%), lamotrigine (33.3%), carbamazepine, (27.3%), oxcarbazepine (15.2%), clobazam (15.2%), ethosuxi-mide (9.1%), topiramate (9.1%), clonazepam (6.1%), and phenytoin (3.0%) |
(18) Pina-Garza et al., 2009 | Multicenter, double-blind, randomized, placebo-controlled study | Refractory partial-onset seizures | 111 patients (58, 96.7% Levetiracetam; 53, 94.6% placebo) | From 1 m to < 4 years | In patients aged 1 to < 6 months, levetiracetam was initiated at 20 mg/kg/day and titrated to 40 mg/kg/day; in patients aged 6 months to <4 years, levetiracetam was initiated at 25 mg/kg/day and titrated to 50 mg/kg/day | Long term follow-up | ↓ ≥50%: in LEV group=25(43.1%) vs.in placebo = 10 (19.6%,) | No data | Adverse event, levetiracetam,/placebo no. (%), Somnolence 8 (13.3) / 1 (1.8), Irritability 7 (11.7)/ 0, Pyrexia 3 (5.0) /4 (7.1), Constipation 2 (3.3)/ 3 (5.4), Vomiting 2 (3.3)/ 3 (5.4), Insomnia 1 (1.7) /3 (5.4), Rash 1 (1.7)/ 3 (5.4) | Levetiracetam/placebo, No. (%): Valproic acid 25 (41.7)/21 (37.5) Phenobarbital 22 (36.7)/18 (32.1), Topiramate 21 (35.0) /16 (28.6), Oxcarbazepine 14 (23.3)/ 8 (14.3), Vigabatrin 8 (13.3)/ 11 (19.6), Clobazam 7 (11.7) / 3 (5.4), Carbamazepine 5 (8.3)/ 13 (23.2), Clonazepam 3 (5.0) / 9 (16.1) |
(11) Grosso et al, 2005 | Multi-centric, prospective and uncontrolled study | Epilepsy syndromes: -localization related epilepsy (53): cryptogenic(22), symptomatic(31);- generalized(45): myoclonic-astatic epilepsy (6); The Dravet syndrome (6); cryptogenic generalized (4); infantile spasms (5); Ohtahara syndrome (2) NR; Lennox-Gastaut (8) startle epilepsy (3) symptomatic generalized (11) - unclassifiable(12) | 110 children, (52 females and 60 males) | < 16 y, mean = 7.7 y (ranging 6 m-15.9 y) | 10 - 60 mg/kg/day (median 38 4.1) | 2 - 20 months (median 7.6) | SF = 10(9%), ↓≥ 50%= 43 (39%), ↓ < 50%= 27, ↓ < 20% unchanged = 28 (25%), ↑≥ 50% = 12 (11%) | - | - The main side effects of somnolence and irritability occurred in 16 (14% ) of patients | - The number of AEDs, administered at onset of LEV treatment ranged, from one to five (median two): - Valproate (46%) - Carbamazepine (37%) - Vigabatrin (27%), - Topiramate (26.5%), - Clonazepam, (24.5%), -Lamotrigine (18.5%), -Chlormethyldiazepam, (9%) -Phenobarbital (5%) |
(16) Kanemura, 2013 | Prospective | -Epilepsy symptomatic/cryptogenic (54); - Idiopathic (7); -Generalized epilepsy (7); -Localization related epilepsy (48); -Undetermined epilepsy (3); -Unclassified epilepsy (3) | 61, F = 25; M = 36 | 16 m - 18 y (mean= 5.9 y) | 10 mg/kg/ day up to a maximum of 60 mg/kg/day according to the participants’ clinical seizures | At least 6 months of follow-up | SF in epileptic syndrome = 15 (24.6%): -Localization-related epilepsy = 12, -Generalized epilepsy = 1; -Undetermined = 2; Responder = 33; (51.4%): -Localization related epilepsy = 28, -Generalized epilepsy = 3, -Undetermined, =1, 25- < 50% minimal response = 17, Unchanged = 3 | - | -Drowsiness: 2 pts (3.3%) | Mean number of AEDs tried, before LEV = 5.2 (ranging 2 – 8) -Number of concomitant medications at the time of LEV (1 - 3, mean = 2.3) |
(13) Glauser et al., 2006 | RCT | Drug-resistant partial-onset seizures | 198 (LEV = 101, placebo = 97), F ≈ 98, M ≈ 100 | 4 - 16 y | Target dose of 60 mg/kg/day | 14w | SF = 7 (6.9%) patients who received leveti racetam and one patient (1.0%) who received placebo, ↓≥ 50% = 45(44.6%), in LEV group vs 19(19.6%) in placebo group | - | Specific adverse event (LEV/placebo), Somnolence 23/ 11, Accidental injury 17/ 10, Vomiting 15/ 13 Anorexia 13/ 8, Rhinitis 13/ 8, Hostility 12/ 6, Cough increased 11/ 7, Pharyngitis 10/ 8, Nervousness 10/ 2, Asthenia 9/ 3, Diarrhea 8/ 7, Personality disorder 8/ 7, Dizziness 7/ 2, Emotional lability 6/ 4, Pain 6/ 3, Agitation 6/ 1 | % Receiving concomitant AEDs, (in 10% of patients) carbamazepine 34.7 38.1, topiramate 28.7 32.0, valproate 25.7 28.9, lamotrigine 22.8 20.6, oxcarbazepine 12.9 10.3 |