Efficacy and tolerability of levetiracetam monotherapy in children, even in very young children, seems to be good. |
Levetiracetam monotherapy in children remains off-label because 32 studies have yielded insufficient formal evidence for its use. |
1 Introduction
2 Methods
3 Overview of Published Articles
3.1 Review, Opinion Statement and Case Reports
References | Diagnosis | Number of children | Age (years)a
| Maximum dosage | Follow-up of monotherapy (months) | Efficacy | AEDs prescribed before levetiracetam |
---|---|---|---|---|---|---|---|
Bello-Espinosa and Roberts [40] | BECTS | 3 | 4 6 10 | 250 mg/day 1000 mg/day 500–1000 mg/day | ND | SF SF SF | None |
Kossoff et al. [41] | Landau–Kleffner syndrome | 1 | 5 | 500–750 mg/day (60 mg/kg) | 9 | SF | CBZ, VPA |
Shoemaker and Rotenberg [42] | Neonatal seizures | 3 | 0 0 0 | 30 mg/kg/day 30 mg/kg/day 30 mg/kg/day | ND | SF SF SF | PHB, MDZ, fos-PHT PHB, MDZ, fos-PHT fos-PHT, OXC |
Papacostas et al. [43] | Tuberous sclerosis | 1 | 7 | 1000 mg/day | 18 | SF | VPA, OXC, CBZ, TPM |
Alehan et al. [44] | PRES → non-convulsive status epilepticus | 1 | 10 | 20 mg/kg/day | 9 | SF | PHT |
García and Rubio [45] | Panayiotopoulos syndrome | 2 | 8 12 | 2000 mg/day 1000 mg/day | 36 36 | SF SF | VPA VPA |
Ledet et al. [46] | Neonatal seizures | 1 | 0 | 40 mg/kg/day | 8 | SF | PHB |
Harbord [47] | Hemiplegic cerebral palsy and epilepsy | 3 | 8 14 17 | ND ND ND | 24 36 36 | SF SF SF | LTG, TPM, VPA CBZ, LTG, VPA CBZ, LTG, PHB, VPA |
Arslan et al. [48] | Acquired epileptiform opercular syndrome | 1 | 5 | 50 mg/kg/day | ND | SF | None |
Verrotti et al. [49] | Epilepsy in patient with Cornelia de Lange syndrome | 1 | ND | ND | 60 | SF | None |
3.2 Retrospective Studies
References | Diagnosis | Number of children | Age (years)a
| Dosage (mg/kg/day) | Follow-up of monotherapy (months) | Efficacy (%) | % AE (% stopped due to AE) | % patients with AEDs before LEV |
---|---|---|---|---|---|---|---|---|
Koukkari and Guarino [32] | Focal or generalized epilepsy | 19 | 0.8–16 | 20–79 | ND | SF or >50 % SR 58 | 33 (10) | 0 |
Khurana et al. [33] | Focal or generalized epilepsy | 18 | 2.5–18 | 14–60 | Mean 10.4 | SF 61, >50 % SR 67 | 22 (11) | 89 |
Sharpe et al. [34] | JME | 30 | 8–23 | 10–59 | Mean 27 | SF 80 | 7 (3) | 60 |
Perry et al. [35] | Focal epilepsy | LEV 66 | 2.8–7.8b
| ND | Mean 17.1 | SF 73 (at 6 months) | 45 (12) | 19.7 |
CBZ 20 | 3.4–9.3b
| ND | Mean 18.5 | SF 65 (at 6 months) | 70 (5) | 5 | ||
Bertsche et al. [36] | Focal epilepsy | LEV 42 | 0.5–16.7 | 27–108 | 12 | Ret. LEV 50 | LEV 10 (10) | 0 |
OXC 34 | 1.9–16.9 | 11–71 | Ret. OXC 71d
| OXC 12 (12) | ||||
Focal or generalized epilepsyc
| LEV 61 | 0.5–16.7 | 27–108 | 12 | Ret. LEV 52 | LEV 7 (7) | 0 | |
VPA 49 | 0.5–16.3 | 5–47 | Ret. VPA 63d
| VPA 14 (14) | ||||
Chen et al. [37] | ESES | 21 | 1.1–11.7e
| 30–60e
| 19e
| Reduction of SWI >50 % 29 Reduction of SWI <50 % 33 | ND (0)e
| ND |
Xiao et al. [38] | BECTS | LEV 33 | 4–11.3 | 15–38 | 18 | SF 6 months 58 SF 18 months 100 | 27 (0) | 0 |
VPA 23 | 4–13.5 | 9–31 | 18 | SF 6 months 61d
SF 18 months 100d
| 22 (0)d
| |||
Bayram et al. [39] | Focal or generalized epilepsy | 9 | 10–16 | 20–50 | Mean 7 | SF 100 | 0 (0) | 100 |
3.3 Prospective Open-Label Studies
References | Trial design | Diagnosis | Number of children | Age (years)a
| Dosageb
| Follow-up | Efficacy (%) | % AE (% stopped due to AE) | Retention rate (%) |
---|---|---|---|---|---|---|---|---|---|
Lagae et al. [12] | OL | All seizure types | 10 | 4–14 | 17–47 | 20 weeks | SF 20, >50 % SR 90 | 10 (0) | 90 |
Di Bonaventura et al. [23] | OL | Idiopathic generalized epilepsy | 4 | 8–16 | 2000–3000 (mg/day) | 6–10 months | SF 100 | 0 (0) | ND |
Verrotti et al. [24] | OL, MC | BECTS | 21 | 5–12 | 1000–2500 (mg/day) | 12 months | SF or >50 % SR 100 | 9.5 Transient (0) | 100 |
Gümüş et al. [25] | OL | West syndrome | 5 | 0 | 30–60 | 4 weeks | SF 40, >50 % SR 80 | ND | 100 |
Kossoff et al. [26] | OL | BECTS + language problems | 6 | 6–12 | 40 | 6 months | SF 67, improvement in language function | 17 (0) | 100 |
Verrotti et al. [27] | OL, MC | JME | 32 | 7–16 | 1000–2500 (mg/day) | 12 months | SF 91, >50 % SR 100 | 0 (0) | 100 |
Verrotti et al. [28] | OL, MC | CAE, JAE | 21 | 5–13 | 31–70 | 6 months | SF 52 | 10 Transient (0) | ND |
12 | 12 months | SF 100 | |||||||
Verrotti et al. [29] | OL, MC | COE-G | 12 | 6–16 | 20–45 | 18 months | SF 100 | 17 Transient (0) | 100 |
Fürwentsches et al. [30] | OL | Neonatal seizures | 6 | 0 | 10–50 | 3 months | SF 100 after 6 days, SF 50 after 3 months | 0 (0) | ND |
Li et al. [31] | OL | All seizure types | 37 | 0–16c
| 10–60 | 12 months | SF 46, >75 % SR 62 | 47.5 (3.3)c
| 73.3c
|
3.4 Randomized Controlled Trials
References | Trial design | Diagnosis | Number of children | Age (years)a
| Dosageb
| Follow-up | Efficacy (%) | % AE (% stopped due to AE) | Retention rate (%) |
---|---|---|---|---|---|---|---|---|---|
Coppola et al. [19] | RCT, OL, PG | BECTS | LEV 21 | 3–14 | LEV 20–30 | 18 months | LEV SF 90c
| LEV 14 (5) | LEV 85.7 |
OXC 18 | OXC 20–35 | OXC SF 72 | OXC 11 (5.5) | OXC 66.7 | |||||
Fattore et al. [20] | RCT, DB, PC, MC | CAE, JAE | LEV 38 | 4–15 | LEV 30 | 2 weeks | LEV SF 24c (18 % also on EEG) | LEV 18 | LEV 97.4 |
Placebo 21 | Placebo SF 5 (0 % on EEG) | Placebo 14 | Placebo 100 | ||||||
Rosenow et al. [21] | RCT, OL, PG, MC | Focal and generalized epilepsy | LEV 17 | 12–17 | LEV 1500–2000 (mg/day) | 6 weeks | No difference | No differences | ND |
LTG 16 | LTG 150–200 (mg/day) | 26 weeks | LEV vs LTG | LEV vs LTG | |||||
Borggraefe et al. [22] | RCT, DB, PG, MC | BECTS | LEV 21 | 6–12 | LEV 20–30 | 24 weeks | LEV TF 19c
| LEV (23.8) vs STMc (4.5c) Except for airways: LEV 23.8 STM 63.6 (p = 0.014) | LEV 57.1 |
STM 22 | STM 4–6 | STM TF 9.1 | STM 86.4 (p = 0.03) |