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. 2017 Jun 29;2017(6):CD011412. doi: 10.1002/14651858.CD011412.pub2

Table 5.

Summary of results of trials without individual participant data

Trial Summary of resultsb
Aikia 1992 1. MANOVA revealed no significant interaction effect of group and time
2. MANOVA revealed no significant interaction effect of group and time
3. MANOVA revealed no significant interaction effect of group and time
4. MANOVA revealed no significant interaction effect of group and time
Bidabadi 2009 1. CBZ: 64%, PHB: 63%
2. No statistically significant difference between groups
3. No statistically significant difference between groups
4. Mean seizure frequency: CBZ: 0.66, PHB: 0.8
5. Mean duration (seconds): CBZ: 12.63; PHB: 15
Brodie 2002 1. Median time to exit: GBP: 69 days, LTG: 48 days
HR: 1.043 (95% confidence interval 0.602 to 1.809)
2. Proportion of evaluable population completing the study – GBP: 71.6%, LTG: 67.1%
No difference between groups for time to withdrawal for any reason
3. No difference between groups for time to first seizure
4. GBP: 76.1%, LTG: 76.8% (ITT population)
5. Withdrawals during titration: GBP: 7, LTG: 10
Withdrawals after titration: GBP: 10, LTG: 13
Callaghan 1985 1a. PHT: 67%; CBZ: 37%; VPS: 53% 1b. PHT: 12%; CBZ: 37%; VPS: 25% 1c. PHT: 21%; CBZ: 25%; VPS: 22%
2. PHT: 10%; CBZ: 8%; VPS:11%
Capone 2008 1. CBZ: 76%, LEV: 76%
2. Proportion with AEs: CBZ: 65%, LEV: 50%
3. CBZ: 2 discontinuations due to failure to control seizures and interactions with other medications
LEV: 3 discontinuations – 1 death from stroke and 2 due to AEs
Castriota 2008 1. No significant difference between groups
2. No significant difference between groups
Chen 1996 1. No significant difference between groups 2. No significant difference between groups
3. 2 children from PHB group, 1 child from CBZ group and no children from VPS group withdrew from the study because of allergic reactions
4. No significant difference between groups
Cho 2011 1. Overall effect on sleep parameters was comparable between groups. LEV group PSG significant increase post treatment compared to baseline in sleep efficiency (P = 0.039) and in decrease of wake time after sleep onset (P = 0.047), no significant change in other sleep parameters. CBZ group post treatment compared to baseline significant increases in the percentage of slow wave sleep (P = 0.038), no significant change in other sleep parameters
2. No significant difference between baseline and post‐treatment between the 2 groups
Christe 1997 1. OXC 56.6% ; VPS 53.8%
2. No significant difference between groups
3. OXC 40.6% ; VPS 33.9%
4. Efficacy no significant difference between groups
Tolerability no significant difference between groups
Therapeutic effect no significant difference between groups
5. Proportion of participants experiencing at least 1 AE regardless of relationship to trial drug OXC 89.8%; VPS 87.6%
6. Seizure frequency per week OXC (n = 106) mean 0.17 median 0, VPS (n = 106) mean 0.40, median 0
Consoli 2012 1. No significant difference between groups
2. Completed study LEV 52/62, CBZ 54/66,
withdrawals: 8 poor compliance (LEV 4, CBZ 4); 7 severe adverse effect (LEV 3, CBZ 4); 7 unknown cause (LEV 3, CBZ 4)
3. Attention deficit on digital span end of follow up greater in CBZ group than LEV (P = 0.03)
Stroop test worse in CBZ than LEV (P = 0.02)
No significant difference between groups for other scales. Impairment of activities of daily living greater CBZ than LEV (P = 0.05)
4. 4 participants (LEV 2, CBZ 2) had abnormal EEG at baseline, normal at end of treatment. Drug dose reduction (LEV 4, CBZ 2). Remaining participants unmodified versus baseline
5. No significant difference between groups
Cossu 1984 1. Significant decrease in visual‐verbal memory for CBZ and acoustic memory for PHB. No significant differences for other tests
Czapinski 1997 1. PHB: 60%, PHT: 59%; CBZ: 62%; VPS: 64% 2. PHB: 33%, PHT: 23%; CBZ: 30%; VPS: 23%
Dam 1989 1. Baseline
OXC mean 2.9 (SD 7.0), median 1, range 0‐60
CBZ mean 5.8 (SD 14.7) median 1, range 0‐99
Maintenance phases
OXC mean 0.4 (SD 3.0) median 0, range 0‐27
CBZ mean 0.3 (SD 1.4) median 0, range 0‐12
2. Severe side effects CBZ 25, OXC 13, statistically significant difference favouring OXC (P = 0.04)
Participants without any side effects CBZ 25, OXC 29 no significant difference between groups (P = 0.22)
3. Global efficacy no significant difference between groups (P = 0.77); global tolerability (P = 0.11)
Participants very good/good CBZ 69 (73%), OXC 76 (84%)
Participants poor/very poor CBZ 26 (27%), OXC 15 (16%)
4. Nature of side effects same between groups, included tiredness, headache, dizziness, ataxia. Participants withdrawn due to severe side effects CBZ 16, OXC 9
5. Clinically relevant changes observed in 2 participants only, both CBZ group, both stopped treatment
Donati 2007 1. Comparison of cognitive results no significant difference between treatment groups (P = 0.195)
No significant difference between treatment groups for secondary variables (psychomotor speed, alertness, memory and learning, attention, intelligence scores)
2. OXC 58%; CBZ 46%; VPS 54%
3. Most common (> 10% reported) side effects
OXC fatigue and headache; CBZ fatigue and rash
VPS headache, increased appetite, alopecia
4. Good/very good: OXC investigators 84%, participants 82%, parents/carers 86%; Combined CBZ/VPS investigators 77%, participants 73%, parents/carers 80%
Feksi 1991 1. Minor adverse effects reported in PHB: 58 participants (39%) reported 86 AEs, CBZ: 46 participants (30%) reported 68 AEs
2. All withdrawals: PHB: 18%, CBZ: 17%
Withdrawals due to side‐effects: PHB: 5%, CBZ: 3%
3. Seizure‐free: PHB: 54%, CBZ: 52%
> 50% reduction of seizures: PHB: 23%, CBZ: 29%
50% reduction‐50% increase in seizures: PHB: 15%, CBZ: 13%
> 50% increase in seizures: PHB: 8%, CBZ: 6%
Forsythe 1991 1. Significant difference favouring VPS test of speed of information processing
No significant differences between treatment groups for any other cognitive tests
2. PHT: 30%; CBZ: 39%; VPS:33%
Fritz 2006 1. Seizure freedom: LTG: 38%, OXC: 44%
< 50% seizure reduction: LTG: 48%, OXC: 55%
2. Both groups showed improvement in verbal learning and in 1/4 measures of attention. In addition, participants under OXC improved in word fluency. Improved mood was reported with OXC only.
Gilad 2007 1. Number of participants experiencing early seizures as first event: LTG 2/32, CBZ 3/32
Number of participants remaining seizure‐free in the follow‐up period:
LTG 23/32 (72%), CBZ 14/32 (44%) P = 0.05
2. Incidence of side effects:
LTG 2/32 (6.25%), CBZ 12/32 (37.5%) P = 0.05
3. Withdrawals from study due to side effects
LTG 1/32 (3%), CBZ 10/32 (31%), P = 0.02
Jung 2015 1. No difference between groups in terms of social competence; school competence; internalising behaviour problems; externalising behaviour problems;
total behaviour problems and anxiety. Significant decrease in depression in LEV group compared to CBZ group (P = 0.027)
2. LEV 95.7% , CBZ 97.1% , P = 0.686
3. LEV 66.7%, CBZ 57.8% , P = 0.317
4. LEV 33.3%, CBZ 46.9%. Number of AEs not significantly different between groups
Kalviainen 2002 1.CBZ: 53% LTG: 56%
2. No significant difference between groups in overall cognitive score. In terms of individual assessments, only Stroop test B showed a statistically significant advantage for LTG.
Kopp 2007 1. No significant difference between groups
2. No significant difference between groups
Korean Lamotrigine Study Group 2008 1. LTG: 65% CBZ: 70%
2. Total seizure‐free rate LTG: 62% CBZ: 63%
Time to first seizure: mean (SD): weeks
LTG: 10 (5.09), CBZ: 10.82 (6.44)
Lukic 2005 1. LTG: 54%, VPS: 55 %, no difference by seizure type
2. LTG: 69%, VPS:68 %
Mitchell 1987 1. No significant differences between treatment groups
2. Compliance: trend towards better compliance in CBZ group (not significant)
Randomised participants only: trend towards higher rate withdrawal from treatment in PHB group (not significant). More mild systemic side‐effects in CBZ group (significant). 3 children switched from CBZ to PHB and 1 from PHB to CB following adverse reactions
3. 6 months: excellent/good: PHB = 15, CBZ = 13
12 months: excellent/good: PHB = 13, CBZ = 9
Miura 1990 1. Partial seizures ‐ PHT: 32%; CBZ: 40%; VPS : 41%
Generalised seizures ‐ PHT :35%; CBZ: 15%; VPS: 7%
1. Partial seizures ‐ PHT: 24%; CBZ: 24%; VPS : 25%
Generalised seizures ‐ PHT :13%; CBZ: 0%; VPS: 0%
Motamedi 2013 1. Seizure recurrence at 2 weeks ‐ LTG: 43% LEV: 35%, p=0.42
Seizure recurrence at 4 weeks ‐ LTG: 39% LEV: 33%, p=0.53
Seizure recurrence at 8 weeks ‐ LTG: 35% LEV: 28%, p=0.50
Seizure recurrence at 12 weeks ‐ LTG: 33% LEV: 24%, p=0.35
Seizure recurrence at 20 weeks ‐ LTG: 31% LEV: 13%, p=0.03
2. No significant difference between groups
3. Proportion with AEs ‐ LTG: 53%, LEV: 67%
NCT01498822 1. LEV: 12.7%, OXC: 23.4%
2. Median months: LEV: 7.6, OXC: NA (fewer than 50% of participants in the OXC group had seizure recurrence)
3. LEV: 53.8%, OXC: 58.5%
4. LEV: 34.7%, OXC: 40.9%
NCT01954121 1. LEV: 47.3%, CBZ: 68.4%
2. LEV: 48.4%, CBZ: 70.2%
3. Number of events: LEV: 88, CBZ: 45
4. Number of events: LEV: 87, CBZ: 39
5. Number of events: LEV: 97, CBZ: 57
Pulliainen 1994 1. Compared to CBZ, participants on PHT became slower (motor speed of the hand) and their visual memory decreased. There was an equal decrease in negative mood (helplessness, irritability, depression) on PHT and CBZ
2. 3 participants taking PHT complained of tiredness, and 1 participant taking CBZ complained of facial skin problems, another tiredness and memory problems
Ramsey 1983 1. Incidence of major side effects (proportion of analysed participants): PHT 23%; CBZ: 23%
Minor side effects: cognitive impairment and sedation twice as likely on CBZ compared to PHT. Other minor side effects similar between groups.
2. Treatment failures among analysed participants: PHT 4/35 (11%); CBZ: 5/35 (14%)
Seizure control (among analysed participants with no major side effects): PHT: 86%; CBZ: 82%
3. Significantly lower mean LDH level at 24 weeks in CBZ participants than PHT participants. Other laboratory results similar across treatment groups
Ramsey 2007c 1. 8 discontinuations; due to generalised rash (n = 1), excessive tiredness (n = 1), withdrew consent (n = 2), renal transplant (n = 1), lost to follow‐up (n = 2), died (n = 1)
2. 6 participants reported treatment‐emergent side effects.
3. No participants withdrew due to lack of seizure control
Rastogi 1991 1(a). PHT: 51%, VPS: 49%
1(b). PHT : 24%, VPS: 35%
1(c). PHT: 18%, VPS: 10%
1(d). PHT: 2%, VPS: 6%
2. All reported AEs were minor and similar rates between groups
Ravi Sudhir 1995 1. No significant differences between any tests of cognitive function taken before treatment and after 10‐12 weeks for both treatment groups
Resendiz 2004 1. Six months of seizure freedom: CBZ: 81%, TPM: 91%
50% reduction of seizures: CBZ: 84% TPM: 97%
The average number of seizures was significantly less in the TPM group compared to the CBZ group at 6 and 9 months
2. AEs were mild and similar between groups
3. No significant differences between groups
Rowan 2005 1. Significant difference between 3 treatment groups (P = 0.00022) CBZ more early terminators than GBP (P = 0.008) or LTG (P < 0.0001)
2. LTG 51.4%, GBP 47.4%, CBZ 64.3% no significant difference between groups P = 0.09
3. No difference between groups for time to first, second, fifth and tenth seizure (P values = 0.18, 0.13, 0.74, 0.95 respectively)
4. More systemic toxicities on GBP than CBZ or LTG
No significant differences in neuro‐toxicities between treatment groups over 12 months
5. Mean serum levels: 6 weeks GBP 8.67 ± 4.83; µg/mL, CBZ 6.79 ± 2.92 µg/mL and LTG 2.87 ± 1.60 µg/mL
52 weeks GBP 8.54 ± 5.57 µg/mL, CBZ 6.48 ± 3.72 µg/mL
and LTG 3.46 ± 1.68 µg/mL
Overall medical compliance 89% without significant group differences
6. 3 months LTG 49.7%, GBP 43.3%, CBZ 36.0% significant difference between groups P = 0.02
6 months LTG 37.2%, GBP 33.0%, CBZ 28.9% no significant difference between groups P = 0.22
12 months LTG 28.6%, GBP 23.2%, CBZ 22.8% no significant difference between groups P = 0.33
Saetre 2007 1. LTG 68 (73%), CBZ 61 (67%), no significant difference between groups
2. LTG 59 (63%), CBZ 69 (76%), not significant difference P = 0.068 ITT analysis
3. LTG 71 (76%), CBZ 81 (89%), significant difference, P = 0.0234 ITT analysis
4.Hazard ratio (lamotrigine/carbamazepine) 1.50, 95% CI 0.94–2.40, p value 0.092
5. During treatment period LTG 82 (88%) reported 378 AEs, CBZ 79 (86%) reported 310 AEs. No significant differences between groups for any AEs except for immune system
Withdrew due to AE LTG 13 (14%), CBZ 23 (25%), P = 0.078
6. No difference between groups even when changes over time corrected for age, gender and baseline score
Shakir 1981 1. PHT: 33%; VPS: 39%
2. All reported AEs were minor and similar rates between groups
So 1992 1. VPS 7/11 (64%), CBZ 9/14 (64%)
2. At least one AE reported VPS 15/16 (94%), CBZ 16/17 (94%)
Steinhoff 2005 1. FE CBZ group 83/88 (94.3%), LTG group 78/88 (88.6%) no significant difference between groups
GE VPS group 25/30 (83.3%) LTG group 20/33 (60.6%) no significant difference between groups
2. FE CBZ group 81%, LTG group 91%, not a significant difference between groups
GE VPS group 97%, LTG group 88%, not stated as significant or non‐significant difference
3. At least 1 AE
FE CBZ 81 participants (91%), LTG 68 participants (77.3%)
GE VPS 25 participants (83.3%), LTG 24 participants (72.7%)
Serious AEs
FE CBZ 8 participants (9%), LTG 6 participants (7%)
GE VPS 1 participant (3%), LTG 5 participants (15%)
AEs considered related to study drug
FE CBZ 65 participants (74%), LTG 38 participants (43%)
GE VPS 16 participants (53%), LTG 15 participants (45.5%)
Suresh 2015 1. Mean quality‐of‐life score at baseline CBZ group 31.14 ± 1.83, LEV group 29.76 ± 1.71 (P value = 0.5861)
Mean quality of life score after 26 weeks of treatment CBZ group 58.41 ± 1.89, LEV 64.58 ± 2.02 (P value = 0.0302)
2.28 participants in CBZ group, 28 in LEV group
Seizure freedom 4 weeks CBZ group 85.72%, LEV group 85.72% (P value = 1); 12 weeks CBZ group 89.29%, LEV group 93.34% (P value = 0.4595); 26 weeks CBZ group 96.43%, LEV group 100% (P value = 0.1212); 6 months CBZ group 71.42% (20 participants), LEV group 78.57% (22 participants) (P value = 0.2529)
3. Participants experiencing at least 1 AE, CBZ group 36.66%, LEV group 40% (P value = 0.77)
Thilothammal 1996 1. PHB: 31%, PHT: 27%, VPS: 21%
2. PHB: 33%, PHT: 63%, VPS: 31%

AE: adverse event; CBZ: carbamazepine; EEG: electroencephalogram; FE: focal epilepsies; GBP: gabapentin; GE: generalised epilepsies; ITT: intention to treat; LDH: lactic acid dehydrogenase; LEV: levetiracetam; LTG: lamotrigine; MANOVA: repeated measures analysis of variance; OXC: oxcarbazepine; PHB: phenobarbitone; PHT: phenytoin; SD: standard deviation; TPM: topiramate; VPS: sodium valproate; ZNS: zonisamide

aFor further details of adverse events see Table 22 and Table 23. bSee Table 7 for details of treatment arms in each trial and number of participants randomised to each arm. cResults not split by treatment arm for Ramsey 2007.