Trial

Outcomes reported

Summary of results

Bidabadi 2009

1. Proportion seizure‐free

2. Response rate

3. Rate of side‐effects

4. Mean seizure frequency per month

5. Mean seizure duration

1. CBZ: 23/36 (64%), PB: 22/35 (63%)

2. No statistically significant difference between groups

3. No statistically significant difference between groups

4. CBZ: 0.66, PB: 0.8

5. CBZ: 12.63 seconds, PB: 15 seconds

Cereghino 1974

1. Behaviour measured with rating scale modified from the Ward Behavior Rating Scale

2. Seizure control

3. Side‐effects

4. Withdrawals

1. No change or improvement in behaviour was more common on PB than CBZ (40% versus 12%); predominant improvement with some deterioration was more common on CBZ than PB (36% versus 12%)

2. No difference between PB and CBZ in terms of seizure control

3. Gastrointestinal and "impaired function" side‐effects were more common on CBZ than PB in the first few study days. Side‐effects of both drugs were minimal in later stages of the study

4. PB: 26/44 (59%), CBZ: 27/45 (60%)

Chen 1996

1. IQ scores measured with WISC‐R scale

2. Time to complete the Bender‐Gestalt test

3. Auditory event‐related potentials

4. Incidence of allergic reactions

5. Seizure control

1. No significant difference between groups

2. No significant difference between groups

3. No significant difference between groups

4. 2 children from PB group and 1 child from CBZ group withdrew from the study because of allergic reactions

5. No significant difference between groups

Cossu 1984

Changes in memory function from baseline after 3 weeks of treatment (verbal, visual, (visual‐verbal and visual‐non‐verbal), acoustic, tactile, and spatial)

1. Significant decrease in visual‐verbal memory for CBZ and acoustic memory for PB

2. No significant differences for other tests

Czapinski 1997

1. Proportion achieving 24‐month remission at 3 years

2. Proportion excluded after randomisation due to adverse effects or no efficacy

1. PB: 60%, CBZ: 62%

2. PB: 33%, CBZ: 30%

Feksi 1991

1. Adverse effects

2. Withdrawals from allocated treatment

3. Seizure frequency (during second 6 months of study, participants completing the study only)

PB (n = 123), CBZ (n = 126)

1. Minor adverse effects reported in PB: 58 participants (39%) reported 86 adverse events, CBZ: 46 participants (30%) reported 68 adverse events

2. PB: all withdrawals: PB: 27 (18%), CBZ: 26 (17%); withdrawals due to side‐effects: PB: 8 (5%), CBZ: 5 (3%)

3. Seizure‐free: PB: 67 (54%), CBZ: 65 (52%); > 50% reduction of seizures from baseline: PB: 28 (23%), CBZ: 37 (29%); between 50% reduction to 50% increase of seizures: PB: 18 (15%), CBZ: 17 (13%); > 50% increase in seizures: PB: 10 (8%), CBZ: 7 (6%)

Mitchell 1987

1. Cognitive/behavioural outcomes at 1, 2, 6, and 12 months

2. Compliance, drug changes, and withdrawal rates

3. Seizure control at 6 and 12 months (excellent/good/fair/poor)

1. No significant differences between treatment groups (children from pilot study included for 6 and 12 months)

2. Compliance (children from pilot study included): trend towards better compliance in CBZ group (not significant)

   • Randomised participants only: trend towards higher rate withdrawal from treatment in PB group (not significant). More mild systemic side‐effects in CBZ group (significant). 3 children switched from CBZ to PB and 1 from PB to CB following adverse reactions

3. Seizure control at 6 months: excellent/good: PB = 15, CBZ = 13 (children from pilot study included) fair/poor PB = 5, CBZ = 3; seizure control at 12 months: excellent/good: PB = 13, CBZ = 9 (children from pilot study included) fair/poor PB = 4, CBZ = 4

Trial

Number randomised

Time to withdrawal of

allocated treatment

Time to 12‐month

remission

Time to six‐month

remission

Time to first seizure

CBZ

PB

Total

CBZ

PB

Total

CBZ

PB

Total

CBZ

PB

Total

CBZ

PB

Total

Banu 2007¹

54

54

108

Information not available

Information not available

Information not available

54

54

108

de Silva 1996²

54

10

64

53

10

63

54

10

64

54

10

64

54

10

64

Heller 1995³

61

58

119

60

55

115

61

58

119

61

58

119

61

58

119

Mattson 1985⁴

155

155

310

154

155

309

154

155

309

154

155

309

151

151

302

Ogunrin 2005⁵

19

18

37

Information not available

Information not available

Information not available

19

18

37

Placencia 1993⁶

95

97

192

94

95

189

95

96

191

95

96

191

95

97

192

Total

438

392

830

361

315

676

364

319

683

364

319

683

434

388

822

Reason for early termination

Classification

de Silva 1996 ¹

Heller 1995 ¹

Mattson 1985

Placencia 1993 ²

Banu 2007 ³

Total⁴

CBZ n = 53

PB = 10

CBZ n = 60

PB = 55

CBZ n = 154

PB = 155

CBZ = 94

PB = 95

CBZ = 54

PB = 54

CBZ = 415

PB = 369

Adverse events

Event

3

2

8

12

11

5

5

5

0

0

27

24

Seizure recurrence

Event

12

2

5

7

3

7

0

0

1

2

21

18

Both seizure recurrence and adverse events

Event

6

4

4

3

30

26

0

0

0

0

40

33

Non‐compliance/participant choice

Event

0

0

0

0

11

19

13

9

6

0

30

28

Another AED added/AED changed

Event

0

0

0

0

0

3

0

0

7

4

7

7

Participant went into remission

Censored

18

1

6

3

0

0

0

0

0

2

24

6

Lost to follow‐up

Censored

0

0

0

0

26

26

11

5

7

15

44

46

Death⁵

Censored

0

0

0

0

4

2

2

1

0

0

6

3

Other⁶

Censored

0

0

0

0

16

13

0

0

0

0

16

13

Completed the study (did not withdraw)

Censored

14

1

37

30

53

54

63

75

33

31

200

191

Analysis

Time to withdrawal of

allocated treatment

Time to 12‐month

remission

Time to six‐month

remission

Time to first seizure¹

Original analysis

Participants

676 (Analysis 1.2)

683 (Analysis 1.4)

683 (Analysis 1.6)

822 (Analysis 1.8)

Pooled HR (95% CI)

P value

1.50 (1.15 to 1.95)

P = 0.003

0.93 (0.72 to 1.20)

P = 0.57

0.99 (0.80 to 1.23)

P = 0.95

0.87 (0.72 to 1.06)

P = 0.18

Heterogeneity

I² statistic = 35%

I² statistic = 55%

I² statistic = 58%

I² statistic = 44%

Sensitivity analysis

for Placencia 1993²

Participants

487

492

492

630

Pooled HR (95% CI)

P value

1.66 (1.25 to 2.20)

P = 0.0005

0.82 (0.61 to 1.09)

P = 0.15

0.88 (0.68 to 1.14)

P = 0.34

0.87 (0.71 to 1.08)

P = 0.22

Heterogeneity

I² statistic = 35%

I² statistic = 0%

I² statistic = 0%

I² statistic = 34%

Sensitivity analysis

for de Silva 1996³

Participants

633

640

640

779

Pooled HR (95% CI)

P value

1.42 (1.08 to 1.86)

P = 0.01

0.90 (0.69 to 1.17)

P = 0.42

0.97 (0.78 to 1.21)

P = 0.79

0.87 (0.71 to 1.06)

P = 0.17

Heterogeneity

I² statistic = 0%

I² statistic = 57%

I² statistic = 60%

I² statistic = 39%

Trial

Adverse event data¹

Summary of reported results

Carbamazepine (CBZ)

Phenobarbitone (PB)

Banu 2007²

Reported list of 'problems' at the last visit (provided as IPD)

CBZ (n = 54): speech/learning delay (n = 6), headaches (n = 3), restlessness/hyperactivity/poor attention/irritability (n = 6), psychomotor deterioration/delay (n = 2), sleep disturbances (n = 2), fatigue (n = 1), hydrocephalus (build up of fluid on the brain) (n = 1), CBZ hypersensitivity (n = 1), aggression (n = 1), temper tantrums (n = 1), other behavioural problems (n = 5), poor cognition (n = 1), mild stroke (n = 1), mild right‐sided weakness (n = 1), intolerable behavioural problems (n = 6)

PB (n = 54): speech/learning delay (n = 7), restlessness/hyperactivity/poor attention/irritability (n = 8), sleep disturbances (n = 1), fatigue (n = 1), poor cognition (n = 2), aggression (n = 1), temper tantrums (n = 3), breath‐holding attacks (n = 1), other behavioural problems (n = 3), facial twitching (n = 1), left‐sided weakness (n = 1), leg pain (n = 1), vomiting (n = 1), intolerable behavioural problems (n = 4)

Bidabadi 2009³

Rate of drug side‐effects

No statistical significant difference was seen after treatment between 2 groups in the rate of drug side‐effects

No statistical significant difference was seen after treatment between 2 groups in the rate of drug side‐effects

Cereghino 1974²^,⁴

Most frequently observed side‐effects

Gastrointestinal side‐effects and "impaired function" (general malaise). Frequency not clearly stated

Gastrointestinal side‐effects and "impaired function" (general malaise). Frequency not clearly stated

Chen 1996

Withdrawal from the study due to 'allergic reactions'

CBZ (n = 24): 1 participant withdrew due to an allergic reaction

PB (n = 23): 2 participants withdrew due to allergic reactions

Cossu 1984

No adverse events reported

Not reported

Not reported

Czapinski 1997³

"Exclusions due to adverse events or no efficacy"

Proportion "excluded": 30% (out of 30 randomised to CBZ)

Proportion "excluded": 33.3% (out of 30 randomised to PB)

de Silva 1996⁵^,⁶

"Unacceptable" adverse events leading to drug withdrawal

CBZ (n = 54): drowsiness (n = 1), blood dyscrasia (n = 1)

PB (n = 10): drowsiness (n = 1), behavioural (n = 5)

Feksi 1991

Reports of minor adverse events and side‐effects leading to drug withdrawal

CBZ (n = 150): withdrawals due to side‐effects: skin rash (n = 4), psychosis (n = 1), aggressive behaviour (n = 1).

Minor adverse events: CBZ: 46 participants reported 68 adverse events

PB (n = 152): withdrawals due to side‐effects: skin rash (n = 1), psychosis (n = 1), hyperactivity (n = 3).

Minor adverse events: 58 participants reported 86 adverse events

Heller 1995⁵

"Unacceptable" adverse events

leading to drug withdrawal

CBZ (n = 61): drowsiness (n = 3), rash (n = 2), headache (n = 1), depression (n = 1)

PB (n = 58): drowsiness (n = 4), lethargy (n = 4), rash (n = 1), dizziness (n = 2), headaches (n = 1), nausea and vomiting (n = 1)

Mattson 1985²

Narrative report of 'adverse effects' and 'serious side‐effects'

CBZ (n = 155): motor disturbance (ataxia, incoordination, nystagmus, tremor ‐ 33%), dysmorphic and idiosyncratic side‐effects (gum hypertrophy, hirsutism, acne, and rash ‐ 14%), gastrointestinal problems (27%), decreased libido or impotence (13%). No serious side‐effects

PB (n = 155): motor disturbance (ataxia, incoordination, nystagmus, tremor ‐ 24%), dysmorphic and idiosyncratic side‐effects (gum hypertrophy, hirsutism, acne, and rash ‐11 %), gastrointestinal problems (13%), decreased libido or impotence (16%). No serious side‐effects

Mitchell 1987

Systemic side‐effects and side‐effects leading to drug change

CBZ (n = 15): 4 participants switched from CBZ to PB; 3 due to systemic side‐effects (1 with persistent rashes and 1 with marked granulocytopenia (decrease of granulocytes (white blood cells)) and 1 due to behavioural changes

PB (n = 18): 1 participant switched from PB to CBZ due to substantial behavioural side‐effects

Ogunrin 2005²

Participant‐reported symptomatic complaints (provided as IPD)

CBZ (n = 19), memory impairment (n = 9), psychomotor retardation (n = 1), inattention (n = 1), transient rash (n = 1), CBZ‐induced cough (n = 1)

PB (n = 18), memory impairment (n = 13), psychomotor retardation (n = 8), inattention (n = 9)

Placencia 1993

Number of participants reporting side‐effects

CBZ (n = 95): 53 participants reported at least 1 side‐effect

PB (n = 97): 50 participants reported at least 1 side‐effect