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Study flow diagram

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Figure 1

Study flow diagram

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Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Comparison 1: Clonazepam versus carbamazepine, Outcome 1: Proportion of participants seizure‐free at 1, 3 and 6 months after randomization

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Analysis 1.1

Comparison 1: Clonazepam versus carbamazepine, Outcome 1: Proportion of participants seizure‐free at 1, 3 and 6 months after randomization

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Comparison 1: Clonazepam versus carbamazepine, Outcome 2: Proportion of participants with treatment‐emergent adverse events (TEAEs)

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Analysis 1.2

Comparison 1: Clonazepam versus carbamazepine, Outcome 2: Proportion of participants with treatment‐emergent adverse events (TEAEs)

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Comparison 1: Clonazepam versus carbamazepine, Outcome 3: Proportion of dropouts/withdrawals due to side effects, lack of efficacy or other reasons

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Analysis 1.3

Comparison 1: Clonazepam versus carbamazepine, Outcome 3: Proportion of dropouts/withdrawals due to side effects, lack of efficacy or other reasons

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Comparison 2: Clonazepam versus ethosuximide, Outcome 1: Proportion of dropouts/withdrawals due to side effects, lack of efficacy or other reasons

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Analysis 2.1

Comparison 2: Clonazepam versus ethosuximide, Outcome 1: Proportion of dropouts/withdrawals due to side effects, lack of efficacy or other reasons

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Summary of findings 1. Clonazepam compared to carbamazepine for treating people with newly diagnosed epilepsy

Clonazepam compared to carbamazepine for treating people with newly diagnosed epilepsy

Patient or population: people with newly diagnosed epilepsy
Setting: outpatients
Intervention: clonazepam
Comparison: carbamazepine

Outcomes

Relative effect
(95% CI)

Anticipated absolute effects* (95% CI)

Certainty of the evidence
(GRADE)

Comments

Without Clonazepam

With Clonazepam

Difference

Proportion of participants seizure‐free at 12 months after randomization ‐ not reported

Outcome not reported

n/a

Proportion of participants seizure‐free at 24 months after randomization ‐ not reported

Outcome not reported

n/a

Proportion of responders (those with at least a 50% reduction in seizure frequency from baseline to end of treatment)

Outcome not reported

n/a

Proportion of participants with treatment‐emergent adverse events (TEAEs) during the treatment period

Outcome not reported

n/a

In the only study included, all participants (except one receiving carbamazepine) had at least one side effect (no further details provided). The duration of side effects was generally short, without significant difference between clonazepam and carbamazepine for sedation, headache, dizziness, irritability and other complaints.

Proportion of participants with treatment‐emergent adverse events (TEAEs) leading to discontinuation during the treatment period (1 RCT; n = 36)

RR 2.61
(0.80 to 8.52)

Study population

⊕⊝⊝⊝
VERY LOW 1,2

15.8%

41.2%
(12.6 to 100)

25.4% more
(3.2 fewer to 118.7 more)

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RCT: randomized controlled trial; RR: Risk ratio

GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Study conducted in a very small population. No calculation of sample size was made. Very wide confidence intervals, indicative of imprecise results.

2 High risk of attrition bias and reporting bias; unclear risk of selection and performance bias.

Figuras y tablas -
Summary of findings 1. Clonazepam compared to carbamazepine for treating people with newly diagnosed epilepsy
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Summary of findings 2. Clonazepam compared to ethosuximide for treating people with newly diagnosed epilepsy

Clonazepam compared to ethosuximide for treating people with newly diagnosed epilepsy

Patient or population: people with newly diagnosed epilepsy
Setting: outpatients
Intervention: clonazepam
Comparison: ethosuximide

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with ethosuximide

Risk with Clonazepam

Proportion of participants seizure‐free at 12 months after randomization

Outcome not reported

n/a

Proportion of participants seizure‐free at 24 months after randomization

Outcome not reported

n/a

Proportion of responders (those with at least a 50% reduction in seizure frequency from baseline to end of treatment)

Outcome not reported

n/a

Proportion of participants with treatment‐emergent adverse events (TEAEs) during the treatment period

Outcome not reported

n/a

In the only study included, drowsiness and ataxia were common side effects and seemed dose‐related (no further details were provided).

Proportion of participants with TEAEs leading to discontinuation during the treatment period

Outcome not reported

n/a

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Figuras y tablas -
Summary of findings 2. Clonazepam compared to ethosuximide for treating people with newly diagnosed epilepsy
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Comparison 1. Clonazepam versus carbamazepine

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1.1 Proportion of participants seizure‐free at 1, 3 and 6 months after randomization Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1.1 Seizure freedom at 1 month after randomization

1

30

Risk Ratio (M‐H, Fixed, 95% CI)

1.97 [0.99, 3.94]

1.1.2 Seizure freedom at 3 months after randomization

1

26

Risk Ratio (M‐H, Fixed, 95% CI)

1.19 [0.62, 2.29]

1.1.3 Seizure freedom at 6 months after randomization

1

9

Risk Ratio (M‐H, Fixed, 95% CI)

0.50 [0.09, 2.73]

1.2 Proportion of participants with treatment‐emergent adverse events (TEAEs) Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.2.1 Leading to discontinuation during the treatment period

1

36

Risk Ratio (M‐H, Fixed, 95% CI)

2.61 [0.80, 8.52]

1.3 Proportion of dropouts/withdrawals due to side effects, lack of efficacy or other reasons Show forest plot

1

36

Risk Ratio (M‐H, Fixed, 95% CI)

1.56 [0.61, 4.02]
Figuras y tablas -
Comparison 1. Clonazepam versus carbamazepine
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Comparison 2. Clonazepam versus ethosuximide

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

2.1 Proportion of dropouts/withdrawals due to side effects, lack of efficacy or other reasons Show forest plot

1

79

Risk Ratio (M‐H, Fixed, 95% CI)

3.63 [1.12, 11.74]
Figuras y tablas -
Comparison 2. Clonazepam versus ethosuximide
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