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Study flow diagram.
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Figure 1

Study flow diagram.

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Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
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Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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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 3

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

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Forest plot of comparison: 1 Topiramate versus placebo/open control, outcome: 1.1 Functional disability component related to tremor.
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Figure 4

Forest plot of comparison: 1 Topiramate versus placebo/open control, outcome: 1.1 Functional disability component related to tremor.

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Forest plot of comparison: 1 Topiramate versus placebo/open control, outcome: 1.2 Withdrawals.
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Figure 5

Forest plot of comparison: 1 Topiramate versus placebo/open control, outcome: 1.2 Withdrawals.

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Comparison 1 Topiramate versus placebo/open control, Outcome 1 Functional disability component related to tremor.
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Analysis 1.1

Comparison 1 Topiramate versus placebo/open control, Outcome 1 Functional disability component related to tremor.

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Comparison 1 Topiramate versus placebo/open control, Outcome 2 Withdrawals.
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Analysis 1.2

Comparison 1 Topiramate versus placebo/open control, Outcome 2 Withdrawals.

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Summary of findings for the main comparison. Topiramate for essential tremor

Topiramate for essential tremor

Patient or population: people with essential tremor

Settings: outpatients

Intervention: topiramate

Comparison: placebo

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Placebo

Topiramate

Functional disability

(follow‐up duration 24 weeks)

TRS subscale B score (motor tasks)

TRS subscale C score (functional disability)

The mean improvement in the control group was
4.9 points for TRS subscale B and 3.7 points for TRS subscale C.

The mean improvement in the intervention groups was
5.4 (2.38 to 8.42) points greater for TRS subscale B and 5.7 (2.66 to 8.74) points greater for TRS subscale C.

‐

223
(1 study)

⊕⊝⊝⊝
Very low1,2,3

‐

Study withdrawal

(follow‐up duration 10 to 24 weeks)

Number of participants withdrawn from the study

Study population

RR 1.78
(1.23 to 2.60)

285
(2 studies)

⊕⊕⊝⊝
Low1,3

‐

217 per 1000

347 per 1000
(252 to 458)

Moderate

‐

‐

Adverse events

(follow‐up duration 24 weeks)

Number of AEs

Study population

‐

221
(1 study)

⊕⊕⊝⊝
Low1,3

‐

71 AEs per 105 participants
(mean 0.7 AEs reported by each participant)

195 AEs per 116 participants
(mean of 1.7 AEs reported by each participant)

Moderate

‐

‐

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (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).

AE: adverse event; CI: confidence interval; RR: risk ratio; TRS: Tremor Rating Scale.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Downgraded due to serious risk of bias: high number of study withdrawals (attrition bias); blinding of outcome assessment probably revealed by the presence of serious AEs in the topiramate group: trials should be regarded as single blind (detection bias); potential conflicts of interest due to the presence of authors sponsored by pharmaceutical companies.
2 Downgraded due to serious indirectness: uncertainty about the relevance of the reported TRS‐score changes as indicators of important clinical improvement.

3 Downgraded due to imprecision: small sample size (< 300 participants) and small number of included studies (three).

Figuras y tablas -
Summary of findings for the main comparison. Topiramate for essential tremor
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Comparison 1. Topiramate versus placebo/open control

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Functional disability component related to tremor Show forest plot

3

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 Change in TRS subscale B score

1

208

Mean Difference (IV, Fixed, 95% CI)

‐5.4 [‐8.42, ‐2.38]

1.2 Change in TRS subscale C score

1

208

Mean Difference (IV, Fixed, 95% CI)

‐5.7 [‐8.74, ‐2.66]

1.3 Change in TRS total score

3

273

Mean Difference (IV, Fixed, 95% CI)

‐8.91 [‐10.50, ‐7.33]

2 Withdrawals Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 Withdrawals: lack of efficacy

2

285

Risk Ratio (M‐H, Fixed, 95% CI)

0.18 [0.02, 1.53]

2.2 Withdrawals: AEs

2

285

Risk Ratio (M‐H, Fixed, 95% CI)

3.17 [1.79, 5.63]

2.3 Withdrawals: other reasons

2

285

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.45, 2.05]

2.4 Withdrawals: total

2

285

Risk Ratio (M‐H, Fixed, 95% CI)

1.78 [1.23, 2.60]
Figuras y tablas -
Comparison 1. Topiramate versus placebo/open control
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