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Topiramato para el temblor esencial

Appendices

Appendix 1. MEDLINE search strategy

1. exp Essential Tremor/ (1183)

2. (essential adj3 tremor*).ab,ti. (2473)

3. (familia* adj3 tremor*).ab,ti. (132)

4. 1 or 2 or 3 (2654)

5. topiramate.ab,ti. (3113)

6. topamax.ab,ti. (75)

7. epitomax.ab,ti. (4)

8. 5 or 6 or 7 (3134)

9. randomized controlled trial.pt. (367656)

10. controlled clinical trial.pt. (87895)

11. randomized.ab. (287683)

12. placebo.ab. (151722)

13. drug therapy.fs. (1677138)

14. randomly.ab. (208754)

15. trial.ab. (298006)

16. groups.ab. (1332158)

17. 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 (3287589)

18. exp animals/ not humans.sh. (3903063)

19. 17 not 18 (2818660)

20. 4 and 8 and 19 (31)

Appendix 2. CENTRAL search strategy

1. MeSH descriptor: [Essential Tremor] explode all trees (62)

2. essential tremor*:ti,ab,kw (Word variations have been searched) (202)

3. familia* tremor:ti,ab,kw (Word variations have been searched) (7)

4. 1 or 2 or 3 (208)

5. "topiramate":ti,ab,kw (Word variations have been searched) (620)

6. "Topamax":ti,ab,kw (Word variations have been searched) (8)

7. epitomax:ti,ab,kw (Word variations have been searched) (0)

8. 5 or 6 or 7 (621)

9. 4 and 8 (6)

Study flow diagram.
Figures and Tables -
Figure 1

Study flow diagram.

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

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

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figures and Tables -
Figure 3

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

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

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

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

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

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

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

Comparison 1 Topiramate versus placebo/open control, Outcome 2 Withdrawals.
Figures and Tables -
Analysis 1.2

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

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).

Figures and Tables -
Summary of findings for the main comparison. Topiramate for essential tremor
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]

Figures and Tables -
Comparison 1. Topiramate versus placebo/open control