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Topiramato para el temblor esencial

Información

DOI:
https://doi.org/10.1002/14651858.CD009683.pub2Copiar DOI
Base de datos:
  1. Cochrane Database of Systematic Reviews
Versión publicada:
  1. 14 abril 2017see what's new
Tipo:
  1. Intervention
Etapa:
  1. Review
Grupo Editorial Cochrane:
  1. Grupo Cochrane de Trastornos del movimiento

Copyright:
  1. Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Autores

  • Elisa Bruno

    Correspondencia a: Department GF Ingrassia, Section of Neurosciences, University of Catania, Catania, Italy

    [email protected]

  • Alessandra Nicoletti

    Department GF Ingrassia, Section of Neurosciences, University of Catania, Catania, Italy

  • Graziella Quattrocchi

    Department GF Ingrassia, Section of Neurosciences, University of Catania, Catania, Italy

  • Roberta Allegra

    Department of Neurological Sciences, Policlinico Universitario G. Martino Messina, Messina, Italy

  • Graziella Filippini

    Scientific Direction, Fondazione IRCCS, Istituto Neurologico Carlo Besta, Milan, Italy

  • Carlo Colosimo

    Department of Neurology, Terni University Hospital, Terni, Italy

  • Mario Zappia

    Department GF Ingrassia, Section of Neurosciences, University of Catania, Catania, Italy

Contributions of authors

EB: protocol and review editing, literature searching, study selection, quality assessment, data extraction.

AN: protocol and review editing.

GQ: literature searching, quality assessment, data extraction.

RA: protocol editing, literature searching, study selection, quality assessment, data extraction.

GF: protocol editing, editing and revising the review.

CC: protocol editing, quality assessment, study selection.

MZ: protocol editing, revising review.

Sources of support

Internal sources

  • None, Not specified.

External sources

  • None, Not specified.

Declarations of interest

EB: none.

AN: none.

GQ: none.

RA: none.

GF: none.

CC: none.

MZ: none.

Acknowledgements

The authors would like to express their gratitude to the Editors of the Movement disorders Group for the comments and guidance provided during the development of the final version of this review.

Version history

Published

Title

Stage

Authors

Version

2017 Apr 14

Topiramate for essential tremor

Review

Elisa Bruno, Alessandra Nicoletti, Graziella Quattrocchi, Roberta Allegra, Graziella Filippini, Carlo Colosimo, Mario Zappia

https://doi.org/10.1002/14651858.CD009683.pub2

2012 Mar 14

Topiramate for essential tremor

Protocol

Elisa Bruno, Alessandra Nicoletti, Graziella Quattrocchi, Roberta Allegra, Carlo Colosimo, Graziella Filippini, Mario Zappia

https://doi.org/10.1002/14651858.CD009683

Differences between protocol and review

In an attempt to provide a standardised and reliable assessment of the quality of the evidence of the study outcomes, we decided to use the GRADE evidence profile, a systematic and explicit system for grading the evidence into four quality categories. We reported the results obtained through this approach in a 'Summary of findings' table”.

Methods for future updates

Two pre‐planned analysis were not performed due to insufficient data. These will be implemented, if possible, in future updates of the review.

Methods for analysing continuous data: the scales used to assess tremor in the majority of the studies are continuous. We will transform ordinal scales with enough categories to continuous scales by assigning a score to each grade so that we can express the intervention effect as a difference in means or as a standardised mean difference. In the case of an ordinal scale with few categories, we will combine data from adjacent categories into two categories, and use methods for binary data as risk ratios (RR) or risk differences (RD) to evaluate the intervention effect.

Sensitivity analysis: we will undertake sensitivity analyses to assess the robustness of results to fixed‐effect versus random‐effects assumptions, and the inclusion or exclusion of studies at high risk of bias (i.e. inadequate allocation concealment and lack of blinded outcome assessor). We will use best‐ and worst‐case scenarios for taking into account missing data.

Keywords

MeSH

PICO

Population
Intervention
Comparison
Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

Study flow diagram.
Figuras y tablas -
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.
Figuras y tablas -
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.
Figuras y tablas -
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.
Figuras y tablas -
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.
Figuras y tablas -
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.
Figuras y tablas -
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.
Figuras y tablas -
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).

Figuras y tablas -
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]

Figuras y tablas -
Comparison 1. Topiramate versus placebo/open control