Scolaris Content Display Scolaris Content Display

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figures and Tables -
Figure 1

'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 2

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

Forest plot of comparison: 1 Topiramate (combined analyses based on most relevant dose in each study) versus placebo, outcome: 1.1 Headache frequency (change from baseline to post‐treatment, or post‐treatment alone).
Figures and Tables -
Figure 3

Forest plot of comparison: 1 Topiramate (combined analyses based on most relevant dose in each study) versus placebo, outcome: 1.1 Headache frequency (change from baseline to post‐treatment, or post‐treatment alone).

Forest plot of comparison: 2 Topiramate (separate analyses of various doses) versus placebo, outcome: 2.1 Headache frequency (change from baseline to post‐treatment, or post‐treatment alone).
Figures and Tables -
Figure 4

Forest plot of comparison: 2 Topiramate (separate analyses of various doses) versus placebo, outcome: 2.1 Headache frequency (change from baseline to post‐treatment, or post‐treatment alone).

Forest plot of comparison: 1 Topiramate (combined analyses based on most relevant dose in each study) versus placebo, outcome: 1.3 RRs for responders (patients with ≥ 50% reduction in headache frequency).
Figures and Tables -
Figure 5

Forest plot of comparison: 1 Topiramate (combined analyses based on most relevant dose in each study) versus placebo, outcome: 1.3 RRs for responders (patients with ≥ 50% reduction in headache frequency).

Comparison 1 Topiramate (combined analyses based on most relevant dose in each study) versus placebo, Outcome 1 Headache frequency (change from baseline to post‐treatment, or post‐treatment alone).
Figures and Tables -
Analysis 1.1

Comparison 1 Topiramate (combined analyses based on most relevant dose in each study) versus placebo, Outcome 1 Headache frequency (change from baseline to post‐treatment, or post‐treatment alone).

Comparison 1 Topiramate (combined analyses based on most relevant dose in each study) versus placebo, Outcome 2 ORs for responders (patients with ≥ 50% reduction in headache frequency).
Figures and Tables -
Analysis 1.2

Comparison 1 Topiramate (combined analyses based on most relevant dose in each study) versus placebo, Outcome 2 ORs for responders (patients with ≥ 50% reduction in headache frequency).

Comparison 1 Topiramate (combined analyses based on most relevant dose in each study) versus placebo, Outcome 3 RRs for responders (patients with ≥ 50% reduction in headache frequency).
Figures and Tables -
Analysis 1.3

Comparison 1 Topiramate (combined analyses based on most relevant dose in each study) versus placebo, Outcome 3 RRs for responders (patients with ≥ 50% reduction in headache frequency).

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 1 Headache frequency (change from baseline to post‐treatment, or post‐treatment alone).
Figures and Tables -
Analysis 2.1

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 1 Headache frequency (change from baseline to post‐treatment, or post‐treatment alone).

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 2 Responders (patients with ≥ 50% reduction in headache frequency).
Figures and Tables -
Analysis 2.2

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 2 Responders (patients with ≥ 50% reduction in headache frequency).

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 3 Any adverse event.
Figures and Tables -
Analysis 2.3

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 3 Any adverse event.

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 4 Anorexia.
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Analysis 2.4

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 4 Anorexia.

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 5 Fatigue.
Figures and Tables -
Analysis 2.5

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 5 Fatigue.

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 6 Memory problems.
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Analysis 2.6

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 6 Memory problems.

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 7 Nausea.
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Analysis 2.7

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 7 Nausea.

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 8 Paresthesia.
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Analysis 2.8

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 8 Paresthesia.

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 9 Taste disturbance.
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Analysis 2.9

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 9 Taste disturbance.

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 10 Weight loss.
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Analysis 2.10

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 10 Weight loss.

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 11 MSQ‐role function restrictive.
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Analysis 2.11

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 11 MSQ‐role function restrictive.

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 12 MSQ‐role function prevention.
Figures and Tables -
Analysis 2.12

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 12 MSQ‐role function prevention.

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 13 MSQ‐emotional function.
Figures and Tables -
Analysis 2.13

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 13 MSQ‐emotional function.

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 14 SF‐36 role physical.
Figures and Tables -
Analysis 2.14

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 14 SF‐36 role physical.

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 15 SF‐36 vitality.
Figures and Tables -
Analysis 2.15

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 15 SF‐36 vitality.

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 16 SF‐36 physical functioning.
Figures and Tables -
Analysis 2.16

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 16 SF‐36 physical functioning.

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 17 SF‐36 bodily pain.
Figures and Tables -
Analysis 2.17

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 17 SF‐36 bodily pain.

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 18 SF‐36 general health.
Figures and Tables -
Analysis 2.18

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 18 SF‐36 general health.

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 19 SF‐36 social functioning.
Figures and Tables -
Analysis 2.19

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 19 SF‐36 social functioning.

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 20 SF‐36 role emotional.
Figures and Tables -
Analysis 2.20

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 20 SF‐36 role emotional.

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 21 SF‐36 mental health.
Figures and Tables -
Analysis 2.21

Comparison 2 Topiramate (separate analyses of various doses) versus placebo, Outcome 21 SF‐36 mental health.

Comparison 3 Topiramate direct dose comparisons, Outcome 1 Headache frequency (change from baseline to post‐treatment, or post‐treatment alone).
Figures and Tables -
Analysis 3.1

Comparison 3 Topiramate direct dose comparisons, Outcome 1 Headache frequency (change from baseline to post‐treatment, or post‐treatment alone).

Comparison 3 Topiramate direct dose comparisons, Outcome 2 Responders (patients with ≥ 50% reduction in headache frequency).
Figures and Tables -
Analysis 3.2

Comparison 3 Topiramate direct dose comparisons, Outcome 2 Responders (patients with ≥ 50% reduction in headache frequency).

Comparison 3 Topiramate direct dose comparisons, Outcome 3 MSQ‐role function restrictive.
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Analysis 3.3

Comparison 3 Topiramate direct dose comparisons, Outcome 3 MSQ‐role function restrictive.

Comparison 3 Topiramate direct dose comparisons, Outcome 4 MSQ‐role function prevention.
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Analysis 3.4

Comparison 3 Topiramate direct dose comparisons, Outcome 4 MSQ‐role function prevention.

Comparison 3 Topiramate direct dose comparisons, Outcome 5 MSQ‐emotional function.
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Analysis 3.5

Comparison 3 Topiramate direct dose comparisons, Outcome 5 MSQ‐emotional function.

Comparison 3 Topiramate direct dose comparisons, Outcome 6 SF‐36 role physical.
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Analysis 3.6

Comparison 3 Topiramate direct dose comparisons, Outcome 6 SF‐36 role physical.

Comparison 3 Topiramate direct dose comparisons, Outcome 7 SF‐36 vitality.
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Analysis 3.7

Comparison 3 Topiramate direct dose comparisons, Outcome 7 SF‐36 vitality.

Comparison 3 Topiramate direct dose comparisons, Outcome 8 SF‐36 physical functioning.
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Analysis 3.8

Comparison 3 Topiramate direct dose comparisons, Outcome 8 SF‐36 physical functioning.

Comparison 3 Topiramate direct dose comparisons, Outcome 9 SF‐36 bodily pain.
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Analysis 3.9

Comparison 3 Topiramate direct dose comparisons, Outcome 9 SF‐36 bodily pain.

Comparison 3 Topiramate direct dose comparisons, Outcome 10 SF‐36 general health.
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Analysis 3.10

Comparison 3 Topiramate direct dose comparisons, Outcome 10 SF‐36 general health.

Comparison 3 Topiramate direct dose comparisons, Outcome 11 SF‐36 social functioning.
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Analysis 3.11

Comparison 3 Topiramate direct dose comparisons, Outcome 11 SF‐36 social functioning.

Comparison 3 Topiramate direct dose comparisons, Outcome 12 SF‐36 role emotional.
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Analysis 3.12

Comparison 3 Topiramate direct dose comparisons, Outcome 12 SF‐36 role emotional.

Comparison 3 Topiramate direct dose comparisons, Outcome 13 SF‐36 mental health.
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Analysis 3.13

Comparison 3 Topiramate direct dose comparisons, Outcome 13 SF‐36 mental health.

Comparison 4 Topiramate versus amitriptyline, Outcome 1 Responders (patients with ≥ 50% reduction in headache frequency).
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Analysis 4.1

Comparison 4 Topiramate versus amitriptyline, Outcome 1 Responders (patients with ≥ 50% reduction in headache frequency).

Comparison 4 Topiramate versus amitriptyline, Outcome 2 MIDAS score.
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Analysis 4.2

Comparison 4 Topiramate versus amitriptyline, Outcome 2 MIDAS score.

Comparison 5 Topiramate versus flunarizine, Outcome 1 Headache frequency (post‐treatment).
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Analysis 5.1

Comparison 5 Topiramate versus flunarizine, Outcome 1 Headache frequency (post‐treatment).

Comparison 5 Topiramate versus flunarizine, Outcome 2 Responders (patients with ≥ 50% reduction in headache frequency).
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Analysis 5.2

Comparison 5 Topiramate versus flunarizine, Outcome 2 Responders (patients with ≥ 50% reduction in headache frequency).

Comparison 6 Topiramate versus propranolol, Outcome 1 Headache frequency (change from baseline to post‐treatment, or post‐treatment alone).
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Analysis 6.1

Comparison 6 Topiramate versus propranolol, Outcome 1 Headache frequency (change from baseline to post‐treatment, or post‐treatment alone).

Comparison 6 Topiramate versus propranolol, Outcome 2 Responders (patients with ≥ 50% reduction in headache frequency).
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Analysis 6.2

Comparison 6 Topiramate versus propranolol, Outcome 2 Responders (patients with ≥ 50% reduction in headache frequency).

Comparison 7 Topiramate versus sodium valproate, Outcome 1 Headache frequency (post‐treatment).
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Analysis 7.1

Comparison 7 Topiramate versus sodium valproate, Outcome 1 Headache frequency (post‐treatment).

Comparison 7 Topiramate versus sodium valproate, Outcome 2 MIDAS score.
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Analysis 7.2

Comparison 7 Topiramate versus sodium valproate, Outcome 2 MIDAS score.

Comparison 8 Topiramate versus relaxation, Outcome 1 Headache frequency (change from baseline to post‐treatment).
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Analysis 8.1

Comparison 8 Topiramate versus relaxation, Outcome 1 Headache frequency (change from baseline to post‐treatment).

Comparison 8 Topiramate versus relaxation, Outcome 2 Responders (patients with ≥ 50% reduction in headache frequency).
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Analysis 8.2

Comparison 8 Topiramate versus relaxation, Outcome 2 Responders (patients with ≥ 50% reduction in headache frequency).

Comparison 8 Topiramate versus relaxation, Outcome 3 Change from baseline in MSQoL.
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Analysis 8.3

Comparison 8 Topiramate versus relaxation, Outcome 3 Change from baseline in MSQoL.

Table 1. NNHs (with 95% CIs), by dose, for placebo‐controlled trials of topiramate and proportion of withdrawals in trials with active intervention or placebo as control

Type of AE

50 mg/day

100 mg/day

200 mg/day

Any AE

NNH not defined*

11 (7 to 33)

5 (3 to 12)

Anorexia

NNH not defined*

17 (10 to 50)

12 (8 to 20)

Fatigue

NNH not defined*

25 (17 to 100)

12 (8 to 25)

Memory problems

NNH not defined*

25 (17 to 100)

12 (9 to 17)

Nausea

NNH not defined*

NNH not defined*

17 (9 to 50)

Paresthesia

NNH not defined*

3 (2 to 6)

2 (2 to 3)

Taste disturbance

7 (5 to 14)

14 (8 to 100)

7 (5 to 11)

Weight loss

25 (14 to 100)

17 (11 to 33)

11 (8 to 14)

Percentage of patients in active group withdrawing because of AEs

Afshari 2012: 5%; Ashtari 2008: 3%; Brandes 2004: 17%; Gupta 2007: 2%; Silberstein 2004: 17%

Brandes 2004: 26%; de Tommaso 2007: 8%; Diener 2004: 28%; Dodick 2009: 20%; Lipton 2011: 12%; Mei 2004: 29%; Silberstein 2004: 19%

Brandes 2004: 21%; Diener 2004: 44%; Edwards 2000: 27%; Silberstein 2004: 32%; Silberstein 2006: 15%; Storey 2001: 11%; Varkey 2011: 12%

* The 95% CI of the difference in AE rates between treatment and placebo arms (the risk difference, RD) crosses zero.

Abbreviations: AE = adverse event; CI = confidence interval; NNH = number needed to harm

Figures and Tables -
Table 1. NNHs (with 95% CIs), by dose, for placebo‐controlled trials of topiramate and proportion of withdrawals in trials with active intervention or placebo as control
Comparison 1. Topiramate (combined analyses based on most relevant dose in each study) versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Headache frequency (change from baseline to post‐treatment, or post‐treatment alone) Show forest plot

9

1793

Mean Difference (IV, Random, 95% CI)

‐1.20 [‐1.59, ‐0.80]

2 ORs for responders (patients with ≥ 50% reduction in headache frequency) Show forest plot

9

1246

Odds Ratio (M‐H, Random, 95% CI)

3.18 [2.10, 4.82]

3 RRs for responders (patients with ≥ 50% reduction in headache frequency) Show forest plot

9

1246

Risk Ratio (M‐H, Random, 95% CI)

2.02 [1.57, 2.60]

Figures and Tables -
Comparison 1. Topiramate (combined analyses based on most relevant dose in each study) versus placebo
Comparison 2. Topiramate (separate analyses of various doses) versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Headache frequency (change from baseline to post‐treatment, or post‐treatment alone) Show forest plot

9

Mean Difference (IV, Random, 95% CI)

Subtotals only

1.1 Topiramate titrated to 50 mg/day or maximum tolerated dose < 50 mg

3

576

Mean Difference (IV, Random, 95% CI)

‐0.95 [‐1.95, 0.04]

1.2 Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg

6

1620

Mean Difference (IV, Random, 95% CI)

‐1.15 [‐1.58, ‐0.71]

1.3 Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg

5

804

Mean Difference (IV, Random, 95% CI)

‐0.94 [‐1.53, ‐0.36]

2 Responders (patients with ≥ 50% reduction in headache frequency) Show forest plot

9

Odds Ratio (M‐H, Random, 95% CI)

Subtotals only

2.1 Topiramate titrated to 50 mg/day or maximum tolerated dose < 50 mg

3

575

Odds Ratio (M‐H, Random, 95% CI)

2.35 [1.60, 3.44]

2.2 Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg

5

852

Odds Ratio (M‐H, Random, 95% CI)

3.49 [2.23, 5.45]

2.3 Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg

6

1025

Odds Ratio (M‐H, Random, 95% CI)

2.49 [1.61, 3.87]

3 Any adverse event Show forest plot

4

Risk Difference (M‐H, Random, 95% CI)

Subtotals only

3.1 Topiramate titrated to 50 mg/day or maximum tolerated dose < 50 mg

1

120

Risk Difference (M‐H, Random, 95% CI)

0.05 [‐0.07, 0.17]

3.2 Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg

2

873

Risk Difference (M‐H, Random, 95% CI)

0.09 [0.03, 0.15]

3.3 Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg

1

213

Risk Difference (M‐H, Random, 95% CI)

0.20 [0.08, 0.32]

4 Anorexia Show forest plot

8

Risk Difference (M‐H, Random, 95% CI)

Subtotals only

4.1 Topiramate titrated to 50 mg/day or maximum tolerated dose < 50 mg

3

584

Risk Difference (M‐H, Random, 95% CI)

0.01 [‐0.04, 0.07]

4.2 Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg

5

1631

Risk Difference (M‐H, Random, 95% CI)

0.06 [0.02, 0.10]

4.3 Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg

5

999

Risk Difference (M‐H, Random, 95% CI)

0.08 [0.05, 0.12]

5 Fatigue Show forest plot

6

Risk Difference (M‐H, Random, 95% CI)

Subtotals only

5.1 Topiramate titrated to 50 mg/day or maximum tolerated dose < 50 mg

2

464

Risk Difference (M‐H, Random, 95% CI)

0.04 [‐0.07, 0.15]

5.2 Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg

5

1631

Risk Difference (M‐H, Random, 95% CI)

0.04 [0.01, 0.06]

5.3 Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg

4

959

Risk Difference (M‐H, Random, 95% CI)

0.08 [0.04, 0.13]

6 Memory problems Show forest plot

5

Risk Difference (M‐H, Random, 95% CI)

Subtotals only

6.1 Topiramate titrated to 50 mg/day or maximum tolerated dose < 50 mg

2

464

Risk Difference (M‐H, Random, 95% CI)

0.04 [‐0.01, 0.09]

6.2 Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg

3

758

Risk Difference (M‐H, Random, 95% CI)

0.04 [0.01, 0.06]

6.3 Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg

5

999

Risk Difference (M‐H, Random, 95% CI)

0.08 [0.06, 0.11]

7 Nausea Show forest plot

6

Risk Difference (M‐H, Random, 95% CI)

Subtotals only

7.1 Topiramate titrated to 50 mg/day or maximum tolerated dose < 50 mg

2

464

Risk Difference (M‐H, Random, 95% CI)

‐0.01 [‐0.10, 0.09]

7.2 Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg

5

1631

Risk Difference (M‐H, Random, 95% CI)

0.02 [‐0.01, 0.04]

7.3 Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg

4

959

Risk Difference (M‐H, Random, 95% CI)

0.06 [0.02, 0.11]

8 Paresthesia Show forest plot

8

Risk Difference (M‐H, Random, 95% CI)

Subtotals only

8.1 Topiramate titrated to 50 mg/day or maximum tolerated dose < 50 mg

3

584

Risk Difference (M‐H, Random, 95% CI)

0.21 [‐0.02, 0.43]

8.2 Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg

5

1631

Risk Difference (M‐H, Random, 95% CI)

0.33 [0.18, 0.48]

8.3 Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg

5

999

Risk Difference (M‐H, Random, 95% CI)

0.44 [0.39, 0.49]

9 Taste disturbance Show forest plot

6

Risk Difference (M‐H, Random, 95% CI)

Subtotals only

9.1 Topiramate titrated to 50 mg/day or maximum tolerated dose < 50 mg

2

464

Risk Difference (M‐H, Random, 95% CI)

0.14 [0.07, 0.21]

9.2 Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg

5

1623

Risk Difference (M‐H, Random, 95% CI)

0.07 [0.01, 0.12]

9.3 Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg

4

786

Risk Difference (M‐H, Random, 95% CI)

0.14 [0.09, 0.19]

10 Weight loss Show forest plot

6

Risk Difference (M‐H, Random, 95% CI)

Subtotals only

10.1 Topiramate titrated to 50 mg/day or maximum tolerated dose < 50 mg

2

464

Risk Difference (M‐H, Random, 95% CI)

0.04 [0.01, 0.07]

10.2 Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg

4

1270

Risk Difference (M‐H, Random, 95% CI)

0.06 [0.03, 0.09]

10.3 Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg

5

999

Risk Difference (M‐H, Random, 95% CI)

0.09 [0.07, 0.12]

11 MSQ‐role function restrictive Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

11.1 Topiramate titrated to 50 mg/day or maximum tolerated dose < 50 mg

2

463

Mean Difference (IV, Random, 95% CI)

5.83 [2.25, 9.41]

11.2 Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg

2

474

Mean Difference (IV, Random, 95% CI)

10.08 [6.55, 13.60]

11.3 Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg

2

458

Mean Difference (IV, Random, 95% CI)

10.36 [6.68, 14.04]

12 MSQ‐role function prevention Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

12.1 Topiramate titrated to 50 mg/day or maximum tolerated dose < 50 mg

2

463

Mean Difference (IV, Random, 95% CI)

2.84 [‐0.24, 5.92]

12.2 Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg

2

474

Mean Difference (IV, Random, 95% CI)

6.39 [3.37, 9.41]

12.3 Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg

2

458

Mean Difference (IV, Random, 95% CI)

5.06 [1.87, 8.25]

13 MSQ‐emotional function Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

13.1 Topiramate titrated to 50 mg/day or maximum tolerated dose < 50 mg

2

463

Mean Difference (IV, Random, 95% CI)

4.58 [0.61, 8.54]

13.2 Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg

2

474

Mean Difference (IV, Random, 95% CI)

10.22 [6.31, 14.14]

13.3 Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg

2

458

Mean Difference (IV, Random, 95% CI)

8.45 [4.38, 12.52]

14 SF‐36 role physical Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

14.1 Topiramate titrated to 50 mg/day or maximum tolerated dose < 50 mg

2

463

Mean Difference (IV, Random, 95% CI)

3.00 [‐3.89, 9.90]

14.2 Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg

2

474

Mean Difference (IV, Random, 95% CI)

10.80 [‐2.42, 24.03]

14.3 Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg

2

458

Mean Difference (IV, Random, 95% CI)

8.59 [0.65, 16.52]

15 SF‐36 vitality Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

15.1 Topiramate titrated to 50 mg/day or maximum tolerated dose < 50 mg

2

463

Mean Difference (IV, Random, 95% CI)

2.08 [‐4.68, 8.84]

15.2 Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg

2

474

Mean Difference (IV, Random, 95% CI)

4.48 [‐7.77, 16.73]

15.3 Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg

2

458

Mean Difference (IV, Random, 95% CI)

1.36 [‐4.52, 7.24]

16 SF‐36 physical functioning Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

16.1 Topiramate titrated to 50 mg/day or maximum tolerated dose < 50 mg

2

463

Mean Difference (IV, Random, 95% CI)

0.54 [‐3.28, 4.36]

16.2 Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg

2

474

Mean Difference (IV, Random, 95% CI)

2.78 [‐3.29, 8.86]

16.3 Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg

2

458

Mean Difference (IV, Random, 95% CI)

‐0.96 [‐5.27, 3.35]

17 SF‐36 bodily pain Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

17.1 Topiramate titrated to 50 mg/day or maximum tolerated dose < 50 mg

2

463

Mean Difference (IV, Random, 95% CI)

4.35 [0.04, 8.66]

17.2 Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg

2

474

Mean Difference (IV, Random, 95% CI)

6.35 [‐1.29, 14.00]

17.3 Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg

2

458

Mean Difference (IV, Random, 95% CI)

5.12 [‐1.25, 11.49]

18 SF‐36 general health Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

18.1 Topiramate titrated to 50 mg/day or maximum tolerated dose < 50 mg

2

463

Mean Difference (IV, Random, 95% CI)

1.45 [‐2.18, 5.08]

18.2 Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg

2

474

Mean Difference (IV, Random, 95% CI)

4.18 [‐1.21, 9.57]

18.3 Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg

2

458

Mean Difference (IV, Random, 95% CI)

2.58 [‐1.00, 6.15]

19 SF‐36 social functioning Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

19.1 Topiramate titrated to 50 mg/day or maximum tolerated dose < 50 mg

2

463

Mean Difference (IV, Random, 95% CI)

2.00 [‐1.92, 5.92]

19.2 Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg

2

474

Mean Difference (IV, Random, 95% CI)

3.13 [‐3.73, 9.99]

19.3 Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg

2

458

Mean Difference (IV, Random, 95% CI)

1.94 [‐2.07, 5.96]

20 SF‐36 role emotional Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

20.1 Topiramate titrated to 50 mg/day or maximum tolerated dose < 50 mg

2

463

Mean Difference (IV, Random, 95% CI)

2.30 [‐4.56, 9.16]

20.2 Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg

2

474

Mean Difference (IV, Random, 95% CI)

4.64 [‐3.39, 12.68]

20.3 Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg

2

458

Mean Difference (IV, Random, 95% CI)

2.75 [‐4.99, 10.48]

21 SF‐36 mental health Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

21.1 Topiramate titrated to 50 mg/day or maximum tolerated dose < 50 mg

2

463

Mean Difference (IV, Random, 95% CI)

1.19 [‐4.59, 6.98]

21.2 Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg

2

474

Mean Difference (IV, Random, 95% CI)

2.58 [‐5.65, 10.81]

21.3 Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg

2

458

Mean Difference (IV, Random, 95% CI)

1.57 [‐4.21, 7.35]

Figures and Tables -
Comparison 2. Topiramate (separate analyses of various doses) versus placebo
Comparison 3. Topiramate direct dose comparisons

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Headache frequency (change from baseline to post‐treatment, or post‐treatment alone) Show forest plot

3

Mean Difference (IV, Random, 95% CI)

Subtotals only

1.1 Topiramate 100 mg versus 50 mg

2

479

Mean Difference (IV, Random, 95% CI)

‐0.71 [‐1.32, ‐0.10]

1.2 Topiramate 200 mg versus 50 mg

2

463

Mean Difference (IV, Random, 95% CI)

‐0.96 [‐1.53, ‐0.40]

1.3 Topiramate 200 mg versus 100 mg

3

756

Mean Difference (IV, Random, 95% CI)

0.03 [‐0.55, 0.61]

2 Responders (patients with ≥ 50% reduction in headache frequency) Show forest plot

3

Odds Ratio (M‐H, Random, 95% CI)

Subtotals only

2.1 Topiramate 100 mg versus 50 mg

2

478

Odds Ratio (M‐H, Random, 95% CI)

1.80 [1.25, 2.60]

2.2 Topiramate 200 mg versus 50 mg

2

462

Odds Ratio (M‐H, Random, 95% CI)

1.66 [1.15, 2.41]

2.3 Topiramate 200 mg versus 100 mg

3

756

Odds Ratio (M‐H, Random, 95% CI)

0.93 [0.69, 1.24]

3 MSQ‐role function restrictive Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

3.1 Topiramate 100 mg versus 50 mg

2

479

Mean Difference (IV, Random, 95% CI)

4.22 [0.65, 7.80]

3.2 Topiramate 200 mg versus 50 mg

2

463

Mean Difference (IV, Random, 95% CI)

4.55 [0.82, 8.28]

3.3 Topiramate 200 mg versus 100 mg

2

474

Mean Difference (IV, Random, 95% CI)

0.31 [‐3.37, 3.99]

4 MSQ‐role function prevention Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

4.1 Topiramate 100 mg versus 50 mg

2

479

Mean Difference (IV, Random, 95% CI)

3.54 [0.48, 6.60]

4.2 Topiramate 200 mg versus 50 mg

2

463

Mean Difference (IV, Random, 95% CI)

2.28 [‐2.13, 6.69]

4.3 Topiramate 200 mg versus 100 mg

2

474

Mean Difference (IV, Random, 95% CI)

‐1.18 [‐6.67, 4.30]

5 MSQ‐emotional function Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

5.1 Topiramate 100 mg versus 50 mg

2

479

Mean Difference (IV, Random, 95% CI)

5.62 [1.67, 9.58]

5.2 Topiramate 200 mg versus 50 mg

2

463

Mean Difference (IV, Random, 95% CI)

3.90 [‐0.21, 8.02]

5.3 Topiramate 200 mg versus 100 mg

2

474

Mean Difference (IV, Random, 95% CI)

‐1.73 [‐5.80, 2.34]

6 SF‐36 role physical Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

6.1 Topiramate 100 mg versus 50 mg

2

479

Mean Difference (IV, Random, 95% CI)

7.70 [‐8.27, 23.67]

6.2 Topiramate 200 mg versus 50 mg

2

463

Mean Difference (IV, Random, 95% CI)

5.51 [‐5.17, 16.19]

6.3 Topiramate 200 mg versus 100 mg

2

474

Mean Difference (IV, Random, 95% CI)

‐2.20 [‐9.31, 4.90]

7 SF‐36 vitality Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

7.1 Topiramate 100 mg versus 50 mg

2

479

Mean Difference (IV, Random, 95% CI)

2.44 [‐3.05, 7.92]

7.2 Topiramate 200 mg versus 50 mg

2

463

Mean Difference (IV, Random, 95% CI)

‐0.63 [‐4.64, 3.39]

7.3 Topiramate 200 mg versus 100 mg

2

474

Mean Difference (IV, Random, 95% CI)

‐3.01 [‐9.38, 3.35]

8 SF‐36 physical functioning Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

8.1 Topiramate 100 mg versus 50 mg

2

479

Mean Difference (IV, Random, 95% CI)

2.35 [‐1.02, 5.72]

8.2 Topiramate 200 mg versus 50 mg

2

463

Mean Difference (IV, Random, 95% CI)

‐1.44 [‐4.92, 2.04]

8.3 Topiramate 200 mg versus 100 mg

2

474

Mean Difference (IV, Random, 95% CI)

‐3.75 [‐7.18, ‐0.32]

9 SF‐36 bodily pain Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

9.1 Topiramate 100 mg versus 50 mg

2

479

Mean Difference (IV, Random, 95% CI)

2.13 [‐1.83, 6.08]

9.2 Topiramate 200 mg versus 50 mg

2

463

Mean Difference (IV, Random, 95% CI)

0.85 [‐3.27, 4.96]

9.3 Topiramate 200 mg versus 100 mg

2

474

Mean Difference (IV, Random, 95% CI)

‐1.16 [‐5.23, 2.91]

10 SF‐36 general health Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

10.1 Topiramate 100 mg versus 50 mg

2

479

Mean Difference (IV, Random, 95% CI)

2.72 [‐0.76, 6.21]

10.2 Topiramate 200 mg versus 50 mg

2

463

Mean Difference (IV, Random, 95% CI)

1.13 [‐4.36, 6.62]

10.3 Topiramate 200 mg versus 100 mg

2

474

Mean Difference (IV, Random, 95% CI)

‐1.60 [‐8.85, 5.65]

11 SF‐36 social functioning Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

11.1 Topiramate 100 mg versus 50 mg

2

479

Mean Difference (IV, Random, 95% CI)

1.13 [‐5.53, 7.79]

11.2 Topiramate 200 mg versus 50 mg

2

463

Mean Difference (IV, Random, 95% CI)

‐0.06 [‐4.07, 3.96]

11.3 Topiramate 200 mg versus 100 mg

2

474

Mean Difference (IV, Random, 95% CI)

‐1.05 [‐5.56, 3.46]

12 SF‐36 role emotional Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

12.1 Topiramate 100 mg versus 50 mg

2

479

Mean Difference (IV, Random, 95% CI)

2.33 [‐3.79, 8.45]

12.2 Topiramate 200 mg versus 50 mg

2

463

Mean Difference (IV, Random, 95% CI)

0.63 [‐5.69, 6.94]

12.3 Topiramate 200 mg versus 100 mg

2

474

Mean Difference (IV, Random, 95% CI)

‐1.65 [‐7.92, 4.63]

13 SF‐36 mental health Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

13.1 Topiramate 100 mg versus 50 mg

2

479

Mean Difference (IV, Random, 95% CI)

1.31 [‐1.87, 4.49]

13.2 Topiramate 200 mg versus 50 mg

2

463

Mean Difference (IV, Random, 95% CI)

0.40 [‐2.87, 3.67]

13.3 Topiramate 200 mg versus 100 mg

2

474

Mean Difference (IV, Random, 95% CI)

‐0.87 [‐4.10, 2.36]

Figures and Tables -
Comparison 3. Topiramate direct dose comparisons
Comparison 4. Topiramate versus amitriptyline

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Responders (patients with ≥ 50% reduction in headache frequency) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

2 MIDAS score Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

Figures and Tables -
Comparison 4. Topiramate versus amitriptyline
Comparison 5. Topiramate versus flunarizine

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Headache frequency (post‐treatment) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

2 Responders (patients with ≥ 50% reduction in headache frequency) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

Figures and Tables -
Comparison 5. Topiramate versus flunarizine
Comparison 6. Topiramate versus propranolol

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Headache frequency (change from baseline to post‐treatment, or post‐treatment alone) Show forest plot

2

342

Mean Difference (IV, Random, 95% CI)

‐0.14 [‐0.61, 0.34]

1.1 Topiramate 50 mg versus propranolol 80 mg

1

60

Mean Difference (IV, Random, 95% CI)

‐0.37 [‐1.15, 0.41]

1.2 Topiramate 100 mg versus propranolol 160 mg

1

282

Mean Difference (IV, Random, 95% CI)

0.0 [‐0.60, 0.60]

2 Responders (patients with ≥ 50% reduction in headache frequency) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

Figures and Tables -
Comparison 6. Topiramate versus propranolol
Comparison 7. Topiramate versus sodium valproate

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Headache frequency (post‐treatment) Show forest plot

2

120

Mean Difference (IV, Random, 95% CI)

‐0.90 [‐1.58, ‐0.22]

2 MIDAS score Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

Figures and Tables -
Comparison 7. Topiramate versus sodium valproate
Comparison 8. Topiramate versus relaxation

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Headache frequency (change from baseline to post‐treatment) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

2 Responders (patients with ≥ 50% reduction in headache frequency) Show forest plot

1

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

3 Change from baseline in MSQoL Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

Figures and Tables -
Comparison 8. Topiramate versus relaxation