Cochrane Clinical Answers - Fulltext - Can topiramate help to prevent episodic migraine in adults?

Question:Can topiramate help to prevent episodic migraine in adults?

Clinical Answer:

Topiramate is an effective treatment for preventing episodic migraine in adults, although there is a dose-dependent increase in adverse events compared with placebo.

Randomized controlled trials including up to 1800 participants support the use of topiramate (at 50, 100 or 200 mg dose) for preventing episodic migraine in adults, with an average reduction of one headache per 28 days and more people reporting at least a 50% reduction in headache frequency. However, there is a dose-dependent increase in adverse events (memory problems, nausea, paresthesia, taste disturbance and weight loss) with topiramate compared with placebo (the average increase in risk for the 200 mg dose ranged from 6% to 44% depending on the adverse event). Despite this, patients receiving topiramate reported a better average quality of life score on the Migraine-Specific Questionnaire than people with placebo.

The comparative study data also reported that outcomes were similar with topiramate compared with other medical therapies (amitriptyline, flunarizine, propranolol) for migraine prophylaxis. However, the numbers of participants in these analyses were much smaller than those comparing topiramate with placebo and equivalence cannot be concluded.

Full outcome data is detailed below:

1.Topiramate versus placebo

  • Population, Intervention, Comparator

    Population:

    Adults (details of gender and age not reported) with migraine for at 12 months and a headache frequency of 3 to 12 attacks/month

    Intervention:

    Topiramate 50-200 mg/daily for 4 to 26 weeks

    Comparator:

    Placebo

  • OUTCOME 1.1: Headache frequency at 28 days

    Risk of bias of studies:

    The reviewers did not perform a GRADE assessment of the quality of the evidence. In this analysis 4/9 (44%) of the studies failed to report adequate allocation concealment and random sequence generation processes, 5/9 (56%) did not report adequate blinding of participants/carers and 2/9 (22%) had high or unclear numbers of withdrawals.

    Narrative result:

    Nine RCTs with 1793 participants found that people on topiramate had lower headache frequency compared with placebo. Subgroup analysis by dose of topiramate (50 mg, 100 mg or 200 mg) found similar results to the main analysis.

    Relative effect or mean difference:

    There was a statistically significant difference between groups, in favor of topiramate (mean difference -1.20 headache per 28 days, 95% CI -1.59 to -0.80).

    Forest plot from Cochrane Review

    Reference:
    Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
    • OUTCOME 1.2: Patients with ≥ 50% reduction in headache frequency

      Risk of bias of studies:

      The reviewers did not perform a GRADE assessment of the quality of the evidence. In this analysis 6/9 (67%) of the studies failed to report adequate allocation concealment and random sequence generation processes, 7/9 (78%) did not report adequate blinding of participants/carers and 2/9 (22%) had high numbers of withdrawals.

      Narrative result:

      Nine RCTs with 1246 participants found that more people on topiramate experienced ≥ 50% reduction in headache frequency compared with placebo. Subgroup analysis by dose of topiramate (50 mg, 100 mg or 200 mg) found similar results to the main analysis.

      Relative effect or mean difference:

      There was a statistically significant difference between groups, in favor of topiramate (OR 3.18, 95% CI 2.10 to 4.82).

      Forest plot from Cochrane Review

      Absolute effect:

      482 per 1000 people (95% CI 380 to 585) with topiramate compared with 226 per 1000 people with placebo.

      Reference:
      Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
      • OUTCOME 1.3: Adverse events

        Narrative result:

        Rates of any adverse event and of memory problems, nausea, paresthesia, taste disturbance and weight loss were higher with topiramate 100 or 200 mg compared with placebo. Except for taste disturbance and weight loss, there were no statistically significant differences in the frequency of adverse effects between placebo and topiramate 50 mg. Click below for full details.

        Reference:
        Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
        • Subgroup analysis 1.3.1: Any adverse event - [subgroup: Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg]
          Risk of bias of studies:

          The reviewers did not perform a GRADE assessment of the quality of the evidence. In this analysis the studies reported adequate allocation concealment and random sequence generation processes, did not report adequate blinding of outcome assessors and 1/2 (50%) had unclear numbers of withdrawals.

          Narrative result:

          Two RCTs with 873 participants found that risk of any adverse event was higher with topiramate compared with placebo.

          Relative effect or mean difference:

          There was a statistically significant difference between groups, in favor of placebo (risk difference 9%, 95% CI 3% to 15%).

          Forest plot from Cochrane Review

          Reference:
          Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
        • Subgroup analysis 1.3.2: Any adverse event - [subgroup: Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg]
          Risk of bias of studies:

          The reviewers did not perform a GRADE assessment of the quality of the evidence. The study failed to report adequate allocation concealment and random sequence generation processes, adequate blinding of participants/carers/outcome assessors but had low numbers of withdrawals.

          Narrative result:

          One RCT with 213 participants found that risk of any adverse event was higher with topiramate compared with placebo.

          Relative effect or mean difference:

          There was a statistically significant difference between groups, in favor of placebo (risk difference 20%, 95% CI 8% to 32%).

          Forest plot from Cochrane Review

          Reference:
          Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
        • Subgroup analysis 1.3.3: Memory problems - [subgroup: Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg]
          Risk of bias of studies:

          The reviewers did not perform a GRADE assessment of the quality of the evidence. In this analysis 1/3 (33%) of the studies failed to report adequate allocation concealment, none reported adequate blinding of outcome assessors but all had low numbers of withdrawals.

          Narrative result:

          Three RCTs with 758 participants found that risk of memory problems was higher with topiramate compared with placebo

          Relative effect or mean difference:

          There was a statistically significant difference between groups, in favor of placebo (risk difference 4%, 95% CI 1% to 6%).

          Forest plot from Cochrane Review

          Reference:
          Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
        • Subgroup analysis 1.3.4: Memory problems - [subgroup: Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg]
          Risk of bias of studies:

          The reviewers did not perform a GRADE assessment of the quality of the evidence. In this analysis 3/5 (60%) of the studies failed to report adequate allocation concealment, none reported adequate blinding of outcome assessors but all had low numbers of withdrawals.

          Narrative result:

          Five RCTs with 999 participants found that risk of memory problems was higher with topiramate compared with placebo,

          Relative effect or mean difference:

          There was a statistically significant difference between groups, in favor of placebo (risk difference 8%, 95% CI 6% to 11%).

          Forest plot from Cochrane Review

          Reference:
          Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
        • Subgroup analysis 1.3.5: Nausea - [subgroup: Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg]
          Risk of bias of studies:

          The reviewers did not perform a GRADE assessment of the quality of the evidence. In this analysis 1/5 (20%) of the studies failed to report adequate allocation concealment, none reported adequate blinding of outcome assessors and 1/5 (20%) of the studies had unclear numbers of withdrawals.

          Narrative result:

          Five RCTs with 1631 participants found no statistically significant difference between groups.

          Relative effect or mean difference:

          There was no statistically significant difference between groups (risk difference 2%, 95% CI -1% to 4%).

          Forest plot from Cochrane Review

          Reference:
          Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
        • Subgroup analysis 1.3.6: Nausea - [subgroup: Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg]
          Risk of bias of studies:

          The reviewers did not perform a GRADE assessment of the quality of the evidence. In this analysis 2/4 (50%) of the studies failed to report adequate allocation concealment, none reported adequate blinding of outcome assessors but all had numbers of withdrawals.

          Narrative result:

          Four RCTs with 959 participants found that risk of nausea was higher with topiramate compared with placebo.

          Relative effect or mean difference:

          There was a statistically significant difference between groups, in favor of placebo (risk difference 6%, 95% CI 2% to 11%).

          Forest plot from Cochrane Review

          Reference:
          Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
        • Subgroup analysis 1.3.7: Paresthesia - [subgroup: Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg]
          Risk of bias of studies:

          The reviewers did not perform a GRADE assessment of the quality of the evidence. In this analysis 1/5 (20%) of the studies failed to report adequate allocation concealment, none reported adequate blinding of outcome assessors and 1/5 (20%) of the studies had unclear numbers of withdrawals.

          Narrative result:

          Five RCTs with 1631 participants found that risk of paresthesia was higher with topiramate compared with placebo.

          Relative effect or mean difference:

          There was a statistically significant difference between groups, in favor of placebo (risk difference 33%, 95% CI 18% to 48%).

          Forest plot from Cochrane Review

          Reference:
          Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
        • Subgroup analysis 1.3.8: Paresthesia - [subgroup: Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg]
          Risk of bias of studies:

          The reviewers did not perform a GRADE assessment of the quality of the evidence. In this analysis 4/5 (80%) of the studies failed to report adequate allocation concealment, none reported adequate blinding of outcome assessors but all had low numbers of withdrawals.

          Narrative result:

          Five RCTs with 999 participants found that risk of paresthesia was higher with topiramate compared with placebo.

          Relative effect or mean difference:

          There was a statistically significant difference between groups, in favor of placebo (risk difference .44%, 95% CI 39% to 49%).

          Forest plot from Cochrane Review

          Reference:
          Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
        • Subgroup analysis 1.3.9: Taste disturbance - [subgroup: Topiramate titrated to 50 mg/day or maximum tolerated dose < 50 mg]
          Risk of bias of studies:

          The reviewers did not perform a GRADE assessment of the quality of the evidence. In this analysis the studies reported adequate allocation concealment, did not report adequate blinding of outcome assessors and both had low numbers of withdrawals.

          Narrative result:

          Two RCTs with 464 participants found that risk of taste disturbance was higher with topiramate compared with placebo.

          Relative effect or mean difference:

          There was a statistically significant difference between groups, in favor of placebo (risk difference .14%, 95% CI 7% to 21%).

          Forest plot from Cochrane Review

          Reference:
          Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
        • Subgroup analysis 1.3.10: Taste disturbance - [subgroup: Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg]
          Risk of bias of studies:

          The reviewers did not perform a GRADE assessment of the quality of the evidence. In this analysis 1/5 (20%) of the studies failed to report adequate allocation concealment, none reported adequate blinding of outcome assessors and 1/5 (20%) of the studies had unclear numbers of withdrawals.

          Narrative result:

          Five RCTs with 1623 participants found that risk of taste disturbance was higher with topiramate compared with placebo.

          Relative effect or mean difference:

          There was a statistically significant difference between groups, in favor of placebo (risk difference 7%, 95% CI 1% to 12%).

          Forest plot from Cochrane Review

          Reference:
          Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
        • Subgroup analysis 1.3.11: Taste disturbance - [subgroup: Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg]
          Risk of bias of studies:

          The reviewers did not perform a GRADE assessment of the quality of the evidence. In this analysis 2/4 (50%) of the studies failed to report adequate allocation concealment, none reported adequate blinding of outcome assessors but all had low numbers of withdrawals.

          Narrative result:

          Four RCTs with 786 participants found that that risk of taste disturbance was higher with topiramate compared with placebo.

          Relative effect or mean difference:

          There was a statistically significant difference between groups, in favor of placebo (risk difference 14%, 95% CI 9% to 19%).

          Forest plot from Cochrane Review

          Reference:
          Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
        • Subgroup analysis 1.3.12: Weight loss - [subgroup: Topiramate titrated to 50 mg/day or maximum tolerated dose < 50 mg]
          Risk of bias of studies:

          The reviewers did not perform a GRADE assessment of the quality of the evidence. In this analysis the studies reported adequate allocation concealment, did not report adequate blinding of outcome assessors but both had low numbers of withdrawals.

          Narrative result:

          Two RCTs with 464 participants found that risk of weight loss was higher with topiramate compared with placebo.

          Relative effect or mean difference:

          There was a statistically significant difference between groups, in favor of placebo (risk difference 4%, 95% CI 1% to 7%).

          Forest plot from Cochrane Review

          Reference:
          Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
        • Subgroup analysis 1.3.13: Weight loss - [subgroup: Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg]
          Risk of bias of studies:

          The reviewers did not perform a GRADE assessment of the quality of the evidence. In this analysis 1/4 (25%) of the studies failed to report adequate allocation concealment and random sequence generation processes, none reported adequate blinding of outcome assessors but all low numbers of withdrawals.

          Narrative result:

          Four RCTs with 1270 participants found that risk of weight loss was higher with topiramate compared with placebo.

          Relative effect or mean difference:

          There was a statistically significant difference between groups, in favor of placebo (risk difference 6%, 95% CI 3% to 9%).

          Forest plot from Cochrane Review

          Reference:
          Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
        • Subgroup analysis 1.3.14: Weight loss - [subgroup: Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg]
          Risk of bias of studies:

          The reviewers did not perform a GRADE assessment of the quality of the evidence. In this analysis 3/5 (60%) of the studies failed to report adequate allocation concealment, none reported adequate blinding of participants/carers/outcome assessors and all had low numbers of withdrawals.

          Narrative result:

          Five RCTs with 999 participants found that risk of weight loss was higher with topiramate compared with placebo.

          Relative effect or mean difference:

          There was a statistically significant difference between groups, in favor of placebo (risk difference 9%, 95% CI 7% to 12%).

          Forest plot from Cochrane Review

          Reference:
          Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
      • OUTCOME 1.4: Quality of life

        Narrative result:

        Data on patient-reported quality of life, measured by the Migraine-Specific Questionnaire (MSQ) showed better quality of life for all doses of topiramate compared with placebo for the restrictive and emotional function and the two higher doses for the preventive function. Click below for full details.

        Reference:
        Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
        • Subgroup analysis 1.4.1: MSQ-role function restrictive - [subgroup: Topiramate titrated to 50 mg/day or maximum tolerated dose < 50 mg]
          Risk of bias of studies:

          The reviewers did not perform a GRADE assessment of the quality of the evidence. In this analysis the studies reported adequate allocation concealment, did not report adequate blinding of outcome assessors but had low numbers of withdrawals.

          Narrative result:

          Two RCTs with 463 participants found that people on topiramate had better scores on MSQ-role function restrictive compared with placebo.

          Relative effect or mean difference:

          There was a statistically significant difference between groups, in favor of topiramate (mean difference 5.83, 95% CI 2.25 to 9.41).

          Forest plot from Cochrane Review

          Reference:
          Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
        • Subgroup analysis 1.4.2: MSQ-role function restrictive - [subgroup: Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg]
          Risk of bias of studies:

          The reviewers did not perform a GRADE assessment of the quality of the evidence. In this analysis the studies reported adequate allocation concealment, did not report adequate blinding of outcome assessors but had low numbers of withdrawals.

          Narrative result:

          Two RCTs with 474 participants found that people on topiramate had better scores on MSQ-role function restrictive compared with placebo.

          Relative effect or mean difference:

          There was a statistically significant difference between groups, in favor of topiramate (mean difference 10.08, 95% CI 6.55 to 13.60).

          Forest plot from Cochrane Review

          Reference:
          Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
        • Subgroup analysis 1.4.3: MSQ-role function restrictive - [subgroup: Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg]
          Risk of bias of studies:

          The reviewers did not perform a GRADE assessment of the quality of the evidence. In this analysis the studies reported adequate allocation concealment, did not report adequate blinding of outcome assessors but had low numbers of withdrawals.

          Narrative result:

          Two RCTs with 458 participants found that people on topiramate had better scores on MSQ-role function restrictive compared with placebo.

          Relative effect or mean difference:

          There was a statistically significant difference between groups, in favor of topiramate (mean difference 10.36, 95% CI 6.68 to 14.04).

          Forest plot from Cochrane Review

          Reference:
          Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
        • Subgroup analysis 1.4.4: MSQ-role function prevention - [subgroup: Topiramate titrated to 50 mg/day or maximum tolerated dose < 50 mg]
          Risk of bias of studies:

          The reviewers did not perform a GRADE assessment of the quality of the evidence. In this analysis the studies reported adequate allocation concealment, did not report adequate blinding of outcome assessors but had low numbers of withdrawals.

          Narrative result:

          Two RCTs with 463 participants found no statistically significant difference between groups.

          Relative effect or mean difference:

          There was no statistically significant difference between groups (mean difference 2.84, 95% CI -0.24 to 5.92).

          Forest plot from Cochrane Review

          Reference:
          Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
        • Subgroup analysis 1.4.5: MSQ-role function prevention - [subgroup: Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg]
          Risk of bias of studies:

          The reviewers did not perform a GRADE assessment of the quality of the evidence. In this analysis the studies reported adequate allocation concealment, did not report adequate blinding of outcome assessors but had low numbers of withdrawals.

          Narrative result:

          Two RCTs with 474 participants found that people on topiramate had better scores on MSQ-role function prevention compared with placebo.

          Relative effect or mean difference:

          There was a statistically significant difference between groups, in favor of topiramate (mean difference 6.39, 95% CI 3.37 to 9.41).

          Forest plot from Cochrane Review

          Reference:
          Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
        • Subgroup analysis 1.4.6: MSQ-role function prevention - [subgroup: Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg]
          Risk of bias of studies:

          The reviewers did not perform a GRADE assessment of the quality of the evidence. In this analysis the studies reported adequate allocation concealment, did not report adequate blinding of outcome assessors but had low numbers of withdrawals.

          Narrative result:

          Two RCTs with 458 participants found that people on topiramate had better scores on MSQ-role function prevention compared with placebo.

          Relative effect or mean difference:

          There was a statistically significant difference between groups, in favor of topiramate (mean difference 5.06, 95% CI 1.87 to 8.25).

          Forest plot from Cochrane Review

          Reference:
          Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
        • Subgroup analysis 1.4.7: MSQ-emotional function - [subgroup: Topiramate titrated to 50 mg/day or maximum tolerated dose < 50 mg]
          Risk of bias of studies:

          The reviewers did not perform a GRADE assessment of the quality of the evidence. In this analysis the studies reported adequate allocation concealment, did not report adequate blinding of outcome assessors but had low numbers of withdrawals.

          Narrative result:

          Two RCTs with 463 participants found that people on topiramate had better scores on MSQ-emotional function compared with placebo.

          Relative effect or mean difference:

          There was a statistically significant difference between groups, in favor of topiramate (mean difference 4.58, 95% CI 0.61 to 8.54).

          Forest plot from Cochrane Review

          Reference:
          Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
        • Subgroup analysis 1.4.8: MSQ-emotional function - [subgroup: Topiramate titrated to 100 mg/day or maximum tolerated dose < 100 mg]
          Risk of bias of studies:

          The reviewers did not perform a GRADE assessment of the quality of the evidence. In this analysis the studies reported adequate allocation concealment, did not report adequate blinding of outcome assessors but had low numbers of withdrawals.

          Narrative result:

          Two RCTs with 474 participants found that people on topiramate had better scores on MSQ- emotional function compared with placebo.

          Relative effect or mean difference:

          There was a statistically significant difference between groups, in favor of topiramate (mean difference 10.22, 95% CI 6.31 to 14.14).

          Forest plot from Cochrane Review

          Reference:
          Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
        • Subgroup analysis 1.4.9: MSQ-emotional function - [subgroup: Topiramate titrated to 200 mg/day or maximum tolerated dose < 200 mg]
          Risk of bias of studies:

          The reviewers did not perform a GRADE assessment of the quality of the evidence. In this analysis the studies reported adequate allocation concealment, did not report adequate blinding of outcome assessors but had low numbers of withdrawals.

          Narrative result:

          Two RCTs with 458 participants found that people on topiramate had better scores on MSQ- emotional function compared with placebo.

          Relative effect or mean difference:

          There was a statistically significant difference between groups, in favor of topiramate (mean difference 8.45, 95% CI 4.38 to 12.52).

          Forest plot from Cochrane Review

          Reference:
          Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]

      2.Topiramate versus amitriptyline

      • Population, Intervention, Comparator

        Population:

        Adults (details re gender and age not available) with migraine with or without aura according to ICHD-II, migraine onset at least 6 months prior to study and migraine frequency of 3 to 12 attacks/month

        Intervention:

        Topiramate 50-100 mg per day for 26 weeks

        Comparator:

        Amitriptyline 50-100 mg per day for 26 weeks

      • OUTCOME 2.1: Patients with ≥ 50% reduction in headache frequency

        Risk of bias of studies:

        The reviewers did not perform a GRADE assessment of the quality of the evidence. The study reported adequate allocation concealment and random sequence generation processes, did not report adequate blinding of outcome assessors and had unclear numbers of withdrawals.

        Narrative result:

        One RCT with 330 participants found no statistically significant difference between groups.

        Relative effect or mean difference:

        There was no statistically significant difference between groups (OR 0.68, 95% CI 0.44 to 1.05).

        Forest plot from Cochrane Review

        Absolute effect:

        459 per 1000 people (95% CI 355 to 567) with amitriptyline 50-100 mg compared with 556 per 1000 people with topiramate 50-100 mg.

        Reference:
        Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
        • OUTCOME 2.2: Headache frequency, Adverse effects, Quality of life

          Narrative result:

          The reviewers found no studies that assessed these outcomes.

          Reference:
          Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]

          3.Topiramate versus flunarizine

          • Population, Intervention, Comparator

            Population:

            Adults (details re gender and age not available) with migraine for at least a year and at least 2 attacks/month that produce disability lasting 3 or more days per month

            Intervention:

            Topiramate titrated to 100 mg (or lower if lack of tolerance) per day for 12 months

            Comparator:

            Flunarizine 5 mg per day for 12 months

          • OUTCOME 3.1: Headache frequency (post-treatment)

            Risk of bias of studies:

            The reviewers did not perform a GRADE assessment of the quality of the evidence. The study failed to report adequate allocation concealment and random sequence generation processes, did not report adequate blinding of participants/carers/outcome assessors and had high numbers of withdrawals.

            Narrative result:

            One RCT with 83 participants found no statistically significant difference between groups, but the trial would have been underpowered to detect a clinically meaningful difference if present.

            Relative effect or mean difference:

            There was no statistically significant difference between groups (mean difference 0.30 attacks per month, 95% CI -0.37 to 0.97).

            Forest plot from Cochrane Review

            Reference:
            Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
            • OUTCOME 3.2: Patients with ≥ 50% reduction in headache frequency

              Risk of bias of studies:

              The reviewers did not perform a GRADE assessment of the quality of the evidence. The study failed to report adequate allocation concealment and random sequence generation processes, did not report adequate blinding of participants/carers/outcome assessors and had high numbers of withdrawals.

              Narrative result:

              One RCT with 83 participants found no statistically significant difference between groups, but the trial would have been underpowered to detect a clinically meaningful difference if present.

              Relative effect or mean difference:

              There was no statistically significant difference between groups (OR 0.83, 95% CI 0.34 to 2.03).

              Forest plot from Cochrane Review

              Absolute effect:

              615 per 1000 people (95% CI 395 to 797) with flunarizine 5 mg compared with 659 per 1000 people with topiramate 100 mg.

              Reference:
              Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
              • OUTCOME 3.3: Adverse effects, Quality of life

                Narrative result:

                The reviewers found no studies that assessed these outcomes.

                Reference:
                Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]

                4.Topiramate versus propranolol

                • Population, Intervention, Comparator

                  Population:

                  Adults (details re age and gender not available) with migraine for at least a year and a migraine frequency of 3-12 attacks per month

                  Intervention:

                  Topiramate 50-100 mg per day for 8 to 18 weeks

                  Comparator:

                  Propranolol 80-160 mg per day for 8 to 18 weeks

                • OUTCOME 4.1: Headache frequency

                  Risk of bias of studies:

                  The reviewers did not perform a GRADE assessment of the quality of the evidence. In this analysis the studies failed to report adequate allocation concealment and random sequence generation processes, did not report adequate blinding of participants/carers/outcome assessors and had unclear numbers of withdrawals.

                  Narrative result:

                  Two RCTs with 342 participants found no statistically significant difference between groups.

                  Relative effect or mean difference:

                  There was no statistically significant difference between groups (mean difference -0.14 attacks per month, 95% CI -0.61 to 0.34).

                  Forest plot from Cochrane Review

                  Reference:
                  Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
                  • OUTCOME 4.2: Patients with ≥ 50% reduction in headache frequency

                    Risk of bias of studies:

                    The reviewers did not perform a GRADE assessment of the quality of the evidence. The study failed to report adequate allocation concealment and random sequence generation processes, did not report adequate blinding of participants/carers/outcome assessors and had low numbers of withdrawals.

                    Narrative result:

                    One RCT with 282 participants found no statistically significant difference between groups.

                    Relative effect or mean difference:

                    There was no statistically significant difference between groups (OR 1.32, 95% CI 0.82 to 2.13).

                    Forest plot from Cochrane Review

                    Absolute effect:

                    434 per 1000 people (95% CI 322 to 552) with propranolol 160 mg compared with 367 per 1000 people with topiramate 100 mg.

                    Reference:
                    Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
                    • OUTCOME 4.3: Adverse effects, Quality of life

                      Narrative result:

                      The reviewers found no studies that assessed these outcomes.

                      Reference:
                      Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]

                      5.Topiramate versus sodium valproate

                      • Population, Intervention, Comparator

                        Population:

                        Adults (details re gender and age not available) with migraine for at least 6 months and a migraine frequency from 3 to 10 attacks per month

                        Intervention:

                        Topiramate 50 mg per day for 8 to 12 weeks

                        Comparator:

                        Sodium valproate 400 mg per day for 8 to 12 weeks

                      • OUTCOME 5.1: Headache frequency (post-treatment)

                        Risk of bias of studies:

                        The reviewers did not perform a GRADE assessment of the quality of the evidence. In this analysis 1/2 (50%) of the studies failed to report adequate allocation concealment and random sequence generation processes, none reported adequate blinding of participants/carers/outcome assessors and both had unclear numbers of withdrawals.

                        Narrative result:

                        Two RCTs with 120 participants found that people on topiramate 50 mg experienced a reduction in headache frequency (post-treatment) compared with valproate 400 mg.

                        Relative effect or mean difference:

                        There was a statistically significant difference between groups, in favor of topiramate (mean difference -0.90 attacks per month, 95% CI -1.58 to -0.22).

                        Forest plot from Cochrane Review

                        Reference:
                        Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]
                        • OUTCOME 5.2: Patients with ≥ 50% reduction in headache frequency, Adverse effects, Quality of life

                          Narrative result:

                          The reviewers found no studies that assessed these outcomes.

                          Reference:
                          Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]

                          Additional Information:

                          DOI

                          10.1002/cca.1481

                          Publication Dates

                          1. Published Online: 19 DEC 2016

                          CCA derived from

                          Linde M, Mulleners WM, Chronicle EP, McCrory DC. Topiramate for the prophylaxis of episodic migraine in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010610. DOI: 10.1002/14651858.CD010610. [Review search date: January 2013]

                          How to Cite

                          Can topiramate help to prevent episodic migraine in adults? Adarsh Gupta (DO, MS, FACOFP) (on behalf of Cochrane Clinical Answers Editors). Cochrane Clinical Answers 2016. DOI: 10.1002/cca.1481.

                          Further Information

                          • CCA Associate editor: Adarsh Gupta (DO, MS, FACOFP), Associate Professor, ROWAN-SOM, Stratford, NJ, USA.
                          • CCA Editor: Karen Pettersen. Correspondence to kpettersen@wiley.com.