European Headache Federation (EHF) critical reappraisal and meta-analysis of oral drugs in migraine prevention – part 3: topiramate

Abstract

Objective Topiramate is a repurposed first-line treatment for migraine prophylaxis. The aim of this systematic review and meta-analysis is to critically re-appraise the existing evidence supporting the efficacy and tolerability of topiramate. Methods A systematic search in MEDLINE, EMBASE, Cochrane CENTRAL, and ClinicalTrials.gov was performed for trials of pharmacological treatment in migraine prophylaxis as of August 13, 2022, following the Preferred Reporting Items for Systematic Reviews (PRISMA). Randomized controlled trials in adult patients that used topiramate for the prophylactic treatment of migraine, with placebo as active comparator, were included. Two reviewers independently screened the retrieved studies and extracted all data. Outcomes of interest were the 50% responder rates, the reduction in monthly migraine days, and adverse events leading to treatment discontinuation. Results were pooled and meta-analyzed, with sensitivity analysis based on the risk of bias of the studies, the monthly migraine days at baseline, and the previous use of other prophylactic treatments. Certainty evidence was judged according to the GRADE framework. Results Eight out of 10,826 studies fulfilled the inclusion/exclusion criteria, accounting for 2,610 randomized patients. Six studies included patients with episodic migraine and two with chronic migraine. Topiramate dose ranged from 50 to 200 mg/day, and all studies included a placebo arm. There was a high certainty that topiramate: 1) increased the proportion of patients who achieved a 50% responder rate in monthly migraine days, compared to placebo [relative risk: 1.61 (95% confidence interval (CI): 1.29–2.01); absolute risk difference: 168 more per 1,000 (95% CI: 80 to 278 more)]; 2) was associated with 0.99 (95% CI: 1.41–0.58) fewer migraine days than placebo; 3) and had a higher proportion of patients with adverse events leading to treatment discontinuation [absolute risk difference 80 patients more per 1,000 (95% CI: 20 to 140 more patients)]. Conclusions There is high-quality evidence of the efficacy of topiramate in the prophylaxis of migraine, albeit its use poses a risk of adverse events that may lead to treatment discontinuation, with a negative effect on patient satisfaction and adherence to care.

CandeSpartan Study: Candesartan Spanish Response-prediction and Tolerability study in migraine

“…The proportion of patients who reported at least one TEAE was 35%, which is between that observed in the first RCT (46%) (8) and the second RCT (30%) (9). In addition, the tolerability profile was quite unique and not that different from that observed in the more novel preventive drugs (23). The most frequently reported AEs in this study were dizziness and tiredness, as expected, which are probably related to decreased blood pressure.…”

“…This is the first study to calculate 30% and 100% responder rates, and the analysis used two different approaches, including only patients who maintained candesartan (PP), and the entire study sample (ITT). In the most conservative assessment (ITT analysis and BCF imputation method for the missing data), the proportion of patients who achieved at least a 30% responder rate was 50% at the third month (weeks 8-12) and 49% at the sixth month (weeks [20][21][22][23][24]. This shows realistic and transparent results, which are not that different from those observed in other "old" oral preventive drugs, such as amitriptyline (20), flunarizine (21), and topiramate (22), where the absolute difference of patients who achieved a 50% response rate in monthly migraine days, compared to placebo, was 16.5% higher following amitriptyline and 16.8% higher following topiramate.…”

Trends and prescribing patterns of antimigraine medicines in nine major cities in China from 2018 to 2022: a retrospective prescription analysis

“…The anticonvulsant topiramate showed an upward trend in prescribing and drug expenditures. Several high-quality studies have shown that topiramate is an effective preventive medicine for migraine [ 25 , 26 ]. Limited data from comparative trials suggest that topiramate may have a modest advantage over valproate for episodic migraine prevention [ 25 ].…”

Influence of metabolic state and body composition on the action of pharmacological treatment of migraine

“…While there was a moderate weight loss and improved glycated hemoglobin levels in T2D patients, a low dose of topiramate treatment had no significant effect on insulin sensitivity in obese females without established diabetes [ 149 ]. Topiramate seems to exhibit insulin secretagogue and sensitizing properties, however, the implications for its therapeutic use necessitate further investigation and consideration of potential severe side effects [ 150 ]. No evidence was found for a change in the pharmacokinetics of topiramate with concomitant insulin use.…”

“…Some antimigraine drugs are associated with weight loss, which may influence the activity of migraines, for instance topiramate, through modulation of GABA receptors [ 5 ]. Moreover, topiramate seems to exhibit insulin secretagogue and sensitizing properties, however, the implications for its therapeutic needs further investigation, considering its potential severe (congenital) side effects [ 61 , 150 ]. In addition, triptans may influence insulin, glucose metabolism and regulation of appetite, resulting in weight loss and potentially impacting glucose metabolism [ 41 , 42 ].…”