DOI: https://doi.org/10.1007/s00228-019-02748-4

Abstract-Summary

This study aimed to establish a pharmacodynamic model to quantitatively compare the efficacy characteristics of seven kinds of triptans and their different dosage forms in the treatment of acute migraines.

Pharmacodynamic models were established to describe the dose-effect and time- course of each kind of triptan for the proportion of patients who became pain free or had pain relief.

After eliminating the placebo effect, oral eletriptan (40 mg) had the highest effi- cacy among all oral drugs at the maximum approved dose, and the proportion of patients who became pain free and had pain relief were 30.9% and 37.9% at 2 h, respectively.

Oral naratriptan (2.5 mg) had the lowest efficacy, and the proportion of patients who became pain free and had pain relief was 10.3% and 21.6% at 2 h, respectively. When the dose was increased from 5 to 20 mg of sumatriptan nasal spray, the proportion of patients who became pain free and had pain relief increased by 16.8%

and 18.3% at 2 h, respectively.
Regarding the time-course, the time of onset of subcutaneous sumatriptan (6 mg)

was the fastest, and the fraction of patients who were pain free at 2 h accounted for 90.6% of that at 4 h. This study evaluated the efficacy characteristics of seven kinds of triptans and their different dosage forms.

Extended: The findings in this study would provide the necessary quantitative information for medication guidelines related to migraines.

This study quantitatively evaluated the dose-effect and time-course of seven kinds of triptans and their different dosage forms, and the present findings would provide the necessary quantitative information for the treatment guidelines of migraines.

Introduction

The efficacy characteristics of different dosage forms of triptans have still not been comprehensively and quantitatively compared; therefore, further information is needed to guide the choice of medication in the clinical practice.

A published network meta-analysis, which compared the efficacies of three NSAIDs and seven triptans, indicates that eletriptan has the best efficacy; however, this study did not analyze the impact of different dosage forms and doses on the drug efficacy [129].

Mandema et al. [130] proposed a novel model-based meta-analysis (MBMA), which can be used to quantitatively describe the dose-effect and time-course characteristics of drugs simultaneously; however, they only compared the efficacy features of sumatriptan and eletriptan using the MBMA, and further studies are thus needed to comprehensively investigate the efficacy features of seven triptans with different dosage forms.

The dose-effect and time-course characteristics of seven triptans with different dosage forms were quantitatively compared using the MBMA.

Methods

The inclusion criteria were as follows: (I) placebo-controlled, randomized, and double-blind clinical trials; (II) patients with acute migraine; (III) headache pain intensity, which was measured using a 4-point categorical scale or converted to a 4-point categorical scale (0 = no pain, 1 = mild pain, 2 = moderate pain, 3 = severe pain); (IV) literature reporting at least one of the two efficacy indicators, i.e., the proportion of patients who became pain free or had pain relief; (V) for the study with a crossover design, only data from the first period were analyzed; (VI) for the literature on the study of other medicines, only the data of triptans were extracted.

The following information was extracted from the included studies: literature characteristics (i.e., author, year of publication, and country), study design (i.e., grouping, dosing regimen, and sample size), characteristics of participants (i.e., age, body weight, proportion of male, migraine history, and proportion of subjects with aura symptoms), and the clinical outcomes (the proportion of patients who became pain free or had pain relief at each observation point).

Results

The results showed that among the drugs of oral dosage forms, eletriptan (40 mg) had the best the efficacy, and its proportions of patients who became pain free and had pain relief at 2 h were 30.9% and 37.9%, respectively.

The efficacies of other oral drugs, such as rizatriptan (10 mg), zolmitriptan (5 mg), and sumatriptan (100 mg), were relatively high, and their proportions of patients who became pain free and had pain relief at 2 h were higher than 25% and 30%, respectively.

The proportions of patients who became pain free and had pain relief with sumat- riptan (20 mg) nasal spray were 23.6% and 31.5% at 2 h, respectively, and those using oral sumatriptan (100 mg) were 25.6% and 29.9%, respectively.

Discussion

Among the oral dosage forms of triptans, those of eletriptan (40 mg), rizatriptan (10 mg), and zolmitriptan (5 mg) had superior efficacies to that of sumatriptan (100 mg); that of eletriptan (40 mg) was the most effective, and the proportions of patients who became pain free and had pain relief at 2 h were 5.3% and 7.9% higher than those of sumatriptan (100 mg), respectively.

The FDA-approved maximum dose of oral sumatriptan is 100 mg, which is about three times the ED50 value (31.3 mg) of the proportion of patients who became pain free at 2 h. The results suggest that the efficacy of oral sumatriptan (100 mg) is close to the maximum, and even if the doses increase, no significant improvement is found in the efficacy.

Acknowledgement

A machine generated summary based on the work of Hou, Mengyuan; Liu, Hongxia; Li, Yunfei; Xu, Ling; He, Yingchun; Lv, Yinghua; Zheng, Qingshan; Li, Lujin. 2019 in European Journal of Clinical Pharmacology.