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Review
. 2023 Sep 18;24(1):129.
doi: 10.1186/s10194-023-01662-6.

Efficacy and safety of intranasal agents for the acute treatment of migraine: a systematic review and network meta-analysis

Guanglu Li #  1   2 , Shaojie Duan #  3 , Tiantian Zhu  4 , Zhiying Ren  1   2 , Hui Xia  1   2 , Ziyao Wang  1   2 , Lei Liu  5 , Zunjing Liu  6
Affiliations
Review

Efficacy and safety of intranasal agents for the acute treatment of migraine: a systematic review and network meta-analysis

Guanglu Li et al. J Headache Pain. .

Abstract

Background: Intranasal agents may be ideal for the treatment of migraine patients. Many new acute intranasal-specific therapies have been developed, but few of them have been directly compared. The aim of this network meta-analysis (NMA) was to compare the efficacy and safety of various intranasal agents for the treatment of acute migraine in adult patients.

Methods: The Cochrane Register of Controlled Trials, Embase, and PubMed were searched from inception to 15 August 2023. Randomized controlled trials (RCTs) using intranasal agents (no restrictions on dose, formulation, dosing regimen or timing of the first dose) to treat adult patients with acute migraine were included. The primary efficacy endpoint was pain freedom at 2 h, and the primary safety endpoint was adverse events (AEs). The analysis process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Results: Nineteen studies (21 RCTs, 9738 participants) were included. Compared to the placebo, 5 mg of zolmitriptan using a conventional liquid nasal spray device was the most effective for pain freedom at 2 h [odds ratio (OR): 4.67, 95% confidence interval (CI): 3.43 to 6.43] and 24 h (OR: 5.49, 95% CI: 3.58 to 8.42) among all the interventions. Butorphanol nasal spray 1 mg was the most effective (OR: 8.62, 95% CI: 1.11 to 66.92) for pain freedom at 1 h, but with low-quality evidence. DFN-02 presented the highest freedom from nausea (OR: 4.95, 95% CI: 1.29 to 19.01) and phonophobia (OR: 5.36, 95% CI: 1.67 to 17.22) at 2 h, albeit with lower odds of achieving complete pain freedom. ROX-828 showed the highest improvement in freedom from photophobia at 2 h (OR: 4.03, 95% CI: 1.66 to 9.81). Dihydroergotamine nasal spray was significantly associated with the highest risk of AEs (OR: 9.65, 95% CI: 4.39 to 21.22) and was not recommended for routine use. Zavegepant nasal spray demonstrated the lowest risk of AEs (OR: 2.04, 95% CI: 1.37 to 3.03). The results of sensitivity analyses for the primary endpoints (pain freedom at 2 h and AEs) were generally consistent with those of the base case model.

Conclusions: Compared with other new intranasal-specific therapies in treating migraine attacks, zolmitriptan nasal spray 5 mg was the most effective agent for pain freedom at 2 h. Zavegepant nasal spray 10 mg had the fewest adverse side effects.

Keywords: Acute treatment; Intranasal agents; Migraine; Network meta-analysis.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flow Chart of the network meta-analysis procedure. A total of 21 trials were included because 2 studies provided the results of 2 trials each
Fig. 2
Fig. 2
Network plot for primary outcomes and secondary outcomes. The lines between nodes represent direct comparisons in various trials, and each circle's size is proportional to the population involved in each specific treatment. The thickness of the lines is proportional to the number of trials connected to the network. DFN-02, sumatriptan nose spray 10 mg with a permeation enhancer; AVP-825, a drug-device combination of 22mg sumatriptan powder; MAP0004, a dihydroergotamine inhaler; ROX-828, ketorolac 31.5mg with 6% of lidocaine
Fig. 3
Fig. 3
Forest plot for primary outcomes and secondary outcomes. The forest plot was based on a random-effects model. The data behind the drug names indicate the following: Trials, number of trials examining the current active drug; Treatment/Placebo, number of patients with events/number of patients in which the drug was examined in these trials; OR, odds ratio; CI, credible interval. 95% CI that did not contain one and a p-value cutoff point of 0.05 was considered statistically significant. I2 values of less than 50% indicate that heterogeneity may not be significant; a value higher than 50% may represent substantial heterogeneity. For the effectiveness endpoint, results to the left of 1 favor placebo, to the right favor intervention, result in adverse events was the opposite. DFN-02, sumatriptan nose spray 10 mg with a permeation enhancer; AVP-825, a drug-device combination of 22mg sumatriptan powder; MAP0004, a dihydroergotamine inhaler; ROX-828, ketorolac 31.5mg with 6% of lidocaine
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