Older Migraine Drugs More Effective Than Newer Ones, Analysis Suggests

Some triptans were better at relieving acute migraine pain than newer, more expensive drugs, a systematic review and network meta-analysis suggested.

The analysis evaluated 137 randomized controlled trials with nearly 90,000 participants who were randomized to one of 17 oral migraine drugs or placebo.

All 17 drugs were more effective than placebo at relieving pain after 2 hours, and most were more effective for sustained pain freedom to 24 hours, said Andrea Cipriani, MD, PhD, of the University of Oxford in England, and colleagues.

Four triptans showed superior efficacy outcomes, the researchers reported in The BMJ.

Eletriptan was the most effective drug for pain freedom at 2 hours, with odds ratios (ORs) ranging from 1.46 to 3.01, followed by rizatriptan (ORs from 1.59 to 2.44), sumatriptan (ORs from 1.35 to 2.04), and zolmitriptan (ORs from 1.47 to 1.96).

Three newer migraine drugs were included in the analysis: lasmiditan (Reyvow), rimegepant (Nurtec), and ubrogepant (Ubrelvy). Lasmiditan is a serotonin (5-HT) 1F receptor agonist. Rimegepant and ubrogepant are calcitonin gene-related peptide (CGRP) antagonists known as gepants.

These newer drugs showed comparable results to acetaminophen and most non-steroidal anti-inflammatory drugs (NSAIDs), Cipriani and colleagues said.

“Our analysis identified eletriptan, rizatriptan, sumatriptan, and zolmitriptan as the most effective medications for treating acute migraine attacks,” Cipriani told MedPage Today. “This insight is novel and suggests a need to revise existing guidelines, which currently treat all oral triptans as equally viable.”

“The newly introduced CGRP small-molecule receptor antagonists — rimegepant and ubrogepant — have garnered considerable attention,” Cipriani pointed out.

“However, our results suggest that their efficacy is comparable to paracetamol [acetaminophen] and less than the aforementioned four triptans,” he continued. “This is important information for clinicians, considering the higher costs of these newer treatments.”

This is “good quality research” with the main take-home message being that triptans are underutilized, observed migraine researcher Peter Goadsby, MD, PhD, of King’s College London, who wasn’t involved with the study.

“As highlighted by the authors, there are some limitations of the work,” Goadsby wrote in an email to MedPage Today. “First, there is a lot of heterogeneity of the trials they looked at, which can mean there’s low or very low confidence in some comparisons between drugs.”

The analysis is based on average treatment effects and can’t offer insights at an individual patient level, Goadsby pointed out. In addition, “clinical trial results do not integrate efficacy, side effects, and consistency, which together impact the patient outcomes in the medium- and long-term,” he said.

The network meta-analysis assessed double-blind randomized trials from 1991 to 2023. Across 137 trials included in the study, 62,682 participants were randomized to drug treatment and 26,763 to placebo. Mean age was about 40, and nearly 86% were women. About a third (32.3%) had a history of migraine with aura.

The primary outcomes of the analysis were the proportion of participants who were pain-free at 2 hours, and the proportion with sustained pain freedom from 2 to 24 hours post-dose without rescue drugs.

Secondary outcomes included the proportion with pain relief at 2 hours post-dose, the proportion with pain relapse within 2 to 48 hours post-dose, and the proportion using rescue drugs after 2 hours and up to 24 hours.

Ubrogepant and rimegepant were the only gepants included (other gepants are available in the U.S. but were not part of the study). Seven triptans were assessed, as were six NSAIDs, one antipyretic (acetaminophen), and one ditan (lasmiditan). All interventions had at least one placebo-controlled trial for one or more outcomes.

All migraine drugs were superior to placebo for pain relief at 2 hours and for the use of rescue drugs from 2 to 24 hours.

Outcome data on pain relapse up to 48 hours were available only for lasmiditan, sumatriptan, and rimegepant; all showed greater efficacy than placebo. Lasmiditan and rimegepant had comparable performances to sumatriptan.

Triptans are widely underused, Cipriani and co-authors noted; their use ranges from 16.8% to 22.7% in the U.S. and from 3.4% to 22.5% in Europe. Triptans are contraindicated in patients with vascular disease, which restricts them from being used in some patients.

“This systematic review and meta-analysis offers the best available evidence to guide the choice of acute oral drug interventions for migraine episodes. Results on both benefits and harms should inform shared clinical decision making, considering the preferences of patients, caregivers, and healthcare professionals,” Cipriani said.

“The inclusion of the most effective triptans, available as generic drugs, into the WHO Model List of Essential Medicines should be considered to promote global accessibility and uniform standards of care,” he added.