Triptans and NSAIDs remain the primary choices to reduce pain and improve function in the acute treatment of episodic migraine in patients who do not have contraindications.

A systematic review and meta-analysis of data from more than 28,000 participants across 115 trials and 15 systematic reviews showed high and moderate strength evidence for the two classes of drugs respectively.

“The combination of triptans and NSAIDs was also effective and well tolerated, and can be used for patients with partial response to either agent,” it said.

The meta-analysis, published in JAMA, also found good evidence for acetaminophen which improved pain freedom at two hours and with no adverse events compared to placebo.

Both CGRP receptor antagonists rimegepant and ubrogepant were associated with significant improvement in pain freedom and pain relief at two hours and sustained pain freedom at one day and at one week.

The investigators noted that the drugs should not be used in patients receiving strong or moderate cytochrome P450 3A4 inducers or inhibitors.

The 5-HT1F receptor agonist lasmiditan was also associated with pain freedom and pain relief at two hours and sustained pain freedom at one day and one week.

However, lasmiditan was associated with a significantly increased risk of gastrointestinal adverse events, neurologic adverse events and serious adverse events.

“Treatment guidelines will need to be updated to determine the place of lasmiditan and calcitonin gene-related peptide receptor antagonists among established therapies, given these unique features and adverse effect profiles, especially in people with vascular comorbidities.”

Antiemetics such as chlorpromazine and droperidol were also associated with pain relief but the strength of the evidence was low.

Dihydroergotamine was associated with pain relief at two hours, one day and one week while ergotamine plus caffeine was effective at two hours.

“In contrast, the evidence for many other interventions, including opioids, was limited,” the investigators said.

Remote electrical neuromodulation was also associated with improved pain and function when compared to sham.

An editorial in JAMA said choice of acute treatment from the many available should include considerations of effectiveness, adverse event profiles, safety concerns and contraindications, and cost.

“A clear message from this review is that opioid medications are not an appropriate acute treatment for migraine.”

“Given the evidence-based effectiveness of many other medication classes, the lack of good evidence for effectiveness of opioids as acute treatment for migraine, and overwhelming evidence of harm with frequent opioid use, it is clear that opioids should be used sparingly, if at all, for treatment of migraine.”

A RCT published in the same issue of JAMA showed the CGRP antagonist eptinezumab, which is approved for preventive treatment, also had acute effects.

Eptinezumab administered intravenously within six hours of migraine onset significantly reduced time to freedom from headache pain and time to absence of the most bothersome symptom compared with placebo.

“When coupled with the established preventive efficacy of eptinezumab, it raises the potential of initiating effective treatment preventing future attacks of migraine with the added benefit of alleviating an active migraine attack,” the RCT said.