Parenteral Agents for Mitigating Migraine Relapse

Study Population: 6,167 adults with acute migraine from 53 randomized controlled trials in an emergency setting comparing parenteral agents with placebo or other agents

Efficacy End Points: Migraine relapse reduction

Harm End Points: No comments about harms in the review

Narrative: Acute migraine can be debilitating because of severe pain and symptoms such as nausea, vomiting, photophobia, and phonophobia.¹ These episodic headaches often require care in an acute care setting when home-based therapies fail.^2,3 American Headache Society and Canadian Headache Society guidelines recommend a variety of parenteral agents for the treatment of an acute migraine episode, including nonsteroidal anti-inflammatory drugs, metoclopramide, neuroleptics, and triptans.^4–8 However, the risk of migraine persistence or relapse within 72 hours is significant despite treatment, often requiring a return visit.^9,10 Corticosteroids have been shown to reduce migraine relapse frequency and severity, but repeated corticosteroid use can result in adverse effects, including hypertension, hyperglycemia, gastrointestinal bleeding, and osteoporosis.^11–13

Several pairwise and network meta-analyses have compared the relative effectiveness of two or more interventions for treating acute migraine pain. No systematic review, however, has evaluated the effectiveness of parenteral agents in reducing the risk of relapse with a network meta-analysis, which allows for simultaneous synthesis of direct and indirect evidence for two or more interventions.^14–19 The systematic review discussed here uses a frequentist network meta-analysis to assess the effectiveness of parenteral agents to reduce migraine relapse.²⁰

The meta-analysis included 53 randomized controlled trials of 6,167 adults receiving treatment for acute migraine headache in an emergency setting.²⁰ Studies including other headache types were eligible if they reported outcomes for migraine separately or if 80% or more of the study population had migraines.

Included studies evaluated the effectiveness of two or more eligible parenteral agents, including antiemetics, nonsteroidal anti-inflammatory drugs, ergot agents, anticonvulsants, neuroleptics, opioids, magnesium sulfate, lidocaine, sedatives or hypnotics (eg, ketamine, propofol), other analgesics (eg, acetaminophen, lysine-acetylsalicylic acid), combination therapy comprising two different parenteral agents provided simultaneously, or placebo. Studies evaluating agents targeting the calcitonin gene–related peptide pathway, greater occipital nerve blocks, or other emergency parenteral agents were excluded because these agents are not recommended or widely available in emergency settings.

The primary outcome was migraine relapse, defined as recurrent or worsening headache pain after discharge that may or may not result in a return to the emergency setting or other health care setting. Time of relapse assessment was classified as short term (72 hours or less) or long term (more than 72 hours). Severe relapse was defined as a return visit to an emergency or other health care setting due to migraine or recurring headache pain designated as severe using a pain score or relapse classification system.