PAIN+ CPN

STUDY OBJECTIVE: We performed a systematic review and Bayesian network meta-analysis to determine which pharmacologic therapies are relatively more effective and safer for migraine in adult patients who present to the emergency department (ED).

METHODS: We searched MEDLINE, Embase, and Web of Science from inception to February 9, 2024. Eligible studies were randomized controlled trials that enrolled adult participants presenting to ED with migraine and compared one pharmacologic therapy to another or placebo. Outcomes were as follows: 1) adequate pain relief at 2 hours, 2) change in pain intensity at 1 hour, 3) need for rescue drug at 2 hours, and 4) significant adverse reaction. We extracted data according to PRISMA-network meta-analysis and appraised trials using Cochrane RoB 2. For dichotomous outcomes, we performed Bayesian network meta-analysis to calculate odds ratios with 95% credible intervals; for continuous outcomes, we performed frequentist network meta-analysis to calculate mean differences with 95% confidence intervals. We assessed confidence using Confidence in Network Meta-analysis. We used Surface under the cumulative ranking curve (SUCRA) to rank agents.

RESULTS: Chlorpromazine intravenous (IV)/intramuscular (IM) (SUCRA=87.3%) was most likely to be superior for "adequate pain relief at 2 hours" (24 trials; n=2,361); metoclopramide IV-ibuprofen IV (SUCRA=94.6%) was most likely to be superior for "need for rescue drug" (not needing rescue drug) at 2 hours (27 trials; n=2,942); dexamethasone IV (SUCRA=79.5%) was most likely to be superior for "significant adverse reaction" (not causing adverse reaction) (22 trials; n=2,450). The network for change in pain intensity demonstrated statistically significant incoherence at the overall level. Confidence in network meta-analysis estimates (certainty of evidence) varied and was mostly "low" or "very low," limiting the validity of the probabilistic analyses.

CONCLUSIONS: According to Bayesian network meta-analysis, ibuprofen IV is definitely among the least effective for adequate pain relief; chlorpromazine IV/IM is definitely among the most effective; valproate IV is definitely among the least effective, and ketorolac IV/IM is possibly among the least effective as single agents. The relative safety of the pharmacologic therapies cannot be determined with sufficient certainty.

Physician rater

This Bayesian Network Meta-analysis is highly transparent and methodologically rigorous; however, the results overall indicate a substantial degree of uncertainty in the effect estimates.

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