Several pharmacological and nonpharmacological therapies were found to improve pain outcomes in adults with migraine, though the strength of the evidence supporting these treatments varied, according to the findings of a systematic review and meta-analysis published in JAMA.

The aim of the study was to assess the benefits and risks associated with various acute treatments for episodic migraine. Following an extensive literature search, independent reviewers identified and extracted data from 15 systematic reviews, which analyzed evidence on triptans and nonsteroidal anti-inflammatory drugs (NSAIDs), and 115 randomized clinical trials (n=28,803), which evaluated other interventions.

Pain freedom, pain relief, sustained pain freedom, and adverse events were the main outcomes of the study. The Agency for Healthcare Research and Quality Methods Guide for Effectiveness and Comparative Effectiveness Reviews was used to grade the strength of evidence (SOE).

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Compared with placebo, significant improvements in short-term pain outcomes were observed with triptans (high SOE), NSAIDs (moderate SOE), calcitonin gene-related peptide receptor antagonists (rimegepant, ubrogepant; low to high SOE), lasmiditan (5-HT1F receptor agonist; high SOE), dihydroergotamine (moderate to high SOE), ergotamine plus caffeine (moderate SOE), acetaminophen (moderate SOE), antiemetics (chlorpromazine, prochlorperazine, metoclopramide, haloperidol, droperidol; low SOE), butorphanol (low SOE), and tramadol plus acetaminophen (low SOE).

An increased risk of mild and transient adverse events was noted with triptans (eg, malaise, nausea, chest pain, flushing, palpitations, paresthesia) and NSAIDs (eg, dyspepsia, nausea, somnolence, dizziness). Ubrogepant was linked to significantly more ear, nose and throat symptoms, while lasmiditan use was associated with an increased risk of gastrointestinal and neurological side effects. Among the antiemetics, a significantly increased risk of adverse events was seen with haloperidol, droperidol, and prochlorperazine.  Gastrointestinal side effects were also noted with the use of ergot alkaloid medications.

Several nonpharmacologic treatment options were associated with an improvement in pain, including remote electrical neuromodulation (moderate SOE), transcranial magnetic stimulation (low SOE), external trigeminal nerve stimulation (low SOE), and noninvasive vagus nerve stimulation (moderate SOE). No significant differences in adverse events were observed when compared with sham.

“This review found the overall SOE to be low or insufficient for opioids, and opioids were associated with higher rates of adverse effects compared with other treatment options or placebo,” the authors stated. “As such, the current guideline recommendations against opioids stand.”


VanderPluym JH, Halker Singh RB, Urtecho M, et al. Acute treatments for episodic migraine in adults: A systematic review and meta-analysis. JAMA. Published online June 15, 2021. doi: 10.1001/jama.2021.7939

This article originally appeared on MPR