Treatment Options for Unilateral Headache

First-Line Treatment

The American College of Physicians recommends NSAIDs as first-line therapy for most patients with unilateral migraine headaches, with options including aspirin, ibuprofen, naproxen sodium, and diclofenac potassium 1, 2, 3
Combination therapy of acetaminophen plus aspirin plus caffeine is effective for migraine treatment, but acetaminophen alone is not recommended 2, 4, 1
Treatment should begin as early as possible during an attack for maximum efficacy, according to the American Academy of Neurology 3, 4

The American Headache Society recommends triptans as second-line therapy for patients who do not respond adequately to NSAIDs, with options including sumatriptan, rizatriptan, naratriptan, and zolmitriptan 2, 3, 5, 1
Triptans are most effective when taken early in an attack while headache is still mild, and if one triptan is ineffective, others may still provide relief 3
For patients with severe nausea or vomiting, consider non-oral triptans or adding an antiemetic such as metoclopramide or prochlorperazine, as recommended by the American College of Emergency Physicians 2, 3, 4, 1

For patients who fail all available triptans or have contraindications to their use, consider CGRP antagonists-gepants, ditans, or dihydroergotamine, according to the American Academy of Neurology 3, 2
The American Headache Society recommends these options for patients with refractory migraine 2

The American College of Physicians recommends avoiding opioids and butalbital for treating acute migraine headaches, as they can lead to dependency and medication overuse headache 2
Medication overuse headache is a risk when acute treatments are used too frequently, defined as ≥15 days per month with NSAIDs or ≥10 days per month with triptans, according to the International Headache Society 2
Combination therapy, such as triptan with NSAID or acetaminophen, improves efficacy, as recommended by the American Academy of Neurology 2

For frequent episodic migraine attacks, consider preventive medications, such as propranolol, timolol, amitriptyline, or divalproex sodium/sodium valproate, according to the American Headache Society 2, 5, 1

The American College of Physicians recommends counseling patients on important lifestyle modifications, including maintaining adequate hydration, regular meals, sufficient and consistent sleep, regular physical activity, stress management techniques, and weight loss if overweight or obese 2, 3