What are the first-line medications for migraine (headache disorder)?

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From the Guidelines

First-line medications for migraine include nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (400-600 mg) or naproxen sodium (500-550 mg), and triptans such as sumatriptan (50-100 mg orally, 4-6 mg subcutaneously, or 20 mg intranasally) 1. These medications should be taken at the first sign of migraine symptoms for best effectiveness. NSAIDs work by reducing inflammation and pain by inhibiting prostaglandin synthesis, while triptans activate serotonin receptors to constrict blood vessels and block pain pathways in the brain. For frequent migraines (more than 4 days per month), preventive medications may be considered, including propranolol (80-240 mg daily), amitriptyline (30-150 mg daily), divalproex sodium (500-1500 mg/d), and sodium valproate (800-1500 mg/d) 1. The choice between these medications depends on the patient's migraine pattern, comorbidities, and previous treatment responses. Some key points to consider when treating migraines include:

  • Taking medication early in an attack
  • Staying hydrated
  • Resting in a dark, quiet room
  • Considering combination therapy or second-line options if first-line treatments fail
  • Educating patients about their treatment options and involving them in the management plan 1.

From the FDA Drug Label

Eletriptan hydrobromide tablets are indicated for the acute treatment of migraine with or without aura in adults. The FDA drug label does not answer the question of what medications are first line for migraine, it only mentions that eletriptan hydrobromide tablets are used for the acute treatment of migraine. Other medications such as almotriptan (Axert®), frovatriptan (Frova®), naratriptan (Amerge®), rizatriptan (Maxalt®), sumatriptan and naproxen sodium, (Treximet®), zolmitriptan (Zomig®), and sumatriptan (Imitrex®) are mentioned as similar medications, but it is not specified if they are first line treatments 2, 2.

From the Research

First-Line Medications for Migraine

The following medications are considered first-line treatments for migraine:

  • Acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) for mild to moderate migraines 3
  • Triptans, such as sumatriptan, rizatriptan, eletriptan, zolmitriptan, almotriptan, frovatriptan, and naratriptan, for moderate to severe migraines 4, 3, 5, 6, 7

Specific First-Line Medications

Some specific first-line medications for migraine include:

  • Ibuprofen, naproxen sodium, diclofenac potassium, and acetylsalicylic acid (NSAIDs) 5
  • Eletriptan, which has been shown to be effective in the acute treatment of moderate to severe migraine attacks 6, 7

Treatment Strategies

Treatment strategies for migraine can be organized into different approaches, including:

  • The acetaminophen-NSAID strategy for patients with mild to moderate attacks 5
  • The triptan strategy for patients with severe attacks or those who do not respond well to NSAIDs 5
  • The refractory migraine strategy, which may include using triptans and NSAIDs simultaneously, dihydroergotamine, or rescue medications 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Acute Migraine Headache: Treatment Strategies.

American family physician, 2018

Research

Pharmacological approaches to migraine.

Journal of neural transmission. Supplementum, 2003

Research

Acute Migraine Treatment.

Continuum (Minneapolis, Minn.), 2015

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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