Acute Management of Primary Headaches in Adults

First‑Line Therapy for Episodic Migraine

• For adults with moderate‑to‑severe episodic migraine who have not previously used simple analgesics, initiate an NSA ID (e.g., ibuprofen 400‑800 mg, naproxen 500‑1000 mg, or aspirin 1000 mg) or acetaminophen 1000 mg as monotherapy, ensuring adequate dosing before deeming the treatment a failure. [1][2]
• High‑certainty evidence shows that adding a triptan to an NSA ID (most studied: sumatriptan + naproxen) yields ≈180 additional sustained pain‑relief events per 1000 patients at 48 h compared with NSA ID monotherapy. 1
• The same combination reduces rescue‑medication use by ≈160 events per 1000 patients versus monotherapy. 1

Escalation Strategy When Monotherapy Fails

• If an adequate‑dose NSA ID or acetaminophen fails, add a triptan (e.g., sumatriptan, rizatriptan) to the NSA ID; if NSA IDs are contraindicated or not tolerated, add a triptan to acetaminophen. [1][2]

Triptan Selection and Switching

• Choose among oral triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan) based on patient preference for route, cost, and side‑effect profile. 2
• Patients who do not respond to one triptan may achieve relief with another triptan within the same class. 2
• For patients with severe nausea or vomiting, consider non‑oral triptan formulations (e.g., nasal spray, injectable) combined with an anti‑emetic. 2

Third‑Line (Advanced) Options

• CGRP antagonists (gepants) such as rimegepant, ubrogepant, or zavegepant are recommended for patients who cannot tolerate or have failed triptan + NSA ID/acetaminophen combinations. 2
• Lasmiditan is reserved for patients who have failed all other acute‑treatment options outlined in this guideline. 2
• These newer agents are substantially more expensive (approximately $6,000–$6,700 USD per year) compared with triptan combinations (≈ $500 USD per year). 1

Contraindicated Acute Treatments for Migraine

• Opioids and butalbital‑containing medications should never be used for acute episodic migraine. 2

First‑Line Therapy for Tension‑Type Headache

• NSA IDs constitute the primary treatment for episodic tension‑type headache; acetaminophen is an acceptable alternative. 3
• Triptans are not recommended for tension‑type headache because they lack demonstrated efficacy for this condition. 3
• Muscle relaxants and opioids are also contraindicated due to limited benefit and higher risk of adverse events. 3

Medication‑Overuse Headache Prevention

• Limit the use of any acute analgesic (NSA ID, acetaminophen, triptan, or combination product) to fewer than 15 days per month to avoid medication‑overuse headache, which typically develops after ≥15 days/month of use for ≥3 consecutive months. 3

Initiation of Preventive Therapy

• Begin preventive medication when a patient experiences ≥2 migraine attacks per month that cause ≥3 days of disability. 4

Special Populations (Reproductive Considerations)

• Discuss potential adverse effects of acute migraine medications with patients of childbearing potential, pregnant, or breastfeeding before initiating therapy. 2
• Most trial data derive from females of reproductive age experiencing 1‑8 migraine attacks per month. 2

Timing of Acute Treatment

• Advise patients to administer acute medication as soon as possible after migraine onset to maximize the chance of achieving pain freedom and sustained relief. [2][1]

Acute Migraine Management

First‑Line Oral Analgesia

Antiemetic Adjuncts

Combination Analgesic Formulations

Parenteral Options for Severe Attacks

Contraindicated Acute Medications

Medication‑Overuse Headache (MOH) Prevention

Clinical Decision Algorithm (Key Decision Points)

Acute Management of Breakthrough Migraine in Adults

First‑Line Acute Therapy

• Combine a triptan with an NSAID (most studied: sumatriptan + naproxen) as the initial treatment for breakthrough migraine attacks in adults; escalation to CGRP antagonists or lasmiditan is reserved for failures or intolerance. Low‑certainty evidence supports this sequencing. 6
• Administer NSAID monotherapy (ibuprofen 400–800 mg, naproxen 500–1000 mg, or aspirin 1000 mg) for moderate‑to‑severe episodic migraine in patients who have not previously used simple analgesics. 6
• Use acetaminophen 1000 mg as an alternative when NSAIDs are contraindicated. 6
• Start treatment as early as possible after migraine onset to maximize pain‑free rates and sustained relief. 6

Second‑Line: Triptan Selection & Formulations

• For patients with severe nausea or vomiting, employ non‑oral triptan formulations (nasal spray or injectable) together with an anti‑emetic (e.g., metoclopramide or prochlorperazine). 6

Third‑Line: CGRP Antagonists (Gepants)

• Prescribe rimegepant, ubrogepant, or zavegepant for patients who cannot tolerate or have failed triptan + NSAID/acetaminophen combinations. 6
• Recognize that gepants provide a lower likelihood of 2‑hour pain freedom and relief compared with triptan + NSAID therapy (low‑certainty evidence). 6
• Consider cost: oral gepants cost approximately $4,959–$5,994 USD per year and intranasal formulations about $8,800 USD, whereas triptan + NSAID regimens cost roughly $500 USD annually. 6

Fourth‑Line: Lasmiditan

• Reserve lasmiditan for patients who have failed all other acute‑treatment options. 6
• Evidence for lasmiditan’s comparative effectiveness on prioritized health outcomes is of insufficient certainty. 6

Contraindicated Medications

• Never use opioids or butalbital‑containing medications for acute episodic migraine because of the risk of dependence, rebound headaches, and loss of therapeutic efficacy. 6

Medication‑Overuse Headache Prevention

• Limit any acute analgesic (NSAID, acetaminophen, triptan, or combination product) to fewer than 15 days per month to avoid medication‑overuse headache. 6
• Specific thresholds: ≥ 15 days/month for NSAIDs and ≥ 10 days/month for triptans. 6

Special Populations

• Discuss potential adverse effects of acute migraine medications with patients of childbearing potential, pregnant, or breastfeeding before initiating therapy. 6
• Trial data primarily derive from females of reproductive age experiencing 1–8 migraine attacks per month, informing the generalizability of recommendations. 6

Initiation of Preventive Therapy (When Acute Management Is Insufficient)

• Add preventive medication when a patient experiences ≥ 2 migraine attacks per month that cause ≥ 3 days of disability, or when acute treatment does not provide adequate response. 6