Management of Prolonged Headache in Adult Females

Initial Assessment and Red Flag Features

Red flag features requiring immediate neuroimaging include sudden onset ("thunderclap" quality) headache. 3
Red flag features requiring immediate neuroimaging include fever with headache. 3
Red flag features requiring immediate neuroimaging include headache worse with Valsalva maneuver or exercise. 2
If any red flags are present, obtain MRI or CT imaging before treating as primary headache. 3
In patients with normal neurologic examination and no red flags, neuroimaging is usually not warranted. 3

In women of reproductive age, consider relationship to menstrual cycle (menstrual migraine). 3
Combined hormonal contraceptives are contraindicated if migraine with aura due to stroke risk. 3

First-line acute therapy includes naproxen sodium 500-825 mg at onset, can repeat every 2-6 hours (maximum 1.5 g/day). 2
First-line acute therapy includes combination therapy with aspirin + acetaminophen + caffeine for moderate-to-severe attacks. 2
Add antiemetic 20-30 minutes before analgesic for synergistic effect: metoclopramide 10 mg orally or prochlorperazine 25 mg orally. 2
If oral therapy fails due to nausea/vomiting, subcutaneous sumatriptan 6 mg is most rapid and effective, with 59% pain-free at 2 hours. 2
If oral therapy fails due to nausea/vomiting, intranasal sumatriptan 5-20 mg can be used. 2

A continuous headache of prolonged duration or frequent attacks requiring acute medication more than twice weekly mandates preventive therapy. 1, 2
First-line preventive medications include propranolol 80-160 mg daily (long-acting formulation). 1
First-line preventive medications include metoprolol 50-100 mg twice daily or 200 mg modified-release once daily. 1
First-line preventive medications include candesartan 16-32 mg daily. 1
Beta-blockers are contraindicated in patients with asthma, cardiac failure, atrioventricular block, or depression. 1
Topiramate is contraindicated in patients with nephrolithiasis, pregnancy, lactation, or glaucoma. 1
Combined hormonal contraceptives are contraindicated in migraine with aura due to stroke risk. 3
Evaluate preventive therapy effectiveness at 2-3 months, as oral agents require this duration to demonstrate efficacy. 1

Medication-overuse headache (MOH) occurs with acute medication use more than twice weekly. 3, 2
Medication-overuse headache creates a vicious cycle of increasing headache frequency leading to daily headaches. 2
Limit acute therapy to no more than 2 days per week to prevent medication-overuse headache. 2
Medications most likely to cause medication-overuse headache include ergotamine, opiates, and analgesics (including NSAIDs when overused). 2, 3

Re-evaluate within 2-3 months to assess attack frequency (headache days per month), attack severity and pain intensity, migraine-related disability, adverse events from medications, and adherence to treatment plan. 1, 2, 3
Use headache calendars to track symptomatic days and acute medication use. 1
If treatment fails after adequate trial (2-3 months for oral preventives), second-line agents include amitriptyline 10-100 mg at night and flunarizine 5-10 mg daily. 1
If treatment fails after adequate trial (2-3 months for oral preventives), third-line agents include onabotulinumtoxinA 155-195 units every 12 weeks and CGRP monoclonal antibodies (erenumab 70-140 mg monthly, fremanezumab 225 mg monthly). 1