What are the alternatives for managing headaches in the absence of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

Headache Management Without NSAIDs

For mild to moderate headaches, use acetaminophen 1000 mg combined with caffeine as first-line therapy; for moderate to severe headaches, use triptans (such as sumatriptan, rizatriptan, or eletriptan) as first-line treatment. 1

First-Line Treatment Strategy

For Mild to Moderate Headaches

• Acetaminophen 1000 mg is the primary non-NSAID option, though it has limited efficacy when used alone for migraine (NNT of 12 for 2-hour pain-free response) 2
• Adding caffeine significantly improves efficacy - the combination of acetaminophen, aspirin, and caffeine is recommended for moderate to severe migraine or when initial treatments fail 3, 1
• Acetaminophen alone should be taken at headache onset, with a maximum daily dose of 4000 mg from all sources 1

For Moderate to Severe Headaches

• Triptans are first-line therapy when NSAIDs cannot be used 1, 4
• Oral triptans with strong evidence include sumatriptan, rizatriptan, eletriptan, zolmitriptan, almotriptan, frovatriptan, and naratriptan 1, 4
• Subcutaneous sumatriptan 6 mg provides the fastest and most effective relief (59% pain-free at 2 hours), particularly useful when nausea or vomiting is present 1
• Triptans should be taken early in the attack when pain is still mild for maximum effectiveness 1

Second-Line and Adjunctive Therapies

Antiemetics as Monotherapy

• Metoclopramide 10 mg IV can be used as monotherapy for acute migraine, providing both antiemetic effects and direct analgesic properties through dopamine receptor antagonism 1
• Prochlorperazine 10 mg IV effectively relieves headache pain and is comparable to metoclopramide in efficacy 1
• These agents are particularly useful when nausea and vomiting are prominent features 3, 1

Combination Therapy

• Acetaminophen 1000 mg plus metoclopramide 10 mg provides efficacy equivalent to oral sumatriptan 100 mg for 2-hour headache relief 3, 2
• Adding an antiemetic 20-30 minutes before other medications can provide synergistic analgesia 1

Dihydroergotamine (DHE)

• Intranasal DHE has good evidence for efficacy and safety as monotherapy for acute migraine attacks 1, 4
• DHE is particularly useful for patients who cannot tolerate triptans or have contraindications to vasoconstricting drugs 5

Critical Medication Overuse Prevention

Limit all acute headache medications to no more than twice weekly to prevent medication-overuse headache, which can transform episodic migraine into chronic daily headache 1, 6

• This applies to triptans, acetaminophen combinations, antiemetics, and especially opioids 1
• Medication overuse headache presents as migraine-like daily headaches or marked increase in attack frequency 6
• If using acute medications more than twice weekly, initiate preventive therapy instead 1

Medications to Avoid

Opioids Should Not Be Used Routinely

• Opioids are reserved only for when other medications cannot be used, sedation is not a concern, or abuse risk has been addressed 1
• Opioids lead to dependency, rebound headaches, and eventual loss of efficacy 3, 1
• If an opioid must be used, butorphanol nasal spray has better evidence than other opioids 1

Butalbital-Containing Compounds

• Limit and carefully monitor use of butalbital-containing analgesics due to risk of dependency and rebound headache 3, 1

Route Selection Based on Symptoms

When Nausea/Vomiting is Present

• Use non-oral routes of administration including subcutaneous, intranasal, or intravenous formulations 3, 1
• Subcutaneous sumatriptan 6 mg provides fastest relief (peak concentration at 15 minutes) 1
• Intranasal sumatriptan 5-20 mg is an alternative 1

For Severe Refractory Attacks

• IV ketorolac 30 mg plus IV metoclopramide 10 mg is first-line combination therapy when NSAIDs are not contraindicated 1
• If NSAIDs are contraindicated, use IV metoclopramide or prochlorperazine alone, or consider DHE 1

Special Populations

Pregnancy

• Acetaminophen is the safest acute migraine drug during pregnancy 5
• Acetaminophen with codeine is also an option if acetaminophen alone is insufficient 5
• Sumatriptan may be considered for selected patients during pregnancy and is compatible with breastfeeding 5

Treatment Algorithm

1. Assess headache severity at onset
2. For mild-moderate pain: Start with acetaminophen 1000 mg plus caffeine 3, 1
3. For moderate-severe pain or failed acetaminophen: Use a triptan (sumatriptan, rizatriptan, or eletriptan) 1, 4
4. If nausea/vomiting present: Add antiemetic or switch to non-oral triptan formulation 3, 1
5. If inadequate response after 2 hours: May repeat dose if allowed by medication-specific guidelines 3
6. For refractory attacks: Consider combination therapy (triptan + acetaminophen) or IV metoclopramide/prochlorperazine 1, 2

Common Pitfalls to Avoid

• Do not delay treatment - triptans are most effective when taken early while pain is still mild 1
• Do not use acetaminophen alone for moderate-severe migraine - it has poor efficacy (NNT 12) compared to triptans 2
• Do not allow escalation of acute medication frequency - this creates medication-overuse headache; transition to preventive therapy instead 1
• Do not use triptans in patients with cardiovascular disease, uncontrolled hypertension, or history of stroke 6