Codeine Should Not Be Used for Severe Acute Headache
Codeine is not recommended as first-line therapy for severe acute headache and should be avoided entirely in favor of evidence-based alternatives. 1
Why Codeine Is Inappropriate
The CDC explicitly recommends against opioids, including codeine, as first-line therapy for headaches including episodic migraine, citing equivalent or lesser effectiveness compared to NSAIDs and significant risks for long-term opioid use after short-term exposure. 1
The American Headache Society and American Academy of Neurology both recommend against prescribing opioid medications as first-line treatment for recurrent headache disorders, reserving them only as a last resort when all other evidence-based treatments have failed. 1
Opioids carry a twofold higher risk for development of medication-overuse headache compared to simple analgesics and triptans, creating a vicious cycle where the treatment itself perpetuates chronic daily headache. 1
Codeine specifically has been associated with higher rates of medication-overuse headache relapse (approximately 30% relapse rate), particularly when combined with caffeine, making it a poor long-term strategy. 2
Evidence-Based First-Line Alternatives
For Mild to Moderate Severe Headache
NSAIDs are the recommended first-line treatment, with the strongest evidence supporting ibuprofen 400-800 mg, naproxen sodium 500-825 mg, or aspirin 1000 mg. 1, 3
Combination therapy with acetaminophen 1000 mg + aspirin 500-1000 mg + caffeine 130 mg achieves pain reduction to mild or none in 59.3% of patients at 2 hours. 3
For Moderate to Severe Headache
Triptans are first-line therapy for moderate to severe attacks, with oral options including sumatriptan 50-100 mg, rizatriptan 10 mg, or eletriptan 40 mg. 1, 3
Subcutaneous sumatriptan 6 mg provides the highest efficacy (59% complete pain relief at 2 hours) with onset within 15 minutes for patients with severe, rapidly progressing headache. 4
Combination therapy of triptan + NSAID is superior to either agent alone and represents the strongest recommendation from current guidelines. 3
For Patients Requiring Parenteral Treatment
IV metoclopramide 10 mg + ketorolac 30 mg is the recommended first-line IV combination, providing direct analgesic effects through central dopamine receptor antagonism plus rapid NSAID analgesia with minimal rebound risk. 3, 5
IV dihydroergotamine (DHE) has good evidence for efficacy and safety as monotherapy for acute migraine attacks when triptans are contraindicated. 1, 3
Critical Medication Frequency Limits
All acute headache medications must be limited to no more than 2 days per week (approximately 10 days per month) to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to daily headaches. 1, 3
If a patient requires acute treatment more than twice weekly, preventive therapy should be initiated immediately with propranolol 80-240 mg/day, topiramate, or amitriptyline 30-150 mg/day. 3, 5
When Opioids Might Be Considered (Rarely)
Opioids should be reserved exclusively for cases where all other evidence-based treatments are contraindicated, sedation effects are acceptable, and the risk for abuse has been formally addressed. 1, 3
If an opioid must be used, butorphanol nasal spray has better evidence than codeine for headache treatment, though this remains a last-resort option. 1, 3
Prescribe immediate-release opioids at the lowest effective dose, for use "as needed" rather than scheduled, and include an opioid taper plan to minimize unintentional initiation of long-term opioid use. 1
Common Pitfalls to Avoid
Do not prescribe codeine simply because the patient requests it or because "nothing else has worked" without first ensuring adequate trials of NSAIDs, triptans, and combination therapy. 1, 6
Do not allow patients to escalate frequency of any acute medication in response to treatment failure, as this creates medication-overuse headache; instead transition to preventive therapy. 3
Never combine codeine with caffeine-containing compounds, as this combination has the highest relapse rate for medication-overuse headache. 2
Recognize that codeine's perceived effectiveness may reflect its sedative properties rather than true analgesic efficacy, and sedation does not equate to headache resolution. 6, 7