Management of Headache No Longer Controlled by Current Medication
When a patient's headache medication (such as sumatriptan) stops working, first try a different triptan, as failure of one triptan does not predict failure of others, and if all triptans fail after adequate trials (at least three consecutive attacks), escalate to third-line agents like ditans (lasmiditan) or gepants (ubrogepant, rimegepant). 1
Immediate Assessment Steps
Before changing medications, evaluate for two critical scenarios:
Rule out medication-overuse headache (MOH): If the patient is using acute medications more than twice weekly, this pattern itself causes increasing headache frequency and can lead to daily headaches 1, 2. This is the most common reason for apparent treatment failure.
Screen for red flags suggesting secondary headache requiring urgent evaluation 1:
- Thunderclap headache (subarachnoid hemorrhage)
- Progressive headache (space-occupying lesion)
- New onset after age 50 (temporal arteritis)
- Focal neurological symptoms
- Fever with neck stiffness (meningitis)
Stepped Escalation Algorithm for Failed Triptan Therapy
Step 1: Optimize Current Triptan Use
Ensure early administration: Triptans are most effective when taken early in the attack while headache is still mild 1. Many treatment failures result from delayed dosing.
Try combination therapy: Add fast-acting NSAIDs (naproxen sodium, ibuprofen lysine, or diclofenac potassium) to the triptan to prevent relapse 1. This addresses the 40% of patients who experience symptom recurrence within 48 hours.
Consider route change: If oral sumatriptan fails, subcutaneous sumatriptan 6mg can be useful, particularly for patients who rapidly reach peak intensity or have vomiting 1.
Step 2: Switch to Alternative Triptan
If one triptan is ineffective, others might still provide relief 1. Patient response to triptans is not uniform, and failure of one does not predict failure of another. Try at least 2-3 different triptans before declaring triptan failure.
Step 3: Define Triptan Failure and Escalate
Triptan failure is defined as no or insufficient therapeutic response in at least three consecutive attacks 1. Once this threshold is met:
First choice: Ditans or Gepants 1
Alternative: Intranasal DHE: Good evidence for efficacy and safety as monotherapy 1, 2
Avoid: Oral ergot alkaloids (poorly effective and potentially toxic), opioids (questionable efficacy, risk of dependency and MOH), and barbiturates 1, 2
Initiate Preventive Therapy
If headaches continue to impair quality of life despite optimized acute therapy, or if the patient uses acute medications more than 2 days per week, preventive therapy is indicated 1. This is essential because:
- Frequent acute medication use (>2 times weekly) increases risk of MOH 1, 2
- Preventive therapy reduces attack frequency and can restore responsiveness to acute treatments
- Efficacy of preventive medications requires 2-3 months for oral agents, 3-6 months for CGRP monoclonal antibodies, and 6-9 months for onabotulinumtoxinA 1
Adjunctive Strategies
For nausea/vomiting: Add prokinetic antiemetics (domperidone or metoclopramide) 1, 2. Metoclopramide also provides synergistic analgesia 2.
Consider non-pharmacologic approaches if medication optimization fails: Behavioral treatments (relaxation, biofeedback, cognitive-behavioral therapy) have strong evidence as first-line preventive options 3. Acupuncture has recent positive randomized trial data supporting its use 3.
Critical Pitfall to Avoid
Do not allow patients to increase frequency of acute medication use in response to treatment failure—this creates a vicious cycle of MOH 1, 2. Instead, transition to preventive therapy while optimizing acute treatment strategy. Acute therapy should be strictly limited to no more than twice weekly 1.