What is the recommended treatment protocol for chronic migraines using Botox (Botulinum toxin) in patients with a history of frequent and severe headaches?

Botox Treatment Protocol for Chronic Migraine

Diagnostic Confirmation Required

OnabotulinumtoxinA (Botox) is the only FDA-approved therapy specifically for chronic migraine prophylaxis and should be administered using the PREEMPT protocol at 155-195 units across 31-39 injection sites every 12 weeks. 1, 2

Before initiating treatment, confirm the patient meets chronic migraine criteria:

• 15 or more headache days per month, each lasting at least 4 hours 1
• 8 or more days per month with migraine features 1
• Duration of at least 3 months 2
• Rule out secondary headache causes through history and examination (look for red flags: thunderclap onset, focal neurological deficits, fever, neck stiffness, new onset after age 50) 3

Treatment Sequencing and Patient Selection

Botox should be considered after failure of oral preventive medications, though it can be initiated earlier if contraindications to oral agents exist. 2

First-line oral preventives to trial first:

• Topiramate (only oral agent with Level A evidence for chronic migraine) 1, 2
• Beta-blockers (propranolol), valproate, amitriptyline, or venlafaxine 2
• Require failure of 2-3 preventive medications before Botox per typical insurance requirements 2

Exceptions allowing earlier Botox initiation:

• Contraindications to oral medications (e.g., beta-blockers in asthma, valproate in pregnancy planning) 2
• Intractable chronic migraine with no pain-free time despite multiple medication trials 4

Critical caveat: Botox is ONLY effective for chronic migraine (≥15 headache days/month) and is ineffective for episodic migraine (<15 headache days/month). 2, 5

PREEMPT Injection Protocol

Administer exactly 155-195 units across 31-39 specific anatomical sites following the Phase III PREEMPT protocol. 2

Injection sites include:

• Frontalis, corrugator, procerus (forehead/glabellar region)
• Temporalis (bilateral)
• Occipitalis (bilateral)
• Cervical paraspinal muscles
• Trapezius (bilateral)

This comprehensive multi-site approach is the only evidence-based injection pattern—deviations from PREEMPT protocol lack efficacy data. 2

Treatment Schedule and Response Assessment

Inject every 12 weeks (3 months) consistently. 2

Response evaluation timeline:

• Require at least 2-3 treatment cycles (6-9 months) before classifying as non-responder 2
• Document at each visit: headache frequency, intensity, medication use days, and quality of life scores 2
• Use validated tools: HIT-6 (Headache Impact Test), MIDAS (Migraine Disability Assessment), or migraine-specific quality of life questionnaires 6, 4

Expected efficacy outcomes:

• Reduction of 1.9-3.1 migraine days per month compared to placebo 2, 5
• Reduction of 1.9 headache days per month 2, 5
• 53-56% reduction in monthly headache/migraine days in real-world settings 6
• Improvement in quality of life scores by 0.6-2.0 standard deviations 6

Concurrent Management Requirements

Address medication overuse headache simultaneously with Botox initiation—do not delay preventive treatment. 2

Medication limits to prevent overuse:

• Simple analgesics: <15 days per month 2, 3
• Triptans: <10 days per month 2, 3
• Medication overuse perpetuates chronic migraine and reduces preventive treatment effectiveness 2

Additional interventions:

• Identify and modify triggers: obesity, caffeine overuse, sleep apnea, psychiatric comorbidities, stress 1
• Maintain acute treatment for breakthrough headaches 1
• Consider combination therapy with another preventive agent if inadequate monotherapy response 2

Safety Profile

Adverse events occur in 60% of Botox-treated patients versus 47% with placebo (RR 1.28), but events are typically mild and transient. 6, 5

Common adverse effects:

• Neck pain, muscle weakness (transient)
• Injection site reactions
• Ptosis (rare with proper technique)

Withdrawal due to adverse events is 72% lower with Botox compared to oral preventive agents. 5

Specialist Referral Considerations

Treatment should be delivered by a neurologist or headache specialist trained in the PREEMPT protocol. 1

Primary care physicians can:

• Initiate oral preventives while awaiting specialist appointment 1
• Diagnose chronic migraine and make referrals 1
• Manage medication overuse and trigger modification 1

96% of chronic migraine patients report benefit from long-term Botox treatment when properly administered. 6