What is the administration frequency of Botox (Botulinum toxin) injections for patients with chronic migraines?

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Last updated: January 13, 2026View editorial policy

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Botox Administration Frequency for Chronic Migraine

Botox (onabotulinumtoxinA) should be administered every 12 weeks (every 3 months) for chronic migraine prophylaxis. 1

Standard Treatment Protocol

  • The established treatment interval is every 12 weeks, which represents the evidence-based dosing schedule validated in the pivotal PREEMPT trials and endorsed by multiple guideline societies including the VA/DoD and European Headache Federation 1

  • Each treatment session involves administering 155-195 units across 31-39 injection sites following the PREEMPT protocol, which is the only evidence-based injection pattern for chronic migraine 1

  • Retreatment should be administered no more frequently than every three months to maintain safety and efficacy 2

Duration of Effectiveness

  • The maximum therapeutic effect typically occurs during the second month after injection, with effectiveness beginning to wane in the third month 3

  • In a real-world study, headache days decreased from baseline (18.95 days/month) to 10.55 days in month one, reached optimal reduction at 9.31 days in month two, then increased to 11.97 days by month three 3

  • Analgesic medication use similarly decreased most significantly in the second month (5.40 tablets/month) compared to the first month (6.53 tablets/month), with a slight increase by the third month (5.85 tablets/month) 3

Treatment Response Timeline

  • Patients require at least 2-3 treatment cycles (6-9 months) before being classified as non-responders, as therapeutic benefit often accumulates with repeated treatments 1

  • Long-term treatment studies demonstrate sustained efficacy over multiple injection series, with 96% of patients reporting benefit after an average of 6.5 injection series over 73 weeks 4

  • The reduction in migraine days becomes more pronounced with higher doses (195 U) after the third injection compared to lower doses (155 U), suggesting dose-dependent efficacy with repeated treatments 5

Critical Timing Considerations

  • Do not administer treatments more frequently than every 12 weeks, as this represents the studied and approved interval with established safety data 1, 2

  • If a patient's last injection was 6 months prior (26 weeks), they have exceeded the standard 12-week interval and should receive treatment promptly 1

  • Reconstituted Botox must be used within 24 hours and stored refrigerated at 2-8°C during this period; it is for single-dose, single-patient use only 2

Efficacy Evidence

  • The PREEMPT 2 trial demonstrated that onabotulinumtoxinA reduced headache days by 9.0 days compared to 6.7 days with placebo (p<0.001) when administered every 12 weeks for two treatment cycles 6

  • High-quality evidence shows chronic migraine patients experience a reduction of approximately 1.9-3.1 headache days per month compared to placebo with the 12-week dosing schedule 1, 7

  • This treatment is only effective for chronic migraine (≥15 headache days per month) and is ineffective for episodic migraine (<15 headache days per month) 1, 8

Common Pitfalls to Avoid

  • Never use Botox for episodic migraine (fewer than 15 headache days per month)—it is ineffective and not recommended by guidelines 1, 8

  • Do not deviate from the PREEMPT protocol injection pattern, as this is the only evidence-based approach validated for chronic migraine 1

  • Avoid injecting closer than 1 cm above the central eyebrow and ensure lateral corrugator injections are at least 1 cm above the bony supraorbital ridge to reduce risk of eyelid ptosis 2

  • Monitor for medication overuse headache concurrently, limiting simple analgesics to fewer than 15 days per month and triptans to fewer than 10 days per month 1, 8

References

Guideline

Botox Treatment for Chronic Migraine

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Research

[Efficacy of different doses of botox in treatment of chronic migraine].

Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova, 2017

Research

Botulinum toxins for the prevention of migraine in adults.

The Cochrane database of systematic reviews, 2018

Guideline

Alternatives to Botox for Headache Treatment

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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