What are the alternatives to Botox (botulinum toxin) injections for treating headaches?

Alternatives to Botox for Headache Treatment

For Chronic Migraine (≥15 headache days/month)

If you have chronic migraine and cannot use Botox, start with oral preventive medications first—specifically topiramate, propranolol, amitriptyline, or valproate—as these are recommended before injectable therapies and cost substantially less. 1

First-Line Oral Preventive Medications

• Topiramate is suggested for prevention of chronic migraine with a weak recommendation and should be tried before Botox 1, 2
• Beta-blockers (propranolol) are recommended for migraine prevention with a weak recommendation 1
• Amitriptyline and venlafaxine are alternative oral preventive options that should be considered before injectable therapies 1
• Valproate is another oral preventive medication option, though it is contraindicated in pregnancy planning 1

CGRP-Targeted Therapies (Monoclonal Antibodies)

If oral preventive medications fail or are contraindicated, CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) represent the strongest alternative to Botox, with strong recommendations for both chronic and episodic migraine. 2

• These CGRP-targeted therapies have strong recommendations from the American Headache Society for both chronic and episodic migraine 2
• The American College of Physicians suggests using oral preventive medications before CGRP-mAbs primarily based on cost differences rather than efficacy differences 1
• CGRP monoclonal antibodies are one of only three evidence-based preventive treatments for chronic migraine (alongside topiramate and Botox) 1

When to Bypass Oral Medications

• Botox or CGRP-mAbs can be initiated directly if you have contraindications to oral medications, such as beta-blockers contraindicated in asthma or valproate contraindicated in pregnancy planning 1
• Regulatory restrictions typically require failure of 2-3 other preventive medications before approving Botox, which is a common insurance requirement 1

For Episodic Migraine (<15 headache days/month)

For episodic migraine, do NOT use Botox—it is ineffective and specifically not recommended; instead, use acute treatments like triptans combined with NSAIDs, or newer CGRP antagonists-gepants. 1, 2

Acute Treatment Options

• Triptans are the primary migraine-specific acute treatment, with rizatriptan having a strong recommendation for acute migraine treatment 1
• NSAIDs (nonsteroidal anti-inflammatory drugs) are effective for acute episodic migraine 3
• CGRP antagonists-gepants (rimegepant, ubrogepant, zavegepant) are newer alternatives for acute treatment 3
• Lasmiditan (a 5-HT1F agonist) is another newer acute treatment option 3
• Combination therapy with a triptan plus NSAID or acetaminophen is superior to monotherapy 3

Preventive Options for Episodic Migraine

• CGRP monoclonal antibodies have strong recommendations for episodic migraine prevention 2
• Oral preventive medications (topiramate, propranolol, amitriptyline) can be used for episodic migraine if attacks are frequent enough to warrant prevention 1

Critical Pitfalls to Avoid

• Do not use Botox for episodic migraine—the VA/DoD Clinical Practice Guideline specifically suggests against it, and research shows it is ineffective for fewer than 15 headache days per month 1, 2, 4
• Do not use Botox for tension-type headaches—it is probably ineffective and should not be offered 1
• Avoid gabapentin for migraine prevention, as guidelines suggest against its use with a weak recommendation 2
• Monitor for medication overuse headache—limit simple analgesics to fewer than 15 days per month and triptans to fewer than 10 days per month to prevent this complication 1

Treatment Sequencing Algorithm

1. Start with oral preventive medications (topiramate, propranolol, amitriptyline, or valproate) unless contraindicated 1
2. If 2-3 oral medications fail or are not tolerated, consider CGRP monoclonal antibodies or Botox (for chronic migraine only) 1, 2
3. For patients preferring oral routes, continue trying different oral preventives, as patients probably prefer oral treatments over injectables when effectiveness is similar 1
4. Address medication overuse concurrently with preventive therapy if present, as withdrawal and preventive therapy can be managed in parallel 1