What are other injectable treatments for headaches similar to Botox (Botulinum toxin type A)?

Alternative Injectable Treatments for Headaches

For chronic migraine (≥15 headache days per month), CGRP monoclonal antibodies are the primary injectable alternative to Botox, with strong evidence supporting their use for both prevention and acute treatment. 1, 2

Injectable Alternatives by Headache Type

For Chronic Migraine Prevention

CGRP Monoclonal Antibodies are the main injectable alternative to onabotulinumtoxinA (Botox):

• These medications have strong recommendations from the American Headache Society for chronic migraine prevention 2
• They work through a different mechanism than Botox, targeting the calcitonin gene-related peptide pathway 2
• The American College of Physicians suggests using oral preventive medications before CGRP-mAbs primarily based on cost differences rather than efficacy differences 3, 2

Treatment Sequencing Algorithm:

• Start with oral preventive medications (topiramate, propranolol, amitriptyline, or valproate) unless contraindicated 2
• If 2-3 oral medications fail or are not tolerated, consider CGRP monoclonal antibodies or Botox for chronic migraine only 3, 2
• Regulatory restrictions typically require failure of 2-3 other preventive medications before either injectable therapy 3

For Episodic Migraine (Acute Treatment)

Injectable triptans are the primary migraine-specific acute treatment:

• Subcutaneous sumatriptan (6 mg) has a strong recommendation for short-term treatment of migraine 1
• This is the only injectable triptan with robust evidence for acute migraine attacks 1

CGRP Antagonists (Gepants) are newer alternatives:

• Rimegepant and ubrogepant are suggested for short-term treatment of migraine 1
• These have a weak recommendation but represent an alternative mechanism of action 1

For Cluster Headache

Galcanezumab (a CGRP monoclonal antibody):

• Suggested for prevention of episodic cluster headache 1
• Specifically suggested against for chronic cluster headache 1

Subcutaneous sumatriptan (6 mg):

• Suggested for short-term treatment of cluster headache attacks 1

Novel Approach - OnabotulinumtoxinA towards the sphenopalatine ganglion:

• Recent 2024 data shows 69% response rate in chronic cluster headache with this specialized injection technique 4
• This represents a different injection approach than standard Botox for migraine 4

Critical Pitfalls to Avoid

Do NOT use Botox for:

• Episodic migraine (<15 headache days per month) - it is ineffective and should not be offered 1, 2
• Tension-type headaches - it is probably ineffective and should not be offered 1, 2

Do NOT use galcanezumab for:

• Chronic cluster headache - guidelines specifically suggest against it 1

Monitor for medication overuse headache:

• Limit simple analgesics to fewer than 15 days per month 3
• Limit triptans to fewer than 10 days per month 3
• Address medication overuse concurrently with preventive therapy, as withdrawal and preventive therapy can be managed in parallel 3

Cost and Patient Preference Considerations

• Injectable therapies (both Botox and CGRP-mAbs) have substantially higher costs compared to oral preventive medications 3
• Patients probably prefer oral treatments over injectable medications when effectiveness is similar (moderate-certainty evidence) 3
• For patients with contraindications to oral medications (β-blockers contraindicated in asthma, valproate contraindicated in pregnancy planning), injectable therapies can be initiated earlier 3

Efficacy Comparison

For chronic migraine:

• OnabotulinumtoxinA reduces headache days by approximately 1.9-3.1 days per month compared to placebo 3
• CGRP monoclonal antibodies have similar efficacy profiles, with the choice often based on cost, patient preference, and insurance coverage 2
• Both require 2-3 treatment cycles before determining non-response 3, 5