What medications can reduce the number of headache days in a migraine patient?

Medications to Reduce Headache Days in Migraine Patients

For chronic migraine (≥15 headache days/month), CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) receive the strongest recommendation, reducing monthly migraine days by approximately 2-3 days, followed by onabotulinumtoxinA (Botox) which reduces headache days by 1.8-1.9 days per month; for episodic migraine (<15 headache days/month), topiramate, beta-blockers, and candesartan are first-line options. 1

Chronic Migraine (≥15 Headache Days/Month)

First-Line: CGRP-Targeting Therapies

CGRP monoclonal antibodies are the most strongly recommended preventive medications for chronic migraine:

• Erenumab, fremanezumab, and galcanezumab have "strong for" recommendations based on high-quality evidence demonstrating reductions in mean monthly migraine days and abortive medication use 1
• These agents reduce monthly migraine days by approximately 0.8-2.3 days compared to placebo 2
• Important caveat: Erenumab may increase risk for development or worsening of hypertension, requiring blood pressure monitoring 1, 2
• Eptinezumab (intravenous CGRP antagonist) is also effective for chronic migraine prevention 1

Oral CGRP receptor antagonists (gepants):

• Atogepant has a "weak for" recommendation for episodic migraine, demonstrating statistically significant reductions in monthly migraine days 1, 2
• Rimegepant has a "neither for nor against" recommendation, with only 0.8 day reduction in monthly migraine days 1, 2

Second-Line: OnabotulinumtoxinA (Botox)

OnabotulinumtoxinA is FDA-approved specifically for chronic migraine prophylaxis:

• Reduces headache days by 1.8-1.9 days per month compared to placebo with a "weak for" recommendation 1, 3, 4
• Critical distinction: Effective ONLY for chronic migraine (≥15 headache days/month); ineffective and NOT recommended for episodic migraine 1, 4
• Administered as 155-195 units every 12 weeks following the PREEMPT injection protocol to 31-39 sites 3, 4
• Efficacy should be assessed after 6-9 months (2-3 treatment cycles) before determining non-response 1, 3
• Improves multiple symptom dimensions including headache frequency, severity, cumulative hours, and quality of life 1, 3, 4

Third-Line: Traditional Oral Preventives

Topiramate is the only traditional oral preventive with proven efficacy in chronic migraine:

• "Weak for" recommendation with reduction of 2.30 monthly migraine days versus placebo 1
• Target dose 100 mg/day, though dosing flexibility from 50-200 mg/day is acceptable 5, 6
• Effective even in patients with medication overuse headache 6, 7
• Common adverse effects: Paresthesias (25-28%), cognitive difficulties (11-15%), weight loss (mean 3.1 kg) 8, 5, 6

Other agents used for chronic migraine (weaker evidence):

• Valproate, amitriptyline, gabapentin, tizanidine, and fluoxetine are commonly used but lack robust placebo-controlled trial data specifically for chronic migraine 1

Episodic Migraine (<15 Headache Days/Month)

First-Line Options

Beta-blockers without intrinsic sympathomimetic activity:

• Propranolol, metoprolol, atenolol, or bisoprolol are recommended first-line 1, 9
• Propranolol demonstrated significant reduction in headache unit index (composite of frequency and severity) 9

Topiramate:

• "Weak for" recommendation with reduction of 1.1 monthly migraine days versus placebo 1
• In episodic migraine patients receiving first-line monotherapy, reduced mean migraine frequency from 5.8 to 1.9 per 28 days 10
• 61% of episodic migraine patients reported marked improvement 10

Candesartan:

• Recommended as first-line option for episodic migraine prevention 1

Second-Line Options

Valproate:

• "Weak for" recommendation for episodic migraine prevention 1
• Absolute contraindication in women of childbearing potential due to teratogenicity 1

Amitriptyline and flunarizine:

• Second-line options when first-line agents fail or are contraindicated 1

Third-Line: CGRP Monoclonal Antibodies

For episodic migraine, CGRP antibodies are reserved for patients who have failed multiple oral preventives:

• Erenumab, fremanezumab, and galcanezumab have "strong for" recommendations 1
• In Europe, regulatory restrictions limit use to patients in whom other preventive drugs have failed or are contraindicated 1
• Cost consideration: Annual costs range from $7,071 to $22,790, substantially higher than traditional preventives 2

Agents to AVOID

Gabapentin:

• "Weak against" recommendation for episodic migraine—no studies met predefined outcomes for migraine prevention 1
• Evidence of misuse, dependence, and withdrawal 1

OnabotulinumtoxinA:

• "Weak against" recommendation for episodic migraine—does NOT reduce monthly migraine or headache days 1, 4

Treatment Algorithm

Step 1: Determine migraine frequency

• ≥15 headache days/month = chronic migraine
• <15 headache days/month = episodic migraine 1

Step 2: For chronic migraine:

• Start with CGRP monoclonal antibodies (erenumab, fremanezumab, or galcanezumab) if accessible and affordable 1
• If CGRP antibodies unavailable or cost-prohibitive, use onabotulinumtoxinA (requires specialist administration) 1, 3
• If neither available, use topiramate 100 mg/day 1, 5

Step 3: For episodic migraine:

• Start with beta-blocker (propranolol preferred), topiramate, or candesartan 1
• If first-line fails, try valproate (if not childbearing potential), amitriptyline, or flunarizine 1
• Reserve CGRP antibodies for patients failing 2-3 oral preventives 1, 2

Step 4: Assess efficacy timeline

• Oral preventives: 2-3 months 1
• CGRP antibodies: 3-6 months 1
• OnabotulinumtoxinA: 6-9 months (2-3 cycles) 1, 3

Step 5: Address modifiable risk factors

• Medication overuse (limit simple analgesics to <15 days/month, triptans to <10 days/month) 4
• Obesity, caffeine use, sleep apnea, psychiatric comorbidities 1

Critical Pitfalls to Avoid

• Never use onabotulinumtoxinA for episodic migraine—it is ineffective and wastes resources 1, 4
• Never prescribe valproate to women of childbearing potential—absolute teratogenicity risk 1
• Monitor blood pressure with erenumab—postmarketing studies show increased hypertension risk 1
• Do not abandon preventive therapy prematurely—efficacy takes weeks to months to manifest 1
• Address medication overuse headache concurrently with preventive therapy, not sequentially 4, 6