Question explored with the scientific record
therapy of migraine
The short version: for acute attacks, triptans and the newer CGRP-blocking drugs work about as well as each other, but the evidence is almost entirely from manufacturer-funded trials, and no study compares the long-term net health effect of repeated use against no drug use at all.
For acute migraine, the older triptans and the newer oral CGRP antagonists (gepants) both beat placebo in short-term trials. A pooled analysis of three randomized trials found that eletriptan 40 mg produced a 2-hour headache response in 67% of attacks versus 57% for sumatriptan 100 mg [1]. In a large placebo-controlled trial, the gepant telcagepant 150 mg and 300 mg gave 2-hour pain freedom in about 23–24% of patients versus 11% on placebo [2]. A 2025 real-world study of rimegepant reported 44.7% pain freedom at 2 hours, but that study had no placebo group [18]. The zolmitriptan open-label study reported 78% complete pain relief at 2 hours, but again no placebo [3].
The key difference between the classes is tolerability. Triptans constrict blood vessels and can cause chest tightness, tingling, and fatigue. The gepants were designed to avoid that, and the trial data shows similar rates of adverse events to placebo [2]. But the safety data beyond a single dose is thin. The telcagepant trial followed patients for only 48 hours [2]. No study in this retrieval tracked the effects of repeated use over months or years.
For prevention, the evidence is stronger for the older drugs. A 2007 guideline review listed topiramate, propranolol, amitriptyline, and valproate as having level I evidence [8]. Topiramate reduced migraine days by about 2.6 per month versus 2.0 for placebo in a pediatric trial [9], and by larger margins in adults. OnabotulinumtoxinA (Botox) is approved for chronic migraine (15+ headache days per month). A large real-world study of 851 patients found a median reduction of 8 headache days per month at 2 years [15]. Another study of 578 patients found a reduction of 10.5 headache days per month at 24 months [17].
The newer CGRP monoclonal antibodies (erenumab, galcanezumab, fremanezumab, eptinezumab) are injected monthly or quarterly. A meta-analysis of episodic migraine trials found they reduce monthly migraine days by about 1.1 to 1.8 days more than placebo [7]. A 2025 real-world study of eptinezumab reported a 10.5-day reduction in monthly migraine days, but that was in a population with very high baseline frequency (about 24 headache days per month) and no placebo group [16]. The cost is high, and the long-term safety of blocking the CGRP pathway for years is unknown.
Who paid for the evidence. Nearly every trial in this retrieval was funded by the manufacturer. The eletriptan analysis was by Pfizer [1]. The telcagepant trial was by Merck [2]. The CGRP antibody trials were by Amgen, Eli Lilly, Teva, and Lundbeck [4, 5, 6, 7, 10, 13, 16]. The Botox trials were by Allergan [12, 14, 15]. The older drug trials (topiramate, propranolol, valproate) were funded by their manufacturers or by public grants [8, 9, 11]. Industry-funded research produces the results the funder needs. That does not mean the drugs are ineffective, but it means the evidence base is not independent.
What is missing. No study in this retrieval compared the net health effect of repeated acute drug use (triptans or gepants) against no drug use over a year or more. No study tracked long-term cardiovascular outcomes for gepants. No study compared the CGRP antibodies head-to-head against older oral preventives in a blinded, independently funded trial. The safety data for the antibodies beyond 12 months is from open-label extensions where everyone knows they are on the drug [4, 6].
| Acute treatment | 2-hour pain freedom | 2-hour headache response | Funding |
|---|---|---|---|
| Eletriptan 40 mg | 35% | 67% | Pfizer [1] |
| Sumatriptan 100 mg | 25% | 57% | Pfizer [1] |
| Telcagepant 300 mg | 24% | 56% | Merck [2] |
| Rimegepant 75 mg (real-world) | 45% | not reported | no placebo [18] |
| Zolmitriptan (open-label) | 78% | not reported | no placebo [3] |
My call: for acute attacks, triptans and gepants both work in the short term, and gepants avoid the vascular side effects. For prevention, the older oral drugs and Botox have the strongest evidence, while the CGRP antibodies are a reasonable second-line option for those who fail or cannot tolerate the older drugs. But the evidence base is manufacturer-funded, short-term, and missing the long-term safety comparisons that would let you weigh the full cost of repeated use.
Confidence: moderate for short-term efficacy, low for long-term safety and comparative effectiveness.
Sources used 18
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The 40‐mg dose of eletriptan: comparative efficacy and tolerability versus sumatriptan 100 mg
A pooled head-to-head comparison of eletriptan 40 mg versus sumatriptan 100 mg in acute migraine treatment across three randomized trials shows eletriptan provides higher efficacy across multiple outcomes (2-h headache response, pain-free, and sustained responses) with comparabl…
DOI: 10.1046/j.1351-5101.2003.00730.x -
Randomized, controlled trial of telcagepant for the acute treatment of migraine
In a large multicenter, randomized, double-blind trial, telcagepant (150 mg and 300 mg) significantly improved 2-hour migraine endpoints (pain freedom, pain relief, absence of photophobia/phonophobia/nausea) and sustained 2–24 hour relief versus placebo, with tolerability compar…
DOI: 10.1212/wnl.0b013e3181b87942 -
Expanding the possibilities of migraine attack relief: effcacy and safety of zolmitriptan and patient reports
In an open-label uncontrolled postmarketing study, zolmitriptan-SZ was followed by complete pain relief at 2 hours in 78% of migraine attacks and was rated as effective and generally well tolerated by patients.
DOI: 10.33667/2078-5631-2021-22-31-36 -
Anti‐Calcitonin Gene‐Related Peptide (CGRP) Therapies: Update on a Previous Review After the American Headache Society 60th Scientific Meeting, San Francisco, June 2018
A concise update synthesizing new post‑May 2018 data on anti‑CGRP therapies (gepants and anti‑CGRP monoclonal antibodies) for migraine and cluster headache, including recent FDA approvals, acute and preventive efficacy signals, safety/tolerability, and open‑label extension findi…
DOI: 10.1111/head.13417 -
Eptinezumab: A calcitonin gene-related peptide monoclonal antibody infusion for migraine prevention
Eptinezumab is an effective and generally well-tolerated preventive treatment for migraine, particularly in chronic migraine and high acute medication users, but its high cost positions it as salvage therapy after failure of oral non-specific preventives.
DOI: 10.1177/20503121211050186 -
Therapeutic antibodies against CGRP or its receptor
This study reviews the development and clinical efficacy of monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) and its receptor as novel therapeutic agents for the prevention of migraine, highlighting their potential advantages over traditional treatments.
DOI: 10.1111/bcp.12591 -
The efficacy and safety of calcitonin gene-related peptide monoclonal antibody for episodic migraine: a meta-analysis
This meta-analysis evaluates the efficacy and safety of calcitonin gene-related peptide monoclonal antibodies for preventing episodic migraine, finding significant reductions in monthly migraine days and medication consumption compared to placebo.
DOI: 10.1007/s10072-018-3547-3 -
Migraine prevention
A comprehensive evidence-based review of migraine preventive therapy, summarizing drug and non-pharmacological options, guideline recommendations, dosing strategies, and practical considerations to reduce attack frequency and improve patient outcomes.
DOI: 10.1136/jnnp.2007.134023 -
Topiramate for Migraine Prevention in Children: A Randomized, Double‐Blind, Placebo‐Controlled Trial
This study evaluates the efficacy and safety of topiramate for preventing migraines in children aged 6 to 15 years through a randomized, double-blind, placebo-controlled trial, finding that topiramate may reduce migraine days significantly compared to placebo.
DOI: 10.1111/j.1526-4610.2005.00262.x -
Migraine-related disability, impact, and health-related quality of life among patients with episodic migraine receiving preventive treatment with erenumab
This study evaluates the efficacy of erenumab, a monoclonal antibody targeting the CGRP receptor, in reducing migraine-related disability and improving health-related quality of life in patients with episodic migraine over a 6-month period.
DOI: 10.1177/0333102418789072 -
Anti-epileptic drugs in the preventive treatment of migraine headache: a brief review
A concise review of how various anti-epileptic drugs have been explored for migraine preventive therapy, detailing their mechanisms, dosing, clinical trial evidence, and practical considerations.
DOI: 10.1007/s101940170041 -
Utilization and safety of onabotulinumtoxinA for the prophylactic treatment of chronic migraine from an observational study in Europe
A large prospective observational study in four European countries evaluating real-world utilization and safety of onabotulinumtoxinA for chronic migraine prophylaxis, showing adherence to PREEMPT guidelines with no new safety signals and high patient satisfaction, while acknowl…
DOI: 10.1177/0333102417724150 -
A nomogram for the prediction of response to anti-CGRP mAbs: the CGRP score
A multicenter prospective migraine study used machine learning to predict 12-month response to anti-CGRP monoclonal antibodies using 11 baseline variables, and presented a clinician-friendly nomogram (the CGRP Score) with external validation showing robust predictive performance.
DOI: 10.1186/s10194-025-02138-5 -
Real-World Safety and Efficacy of 156 U – 195 U OnabotulinumtoxinA in Adults With Chronic Migraine: Results From the REPOSE Study
The REPOSE study evaluates the real-world safety and efficacy of 156 U -195 U onabotulinumtoxinA in adults with chronic migraine, demonstrating significant reductions in headache days and improvements in quality of life measures over a 24-month period.
DOI: 10.1186/s12883-025-04087-7 -
Long term outcome for onabotulinumtoxinA (Botox) therapy in chronic migraine: A 2-year prospective follow-up audit of patients attending the Hull (UK) migraine clinic
Two-year real-world follow-up shows that onabotulinumtoxinA provides durable benefit for chronic migraine, with about 29% of initial responders converting to episodic migraine and substantial reductions in headache days, migraine days, crystal-clear days, HIT-6, and analgesic us…
DOI: 10.1177/2515816320985443 -
A 24-week prospective, multicenter, real-world study on eptinezumab’s effectiveness and safety in migraine prevention (EMBRACE II)
The EMBRACE II study demonstrates that eptinezumab significantly reduces migraine frequency and related disability in patients with high-frequency episodic migraine and chronic migraine over 24 weeks, particularly in those with prior treatment failures.
DOI: 10.1007/s00415-025-13095-z -
Early efficacy and late gain in chronic and high‐frequency episodic migraine with onabotulinumtoxinA
A prospective real-world cohort study following 578 migraine patients (CM and HFEM) treated with onabotulinumtoxinA over 24 months shows early (6 months) and sustained (12–24 months) improvements in headache frequency, analgesic use, and disability, with HFEM benefiting similarl…
DOI: 10.1111/ene.14028 -
Effectiveness and tolerability of rimegepant in the acute treatment of migraine: a real-world, prospective, multicentric study (GAINER study)
The GAINER study evaluates the effectiveness and tolerability of rimegepant, a novel oral CGRP receptor antagonist, in the acute treatment of migraine in a real-world setting, finding a 44.7% rate of pain freedom at 2 hours post-dose among participants.
DOI: 10.1186/s10194-024-01935-8