Does Rimegepant (gepant) have a faster onset of action or longer half-life than triptans, is it more effective than Lasmiditan (ditan), or does it frequently cause medication overuse headache?

Rimegepant vs Triptans and Lasmiditan: Comparative Analysis

Onset of Action

Rimegepant does NOT have a faster onset than triptans. Rimegepant reaches maximum concentration at 1.5 hours 1, while the most effective triptan, rizatriptan, reaches peak concentration in 60-90 minutes 2. This gives triptans a clear advantage in speed of onset, with rizatriptan achieving therapeutic levels approximately 30 minutes faster than rimegepant.

Half-Life Comparison

Rimegepant has a similar half-life to triptans, not a longer one. The elimination half-life of rimegepant is approximately 11 hours 1, which is comparable to most triptans and does not represent a clinically meaningful advantage in duration of action.

Efficacy vs Lasmiditan

Evidence is insufficient to conclude that rimegepant is more effective than lasmiditan. The 2025 American College of Physicians guidelines explicitly state that comparative evidence between rimegepant and lasmiditan is very limited, with insufficient-certainty evidence for any comparative effectiveness findings 3.

• A 2022 network meta-analysis found that efficacy outcomes (pain freedom and relief at 2,24, and 48 hours) tended to be highest for lasmiditan 200 mg and rimegepant, followed by lower doses of lasmiditan 4
• The same analysis showed rimegepant had higher rates of pain freedom and relief than lower doses of lasmiditan (50 mg and 100 mg), but the comparison with lasmiditan 200 mg was equivocal 4
• Lasmiditan 200 mg was associated with significantly higher rates of adverse events, particularly somnolence and dizziness, compared to rimegepant 4

The 2021 Nature Reviews Neurology guidelines indicate that indirect comparison of data from randomized controlled trials suggests lasmiditan efficacy is comparable to triptans 3, and since rimegepant appears less effective than triptans based on the 2025 ACP guidelines 3, this suggests lasmiditan may have a slight efficacy edge over rimegepant.

Medication Overuse Headache Risk

Rimegepant appears to have a lower risk of causing medication overuse headache compared to triptans, though definitive evidence is limited.

• A 2021 expert review states that rimegepant "does not seem to induce medication-overuse headache" 5
• The threshold for medication overuse headache is ≥10 days per month with triptans 3, while no specific threshold has been established for rimegepant
• The 2023 review notes that "the risk of developing medication overuse headache may differ between triptans, ditans and gepants, but further studies are needed to confirm this difference" 6
• Rimegepant's mechanism as a CGRP receptor antagonist (non-vasoconstrictive) theoretically carries lower risk than triptans' serotonergic mechanism 5

However, the 2025 ACP guidelines caution that patients should be aware of medication overuse headache as a potential complication of migraine treatment, defined as headache occurring on 15 or more days per month for at least 3 months due to overuse of acute medication 3.

Clinical Context

The 2025 ACP guidelines position rimegepant as a third-line option, to be considered only in patients who do not tolerate or have inadequate response to combination therapy of a triptan and an NSAID or acetaminophen 3. This positioning reflects that:

• Rimegepant monotherapy may have lower likelihood of pain freedom and relief at 2 hours compared to triptan-NSAID combination therapy 3
• The therapeutic gain of rimegepant over placebo is small 5
• Rimegepant's primary advantage is its non-vasoconstrictive mechanism, making it suitable for patients with cardiovascular contraindications to triptans 3, 5