The implications of losing treatment options: Why lasmiditan's discontinuation matters

At least once per day, a patient asks me, “What new things are available for migraine treatment?” Recently, there has been a lot to talk about regarding new treatment options. However, now it is a matter of talking about what we are losing. Over the years, treatments for migraine have come and gone. One example is isometheptene-containing medications.1 I remember patients who tracked down the remaining name brand products from any pharmacy within a few hours' radius of their home. When the name brand supplies ran out, they utilized compounding pharmacies to recreate it. When the isometheptene ran out, they were without their effective treatment and looking for something else. Unfortunately, history often repeats itself. “A business decision was made to discontinue manufacture of the 50 mg and 100 mg tablets.” Effective acute therapies for migraine are not universal, and many patients struggle with unmet needs. Lasmiditan occupied a distinctive role in migraine treatment. Unlike triptans, which can induce vasoconstriction based on their selective serotonin 5-HT1B/D receptor agonist effects, lasmiditan was not vasoactive, making it a valuable option for patients with vascular contraindications. Moreover, lasmiditan could have utility even when triptans had failed, with some studies suggesting it could relieve headache after inadequate triptan response.4 The flexibility for use as either first-line treatment or back-up treatment was precisely what made it valuable. In the GLADIATOR open-label long-term safety study, patients treated thousands of migraine attacks over a year; while side effects were reported, serious events were rare, and efficacy was consistent over time.5 The 12-month open-label extension of the CENTURION trial also showed durable quality-of-life and disability improvements, with no new safety signals.6 These data supported long-term, intermittent use and showed that lasmiditan could sustainably reduce migraine burden over time. Lasmiditan had several side effects including dizziness and sedation.7 It was classified as a Schedule V controlled substance with an 8-hour driving restriction. However, long-term extension studies indicated that many side effects decreased with repeated dosing, and discontinuation rates were modest.5 The side effects were real concerns. But these risks were known, manageable, and accepted in the context of clinical care, especially when balanced against the disability of untreated migraine. For many patients with migraine, losing lasmiditan represents not just a loss of drug, but a loss of hope. There are patients who cannot take triptans due to vascular diseases, and who also struggle with side effects or insufficient efficacy from other available treatments such as calcitonin gene-related peptide-targeted therapies or traditional analgesics. Without this option, those patients may be forced back into therapies with less favorable risk profiles. Discontinuing lasmiditan also sends a chilling signal to researchers and drug developers. As a molecule designed to avoid the cardiovascular risks inherent to older abortive drugs, the ditan class was a bold innovation. If that investment is withdrawn, the message could be that migraine drug development is less viable potentially stifling future breakthroughs. Discontinuing lasmiditan is more than a treatment option loss; it undermines the progress made by a vulnerable subgroup of patients with migraine. The headache community should not treat medication discontinuations as a footnote, but as a headline. We must protect existing options and ensure we do not close the door on future innovation. Juliana H. VanderPluym: Conceptualization; writing – original draft; writing – review and editing. This study had no funding. Juliana H. VanderPluym reports research support from Patient-Centered Outcomes Research Institute (MI-2023C2-33021) and State of Arizona (RFGA2023-008-26). She received Honoria from BMJ (for authorship and editing). She acts as Current Neurology and Neuroscience Reports, Headache Section Co-editor.