What are the differences between ditans like lasmiditan and triptans in the treatment of migraine attacks?

Triptans are selective 5-HT1B /D receptor agonists. They inhibit neurogenic inflammation and have a vasoconstrictive effect. These vasoconstrictive properties justify contraindications in cases of coronary artery disease, myocardial infarction, stroke, and other vascular diseases. Triptans should also not be used during the aura phase of a migraine attack. Renal insufficiency is another contraindication. The development of ditans aimed to provide acute migraine medications without these contraindications. By activating the 5-HT1F receptor in the trigeminal ganglion and the caudal trigeminal nucleus, ditans can inhibit dural plasma protein extravasation and c-Fos induction in the caudal nucleus of the trigeminal nerve. Unlike triptans, lasmiditan activates the 5-HT1F receptor with high affinity and high selectivity , without exhibiting the contraindications of triptans. The cardiovascular safety of lasmiditan was thoroughly investigated in phase 3 trials for the treatment of acute migraine attacks. The Spartan trial included patients with migraine and concomitant cardiovascular comorbidities, such as coronary artery disease, cardiac arrhythmias, and poorly controlled hypertension. Cardiovascular adverse events occurred in 0.9% of patients treated with lasmiditan and in 0.4% of patients treated with placebo. The most common symptoms were palpitations, tachycardia, and increased heart rate. Severe hepatic impairment, pregnancy, and breastfeeding are contraindications. Unlike triptans, impaired renal function is not a contraindication. Common side effects of lasmiditan include drowsiness, sleepiness, impaired coordination, blurred vision, dizziness, vomiting, muscle weakness, and fatigue. Lasmiditan therefore significantly impairs the ability to drive and operate machinery. Patients must be advised to refrain from any activity requiring increased caution for at least 8 hours after each dose of lasmiditan.

What is the current significance of the Ditane in practice?

Indirect comparisons of the efficacy of lasmiditan versus triptans show similar efficacy. In terms of tolerability and cost-effectiveness, lasmiditan can be used for patients whose migraine attacks cannot be adequately controlled with analgesics or triptans, or for whom their use is contraindicated. Due to its lack of vasoconstrictive properties, lasmiditan can be used in patients with cardiovascular contraindications to triptans. It can also be used during the aura phase, providing a treatment option for patients with severe and prolonged auras. Furthermore, its use in patients with renal insufficiency can be considered.

What relevance do gepantes have in the acute therapy of migraine?

Gepants act as antagonists at the CGRP receptor. They are small molecules that can be administered orally. In Europe, rimegepant is approved for the treatment of acute migraine attacks, and in the USA, both rimegepant and ubrogepant are approved. Rimegepant is also approved for migraine prophylaxis. The efficacy and tolerability of atogepant for migraine prophylaxis are currently being investigated. Two hours after administration, rimegepant showed pain relief in 19.6% of treated patients, compared to 12% with placebo. The most common side effects are nausea, urinary tract infections, and dizziness. In phase 3 trials comparing the efficacy of gepants as acute medications, ubrogepant and rimegepant demonstrated a therapeutic benefit, defined as a 5-10% difference in pain relief after two hours between the active treatment and placebo. The therapeutic benefit of triptans after 2 hours ranges from 16% to 32% (sumatriptan, eletriptan, and rizatriptan). Non-specific analgesics such as acetylsalicylic acid or diclofenac, which were not specifically developed for the treatment of migraine attacks, show a therapeutic benefit of between 11% and 13%. These comparisons demonstrate that triptans remain the standard of care in the acute treatment of migraine. The newer drug classes of ditans and gepants can be helpful in treating acute migraine attacks for patients who do not respond to triptans, have contraindications for triptans, or cannot tolerate them. The risk of developing medication-overuse headache remains unclear. Data from comparative studies on this topic are not yet available.