What differences do ditans such as lasmiditan have compared to triptans for the treatment of migraine attacks?

Triptans are selective 5-HT 1B/D receptor agonists. They inhibit neurogenic inflammation and have a vasoconstricting effect. These vasoconstrictive properties give rise to contraindications in coronary heart disease, heart attack, stroke and other vascular diseases. Triptans should also not be used during the aura phase of the migraine attack. Renal insufficiency is also a contraindication. The development of Ditane aimed to provide acute migraine medications without these contraindications. By activating the 5-HT 1F receptor in the trigeminal ganglion and caudal trigeminal nucleus, dural plasma protein extravasation and c-Fos induction in the caudal nucleus of the trigeminal nerve can be inhibited. In contrast to triptans, lasmiditan activates the 5-HT 1F receptor with high affinity and high selectivity, without having the mentioned contraindications of triptans. The cardiovascular safety of lasmiditan has been extensively evaluated in phase 3 trials for the treatment of acute migraine attacks. The Spartan study included patients with migraine and concurrent cardiovascular comorbidities such as coronary heart disease, cardiac arrhythmias, and poorly controlled arterial hypertension. Cardiovascular adverse events occurred in 0.9% with lasmiditan treatment and 0.4% with placebo treatment. The most common symptoms were palpitations, tachycardia and increased heart rate. Severe liver dysfunction, pregnancy and breastfeeding are contraindications. In contrast to triptans, impaired kidney function is not a contraindication. Common side effects of lasmiditan include drowsiness, sleepiness, incoordination, vision problems, dizziness, vomiting, muscle weakness, and fatigue. Lasmiditan therefore has a significant influence on the ability to drive and use machines. Patients must therefore be advised not to engage in any activity requiring increased caution for at least 8 hours after each dose of lasmiditan.

What is the current value of Ditane in practice?

Indirect comparisons of the effectiveness of lasmiditan compared to the triptans show similar effectiveness. In terms of tolerability and cost-effectiveness, lasmiditan can be used for patients who cannot adequately treat migraine attacks with analgesics or triptans or who have contraindications to their use. Due to the lack of vasoconstrictor properties, lasmiditan can be used in cardiovascular contraindications to triptans. It can also be used during the aura phase. This represents a therapeutic option for patients who have severe and prolonged auras. Its use in cases of renal insufficiency can also be considered.

What relevance do gepantes have in the acute treatment of migraines?

Gepante acts as antagonists at the CGRP receptor. They are small molecules that can be administered orally. In Europe, rimegepant and in the USA, rimegepant and ubrogepant are approved for the treatment of acute migraine attacks. Rimegepant is also approved for migraine prophylaxis. The effectiveness and tolerability of atogepant for migraine prophylaxis is being investigated. Rimegepant demonstrated pain relief 2 hours after taking the dose in 19.6% and placebo in 12% of treated patients. The most common side effects are nausea, urinary tract infections and dizziness. When comparing the effectiveness of Gepante as acute medication, ubrogepant and rimegepant show a therapeutic benefit in phase 3 studies, which is the difference between the effectiveness of verum minus placebo, of 5-10% in terms of freedom from pain after 2 hours. The therapeutic benefit for triptans after 2 hours is between 16% and 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, have a therapeutic benefit of between 11% and 13%. These comparisons show that triptans continue to be standard in the acute treatment of migraines. The new drug group Ditane and Gepante may be helpful in the treatment of acute migraine attacks for patients who do not respond to triptans, who have contraindications to triptans or who cannot tolerate them. It is still unclear how high the risk of developing a medication overuse headache is. Data from comparative studies are not yet available.