Ditans
Posted on June 07 2025,
Ditans
The first medication in a class that targets serotonin receptors without cardiovascular risks
A New Era in Migraine Treatment
Ditans are a relatively new class of migraine medications that offers hope for those who cannot use traditional treatments.
What Makes Ditans Different?
Unlike triptans, which can cause blood vessel constriction, ditans work through a completely different mechanism that doesn't affect cardiovascular function, making them suitable for patients with heart conditions.
Lasmiditan, marketed under the brand name Reyvow, is currently the only FDA-approved medication in the ditan class. This treatment has opened new possibilities for migraine management, especially for patients who have been unable to use triptans due to cardiovascular contraindications.
Understanding How Ditans Work
Let's start by exploring how they differ from existing migraine treatments at the molecular level.
Mechanism of Action: Targeting the Right Receptors
5-HT₁F Receptor
Targeted by Ditans
→
Pain Relief
Without Vasoconstriction
5-HT₁F Receptors: The Key to Understanding Ditans
The 5-HT₁F receptor is a specific type of serotonin receptor found primarily in the brain and trigeminal system. Unlike other serotonin receptors targeted by triptans (5-HT₁B and 5-HT₁D), the 5-HT₁F receptor doesn't cause blood vessel constriction when activated. This selective targeting is what makes ditans cardiovascular-safe.
Ditans work by selectively binding to 5-HT₁F receptors, which are located in key areas involved in migraine pain processing. This includes the trigeminal ganglion and brainstem regions that control pain signaling. When activated, these receptors help interrupt the pain signals associated with migraine attacks without affecting blood vessel function.
Lasmiditan: The First Ditan in Clinical Practice
Lasmiditan has undergone extensive clinical testing through multiple phases of trials, demonstrating both efficacy and safety across diverse patient populations.
3
Phase III Trials
SAMURAI, SPARTAN, and CENTURION studies validated lasmiditan's effectiveness
32%
Pain Freedom at 2 Hours
With 200 mg dose compared to 15% with placebo
54%
Pain Relief at 2 Hours
Significant improvement from moderate-severe to mild-none
1.8h
Peak Plasma Concentration
Rapid absorption for timely migraine relief
Key Clinical Trial Results
SAMURAI Trial Results
100 mg Lasmiditan Pain Freedom 28%
200 mg Lasmiditan Pain Freedom 32%
Placebo Pain Freedom 15%
Most Bothersome Symptom Relief 41% (200 mg)
The SAMURAI trial, one of the pivotal Phase III studies, demonstrated that lasmiditan significantly outperformed placebo in achieving both pain freedom and relief from the most bothersome migraine symptoms at 2 hours post-dose. Importantly, nearly 80% of participants had at least one cardiovascular risk factor, proving the medication's safety in this vulnerable population.
Clinical Dosing and Administration
Lasmiditan is available in two tablet strengths, allowing for personalized treatment approaches based on individual patient needs and tolerability.
Available Dosing Options
- 50 mg tablets: Starting dose for patients new to lasmiditan or those sensitive to CNS effects
- 100 mg tablets: Standard effective dose with good tolerability profile
- 200 mg dose: Maximum dose for optimal efficacy (given as two 100 mg tablets), shown most effective in clinical trials
Clinical trials have shown a clear dose-response relationship, with higher doses providing greater efficacy. However, the optimal dose for each patient should be determined individually, considering both effectiveness and tolerability. Patients can take a second dose if the initial dose is insufficient, but should not exceed 200 mg in a 24-hour period.
Pharmacokinetic Profile
Time to Peak Concentration 1.8 hours
Protein Binding 55-60%
Food Effect Minimal Impact
Metabolism Hepatic
Safety Profile and Side Effects
Like all medications, lasmiditan does have side effects that patients and healthcare providers should understand.
Important CNS-Related Side Effects
The most common side effects of lasmiditan are related to the central nervous system and include dizziness, somnolence (sleepiness), fatigue, and paresthesia (tingling sensations). These effects are dose-dependent and typically occur within the first 2 hours after taking the medication.
Common Side Effects by Frequency
17%
Dizziness
Most common side effect with 200 mg dose, typically lasting 1.5-2 hours
7%
Somnolence
Sleepiness that may impair driving ability
5%
Fatigue
General tiredness reported by patients
9%
Paresthesia
Tingling sensations, usually mild and transient
Driving and Operating Machinery
Due to CNS effects, patients should not drive or operate machinery for at least 8 hours after taking lasmiditan. Clinical studies have shown impaired driving performance on simulator assessments, making this precaution essential for patient safety.
Importantly, unlike triptans, lasmiditan has not been associated with cardiovascular adverse events such as chest pain, blood pressure changes, or cardiac rhythm abnormalities. This makes it particularly valuable for patients with coronary artery disease, uncontrolled hypertension, or other cardiovascular conditions.
Who Can Benefit from Ditans?
Lasmiditan is a significant advancement for specific patient populations who have been underserved by traditional migraine treatments.
Ideal Candidates for Lasmiditan
Cardiovascular Disease Safe to Use
Uncontrolled Hypertension Safe to Use
Triptan Non-Responders Alternative Option
Elderly Patients Fewer Restrictions
Patients who have not responded well to triptans or have experienced intolerable side effects may find lasmiditan to be an effective alternative.
"Lasmiditan is an important new option for people with migraine who couldn't use many older medications because of heart problems. It offers new hope for millions who previously had very few treatment choices." - Cerebral Torque
Long-Term Use and Consistency of Effect
The GLADIATOR study provided valuable insights into the long-term use of lasmiditan, demonstrating sustained efficacy over extended periods.
GLADIATOR Study Key Findings
- Duration: 12-month open-label follow-up study
- Participants: Over 2,000 patients from previous clinical trials
- Completion Rate: 41.2% completed 12 months of treatment
- Discontinuation Rate: 22% due to personal decision, 13% due to adverse events
- Safety Profile: Consistent with previous trials, no new safety signals
The CENTURION study specifically evaluated the consistency of lasmiditan's effects across multiple migraine attacks. Participants treated four separate migraine episodes, with results showing sustained efficacy across all treated attacks. This consistency is crucial for patients who need reliable acute treatment for their recurring migraines.
41%
GLADIATOR Completion
12-month completion rate with good tolerability
4
Attacks Studied
CENTURION evaluated consistency across multiple episodes
Comparison with Other Acute Migraine Treatments
This comparison highlights the key differences between ditans and other acute migraine medications
| Treatment Class | Mechanism & Clinical Profile |
|---|---|
| Ditans (Lasmiditan) |
5-HT₁F receptor selective agonist
|
| Triptans |
5-HT₁B/1D receptor agonists
|
| CGRP Antagonists (Gepants) |
Block CGRP receptor activity
|
| NSAIDs/Analgesics |
|
Clinical Considerations and Patient Selection
The decision to prescribe lasmiditan should be based on careful consideration of patient-specific factors, including migraine characteristics, comorbidities, and previous treatment responses.
Clinical Decision Points
- Cardiovascular Risk Assessment: Lasmiditan is preferred for patients with known cardiovascular disease or multiple risk factors
- Occupation Considerations: CNS side effects may impact patients in safety-sensitive jobs
- Migraine Severity: Most effective for moderate-to-severe attacks requiring acute intervention
- Previous Treatment Failures: Viable option for triptan non-responders or those with contraindications
Prescribing Recommendations
Starting Dose 50-100 mg
Maximum Single Dose 200 mg (as two 100mg tablets)
Maximum Daily Dose 200 mg
Driving Restriction 8 hours post-dose
Healthcare providers should discuss the CNS side effect profile with patients and ensure they understand the driving restrictions. Patients should be advised to take lasmiditan when they can remain in a safe environment for several hours after dosing, especially when first starting treatment or adjusting doses.
Future Directions in Ditan Development
While lasmiditan is a significant breakthrough, research into the ditan class continues, with potential for additional medications and delivery methods in development.
Beyond Lasmiditan: The Future of Ditans
Researchers are exploring other selective 5-HT₁F receptor agonists that may offer improved side effect profiles or different pharmacokinetic properties. Additionally, investigations into combination therapies and alternative delivery methods (such as intranasal formulations) are ongoing.
The success of lasmiditan has validated the 5-HT₁F receptor as an important therapeutic target for migraine. This has opened new avenues for drug development, potentially leading to additional treatment options that could further expand the management arsenal.
Research Areas of Interest
- Novel Formulations: Investigating faster-acting delivery methods
- Combination Therapies: Exploring synergistic effects with other migraine medications
- Preventive Applications: Research into whether 5-HT₁F agonism could have preventive benefits
- Pediatric Applications: Studies to establish safety and efficacy in younger patients
Patient Education and Expectations
Successful treatment with lasmiditan requires proper patient education about what to expect, how to use the medication effectively, and when to seek medical attention.
Important Patient Counseling Points
- Timing: Take at the onset of a migraine attack, not as a preventive measure
- Driving: Do not drive or operate machinery for 8 hours after taking lasmiditan
- Alcohol: Avoid alcohol consumption as it may enhance CNS side effects
Patients should be counseled on realistic expectations for treatment outcomes. While lasmiditan is highly effective, not every patient will achieve complete pain freedom, and individual responses may vary. The goal is meaningful pain reduction and functional improvement that allows patients to resume normal activities.
Economic Considerations and Access
As with any medication, cost and insurance coverage considerations play important roles in patient access to lasmiditan therapy.
$$
Brand Medication Cost
Higher cost than generic triptans but may be cost-effective for appropriate patients
PA
Prior Authorization
Many insurance plans require documentation of triptan contraindications or failures
Healthcare providers may need to provide documentation of medical necessity, particularly for patients with cardiovascular contraindications to triptans or those who have failed multiple triptan trials. Patient assistance programs may be available to help reduce out-of-pocket costs for eligible individuals.
Summary
- New treatment option available for those who cannot use traditional triptans
- Effective pain relief without cardiovascular side effects
- Important to follow driving and safety restrictions
- Work with healthcare provider to determine optimal dosing
As our understanding of migraine pathophysiology continues to evolve, ditans are just one example of how targeted therapeutic approaches can provide new hope for patients. The success of lasmiditan validates the importance of continued research into novel mechanisms for migraine treatment and highlights the value of developing medications that address the specific needs of diverse patient populations.
Medical Disclaimer
This article is for educational purposes only and should not replace professional medical advice. Always consult with your healthcare provider before starting, stopping, or changing any medication. Individual responses to treatment may vary, and what works for one person may not work for another. If you experience severe side effects or your migraine attacks worsen, seek immediate medical attention.
References
- Kuca, B., Silberstein, S. D., Wietecha, L., Berg, P. H., Dozier, G., & Lipton, R. B. (2018). Lasmiditan is an effective acute treatment for migraine: A phase 3 randomized study. Neurology, 91(24), e2222–e2232.
- Goadsby, P. J., Wietecha, L. A., Dennehy, E. B., Kuca, B., Case, M. G., Aurora, S. K., & Gaul, C. (2019). Phase 3 randomized, placebo-controlled, double-blind study of lasmiditan for acute treatment of migraine. Brain, 142(7), 1894–1904.
- Brandes, J. L., Klise, S., Krege, J. H., Case, M., Khanna, R., Vasudeva, R., Raskin, J., Pearlman, E. M., & Kudrow, D. (2019). Interim results of a prospective, randomized, open-label, Phase 3 study of the long-term safety and efficacy of lasmiditan for acute treatment of migraine (the 'GLADIATOR' study). Cephalalgia, 39(11), 1343–1357.
- Färkkilä, M., Diener, H. C., Géraud, G., Láinez, M., Schoenen, J., Harner, N., Pilgrim, A., & Reuter, U. (2012). Efficacy and tolerability of lasmiditan, an oral 5-HT 1F receptor agonist, for the acute treatment of migraine: A phase 2 randomised, placebo-controlled, parallel-group, dose-ranging study. The Lancet Neurology, 11(5), 405–413.
- Pearlman, E. M., Wilbraham, D., Dennehy, E. B., Berg, P. H., Tsai, M., Doty, E. G., & Rey, G. G. (2020). Effects of lasmiditan on simulated driving performance: Results of two randomized, blinded, crossover studies with placebo and active controls. Human Psychopharmacology, 35(5).
- Lamb, Y. N. (2019). Lasmiditan: First approval. Drugs, 79(18), 1989–1996.
- Nelson, D. L., Phebus, L. A., Johnson, K. W., Wainscott, D. B., Cohen, M. L., Calligaro, D. O., & Xu, Y. C. (2010). Preclinical pharmacological profile of the selective 5-HTTIF receptor agonist lasmiditan. Cephalalgia, 30(10), 1159–1169.
- Krege, J. H., Rizzoli, P. B., Liffick, E., Doty, E. G., Dowsett, S. A., Wang, J., & Buchanan, A. S. (2019). Safety findings from Phase 3 lasmiditan studies for acute treatment of migraine: Results from SAMURAI and SPARTAN. Cephalalgia, 39(11), 1378–1393.
- Rubio-Beltrán, E., Labastida-Ramírez, A., Villalón, C. M., & MaassenVanDenBrink, A. (2018). Is selective 5-HT1F receptor agonism an entity apart from that of the triptans in antimigraine therapy? Pharmacology & Therapeutics, 186, 88–97.
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