Treating Migraine with Confidence
Legacy therapies for migraine, including both acute and preventative treatments, have not changed significantly in recent years, although our understanding of migraine as a condition has grown.
Migraine is a serious neurological disease, with underlying mechanisms that may have serious implications to overall health risks, particularly those associated with coronary artery disease (CAD) events.
An analysis of insurance claims data from the PharMetrics database by IMS Health indicates that treatment rates are lower among migraine patients with high risk for a CAD events—47% compared to 53% among those who have less risk. They are also less likely to be treated with a triptan and more likely to be given opioid treatments.1
The concern over triptan use in people who have had a previous CAD event or those who have multiple risk factors for a future event has contributed to a pool of 52% of adult diagnosed patients who are left untreated (by standard legacy therapies) for migraine.
Of those who are given triptan therapies, 76%—or 2.8 million patients—carry some degree of risk that warns against or contraindicates the use of these therapies.
These data suggest that large numbers of patients with migraine are not well served by current therapies—and need effective alternatives.
Triptans were specifically developed for the acute treatment of migraine with the belief that their vasoconstrictive properties would eliminate the pressure on nerves that caused migraine pain. Triptans have been shown to be effective in some persons with migraine, but the vasoconstrictive mechanism of action increases concern for patients with known cardiovascular risk factors.
For persons with migraine who cannot take triptans due to side effects or lack of response, or those who should not take triptans due to contraindications, new therapies in development, like lasmiditan, may offer efficacy for the acute treatment of migraine without vasoconstrictive concerns.
- Migraine is considered a multisystem neurological disease that originates in the brain.
- The pathophysiology of migraine is not fully understood; however, collective evidence supports a multifactorial etiology involving both the peripheral and central nervous systems causing activation of the trigeminovascular system.
Causes of Migraine Pain
- Brainstem activation is believed to be a source of migraine pain.2
- Some research has indicated that the pain of migraine may be partially mediated by stimulation of secondary pain pathways of the trigeminothalamic system during a migraine attack.3
Other Component Factors in Migraine1
- A dopaminergic hypersensitivity has been proposed as a potential mechanism for secondary symptoms of migraine, including nausea, vomiting, yawning, irritability, hypotension, and hyperactivity.4
- Neuronal hyper excitability leading to susceptibility of migraine may be largely genetic: 80% of people with migraine have a family history of migraine.5
- Serotonin receptors 5-hydroxytryptamin (5-HT) subtypes have long been identified in trigeminal sensory neurons as part of a signature pathway in migraine.
- Triptan activity is mediated via selective 5-HT1B/D agonist effects.
- Lasmiditan activity is mediated via selective 5-HT1F agonist effects.
- Medscape: http://emedicine.medscape.com/article/1142556-overview#a3
- Weiller C, May A, Limmroth V, et al. Nat Med. 1995.
- Burstein R, Yarnitsky D, Goor-Aryeh et al. Ann Neurol. 2000..
- Peroutka SJ. Neurology. 1997.
- American Headache Society. Friedman 2016.
Vascular Theories of Migraine
Before the advent of sophisticated imaging technologies available today, migraine could only be clinically reported. The early theories of vasodilatory mechanisms of migraine were originally developed by Harold Wolff in the 1930s to 1960s, from experiments showing the vasodilation of intracranial vessels in attacks, and the effects of vasoconstrictor ergotamine medications and vasodilators such as nitroglycerine on migraine.1
The vascular theory was the basis for the development of triptan therapies for migraine; however, it is inadequate to explain migraine aura and other prodromal features, as well as the associated signs of nausea and vomiting, and visual and auditory disturbances. Imaging studies also indicated that intracranial blood flow patterns before and during migraine attacks were largely inconsistent with the vascular theories of migraine.2
- Eadie MJ. J Clin Neurosci. 2005.
- May A, Goadsby PJ.. J Cereb Blood Flow Metab. 1999.
Migraine and Stroke
A diagnosis of migraine by itself is a risk factor for stroke, occurring separately from an attack. A report published by the American Headache society states that one-third of people with stroke report a history of migraine.1 The risk is doubled in migraine with aura, and increases with other risk factors including smoking and the use of combination oral contraceptives.2
- American Headache Society Fact Sheet.
- Schürks M, Rist PM, Bigal ME et al. BMJ. 2009.
NSAIDS and Risks of Heart Attack and Stroke
In July of 2015, the U.S. Food & Drug Administration (FDA) strengthened its warnings1 on the use of nonsteroidal anti-inflammatory drugs (NSAIDs) after identifying an elevated risk of heart attack and stroke to NSAID use, even for those who have no known heart disease or stroke risk factors.
The FDA warning recommended that physicians “prescribe NSAIDs with caution, and consider other treatment options, especially for longer term treatment," and further, that NSAIDs should be used for the shortest possible duration, in the lowest effective doses.
The report indicated that heart attack or stroke risk can occur as early as a few weeks after beginning NSAIDs, and longer use may further increase risk. Use of NSAIDs after a heart attack raises risk of death within the first year. The use of NSAIDs also increases the chances of developing heart failure. It is unknown if some NSAIDs are riskier than others.
FOR MORE INFORMATION ON NSAIDS CLICK HERE.
Source: FDA Safety Announcement, 2015.