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EDITORIAL
Year : 2015  |  Volume : 63  |  Issue : 6  |  Page : 822-823

Cheaper may be safer in migraine


Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Date of Web Publication20-Nov-2015

Correspondence Address:
Jayantee Kalita
Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.170061

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How to cite this article:
Kalita J, Misra U. Cheaper may be safer in migraine. Neurol India 2015;63:822-3

How to cite this URL:
Kalita J, Misra U. Cheaper may be safer in migraine. Neurol India [serial online] 2015 [cited 2019 Dec 12];63:822-3. Available from: http://www.neurologyindia.com/text.asp?2015/63/6/822/170061


Pain is responsible for the greatest morbidity of mankind, and headache is one of the most common reasons for a visit to the physician. The estimated lifetime prevalence of headache is 66%; migraine accounts for 14%–16% of cases; tension headache, 46%–78%; and cluster headache, 0.1%–0.3%. Approximately 90% of patients suffering from migraine have moderate to severe pain, 70% have functional impairment, and 20% require bed rest during an attack. The 2012 Global Burden of Disease study placed migraine as the eighth most bothersome disease in the world and the fourth most common disease in female patients.[1] Migraine poses a huge economic burden, as headache accounts for 20% of work absence and incurs an estimated annual cost of as much as $17 billion in the United States. The greatest portion of this economic burden is due to the cost of triptans, which are used as medications for abortive treatment of the migraine attacks.

An increased sensitivity of cortical sensory neurons because of dysfunction of the monoaminergic sensory system located in the brain stem and hypothalamus is reported to be contributing to the migraine attacks. Treatment of migraine is a success story of modern medicine, in which several targeted therapies based on pathophysiology have succeeded and are in contemporary clinical practice. Dopamine receptor hypersensitivity in migraine clinically manifests with yawning, nausea, vomiting, and hypotension; therefore, a dopamine receptor antagonist is effective in migraine. Activation of trigeminal nucleus releases vasoactive calcitonin gene-related peptide (CGRP) from the nerve endings and trigeminal nuclear cells, resulting in vasodilation of meningeal vessels. CGRP antagonists, such as gepants, have been reported to be effective. Currently, other targeted molecules such as 5-hydroxytryptamine receptor (5HT)1F agonists, combination of 5HT1B/1D and nitrous oxide synthase inhibitor, transient receptor potential vanilloid receptor modulator, glutaminergic agents, as well as propofol and benzopyran derivatives are in various phases of clinical trial.[2]

Three main categories of drugs are recommended for the abortive therapy of migraine: (1) Nonsteroidal anti-inflammatory drugs (NSAIDs), (2) 5HT agonists, and (3) dopamine receptor antagonists. In the 1980s, it was observed that intravenous infusion of 5-HT (serotonin) aborted migraine attack. Till 1991, ergotamine and dihydroergotamine were the monoaminergic targeted drugs used for the abortive treatment of acute migraine. Ergotamine and dihydroergotamine are nonspecific 5HT agonists and have several side effects, such as platelet aggregation, bronchoconstriction, generalized vasoconstriction, and gastrointestinal upset. Migraine headache is primarily due to vasodilation of cranial vessels rich in 5HT1B/1D receptors. Triptans were designed to produce selective vasoconstriction of cranial vessels, such as meningeal arteries, which are inflamed and distended in migraine. Sumatriptan was first available in Europe in 1991 and revolutionized the treatment of migraine attack. Unfortunately, sumatriptan was associated with symptoms suggestive of ischemic heart disease (chest pressure, tightness, and discomfort) in 15% patients, and rarely, resulted in myocardial infarction. Moreover, in triptan responders, migraine recurs within 24 hours in up to 50% of patients. Several other triptan molecules, such as naratriptan, rizatriptan, frovatriptan, almotriptan, eletriptan, and zolmitriptan, have been developed to reduce these side effects, have a longer duration of action and, therefore, avoid recurrence to a greater extend. 5HT1B/1D receptors were initially believed to be present mainly in the cerebral vessels. Subsequently, these receptors have also been detected in the pulmonary, coronary, and other systemic blood vessels. The questions that arise include—are triptans better than ergots? Are the newer triptans more effective and safer than the older drugs? Are vascular complications in the case of triptan use due to direct vasoconstriction or due to autonomic dysfunction?In vitro and in vivo studies have shown direct coronary vasoconstriction following triptan use without any underlying pathology in the coronary artery.[3] In a study, the extent and the duration of coronary artery vasoconstriction were evaluated in vitro using all 5HT agonists (ergotamine, dihydroergotamine) and 5HT1B/1D agonists (sumatriptan, naratriptan, rizatriptan, avitriptan, zolmitriptan). Compared with sumatriptan, all other drugs were more potent (contracting at lower EC50 [half maximal effective concentration; concentration eliciting 50% of its own Emax] values) in contracting the coronary arteries but had similar efficacy (Emax, maximum contraction). Ergotamine- and dihydroergotamine-treated coronary artery had sustained contraction for up to 90 minutes even after washout, which was only 30 minutes for triptans.[4] This study focuses on similar coronary complication related to triptans. Ditans, an exclusive neural 5HT1F agonist, has been developed to avoid the systemic complications of triptans and may be promising for the acute and preventive treatment of migraine.

In this issue of Neurology India, Kilit et al., have reported the effect of zolmitriptan on cardiac autonomic modulation in patients with migraine in a double-blind, placebo-controlled, crossover study in 10 patients. The investigators measured domain parameters (mean R-R interval, root mean square of R-R interval difference) and frequency domain parameters (low frequency, high frequency, low frequency/high frequency ratio) of heart rate variability. These parameters were measured in supine position, controlled respiration, and hand grip exercise, before and 2 hours after 2.5 mg of zolmitriptan and placebo administration, for the detection of sympathetic and parasympathetic activity. They did not find any difference in the heart rate variation parameter in the zolmitriptan and control groups.[5] Heart rate variation can occur in autonomic dysfunction, smokers, diabetic patients, and those with myocardial ischemia. The sensitivity and specificity of heart rate variations in detecting myocardial ischemia are not very high. Therefore, mild coronary spasm or cardiac ischemia may be missed in their evaluation. Moreover, chronic migraine attacks are known to be associated with autonomic dysfunction, which may result in heart rate variation. In view of these concerns, triptans have been recommended as a second-line drug for aborting migraine attacks.[6] The first-line abortive medicines such as ibuprofen 400 mg, acetyl salicylic acid 1000 mg, naproxen sodium 500–550 mg, or acetaminophen 1000 mg are better, cheaper, and safer, provided they are used judiciously. The concern regarding medication-overuse headache is equally common with NSAIDs and triptans. The search for newer, more effective, and safer drugs has to go on, but at the present stage of knowledge, we believe that cheaper medications may be better in aborting a migraine attack.

 
  References Top

1.
Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: A systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380:2163-96.  Back to cited text no. 1
[PUBMED]    
2.
Diener HC, Charles A, Goadsby PJ, Holle D. New therapeutic approaches for the prevention and treatment of migraine. Lancet Neurol 2015;14:1010-22.  Back to cited text no. 2
    
3.
Pacheco-Coronado R, McMullan PW, Galbut BH, Galbut EJ, Snell J, Schaer GL, et al. Myocardial infarction after taking zolmitriptan. Yale J Biol Med 2005;78:147-50.  Back to cited text no. 3
    
4.
MaassenVanDenBrink A, Reekers M, Bax WA, Ferrari MD, Saxena PR. Coronary side-effect potential of current and prospective antimigraine drugs. Circulation 1998;98:25-30.  Back to cited text no. 4
    
5.
Kilit C, Oruc S, Kilit TP, Onrat E. The effect of zolmitriptan on cardiac autonomic modulation in patients with migraine: A double-blind, placebo-controlled, crossover study. Neurol India 2015;63:861-6.  Back to cited text no. 5
    
6.
Becker WJ, Findlay T, Moga C, Scott NA, Harstall C, Taenzer P. Guideline for primary care management of headache in adults. Can Fam Physician 2015;61:670-9.  Back to cited text no. 6
    




 

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