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Triptans are a family of tryptamine-based drugs used as abortive medication in the treatment of migraines and cluster headaches. They were first introduced in the 1990s. While effective at treating individual headaches, they do not provide preventative treatment and are not considered a cure.

Triptans include sumatriptan (Imitrex, Imigran, Cinie, Illument, Migriptan), rizatriptan (Maxalt), naratriptan (Amerge, Naramig), zolmitriptan (Zomig), eletriptan (Relpax), almotriptan (Axert, Almogran), frovatriptan (Frova, Migard, Frovamig), and avitriptan (BMS-180,048).

Contents

Mechanism of action

Their action is attributed to their binding to serotonin 5-HT1B and 5-HT1D receptors in cranial blood vessels (causing their constriction) and subsequent inhibition of pro-inflammatory neuropeptide release. Evidence is accumulating that these drugs are effective because they act on serotonin receptors in nerve endings as well as the blood vessels. This leads to a decrease in the release of several peptides, including CGRP and substance P.

Discovery and development

Availability

These drugs have been available only by prescription (US, Canada and UK), but sumatriptan became available over-the-counter in the UK in June, 2006.[1] The brand name of the OTC product in the UK is Imigran Recovery. Injectable sumatriptan should be available in generic formula in early 2007 as the patent on Imitrex STATDose expires in December, 2006. Sumavel Dosepro is a needle free delivery of injectable sumatriptan that was approved in the US by the FDA in July of 2009[2]. The patent on Imitrex tablets expires in the USA in 2009, and the generic sumatriptan tablets should be available shortly thereafter. As of October 2009, Sumatriptan is over-the-counter in Romania, under the Imigran brand.

Effectiveness

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Migraines

Sumatriptan and related selective serotonin receptor agonists are excellent for severe migraines or those that do not respond to NSAIDs [3] or other over-the-counter drugs.[4] Triptans are a mid-line treatment suitable for many migraineurs with typical migraines. They may not work for atypical or unusually severe migraines, transformed migraines, or status (continuous) migraines.

Triptans are highly effective, reducing the symptoms or aborting the attack within 30 to 90 minutes in 70-80% of patients.[citation needed] Many patients have a recurrent migraine later in the day, and only one such recurrence in a day can be treated with a second dose of a triptan.

Triptan therapy has been shown to result in a reduction in lost productivity.[citation needed] Sumatriptan has been shown to result in an average of 0.5 fewer missed workdays during the first three months of therapy and 0.7 fewer missed workdays within the first six months, as well as a reduction in the number of days spent working while symptomatic.[citation needed]

The average reduction in lost productivity has been estimated at $1,249, at a cost of $25 per day of disability avoided. The annual net savings in reduced health care costs and lost productivity, over the increased cost of triptan therapy, has been estimated at between $114 and $540 per patient; thus the use of these pharmaceuticals represents a cost savings as well as an improvement in the patients' quality of life.[citation needed]

Assessment of efficacy may be contaminated by how the triptan is encapsulated in order to mask active treatment.[5]

A test measuring a person's skin sensitivity during a migraine may indicate whether the individual will respond to treatment with triptans.[citation needed] Triptans are most effective in those with no skin sensitivity; with skin sensitivity, it is best to take triptans within twenty minutes of the headache's onset.

Altitude sickness

A single randomized controlled trial found that sumatriptan may be able to prevent altitude sickness.[6]

Adverse effects

Triptans have few side effects if used in correct dosage and frequency. The most common adverse effect is recurrence of migraine. A systematic review found that "rizatriptan 10 mg was the only triptan with a recurrence rate greater than that of placebo".[7]

There is a theoretical risk of coronary spasm in patients with established heart disease, and cardiac events after taking triptans may rarely occur.[8]

There is the potential for life-threatening serotonin syndrome (a syndrome of changes in mental status, autonomic instability, neuromuscular abnormalities, and gastrointestinal symptoms) in patients taking triptans and selective serotonin reuptake inhibitors (SSRIs) or selective serotonin/norepinephrine reuptake inhibitors (SNRIs) at the same time. [9]

At least two types of triptans (sumatriptan and rizatriptan) have been listed under the unacceptable medication by the Canadian Blood Services, as a potential risk to the recipient; hence, donors are required not to have taken the medication for the last 72 hours.[citation needed]

Cost

A systematic review concluded "Triptans' cost, typically $25 USD per oral dose and $71 for injectible (2008) and up to two doses per headache, is a serious problem for low-income and middle-income patients."[7] In most non-US countries these costs are considerably lower — typically $5–10 per dose.[citation needed]

References

  1. ^ "Pharmacies to sell migraine drug". BBC NEWS. 2006-05-19. http://news.bbc.co.uk/1/hi/health/4996712.stm. Retrieved 2006-09-05. 
  2. ^ Zogenix, inc. Press release http://www.zogenix.com/index.php/news/sumavel-dosepro-sumatriptan-injection-approved-by-fda-for-acute-migraine-and-cluster-headache/
  3. ^ Brandes JL, Kudrow D, Stark SR, et al. (2007). "Sumatriptan-naproxen for acute treatment of migraine: a randomized trial". JAMA 297 (13): 1443–54. doi:10.1001/jama.297.13.1443. PMID 17405970. 
  4. ^ Lipton RB, Baggish JS, Stewart WF, Codispoti JR, Fu M (2000). "Efficacy and safety of acetaminophen in the treatment of migraine: results of a randomized, double-blind, placebo-controlled, population-based study". Arch. Intern. Med. 160 (22): 3486–92. doi:10.1001/archinte.160.22.3486. PMID 11112243. 
  5. ^ Fuseau E, Petricoul O, Sabin A, et al. (2001). "Effect of encapsulation on absorption of sumatriptan tablets: data from healthy volunteers and patients during a migraine". Clinical therapeutics 23 (2): 242–51. doi:10.1016/S0149-2918(01)80006-0. PMID 11293557. 
  6. ^ Jafarian S, Gorouhi F, Salimi S, Lotfi J (2007). "Sumatriptan for prevention of acute mountain sickness: randomized clinical trial". Ann. Neurol. 62 (3): 273–7. doi:10.1002/ana.21162. PMID 17557349. 
  7. ^ a b Pascual J, Mateos V, Roig C, Sanchez-Del-Rio M, Jiménez D (2007). "Marketed oral triptans in the acute treatment of migraine: a systematic review on efficacy and tolerability". Headache 47 (8): 1152–68. doi:10.1111/j.1526-4610.2007.00849.x. PMID 17883520. 
  8. ^ Dahlöf CG, Mathew N (1998). "Cardiovascular safety of 5HT1B/1D agonists--is there a cause for concern?". Cephalalgia : an international journal of headache 18 (8): 539–45. doi:10.1046/j.1468-2982.1998.1808539.x. PMID 9827245. 
  9. ^ US Food and Drug Administration (2006-07-19). "Information for Healthcare Professionals". Food and Drug Administration. http://www.fda.gov/CDER/Drug/InfoSheets/HCP/venlafaxineHCP.htm. Retrieved 2008-01-10. 

See also

  • Tepper S. J., Rapoport A. M. (1999). "The triptans - A summary". CNS Drugs 12 (5): 403–417. doi:10.2165/00023210-199912050-00007. 
  • Triptans: Drug Discovery and Development

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