News Release

New drug for migraine treatment: Telcagepant

Peer-Reviewed Publication

The Lancet_DELETED

A new drug for migraine treatment, telcagepant, is in the final stages of development. This new drug relieves pain to a similar extent as currently available migraine drugs such as triptans, but does not cause constriction of the blood vessels (vasoconstriction), making it suitable for use in people with cardiovascular disease as well as the general population. Furthermore, topiramate—an anti-epileptic drug currently a first-line treatment for migraine treatment in many countries—could also be used prophylactically to prevent migraine attacks in people with chronic migraine. The issues are discussed in a New Drug Class paper published Online First and in an upcoming Lancet. The paper is written by Professor Lars Edvinsson, University Hospital, Lund, Sweden, and Dr Mattias Linde, Norwegian University of Science and Technology, and St Olavs Hospital, Trondheim, Norway.

Telcagepant represents a new class of antimigraine drug—the calcitonin-gene-related peptide (CGRP) receptor blockers. This compound exerts its effects by blocking receptors for the calcitonin-gene-related peptide at several sites in the trigeminal nerves and central nervous system, thereby interrupting the metabolic process causing the pain and resulting in pain relief. The common adverse effects caused by telcagepant include dry mouth, dizziness, nausea, fatigue, and drowsiness.

Triptans, which act on serotonin receptors, are currently deemed the best acute migraine-specific treatment, and have provided relief to many patients; these drugs are generally well tolerated but are not without shortcomings. In a meta-analysis of migraine treatment with triptans, up to a third of all people with migraine and 40% of all migraine attacks did not respond to these drugs. Use of triptans is also associated with a range of adverse effects: dizziness, paraesthesia (tingling/numbness in the skin), throat tightness, and chest discomfort. The authors say: "Notably, these compounds are contraindicated in individuals with active cardiovascular disease and uncontrolled hypertension, because they can sometimes cause coronary and cerebral artery vasoconstriction."

The authors add that the most important advance in migraine prophylaxis has been the introduction of topiramate, and explain the rationale for the use of this antiepileptic drug in migraine in part by the hypothesis that migraine and epilepsy share several pathogenic mechanisms. Thus although topiramate is an old drug, its use in migraine prophylaxis is a new indication, hence its inclusion in this New Drug Class paper. Topiramate in migraine prevention is associated with a lowered use of health-care resources, and it seems to be a cost-effective intervention for prevention of migraine relative to no preventive therapy at all. Topiramate, unlike other migraine drugs, tends to cause weight loss rather than gain, in two out of every three patients. Mean weight loss is around 2.5 kg in clinical trials, with around 10% of patients losing 10% or more of their initial bodyweight.

The authors conclude: "The clinical trials we have reviewed provide evidence that CGRP receptors are important molecular targets for development of antimigraine drugs. Telcagepant seems to be one such promising compound, although further investigation is warranted to firmly establish its role... Outstanding questions include whether CGRP-receptor antagonists can be combined with triptans to give more effective therapy and whether they will be of value in patients who do not respond to a triptan. Additionally, effectiveness of triptans in children has not been proven, a group that might benefit after such research... Topiramate is a first-line migraine preventive drug in many countries and should especially be considered for adult patients who are overweight, or have epilepsy or a contraindication to β-blockers. It is generally safe and well tolerated. Data suggest that topiramate could reverse chronic migraine with or without drug overuse to episodic migraine. Thus topiramate is an important drug for difficult cases."

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Professor Lars Edvinsson, University Hospital, Lund, Sweden. T) +46 46171484 / +46 703271484 E) lars.edvinsson@med.lu.se

For full New Drug Class, see: http://press.thelancet.com/ndcmigraine.pdf


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