An Overview of the Treatment Options for Acute Migraine was superior to rectal sumatriptan.24 Formulations containing


NSAIDs (ASA or paracetamol) with metoclopramide are available in some countries, and paracetamol (1,000 mg) in association with metoclopramide (10 mg) is superior to placebo.25–27


Furthermore, the


combination of ASA or paracetamol with caffeine has been shown to be more effective than simple analgesics.


Specific Anti-migraine Drugs Ergot Derivatives


Ergotamine, introduced in 1926 by Maier,28 was the first drug used for


migraine attack treatment. In many countries it is the most widely used specific symptomatic migraine drug, probably because it is inexpensive and has a long duration of action. This drug is used in the treatment of long-lasting attacks with headache recurrence. However, ergotamine can no longer be considered the drug of choice as it carries a high risk of overuse, especially when combined with caffeine; indeed, the addition of caffeine enhances the absorption and possibly the vasoconstrictor action of ergotamine. The drug is associated with a high generalised vasoconstrictor effect if dosing is not carefully monitored.


Like the triptans, ergot derivatives exert an agonist action on serotonin (5-HT) receptors, and this is the reason for their anti-migraine effect. Because of their complex pharmacology and interaction with many other receptors (5-HT1A, 5-HT5, 5-HT2, 5-HT7, α-adrenoceptors and dopamine D2 receptors) beyond their long duration of action, they generate frequent and varied adverse effects (nausea and vomiting are the most common, but also cramps, sleepiness and transient lower limb muscle pain). The powerful and spreading vasoconstrictor action of ergotamine also underlies its contraindications (cardiac and peripheral vascular diseases, hypertension, liver and kidney diseases, sepsis, peptic ulcer, concomitant use of triacetyloleandomycin, pregnancy).


Dihydroergotamine (DHE) is usually better tolerated than ergotamine but has poor oral bioavailability, which reduces its efficacy. Intranasal DHE has better bioavailability (about 40 %) but its onset of action is relatively slow and in two trials, in which it was compared with intranasal and subcutaneous sumatriptan, it was clearly shown to be inferior to the triptan.29,30


Parenteral DHE, i.e. an injectable,


intravenous and subcutaneous solution, is more effective in severe migraine attacks but produces more side effects;31


furthermore, in


comparison with sumatriptan, it showed lower efficacy for the first two hours, even though it was apparently comparable thereafter.32


Triptans


Since their advent, more than 10 years ago, the triptans, a class of selective and highly effective 5-HT1B/1D receptor agonists, have largely replaced the ergot derivatives. They are potent vasoconstrictors that seem to act on migraine by three main mechanisms: 1) intracranial extracerebral vasoconstriction and inhibition of neurotransmitter release at 2) peripheral as well as 3) central trigeminal nociceptive terminals, mainly via 5-HT1B/1D receptors (trigeminovascular afferents and trigeminal nucleus caudalis).33


Sumatriptan was the pioneer


triptan. Later came the development of newer 5-HT1B/1D receptor agonists (zolmi-, nara-, riza-, ele-, almo- and frovatriptan). Known as the second-generation triptans, these drugs effectively penetrate the blood–brain barrier, binding to key structures in central nociceptive areas.6


Although currently available in various formulations (tablets, nasal spray, subcutaneous injection, suppositories), most triptans are effective by the oral route of administration (see Table 3). Sumatriptan offers the most flexibility of formulation.


EUROPEAN NEUROLOGICAL REVIEW


Untreated arterial hypertension, coronary heart disease, Raynaud’s disease, a history of ischaemic stroke, pregnancy, breastfeeding and severe liver or renal failure contraindicate the use of triptans. The administration of other vasoconstrictors, such as ergotamine and its derivatives and also other triptans, is contraindicated within 24 hours of taking a triptan.


Despite the improved pharmacokinetics and pharmacodynamics of this drug class, up to 40 % of all attacks and up to 25 % of patients still fail to respond to triptans. Moreover, headache recurrence (return of pain after initial treatment success) can occur in about 15–40 % of patients taking oral triptans. Criteria for measuring the efficacy of triptans include: degree of pain relief, pain freedom at two hours, sustained pain freedom (pain-free at two hours plus no use of rescue medication and no recurrence within 24 hours) and sustained pain freedom associated with no adverse events. Sustained pain freedom is now widely considered the outcome that most closely reflects patient expectations.34


If switching triptans fails to produce the desired effectiveness, the efficacy of treatment with these drugs could be improved by adding


267


Table 2: Recommended Antiemetics Antiemetic


Prochlorperazine Domperidone


Metoclopramide


Available Strengths and Formulations Tablets 3 mg


Tablets 10 mg or suppositories 30 mg Tablets 10 mg or oral solution 5 mg/5 ml


Table 3: Triptans – Routes of Administration and Recommended Doses


Drug Sumatriptan


Available Formulations Recommended Doses (mg) Tablet


Nasal spray Suppository


Zolmitriptan Eletriptan


Almotriptan Rizatriptan Frovatripan


Subcutaneous injection Tablet or wafer or nasal spray Tablet Tablet


Tablet or wafer Tablet


25, 50, 100 10, 20 25, 50 6


2.5, 5


20, 40 12.5 5, 10 2.5, 5


Many randomised, double-blind, placebo-controlled clinical trials have been performed to demonstrate the efficacy of the triptans in migraine attack treatment and also to define their optimal doses. Head-to-head comparisons of oral triptans have revealed differences in some outcome measures. The choice of triptan and formulation depends on the individual patient’s characteristics, preferences and headache features, as well as on convenience and cost considerations. The individual response to a triptan cannot be predicted. The triptans are most beneficial if they are taken at the very onset of headache, when the intensity of the pain is mild or moderate.34


All the triptans have similar side effects, and variability in this regard depends on the preparation and the route of delivery (side effects are greater with the subcutaneous than with the oral route). The most common side effects are known as ‘triptan sensations’ and they include paraesthesias, flushing, tingling, neck pain and mild transient chest pressure. Switching to a different triptan or another route of administration can mitigate the side effects. Although rare, cardiovascular complications have occurred in treated patients.35


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68