Migraine Headache Treatment And Drugs Used For Migraine Treatment


Drug names and migraine headache treatments availability vary widely from the USA and UK. Migraine headache treatments fall into two broad categories: first with migraine treatments are analgesics and analgesic combinations and, secondly, migraine-specific therapies, such as the triptans, ergotamine and dihydroergotamine. Many of these are available only on prescription but there is a variety of therapeutic options available over the counter (OTC) and pharmacists can often advise patients about these.

Analgesics and analgesic combinations. Most patients will have tried taking analgesics for migraine headache treatment before consulting a health care professional. However, they may not have used the appropriate dosage of the drugs or used them at the correct time. Because of the worries about gastric stasis, to achieve reasonable blood levels, higher doses of analgesics than are usually recommended for migraine treatment are suggested. Usually 900mg of aspirin, 1.5g of paracetamol (acetaminophen -USA) or 600mg of ibuprofen to be taken at the beginning of a migraine attack will suffice. Preferably, drugs should be taken even before the migraine headache develops, if possible. The timing of the dose is paramount in achieving the best possible outcome.

There is little evidence from clinical trials across large populations that combination drugs with caffeine and codeine are more effective than simple analgesics for migraine headache treatment. However, individual patients can experiment with different OTC analgesics. As long as the patient achieves the goal of being back to normal within a couple of hours with OTC therapy and frequency of headaches does not increase (as in analgesic dependent CDH), this can make sense. Patients using large amounts of analgesics for migraine headache treatment, particularly those containing codeine, may be developing, or indeed have, CDH. These patients would be best referred to their general practitioner.

The addition of a gastric motility agent, such as metoclopramide or domperidone, not only helps increase oesophageal motility and gastric emptying but is of particular benefit to those patients in whom vomiting is a major part of their migraine. Increasing gastric motility also allows better absorption and efficacy of analgesics. Soluble aspirin 900mg with metoclopramide 10mg tends to give migraine headache relief in about one-third to one-half of patients at two hours. Another recent migraine-specific combination, Migramax, contains both metoclopramide and lysine acetylsalicylate. The lysine makes the drug more soluble resulting in rapid absorption of the aspirin. Aspirin is, therefore, in contact with the gastric mucosa for a shorter length of time, potentially giving fewer gastric side effects and enhanced efficacy.

Another drug with a specific migraine indication is tolfenamic acid (Clotam Rapid) which is a non-steroidal anti-inflammatory drug.11 A placebo-controlled, randomised trial has shown tolfenamic acid to be equivalent to sumatriptan. However, in the trial, the success rates were above those normally expected from sumatriptan 100mg at a two-hour interval. It would, therefore, be useful to have other studies to confirm these results.

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The Triptans appear to work by stimulation of 5-HT1B and 5-HT1D receptors. During a migraine attack, the trigemino-vascular system is activated, particularly peripheral blood vessels and the trigeminal nerve. This nerve communicates peripherally with these blood vessels and centrally with the trigeminal nuclei. The important receptors are serotonergic, as the blood vessel is driven by the 5-HT1B and the trigeminal nerve by the 5-HT1D subtypes at both ends. In the UK, there are four licensed triptans - sumatriptan (Imigran® or Imitrex®), zolmitriptan (Zomig®), naratriptan (Naramig ® or Amerge®) and rizatriptan (Maxalt®). All these drugs are used for migraine headache treatment in clinical practice but the mainstay is still sumatriptan. Three newcomers from this family are eletriptan, frovatriptan and almotriptan.

Sumatriptan was launched about a decade ago and there is now substantial clinical experience of this agent. For patients who do not gain control with more general approaches, the triptans have proved to be a life-changing therapeutic option, although only a minority of those who could possibly benefit from them have been exposed to them. Sumatriptan is available in a subcutaneous and intranasal formulation to avoid the upper GI tract. This drug is, therefore, an attractive migraine headache treatment for patients who have early vomiting as a major feature of their migraine. These formulations also have a quicker action than tablets. Sumatriptan is available in both 50mg and 100mg tablets. Both Sumatriptan and Zolmitriptan have ranges of modes of administration allowing the patient to individualise care to achieve best outcome.

Zolmitriptan was the second agent to be launched in the triptan family. It was originally thought that it had activity at all three of the 5-HT1 sites and was, therefore, expected to penetrate the trigeminal nucleus better than sumatriptan. However, it remains unclear whether this actually confers additional benefits. Zolmitriptan is available in 2.5 and 5 mg tablets , 2.5 mg melt on the tongue tablet and 5mg nasal spray.

Naratriptan is given at a dose of 2.5mg to minimise side effects. The drug's summary of product characteristics says that side effect rates are similar to those of placebo. In studies, a disadvantage was that, at two hours, some patients found it less effective for migraine headache treatment than other drugs in the family. In those who find the drug effective, an advantage is a reduction in recurrence rate (recurrence being defined as a headache successfully relieved but returning within 24 hours). Recurrence occurs about one-fifth of the time with naratriptan compared with one-third achieved with the other triptans. In summary, it would appear that naratriptan has advantages for those patients who have recurrence or adverse events and this leads some practitioners to favour using the drug first-line, then moving to the other triptans if it is ineffective.

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Rizatriptan was launched in 1998 and was designed as a very small molecule, allowing rapid absorption and quick access to the target areas. It was also designed to have little stimulation of other 5-HT receptors, particularly 5-HT1A. This may be of some benefit in the early phase of migraine headache treatment, as there may be less nausea caused by 5-HT1A stimulation. Tablets are available in 5mg and 10mg and there is a 10mg melt-on-the-tongue wafer version (Maxalt Melt). With the wafers, the patient merely places the wafer on the tongue and it dissolves in the saliva within a few seconds. The solution is then swallowed and absorbed from the stomach. It appears to be well tolerated and rarely causes any taste disturbance. The most commonly reported advantage of Maxalt Melt is that the drug is convenient to take; the patient can take the migraine headache treatment earlier in the attack because no glass of water is required. This gives the wafer formulation a better chance of success because the hurdle, in terms of severity, is lower early in the migraine attack.

The drugs for migraine headache treatment in this class have a similar range of unwanted effects. The most common are tiredness, dizziness, nausea, neck and shoulder stiffness and a sensation of heaviness or pressure in various parts of the body, including the chest and throat. All drugs in the class have been extensively investigated and evidence, including ECG monitoring, suggests that the chest and throat symptoms are not necessarily of cardiac origin. Although the mechanism has yet to be determined, causes such as oesophageal spasm have been postulated. In practical terms, it is usually best to warn the patient that these side effects may occur but also to reassure them that true cardiac symptoms are extremely rare. All the triptans are contraindicated in patients with known ischaemic heart disease or uncontrolled hypertension and they are not recommended in patients over the age of 65 years.

Eletriptan is available as 40 mg tablets but if consistently less than optimal efficacy is seen, it is possible to increase the dose to 80 mg.

Frovatriptan is now available in a 2.5mg tablet. The unique characteristic of the drug for migraine headache treatment is its long half-life of 25 hrs [more than 4 times any of the other drugs in the class]. This means that its duration is potentially increased and it is hoped that the chance of a return of headaches is minimised. Although we wait to see if patients in the clinic find this to be useful for particularly those associated with a period, so far the research is not conclusive.

Ergotamine: The use of ergotamine has been almost completely superseded by the triptans because of its potential to cause acute side effects, such as nausea, abdominal pains and cramps, and also because of its relatively low efficacy, particularly in the oral formulation. Patients who are currently using ergotamine for migraine headache treatment on an infrequent basis and who find it efficacious without side effects would appear to be using the drug optimally and do not necessarily require a change in therapy. The most worrying aspect would be the possibility of increasing use of ergotamine leading to ergotism, a form of chronic daily headache. In this circumstance, the patient should be referred for further GP assessment.

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Dihydroergotamine (Migranal) is superior to ergotamine for migraine headache treatment but is inferior to the triptans in terms of efficacy two hours post dose. Its side effect profile is reduced in comparison with ergotamine. Currently, the drug is available as a nasal spray and is used by specialists in cases of triptan failure. It is no longer available in the UK.

Prophylactic therapies. Drugs that reduce the frequency of migraine have been used for decades and not always with good reason. The mode of action of these drugs is poorly understood but it is thought that antagonism at the 5-HT2 receptor may be important. In general, drugs are thought to be successful if there is a 50 per cent reduction in the rate of attacks in 50 per cent of patients. The most commonly used licensed drugs for migraine headache treatment in the UK are beta-blockers and 5-HT2 antagonists. The general rule in prophylaxis is that, because prescription agents have relatively low efficacy and a reasonable risk of causing side effects, compliance becomes a major issue. Because of this, it is probably best to start with modest doses and gradually titrate up, if necessary.

Beta-blockers: This class of drug is the most commonly used world-wide for migraine prophylaxis. Beta-blockers are contraindicated in patients with conditions such as asthma and peripheral vascular disease. Propranolol, atenolol, metoprolol and timolol are all used, although propranolol is the most commonly prescribed in the UK. Our approach for migraine headache treatment is to start with a low dose (10mg bd), building up gradually. Inderal LA 160mg or Half-Inderal LA 80mg is commonly used, but the larger daily dose does confer the problem of additional side effects. One analysis of propranolol reported that, on average, there was a 44 per cent reduction in the frequency, duration and intensity of migraine attacks.

Pizotifen: (Sanomigran®) has antihistamine and 5-HT2 receptor blocking activity and, in adults, the reduction in frequency of migraine attacks is less than that of beta-blockers. This effect is at the expense of side effects, such as weight gain and sedation.

Methysergide (Deseril) is an effective prophylactic agent for migraine headache treatment but it carries the serious side effect of fibrotic conditions, such as retroperitoneal fibrosis (fibrous material that can affect the ureters and, therefore, urinary flow). Because of this adverse effect, the drug is usually reserved for those patients who require prophylaxis but who have failed to respond to alternatives. Methysergide is now withdrawn in the USA but di-methyl ergometrine still available and used as its alternative for migraine headache treatment.

Other prescribed prophylactic agents: include tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs) and sodium valproate, topiramate and gabapentin have all been shown to have some efficacy in migraine prophylaxis.

Herbal & Dietary Additives: Non-prescription prophylactic agents OTC medicines, such as vitamin B2 (riboflavin) 400mg daily, magnesium 200mg daily, feverfew and even aspirin 75mg daily are all options for prophylaxis. When using prophylactic agents, it is always useful to explain to patients that they should only change one migraine headache treatment at a time. In this way, they can reduce the possibility of confusion over which drugs are effective.

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Migraine Management:

The management of migraine initially requires an accurate diagnosis, especially to exclude chronic daily headache. Once the migraineur is correctly identified, an appropriate strategy needs to be developed with the patient, which includes the avoidance of trigger factors, the use of an effective intervention and, in the case of high frequency sufferers, the use of a prophylactic agent. It should be remembered that, during patients' lives, the expression of their migraine may vary and the intervention required may need to be reassessed and adjusted from time to time. Patients may have a variety of migraine types in the short term and can require a range of migraine headache treatments to achieve optimal control. In the general population, soluble oral preparations, such as aspirin or paracetamol (acetominophen-USA), with or without an anti-emetic, may be all that is required.

More specific migraine therapies, such as the triptans, are available for those in whom this approach fails. Prophylaxis is also available and there are forms that can be bought over the counter, as well as those on prescription. Due to the relatively low efficacy and high tolerability of prescribed migraine headache treatments, patients often prefer to try OTC options first. During the past decade, with the advent of the high efficacy triptans, there has been a change, with less emphasis now being placed on prescription prophylactic agents. The aim of a good management strategy should be to enable patients to be in control of their migraine rather than have it control them.

Typically most migraine headache sufferers will have approximately one or two attacks a month and be between the ages of 25 and 55 years. Rarely migraineurs experience more than 40 attacks in a year (about 20 per cent of patients have more than 40 a year).

The most commonly used aid to diagnosis is the IHS classification. However, a more modern approach might include questions relating to the disruption of normal activity and quality of life. It should be remembered that, untreated, an average migraine attack would last approximately one day. It must be stressed that it is extremely important to include the patient in all decisions regarding migraine management. It is the patient who needs to develop the strategy that works specifically for them. This strategy usually includes:

1. The avoidance of trigger factors, where possible and identify causes & patterns of stress take our SPI© test)
2. Acute intervention for breakthrough attacks
3. Use of prophylactic agents in "high frequency" patients.
4. Patients with less frequent but more prolonged attacks may warrant prophylactic treatment if their migraine is unresponsive to the full range of acute therapies.

Avoiding migraine trigger factors:

A common trigger source may involve being over tired and stressed (take our SPI© test). Indeed, any large emotional stressor caused at home or at work may precipitate migraine. Some experts believe that a patient is born with a susceptibility to migraine headache attacks and that various trigger factors will come together on a particular day to tip the patient into the acute symptoms described above. Once identified, many risk factors, especially foods, are easily avoided. Others, such as weather changes or menstrual cycles, are more difficult or impossible to avoid. Nevertheless, appreciation of their importance can be put to good use.

Source: Dr Andrew Dowson

Publication Date: July 2003


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