Weekly Dose: triptans, drugs that relieve migraine but only if taken at the right time

Triptans are a group of drugs targeted at alleviating symptoms of migraine, a severe and often debilitating headache that can affect sight and speech.

Triptans are derived from the amino acid tryptophan and designed to resemble the serotonin molecule and mimic its effects on subgroups of serotonin receptors in the brain. Biochemically derived from tryptophan, serotonin is a neurotransmitter known to contribute to feelings of happiness and wellbeing.

The triptans available in Australia are: sumatriptan (Imigran and other brands), zolmitriptan (Zomig), naratriptan (Naramig), rizatriptan (Maxalt) and eletriptan (Relpax).

History

The making of the triptan class of drugs is a case study in rational drug development. Early research in the 1960s suggested the anti-migraine effect of known drugs such as ergotamine was due to them causing constriction of certain blood vessels in the brain, known as vasoconstriction.

Further work established that several subgroups of receptors, activated by the common neurotransmitter serotonin, appeared protective against migraine.

Although it took a couple of decades, the first triptan drug (sumatriptan) went into commercial production in the early 1990s. Compared to existing migraine treatments, it was a quantum leap forward in effectiveness: more than half of acute migraine attacks substantially improved within two hours.

Now, about a third of migraines treated with sumatriptan are completely gone within two hours.

New triptans with improved penetration into the bloodstream, and potentially better risk-to-benefit ratios, have been introduced.

What they do

Triptans activate subtypes of the serotonin receptor, which is believed to produce vasoconstriction and oppose the cascade of events that leads to migraine headache.

Migraines occur when there is unwanted dilation of blood vessels inside the brain, so the timing of the drug’s effect of vasoconstriction needs to coincide with the period of dilation. There is some evidence triptans are less effective when taken too late.

There may also be secondary effects that are less understood. All drugs in this class are used to terminate acute attacks of migraine, not for prevention of recurrent attacks. They also tend to have relatively short-lived benefits. As many as 35% of attacks may require a dose of extra medication some hours later.

How they are used

Because of their ability to short-circuit attacks, the ideal time to treat any migraine with a triptan is in the very early stages, when it becomes clear a migraine is unavoidable.

If the migraineur is experiencing an aura (disturbances that can include flashes of light, blind spots and other vision changes, or tingling in hands or face), it is preferable to wait until the headache begins.

Sumatriptan comes in tablets, a nasal spray or injection. The latter options are convenient as many migraineurs are unable to take down tablets due to nausea and vomiting once the headache begins.

Zolmitriptan, eletriptan and naratriptan come as tablets only, while rizatriptan is also formulated in wafers that can be dissolved in the mouth.

When they shouldn’t be used

Because triptans constrict blood vessels, therefore creating barriers to blood flow, they should be avoided by people with ischaemic heart disease – such as heart attack or angina – or other diseases of circulation.

They should also be avoided by the elderly and those with significant liver problems, as the drug itself has a reduced metabolism. This can lead to prolonged high blood levels of active drug and enhanced risk of vasoconstriction-related harm as detailed below.

Triptans have not been properly evaluated for safety or effectiveness in children and in teenagers, so should be used only for severely disabling migraines in these groups. They should be avoided in pregnancy and while breastfeeding.

Which triptan should be used?

Most doctors start with sumatriptan. It’s available in several formulations and is the best-documented for migraine alleviation.

The small differences in shape between the different triptan molecules can mean, in practice, that some work better than others for individuals.

Looked at as a group, though, they are similarly safe and effective.

Side-effects

It is fairly common for triptans to produce sensations of flushing or dizziness soon after they are taken. Tingling, pins and needles, heaviness or tightness in the chest and throat may also occur due to transient vasoconstriction effects.

More widespread vasoconstriction may produce an increase in blood pressure for a few hours. This increases the the risk of severe injury such as heart attack, stroke or gangrene of fingers or toes.

Potential interactions

Other serotonin-boosting agents, such as antidepressant drugs or St John’s Wort extracts, need to be used with caution. As these also stimulate serotonin receptors, there is potential for triggering symptoms of serotonin overload (known as serotonin syndrome), which can be fatal in extreme cases.

Taking other migraine-terminating treatments, such as dihydroergotamine, with triptans must be avoided as they will enhance vasoconstriction.

Other things to note

Triptans are major contributors to headaches that can come about through overuse of medication, if taken more than ten times a month.

They should be reserved for episodic but severe migraines that consistently respond well to the medication.

More frequent headaches should be re-evaluated and are probably better managed by preventive treatments rather than repeated acute treatment with triptans.

Cost

Sumatriptan is the cheapest triptan as it is out of patent. It costs around A$3.50 a dose. The newer triptans cost a bit more, but, overall, none of them makes the top 50 PBS drugs either by cost or volume of prescribing, so there are few concerns about widespread over-prescribing.

Data from a large study estimates up to 200,000 Australians may be using triptans every year.

Michael Vagg does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond the academic appointment above.