Headache Medicine, v.10, n.1, p.29-31, 2019

ABSTRACT

VIEW AND REVIEW

Of the available triptans, which should be chosen and how

should they be used?

Dos triptanos disponíveis, quais devem ser escolhidos e como

devem ser usados?

Marcelo Moraes Valença

Emanuela Paz Rosas

Raisa Ferreira Costa

Amanda Araújo da Silva

Maria Rosana de Souza Ferreira

Rita Santana dos Reis

Marcelo Andrade Valença

Luciana Patrízia Alves de Andrade-

Valença

Neurology and Neurosurgery Unit, Federal

University of Pernambuco, Recife, Brazil.

*Correspondence

Marcelo M. Valença

E-mail: mmvalenca@yahoo.com.br

Received: October 2, 2018.

Accepted: December 12, 2018

There is a plethora of articles dealing with the use of triptans to treat migraine,

but so far no unanimity exists regarding the optimal form of using this group

of drugs in a patient with recurrent attacks of migraine. Although all of them

may exert their pharmacological effects through a known specic mechanism

of action, i.e. agonist effects on serotonin 5-HT (1B/1D) receptors, distinct

differences exist. The author comment a few facts on the prescription of

triptans and possible adverse effects, depending on the clinical scenario. Thus,

even though an enormous amount of information has accumulated over the last

few decades on triptans, several questions remain to be answered, and research

priorities need to be addressed.

Keywords: Triptans, Adverse Effect, Migraine, Prescription.

RESUMO

Descritores: Triptanos, Efeito Adverso, Enxaqueca, Prescrição.

Há uma innidade de artigos que tratam do uso de triptanos no tratamento

da enxaqueca, mas até agora não existe unanimidade em relação à forma

ideal de usar esse grupo de medicamentos em um paciente com ataques

recorrentes de enxaqueca. Embora todos eles possam exercer seus efeitos

farmacológicos através de um mecanismo de ação especíco conhecido, isto é,

efeitos agonistas nos receptores da serotonina 5-HT (1B/1D), existem diferenças

distintas. Os autores comentam alguns fatos sobre a prescrição de triptanos

e possíveis efeitos adversos, dependendo do cenário clínico. Assim, embora

uma quantidade enorme de informações tenha se acumulado nas últimas

décadas sobre triptanos, várias questões ainda precisam ser respondidas e as

prioridades de pesquisa precisam ser abordadas.

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Triptans, which should be chosen?

Valença, MM

Headache Medicine, v.10, n.1, p.29-31, 2019

There is a plethora of articles dealing with the use

of triptans to treat migraine, but so far no unanimity

exists regarding the optimal form of using this group

of drugs in a patient with recurrent attacks of migraine.

Although all of them may exert their pharmacological

effects through a known specic mechanism of action,

i.e. agonist effects on serotonin 5-HT (1B/1D) receptors,

distinct differences exist.

Rapoport and coworkers

suggested a few strategies

to be adopted when choosing a triptan. They pointed

out that some patients prefer a form of treatment that

works quickly, some consider as satisfactory treatment

triptans that provide complete relief of the pain, while

others expect consistent effects as the most important

result of triptan treatment. In addition, adverse effects

are not tolerated by some migraineurs.

1,2

Almas and coleagues

reported that eletriptan

provides consistent migraine relief with an 80-mg

dose. Some of these individuals reported failure with a

lower dose of 40 mg. This is of major importance since

the failure of triptan treatment may be caused by the

use of subtherapeutic doses. However, 80 mg is the

maximum daily dose allowed and a subsequent intake of

eleptriptan must be avoided to prevent serious adverse

effects. Nevertheless, only 18.6% and 8% of the patients

achieved pain-free status at 2 hours or 24 hours sustained

headache response, respectively, on all three sequential

treated attacks.

Although this is an excellent clinical

outcome in terms of current treatment of migraine

attacks, it is far from the ideal goal of a foreseeable 100%

effective antimigrainous drug.

Seven triptans are currently being used in clinical

practice (almotriptan, eletriptan, frovatriptan, naratriptan,

rizatriptan, sumatriptan and zolmitriptan)

1, 2

. The relevant

literature is controversial regarding the most successful

triptan in the treatment of migraine attacks. A number

of specic advantages are claimed for some of them as

compared with the others. Thus, among the available

triptans, which one should be chosen to treat a given

patient is still a moot point. In part, this is also due to

the different ways in which triptans are tested for their

efcacy and possible adverse effects.

Different study end-points are evaluated during

trials using triptans.

Even though an attempt is always

made to attenuate bias during clinical trials, it is virtually

impossible to eliminate completely. The ‘negative result’

bias and the supposed inuence of pharmaceutical

companies over the publication of favorable results of a

given drug produced by them must be considered when

interpreting study outcomes.

Huge amounts of money have been spent by

pharmaceutical companies to develop new drugs,

and the companies’ efforts in this regard should be

recognized. As a result, we have acquired a very high

level of understanding of the mechanisms of action of

triptans and their possible clinical applications.

Regarding the clinical use of triptans for migraine

attacks, a long-action triptan is the ideal treatment

for patients with crises of headache lasting over six

hours. Among the triptans naratriptan (5-6 hours) and

frovatriptan (26 hours) present a relatively long half-life,

and should therefore be remembered when prescribing

for such patients.

If a short-action triptan is to be used,

the physician may recommend an abortive dose of the

triptan in addition to a complementary “prophylactic”

dose a few hours later, and before the expected

recurrence of the headache, in order to maintain the

patient free of headache, bearing in mind the maximum

safety dose of the drug that one may use daily. This form

of treating (abortive/preventive) is not usual in clinical

practice. Some authors use the combination of a triptan

and NSAIDs to treat such migraine attacks.

The efcacy of a specic triptan does not always

correlate with the patient’s preferred treatment. The

choice of a triptan by the physician will depend upon his

or her previous experience, the brand name, marketing

pressure, the usual features of the migraine attacks,

drug availability, cost, possible adverse side effects, the

patient’s risk of concomitant atheromatosis, vasospasm

susceptibility, or a previous failure or side effect with a

particular triptan reported by the patient.

The consensus is that triptan treatment in migraineurs

does not increase the risk of stroke, cardiovascular death,

or ischemic heart disease.

The contraindications for the

use of triptans are still poorly dened. There is general

agreement that triptans should not be used by patients

with a previous stroke or cardiovascular events. However,

we should be concerned when dealing with patients

with more than two of the following risk factors for

atheromatous disease: age >55 years, smoking, arterial

hypertension, dyslipidemia, diabetes mellitus or a familial

history of myocardial infarction at a young age. Migraine

with aura by itself seems to be a risk factor for ischemic

cardiovascular disease in women, and the widespread

use of hormonal contraception further enhances this risk.

Considering the potential vasoconstriction of the

coronary artery elicited by triptans as in vitro studies have

shown, the number of cardiovascular adverse events

reported is surprisingly low.

I wonder whether this is

a consequence of the characteristic behavior of the

migraineurs in avoiding intense physical activities or to

the attempt to remain at rest during a migraine attack.

Considering the abovementioned risk factors, we still

do not know if there is a signicant risk of symptomatic

vasoconstriction if we treat an athlete performing a

sporting activity with triptan. This scenario must be

relatively frequent since the current recommendation is

an early treatment of a migraine attack when the pain is

still mild.

6, 7

In this line of thinking, should one be afraid of

an ischemic event if during an exercise a person presents

“triptan sensations” (i.e. chest, jaw or arm discomfort)?

This question remains to be answered.

As future research priorities we should address the

following questions: Why do some patients not respond

to triptan? What are the clinical and demographic

characteristics of patients who respond, compared to

nonresponders

? By answering this, we can, therefore,

identify those less likely to respond to triptan before

prescribing this particular pharmacological agent. Could

rest or sleep in a dark room potentiate the action of a

triptan compared to subjects that continue their daily

activities? Do some environmental conditions (light/

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Triptans, which should be chosen?

Valença, MM

Headache Medicine, v.10, n.1, p.29-31, 2019

darkness, noise, weather), physiological events or mental

states (sleep, anxiety, stress, fear, hunger) inuence the

action of the drug on the specic migraine attack treated

with triptan? It seems that this may be so, which would

account for the absence of consistency observed with

the use of triptans used at the same dose at different

times and by the same individual.

Could variables such as age and gender inuence

the response to triptans? Why do some patients respond

to a specic triptan after reporting a failure of response

to a different triptan? Pharmacogenetics may explain

this at some future date.

One topic to be discussed is the use of triptans

by sexually active women during their fertile period.

Although triptans should be avoided during pregnancy,

women may use this drug in the rst month before

realizing that they are pregnant. Does this increase

the chance of a possible teratogenic effect of the drug

compared to other classes of analgesics? Evidence has

suggested that the use of triptans during pregnancy

is associated with atonic uterus and blood loss during

labor, but the risk of major birth defects is comparable to

that of the general population.

Another important issue is whether the physician

should explain the contraindications of triptans to the

patient. Some may argue that this is not necessary for

young patients with no cardiovascular risks. However, it

is not uncommon for patients to recommend a painkiller

to colleagues and family members, so they need to be

made aware that triptans may have serious adverse

effects when taken inappropriately. Furthermore, a

patient may use triptans for decades without returning

to the prescribing physician and his or her safety prole

may change with age. This is another point to be borne in

mind, considering the importance of patient education.

Thus, despite the fact that an enormous amount of

information has accumulated over the last few decades

on triptans, several questions still remain to be answered

and research priorities need to be addressed.

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