2114 Migraini Ddications

Migraine is(^in_episodicimadache disorder, sometimes preceded by a prodrnm(zE^jui auri^EE^- relationship between migraine and sex hormones (Particularl^strogen) is well accepted, and prcvalcncc of migraine is highest among women of childbearing age. When pregnant, migraine attacks most commonly occur during the first trimester. During pregnancy, 60-70% of the women improve. However, attacks often recur in the postpartum period (Silberstein 2004).

In migraine attacks there are three different phases:

1. The prodromal stage, with vasoconstriction of the vessels in the part of the brain affected

2. The painful stage, with vasodilatation

3. The edema stage, which involves increased vessel permeability and can last a long time.

There are different starting points for drug therapy. The drugs mentioned in the following section may be discussed in detail in other parts of this volume.

Ergot alkaloids

Ergo! alkaloid{=j>h as ergotamine-tartrat[=j dihydroergotamine (DHE), are helpful in many cases, but are rontraindicated during pregnancy because of their ability to disrupt fetal blood supply, which can lead to fetal damage or death. They also can produce uterine contractions and perfusion disturbances in the placenta (Fox 2005, Silberstein 2004). Individual cases of birth defects due to vascular disruption and stillbirths have been observed (Hughes 1988, Schaefer unpublished observations). Epidemiological studies have not, as yet, documented a clear increase in the rate of birth defects (Raymond 1995). The other ergotamine derivatives, which arc available in oral form, lisuride and methysergide, are not well studied for their tolerability during pregnancy, and should also be avoided (Fox 2005, Silberstein 2004).

Triptan-serotonin agonists

For severe acute attacks, sumatriptan (intranasal, s.c., oral or rectal application) is offered to patients who are unresponsive to other medications. Sumatriptan is a selective serotonin-receptor agonist, the receptors being present mainly in cranial vessels. More than 700 pregnancies have been studied prospectively by the producer in a registry and in some other prospective studies (GlaxoSmithKline 2005, Reiff-Eldridge 2000, OQuinn 1999, Shuhaiber 1998, Eldridge 1997), and some 700 have been studied in retrospective studies (Kiillen 2001, Olesen 2000), the majority of them being exposed in the first trimester. These data do not indicate a teratogenic potential in human beings.

The manufacturer recorded 38 pregnancies exposed to naratrip-tan during the first trimester (GlaxoSmithKline 2005) without indication of teratogenicity, Animal experiments have shown skeletal and vascular anomalies associated with plasma concentrations only 2.5 times greater than the human therapeutic level.

There are almost 100 prospective and retrospective case reports on rizatriptan collected by the Swedish medical birth registry and the producer, and these do not indicate teratogenicity (Fiore 2005).

Among 28 pregnancies exposed to zolmitriptan during the first trimester, there were two major birth defects (microphthalmia plus cataract, ventricular septal defect). These data are insufficient for risk assessment.

There are insufficient data on almotriptan, eletriptan, and frova-triptan.

Other migraine medications

In the edema stage of a migraine, diuretics such as furosemide have proven useful for many (non-pregnant) patients. Diuretic-induced maternal hypovolemia, however, may impair placental perfusion, with possible adverse effects on fetal well-being (see Chapter 2.8).

For clonidine, flunarizine, ketanserin, and pizotifen there are insufficient data on the use during pregnancy.

Recommendation. Migraine suffering is frequently positively influenced by pregnancy. Non-drug processes such as muscle relaxation therapy, biofeedback, acupuncture and acupressure, as well as changes in lifestyle and nutrition, are preferable in the prodromal stage and in the intervals that are free from pain. The analgesic of choice is paracetamol, perhaps combined with caffeine or codeine (see Chapter 2.1.7). Ibuprofen or aspirin can also be considered, but these should not be used from the early third trimester onwards. If necessary, antiemetics like medozine or metoclo-pramide should be given prior to analgesics. To prevent dehydration, intravenous (i.v.) fluids should be given. To control nausea and pain, phenothiazines (prochlorperazine) can be administered intravenously, supplemented if necessary by i.v. narcotics (like codeine) or i.v. corticosteroids. Severe attacks can be treated with sumatriptan (preferably intranasal, s.c. or rectal); other "triptanes" should be used only when compellingiy indicated.

For prophylactic interval therapy, proven tt-receptor blockers such as propranolol o[ metoprolol can be used, and when compellingiy indicated tricyclic antidepressants can be considered.

If one of the medications not recommended is taken, termination of pregnancy is not justified. Following an accidental injection of ergotamine derivatives in the last trimester, effects on contractions and fetal well-being can be determined by cardiotocography and ultrasound.

The Prevention and Treatment of Headaches

The Prevention and Treatment of Headaches

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