10/26/04njm

**Q**. What do you use to treat pregnant women with migraines? 

I have a young otherwise healthy woman who used motrin very succesfully
prior to pregnancy, but I would prefer her not to use
this\....especially in the third trimester.  Narcotics have made it
worse\....given Nubain, and vicodin via ER.

**A**. First of all make sure these are migraine headaches, then treat
appropriately. See below

All the common types of headaches can occur in pregnancy, so first
consider other etiologies. In addition, some therapies known to treat
other types of headache, e.g., use of 100% oxygen**\*\*** for cluster
headaches have been used successfully in migraines during pregnancy and
don't have the concerns of other medications.

Go here to rule out other causes.

<http://www.uptodateonline.com/application/topic.asp?file=maternal/5476>

Now here is some information on migraines in pregnancy.

The prevalence of migraine is higher in women than in men and peaks
during the childbearing years. Approximately 18 percent of American
women suffer from severe migraine headaches; many others have mild to
moderate disability
\[[[6]{.underline}](http://www.uptodateonline.com/application/abstract.asp?TR=maternal/5476&viewAbs=6&title=6)\].

**Pathophysiology and hormonal effects** --- Migraine headaches are
associated with menarche, menstruation, oral contraceptive use,
pregnancy, menopause, and hormone replacement therapy, all of which are
partially mediated by fluctuations in estrogen levels. As an example,
migraine headaches may worsen during periods of estrogen decline such as
menstruation and the puerperium, but improve during high estrogen states
such as pregnancy
\[[[7]{.underline}](http://www.uptodateonline.com/application/abstract.asp?TR=maternal/5476&viewAbs=7&title=7)\].
In addition, supplementation with estrogen, but not
[[progesterone]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/212059&drug=true)\[[[8,9]{.underline}](http://www.uptodateonline.com/application/abstract.asp?TR=maternal/5476&viewAbs=8~9&title=8,9)\],
has been demonstrated to prevent menstrual migraines.

[[Estradiol]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/95612&drug=true)
receptors are located in close proximity to 50 to 80 percent of
catecholamine receptor sites in the brain, suggesting a possible
functional effect of estrogen on pain pathways
\[[[10]{.underline}](http://www.uptodateonline.com/application/abstract.asp?TR=maternal/5476&viewAbs=10&title=10)\].
Exposure to trigger factors in sensitive patients may lead to
intracerebral release of neurotransmitters which stimulate the
intracranial extracerebral vessels to dilate. The dilation of these
vessels stimulates perivascular neurons that activate the trigeminal
nucleus which triggers headache pain.

Peripheral serotonin (5-HT) appears to exert autoregulatory inhibition
of the dorsal raphe nucleus, the putative site of action of a variety of
antimigraine medications (eg,
[[ergotamine]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/93953&drug=true)
and the
[[triptans]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/253194&drug=true)).
Therefore, women should be less susceptible to headache triggers when
peripheral 5-HT levels (measured in blood) are high and more susceptible
to headaches when 5-HT levels are low. Several studies support this
model
\[[[11]{.underline}](http://www.uptodateonline.com/application/abstract.asp?TR=maternal/5476&viewAbs=11&title=11)\].
For example, peripheral 5-HT levels were found to decrease during both
migraine and tension-type headaches, and intravenous serotonin was able
to arrest migraine
\[[[12]{.underline}](http://www.uptodateonline.com/application/abstract.asp?TR=maternal/5476&viewAbs=12&title=12)\].
Medications used to prevent migraine appear to act at central serotonin
receptors. ([[See \"Pathophysiology, clinical manifestations, and
diagnosis of migraine in
adults\"]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=headache/4701)).

**Effect of pregnancy** --- Most women with migraine headaches report
improvement during pregnancy with deterioration postpartum
\[[[13]{.underline}](http://www.uptodateonline.com/application/abstract.asp?TR=maternal/5476&viewAbs=13&title=13)\],
although 30 to 40 percent describe worsening or no change in their
migraine frequency
\[[[2]{.underline}](http://www.uptodateonline.com/application/abstract.asp?TR=maternal/5476&viewAbs=2&title=2)\].
Migraine headaches developing for the first time during pregnancy
usually do so in the first trimester. However, one prospective
longitudinal study found that recurrent migraine headaches primarily
occurred in the third trimester, particularly in multiparous women
\[[[4]{.underline}](http://www.uptodateonline.com/application/abstract.asp?TR=maternal/5476&viewAbs=4&title=4)\].

Pregnancy outcome does not appear to be affected by the presence of
maternal migraine headaches. Two large series examining the risk of
stroke in pregnancy did not identify migraine headaches as a risk factor
\[[[14,15]{.underline}](http://www.uptodateonline.com/application/abstract.asp?TR=maternal/5476&viewAbs=14~15&title=14,15)\].

**Treatment** --- The treatment of migraine headaches in pregnant women
differs from that in nonpregnant women because of concerns about the
effects of certain drugs on the fetus.
[[Acetaminophen]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/5275&drug=true)
is effective in some women and safe for mother and fetus. A
population-based study of patients with self-reported migraine found
acetaminophen at a dose of 1000 mg to be highly effective for treating
pain, functional disability, photophobia, and phonophobia, although the
study excluded patients with severe symptoms requiring bed rest or
associated with vomiting more than 20 percent of the time
\[[[16]{.underline}](http://www.uptodateonline.com/application/abstract.asp?TR=maternal/5476&viewAbs=16&title=16)\].
Acetaminophen and many other analgesics are safe to use during
pregnancy; however, analgesic rebound headaches may develop with
frequent (daily) use in women with recurrent headaches.

Rebound headaches may be confused with migraine; the diagnosis should be
suspected in patients who have persistent daily headaches despite the
regular use of analgesic medications
\[[[17]{.underline}](http://www.uptodateonline.com/application/abstract.asp?TR=maternal/5476&viewAbs=17&title=17)\].
In one study, no one analgesic was consistently identified as causative,
although
[[acetaminophen]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/5275&drug=true),
butalbital-aspirin-caffeine (Fiorinal), and
[[aspirin]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/21595&drug=true)
were commonly implicated
\[[[18]{.underline}](http://www.uptodateonline.com/application/abstract.asp?TR=maternal/5476&viewAbs=18&title=18)\].
Improper use of acetaminophen and other over-the-counter analgesics in
the general population may be a bigger problem than abuse of opioids,
barbiturates, or benzodiazepines, since these simple analgesics are so
easily available and thought to be benign. The only therapy of rebound
headaches is cessation of the offending drug.

Women who do not respond to
[[acetaminophen]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/5275&drug=true)
alone may obtain relief with combination therapy such as acetaminophen
(650 to 1000 mg) and
[[metoclopramide]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/165291&drug=true)
(10 mg), acetaminophen and
[[codeine]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/64269&drug=true)
(30 to 60 mg), or acetaminophen (325 mg),
[[caffeine]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=ped_drug/27114&drug=true)
(40 mg), and butalbital (50 mg) (eg, Fioricet 1 or 2 tablets every four
hours, not to exceed six tablets per day). These drugs should not be
taken continuously for prolonged periods of time.

Nonsteroidal antiinflammatory drugs (NSAIDs) can be given for headache
treatment. Their use should be limited to fewer than 48 hours in the
third trimester due to concerns about premature ductal closure in the
fetus, platelet inhibition problems, and oligohydramnios.

Opioids (eg,
[[oxycodone]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/188273&drug=true),
[[propoxyphene]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/214116&drug=true),
[[hydromorphone]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/126168&drug=true),
[[meperidine]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/156374&drug=true),
and
[[morphine]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/171919&drug=true))
are a second-tier option, but should not be used on a chronic basis
since they are habit-forming and can contribute to the development of
rebound and chronic daily headaches
\[[[19,20]{.underline}](http://www.uptodateonline.com/application/abstract.asp?TR=maternal/5476&viewAbs=19~20&title=19,20)\].
All narcotics have potential for maternal and neonatal addiction, thus
they should not be used for prolonged periods of time. Rectal,
intravenous, or intramuscular administration may be required for severe
migraine or in women with nausea and vomiting.

Compazine and other centrally acting antiemetic medications can be
administered to relieve nausea and vomiting associated with migraine or
migraine therapy. These medications can be used safely in pregnancy.
Acute dystonic reactions sometimes occur, but are not harmful.

[[Sumatriptan]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/253194&drug=true),
[[rizatriptan]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/74144&drug=true),
[[zolmitriptan]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/7132&drug=true),
and
[[naratriptan]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/55607&drug=true)
are newly approved selective serotonin agonists that are highly
effective in treating migraine headaches. A pregnancy registry for
sumatriptan exposure during pregnancy has not found an increased risk of
birth defects in 183 exposed women compared to controls (3.8 versus 3 to
5 percent)
\[[[21]{.underline}](http://www.uptodateonline.com/application/abstract.asp?TR=maternal/5476&viewAbs=21&title=21)\].
However, there are inadequate data on which to assess the safety of
these drugs in pregnant women
\[[[22,23]{.underline}](http://www.uptodateonline.com/application/abstract.asp?TR=maternal/5476&viewAbs=22~23&title=22,23)\].
([[See \"Acute and preventive treatment of migraine headache in
adults\"]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=headache/4364)).

Ergot alkaloids, commonly used in the nonpregnant state to abort
migraine headaches, are absolutely contraindicated during pregnancy
because of the potential to induce hypertonic uterine contractions
resulting in fetal hypoxia and loss. Postpartum use is permitted.

**Intractable migraine** ---
[[Corticosteroids]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/209553&drug=true)
or intravenous
[[droperidol]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/89569&drug=true)
are useful in refractory cases
\[[[24]{.underline}](http://www.uptodateonline.com/application/abstract.asp?TR=maternal/5476&viewAbs=24&title=24)\].
[[Prednisone]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/209842&drug=true)
(20 mg orally QID for two days) and
[[methylprednisolone]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/164289&drug=true)
(4 mg orally, 21 tablets over six days) are the preferred
corticosteroids because they are metabolized by the placenta and have
minimal fetal effects, whereas
[[dexamethasone]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/74688&drug=true)
and
[[betamethasone]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/30377&drug=true)
readily cross the placenta and remain metabolically active
\[[[24]{.underline}](http://www.uptodateonline.com/application/abstract.asp?TR=maternal/5476&viewAbs=24&title=24)\].
Droperidol (2.5 mg intravenously every 30 minutes up to three doses)
also appears to be effective, but can be associated with extrapyramidal
symptoms
\[[[25]{.underline}](http://www.uptodateonline.com/application/abstract.asp?TR=maternal/5476&viewAbs=25&title=25)\].

**Prophylaxis** --- Women with frequent migraine or tension headaches
may require preventative therapy. This may include daily use of
beta-blockers and calcium channel blockers in the lowest effective dose
and cognitive and behavioral therapy. Comanagement with a neurologist is
essential in these difficult cases.

  ![](media/image1.png){width="6.25e-2in"
height="7.152777777777777e-2in"} Beta-blockers such as
[[atenolol]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_a_k/22438&drug=true),
[[metoprolol]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/165794&drug=true),
and
[[propranolol]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/214749&drug=true)
are not teratogens, but fetal and neonatal complications may occur.
Antenatal surveillance for fetal growth restriction and bradycardia
should be considered. Transient bradycardia, respiratory depression,
hyperbilirubinemia, hypoglycemia, and other signs of beta-blockade can
occur in the neonate.\
\
  ![](media/image1.png){width="6.25e-2in"
height="7.152777777777777e-2in"} Short and long acting calcium channel
blockers appear to be safe in pregnancy, although information is limited
\[[[26,27]{.underline}](http://www.uptodateonline.com/application/abstract.asp?TR=maternal/5476&viewAbs=26~27&title=26,27)\].
Hypotension should be avoided. In particular, case reports have
described severe hypotension and potentiation of neuromuscular blockade
when
[[nifedipine]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/181147&drug=true)
and [[magnesium
sulfate]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=drug_l_z/150634&drug=true)
have been administered concurrently
\[[[28,29]{.underline}](http://www.uptodateonline.com/application/abstract.asp?TR=maternal/5476&viewAbs=28~29&title=28,29)\].

Low dose antidepressants and antiepileptic medications may also be
considered in refractory patients, particularly those with suspected
underlying chronic depressive illness and postpartum depression. ([[See
\"Acute and preventive treatment of migraine headache in
adults\"]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=headache/4364)
section on Prophylactic therapy and [[see \"Epilepsy and
pregnancy\"]{.underline}](http://www.uptodateonline.com/application/topic.asp?file=epilepsy/3066)
section on Effect of antiepileptic drugs on the fetus).

Reference:

<http://www.uptodateonline.com/application/topic.asp?file=maternal/5476>

**\*\* Editorial Comment:** njm

Though the following is posted under Cluster HA (s), it is has been
successful in the acute treatment of migraines in pregnancy and is low
risk.

**Treatment** --- Abortive therapy of cluster headaches can be difficult
because of the short duration of each episode. Acute cluster headaches
can be aborted by inhalation of 100 percent oxygen in the majority of
patients
\[[33](http://www.uptodateonline.com/application/abstract.asp?TR=maternal/5476&viewAbs=33&title=33)\].

[33.](http://www.uptodateonline.com/application/abstract.asp?TR=maternal/5476&viewAbs=33&title=33)
 Fogan, L. Treatment of cluster headache. A double blind comparison of
oxygen V. air inhalation. Arch Neurol 1985; 42:362