Migraine Medications

Migraine is a serious, potentially life-threatening neurological disease that affects nearly 36 million Americans, the majority of whom are women. The American Migraine Foundation estimates that one in every four American households has at least one member with migraine. The hallmark symptom of migraine is an escalating, often unbearable, debilitating headache that is commonly described as intense throbbing or pulsating pain in one area of the head. The pain may be accompanied by extreme sensitivity to light and sound, nausea, and vomiting. In some people, migraines are preceded by visual disturbances known as auras that may include flashing lights, zigzag lines, or temporary blindness.

Migraine medications do not cure migraines. Instead, migraine drugs treat the symptoms using one of two approaches.

• Some migraine drugs relieve symptoms.
• Other migraine drugs are used to prevent a migraine attack.

Many migraine sufferers rely on simple pain relievers to get through an attack. These range from over-the-counter analgesics like acetaminophen to anti-inflammatories like naproxen or ibuprofen (Motrin) to prescription barbiturate combinations and narcotics. While this type of treatment provides relief, it doesn't target the physiological processes that underlie a migraine attack.

Migraine symptoms occur, in part, because of the dilation of blood vessels in the brain. Until recently, migraine sufferers had few choices when it came to drugs to counteract this effect. But newer migraine drugs known as triptans cause constriction of blood vessels and also bring about a general interruption in the chain of chemical events that leads to a migraine.

At some point, a migraine sufferer may need to move on to preventative therapy. This usually becomes necessary when migraine attacks happen more than once a week and/or abortive medications fail to work more than half the time.

No migraine drugs specifically prevent migraines. But many drugs used for other conditions can help keep migraines at bay. These include certain blood pressure medications as well as some antidepressants, anti-seizure drugs, and herbals.

Some of the migraine medications used to treat or prevent migraine headaches are also used for other conditions. Here are the pain reliever medications for migraine therapy.

• Antidepressants,
• anticonvulsants,
• antihistamines, and
• narcotics

There are some migraines drugs, though, that are used because they directly target the pain pathways associated with migraine headaches rather than pain pathways in general.

Migraine medications fall into two major categories.

• The first contains drugs that abort or stop migraines from progressing once they begin. The earlier these drugs are used in a migraine attack, the better they work.
• The second category contains drugs that prevent migraines from happening.

Over-the-counter migraine medications used to address pain include analgesics, NSAIDS, and caffeine, including:

• Aspirin
• Naproxen (Aleve, Naprosyn, Anaprox, Anaprox DS)
• Ibuprofen (Advil, Motrin)
• Acetaminophen (Tylenol)
• Or combinations of these

One drawback to using analgesics and NSAIDs is that taking them daily can make headaches worse due to medication overuse.

Prescription drugs used to provide relief from pain include:

• Nonsteroidal anti-inflammatory drugs (NSAIDs) and
• Narcotics

Like over-the-counter medications, prescription drugs often come in combinations:

• A barbiturate called butalbital is often used in combination with acetaminophen, and
• Caffeine with or without codeine (a narcotic)

Barbiturates are a sedative and may be useful to help people sleep off the pain.

While analgesics, NSAIDs, and narcotics relieve pain, they don't address the underlying physiology -- primarily the dilation of blood vessels in the brain. Two classes of migraine drugs are:

• Ergotamines and 
• Triptans

Ergot alkaloids -- such as ergotamine tartrate (Cafergot) and dihydroergotamine mesylate (D.H.E. 45 Injection, Migranal Nasal Spray) -- are potent drugs that constrict blood vessels. Because nausea is a possible side effect of these migraine drugs, some people take ergotamines in combination with other drugs to prevent nausea.

Triptans target serotonin receptors. These drugs cause constriction of blood vessels and bring about a general interruption in the chain of chemical events that lead to a migraine. Triptans include:

• Almotriptan (Axert)
• Eletriptan (Relpax)
• Frovatriptan (Frova)
• Naratriptan (Amerge)
• Rizatriptan (Maxalt, Maxalt-MLT)
• Sumatriptan (Imitrex, Zecuity)
• Zolmitriptan (Zomig, Zomig-ZMT)

While specific triptans differ in their ability to prevent a recurrence of migraine headaches, they are generally equally effective in their ability to provide relief. Triptans are more migraine-specific than the earlier ergotamines.

Another migraine drug used to abort the pain of a migraine is a combination product containing the vasoconstrictor isometheptene mucate, the sedative dichloralphenazone, and the analgesic acetaminophen (Midrin). The FDA has classified isometheptene mucate as "possibly" effective for migraines, pending further review.

Antihistamines are also used to ease migraine symptoms. These drugs counteract the effect of histamine, a substance that dilates blood vessels and causes an inflammatory response in the body -- the same kinds of response seen during a migraine attack. Antihistamines are broadly grouped into sedating and non-sedating types. An example of a sedating type is diphenhydramine; an example of the non-sedating type is loratadine (Claritin).

Calcitonin-gene related peptide (CGRP) antagonists are a newer type of migraine medication. CGRP is a neuropeptide, which neurons use to communicate. It was discovered in the 1980s and it seems to play a key role in migraine. It is not entirely understood how CGRP causes the pain of migraines. One theory is that CGRP sensitizes peripheral nerves, which in turn send signals to the central nervous system (CNS) that trigger the pain and sensitivity to sensory stimuli associated with migraine. This may occur because when CGRP binds to its receptor, it sensitizes the nerves by increasing their rate of firing. CGRP might also activate pain receptors by dilating blood vessels, which could push on pain receptors on adjacent nerves. 

There are two kinds of CGRP antagonists: 

• Monoclonal antibodies
  • Eptinezumab (Vyepti)
  • Erenumab (Aimovig)
  • Fremanezumab (Ajovy)
  • Galcanezumab (Emgality)
• Oral gepants (an older class of CGRP antagonist) 
  • Rimegepant (Nurtec) 
  • Ubrogepant (Ubrelvy)

CGRP antagonists have fewer side effects than many other migraine medications, and often work where others have failed.

Preventative therapy should be considered for patients who suffer from recurrent migraines that cause significant disability, frequent migraines that require treatment more than twice a week, or migraines that do not respond or respond poorly to symptomatic treatments. Currently there are no drugs that specifically target and prevent migraines. Certain blood pressure medications as well as some antidepressants, anti-seizure drugs, and herbals have been shown to have beneficial effects in preventing migraine headaches. It's important to understand that prophylactic medicines may not produce any significant benefits right away and maximal effects may not be seen for weeks to up to 6 months.

Although a number of medications have been used for the prevention of migraines, the medications that have been shown to be effective in controlled clinical trials, and are therefore recommended by the American Headache Society and the American Academy of Neurology (AAN) migraine prevention guidelines include:

• Divalproex sodium/sodium valproate
• Topiramate (Topamax)
• Metoprolol (Lopressor, Toprol XL)
• Propranolol (Inderal)
• Timolol (Blocadren, Betimol)

Other medications that are used to prevent migraine headaches include:

ACE Inhibitors

• Lisinopril (Prinivil/Zestril)

Angiotensin II Receptor Antagonists (ARBS)

• Candesartan (Atacand)

Beta-blockers

• Atenolol (Tenormin)
• Nadolol

Calcium Channel Blockers

• Diltiazem (Cardizem LA)
• Nimodipine (Nimotop)
• Verapamil (Isoptin, Calan)

Tricyclic Antidepressants

• Amitriptyline (Elavil)
• Nortriptyline (Nortriptyline Hydrochloride, Nortriptyline Hydrochloride Oral Solution, Pamelor)
• Imipramine
• Doxepin (Silenor)
• Protriptyline (Vivactil)

Other Antidepressants

• Paroxetine (Paxil)
• Fluoxetine (Prozac)
• Sertraline (Zoloft)

Antiseizure Medications

• Topiramate (Topamax)
• Gabapentin (Neurontin)
• Divalproex sodium (Depakote)

Herbals

• Feverfew
• Butterbur
• Coenzyme Q10 (CoQ10)
• Magnesium supplements

CGRP Antagonists

• Monoclonal antibodies
  • Eptinezumab (Vyepti)
  • Erenumab (Aimovig)
  • Fremanezumab (Ajovy)
  • Galcanezumab (Emgality)
• Oral gepants (an older class of CGRP antagonist) 
  • Rimegepant (Nurtec) 
  • Ubrogepant (Ubrelvy)

Triptans can cause:

• Tingling
• Sleepiness
• Flushing
• Throat and chest tightness

The most common side effect of ergotamines is nausea.

Side effects of beta-blockers include:

• Fatigue
• Depression
• Nausea
• Insomnia
• Dizziness
• Lowered blood pressure

Calcium channel blockers can cause:

• Weight gain
• Constipation
• Dizziness
• Low blood pressure

Tricyclic antidepressants are associated with:

• Weight gain
• Dry mouth
• Sedation
• Decreased libido

Other antidepressants may cause weight change and decreased libido.

The side effects of anti-seizure medications depend on the specific drug.

Divalproex sodium can cause:

• Diarrhea
• Dizziness
• Drowsiness
• Hair loss
• Ringing in the ears
• Visual changes
• Shakiness
• Unsteadiness
• Weight changes

Gabapentin may cause:

• Drowsiness
• Dizziness
• Unsteadiness
• Fatigue
• Visual changes
• Dry mouth
• Weight gain
• Nausea
• Constipation

Side effects of topiramate include:

• Weakness
• Fatigue
• Drowsiness
• Dizziness
• Confusion
• Difficulty concentrating
• Tingling of hands and feet
• Loss of appetite
• Diarrhea
• Impotence
• Weight loss

The side effects associated with the herbals used for migraines include burping and gastrointestinal issues.

CGRP antagonists have fewer side effects than many other migraine medications and may include: 

• Pain at the injection site
• Constipation

In 2006, the FDA warned about combining triptan drugs with selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs). Taking the drugs together could cause an overload of serotonin in the body, causing what is known as the "serotonin syndrome.” Symptoms of this life-threatening condition include a rapid increase in blood pressure, fast heart rate, and increased body temperature.

SSRIs include:

• Citalopram (Celexa)
• Escitalopram (Lexapro)
• Fluoxetine (Prozac)
• Fluvoxamine (Luvox)
• Olanzapine/fluoxetine (Symbyax)
• Paroxetine (Paxil)
• Sertraline (Zoloft)

SNRIs include:

• Duloxetine (Cymbalta)
• Sibutramine (Meridia)
• Venlafaxine (Effexor)

Ergot alkaloids should not be used concurrently with drugs that inhibit a certain liver enzyme. Doing so could result in a life-threatening decrease in blood flow to the extremities and/or brain. These drugs include:

• Macrolide antibiotics such as erythromycin (Benzamycin, Engel, Ilotycin), clarithromycin (Biaxin, Biaxin XL), and troleandomycin (Tao)
• HIV protease inhibitors such as ritonavir (Norvir) or indinavir (Crixivan)
• Azole antifungals such as ketoconazole, fluconazole (Diflucan), itraconazole (Sporanox)

The use of topiramate (Topamax) can result in decreased sweating and increased body temperature. This may be especially concerning during hot weather. Wearing light clothes and drinking plenty of fluids while using topiramate during warmer months is very important. A physician should be consulted if body temperature rises. 

Serious complications of constipation and new-onset or worsening of pre-existing high blood pressure (hypertension) may occur with the calcitonin-gene related peptide (CGRP) antagonist erenumab (Aimovig).

Migraine headaches may become less frequent during pregnancy. However, in rare cases, migraines may appear for the first time during pregnancy or become worse. Non-drug therapies are considered to be safer during pregnancy, they should be tried first. Non-drug therapies such as relaxation, sleep, massage, ice packs, and lifestyle changes are considered first-line options during pregnancy.

If drug treatment is required, acetaminophen (Tylenol) is usually the treatment of choice. When used appropriately, acetaminophen treatment does not affect the pregnancy or the unborn baby.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered second-line options and thought to be safest in the second trimester. They should not be used near the time of birth. Opioids are third-line options. Prolonged use of opioids may cause addiction and dependence in mothers and children.

Triptans are reserved for moderate-to-severe symptoms in women who have failed to adequately respond to other treatments. Sumatriptan is the oldest and most studied triptan in pregnancy. A pregnancy registry for sumatriptan did not find an increased risk of birth defects or miscarriage in 600 patients who were treated with sumatriptan during pregnancy.

Ergotamines should not be used during pregnancy as they may potentially induce hypertonic uterine contractions and vasospasms/vasoconstrictions which can cause harm to the unborn baby.

Pregnant women who suffer from frequent migraine headaches may benefit from preventative therapy. Beta-blockers such as propranolol, metoprolol, and atenolol are generally considered to be safe options. Verapamil is the preferred calcium channel blocker because it is relatively safe and has good tolerability. Low-dose antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants (TCAs) may also be considered in some patients, especially those who have underlying depression.

Although it is safest to avoid all medications if breastfeeding, this is not always feasible. Therefore, to avoid unwanted side effects in the breastfeeding infant, medications should be used at the lowest effective dose and for the shortest duration. Generally, the same medications used during pregnancy can be continued after delivery and while breastfeeding. An exception is an aspirin which may cause bleeding problems and Reye's syndrome in the nursing baby and should therefore be avoided. Mothers who must take medications should also consider not breastfeeding.

Divalproex (Depakote ER, Depakote Sprinkle Capsules, Depakote) should not be used in patients with liver or pancreatic disease.

SOURCES:
American Headache Society
Annals of Allergy, Asthma, and Immunology
Food and Drug Administration
Kaiser Permanente Drug Encyclopedia
Migraine Research Foundation
The Migraine Trust
National Migraine Association
National Headache Foundation
“Headache in pregnant and postpartum women.” UpToDate.
“Report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society.” Neurology
WebMD