Headache Medication Guide

1. Fluctuations in the amount of “neurotransmitters,” especially serotonin, circulating in the body. Neurotransmitters such as serotonin, norepinephrine and dopamine are chemicals that special cells release to produce changes in your body. Inappropriate amounts of neurotransmitters can contribute to headaches, particularly chronic headache.

2. Inflammation around nerves and blood vessels in your head can result in pain.

3. In the past, medical experts thought that migraine was caused by blood vessel changes. When blood vessels enlarge (dilate), they can release irritating chemicals and physically stimulate surrounding nerves, both of which may lead to pain. We now know that blood vessel changes, though they do occur, are not the primary biological cause of migraine and other headaches.

4. Muscle tension previously was also viewed as the main cause of headaches. Today, we know that muscle tension can contribute to headaches but is not typically the main cause.
 

Most medications used in headache treatment are intended to help with at least one of the following:

1. Mimic serotonin effects

2. Maintain appropriate levels of your body’s own serotonin (or other neurotransmitters)
3. Limit inflammation
4. Stabilize blood vessels
5. Reduce muscle tension
 

Treatment of chronic headaches is often a challenging, long-term process. Though medications can provide benefits by themselves, they are usually more effective when combined with other therapies. These may include proper diet, stress management, adequate sleep, counseling and exercise.

Abortive Medications

Abortive medications can reverse, stop ("abort") or significantly relieve a headache that is beginning or is about to occur. The sooner that you use an abortive medication at the onset of a headache, the more effective they may be. Do not take abortive medication every day. Use it only “as needed.” Overuse of abortive medication contributes to rebound headaches. Talk to your health care provider if you think you are taking too much abortive medication. 

•  Antihistamines – Antihistamines such as hydroxyzine (Vistaril) and diphenhydramine (Benadryl) can be effective for relieving pain. They may also decrease nausea and can stop the side effects of other medications such as droperidol. Possible side effects include drowsiness, dry mouth, urinary retention and constipation. 

• Corticosteroids – Steroids work by decreasing inflammation around blood vessels during a headache attack. Steroid tablets are often given on a tapering schedule, or a long-acting steroid injection may be used. Take steroids with food, as they commonly cause upset stomach. Steroids may also lead to higher energy/trouble sleeping and changes in blood sugar levels (especially in people with diabetes). Long-term use of steroids can cause serious side effects. However, steroid use in headaches is normally limited to less than a week, making possible complications less likely. Steroids used for headache treatment include prednisone (Deltasone), dexamethasone (Decadron) and methylprednisolone (Medrol). 

• Depacon – When given by rapid intravenous (IV) infusion, valproic acid (Depacon) appears to have some added anti-pain properties that are not seen when given by mouth. Depacon may stop the actions of neurotransmitters which conduct pain signals. Side effects are rare. 

• Dihydroergotamine (DHE-45) – DHE-45 by mimicking some effects of serotonin, and to a lesser extent, by directly decreasing the size of blood vessels. Typically, a course of DHE-45 is every eight hours for a total of nine doses. If the first course of DHE-45 is not successful, it may be repeated. DHE-45 can cause stomach upset. So before having DHE-45, you may be given a medication that stops stomach upset (an "anti-emetic"). DHE-45 is similar to ergotamine. Both medications can cause tingling in the hands or lower legs, increased blood pressure and dry mouth. Examples are DHE-45 (injectable solution) and Migranal (nasal spray DHE-45).

• Ergotamine – This medication helps headaches by decreasing the size of enlarged blood vessels. Though widely used several decades ago, ergotamine use has significantly decreased. Today, more effective and better tolerated medications are available. Examples of some ergotamines include Bellergal-S (a combination ergotamine product) and Cafergot tablets. (Wigraine and Cafatine have been discontinued by the manufacturer.)

• Magnesium  – How intravenous (IV) magnesium stops a headache attack is not known. However, inhibition of blood vessel changes and decreased inflammation are thought to be involved. Side effects are few and tend to be mild. They include flushing of the face/neck and brief decreases in blood pressure. Magnesium deficiency has been suggested as a potential trigger of migraine attacks in some people. This problem can be treated with magnesium supplements taken by mouth (oral).

• Muscle relaxants – These medications help relax tense muscles and block the body’s perception of pain. While drowsiness is common, other side effects include muscle weakness, insomnia and vertigo. Examples of muscle relaxants include orphenadrine (Norflex), baclofen (Lioresal), metaxalone (Skelaxin), cyclobenzaprine (Flexeril), carisoprodol (Soma), chlorzoxazone (Parafon forte), tizanidine (Zanaflex) and orphenadrine with caffeine and aspirin (Norgesic Forte). Lioresal, flexeril and zanaflex can also be used as preventive medication.

• Non-steroidal anti-inflammatory drugs (NSAIDs) – NSAIDs decrease inflammation (release of chemicals that cause pain, redness and swelling) that can occur during a headache. All NSAIDs can irritate the stomach; therefore, always take them with food and plenty of water. Examples include ketorolac (Toradol), ibuprofen (Motrin), flubiprofen (Ansaid), Naproxen (Anaprox, Aleve), indomethacin (Indocin) and etodolac (Lodine). Cox-2 inhibitors (Celebrex), which are similar to NSAIDs, may also be used for treatment of headache pain and inflammation. 

• Opioids – Opioids, or "narcotics," work on the body’s nervous system to block the perception of pain. Opioids should not be used daily. Use them only "as needed," as they typically do not provide long-term headache relief. Possible side effects include drowsiness, constipation, upset stomach, low blood pressure and physical dependence. Some opioids used for chronic headache relief include dolophine (methadone), nalbuphine (Nubain) and butorphanel (Stadol injection and nasal spray). Poor choices for chronic headache treatment include Demerol, butalbital (Fiorinal, Fioricet, Esgic), morphine, hydrocodone products (Vicodin, Lortab, Norco), codeine products, oxycodone products (Percocet, Percodan). 

• Phenothiazines – The exact way that phenothiazines relieve headache is not completely understood, but is believed to be due to effects on the neurotransmitters. In addition to headache pain, phenothiazines can also relieve nausea and vomiting. Phenothiazines may cause drowsiness, low blood pressure and tremors. Phenothiazines used to treat headaches include droperidol (Inapsine), promethazine (Phenergan) and prochlorperazine (Compazine).

• Triptans – Triptans work by copying the effects of serotonin and restoring normal blood vessel size. If one triptan doesn't provide effective relief for a headache sufferer, it is reasonable to try a different triptan. In special situations such as menstrual migraine, triptans can be used on more than two or three consecutive days. Side effects may include chest tightness, tingling and facial flushing. Your health care provider may give you an initial "test-dose" in his or her office to see what effects, if any, the medication will have on you. Some commonly used triptans are listed in the table below.

Drug	Form	Usual maximum dose	Injection Form	Nasal Spray	Onset of Action	Duration of action
Imitrex (sumatriptan)	Yes	200mg (tabs)	Yes	Yes	Rapid	Normally repeated in 2 hours
Maxalt (rizatriptan)	Yes (meltable)	30mg	No	No	Rapid	Normally repeated in 2 hours
Zomig (zolmitriptan)	Yes (meltable)	10mg	No	Yes	Rapid	Normally repeated in 2 hours
Axert (almotriptan)	Yes	25mg	No	No	Rapid	Normally repeated in 2 hours
Relpax (eletriptan)	Yes	40mg	No	No	Rapid	Normally repeated in 2 hours
Frova (frovatriptan)	Yes	5mg	No	No	Medium	Normally repeated in 2 hours
Amerge (naratriptan)	Yes	5mg	No	No	Slower	Normally repeated in 4 hours

Abortive Medications Used Primarily in Cluster Headache

• Anesthetics  – Liquid cocaine and lidocaine are commonly used. They stop nerves from sending pain signals. These medications have a short duration of action, sometimes only 15 minutes of relief. They are given in the nose, which allows the drug to physically contact the nerves. 

• Oxygen – Breathing oxygen through a mask can quickly increase the amount of oxygen delivered to the blood vessels in your head and result in blood vessel changes that stop a headache attack.

Preventive Medications

Preventive medications can help decrease the frequency, severity and/or duration of headaches. Preventives are normally prescribed for people

Preventive medication may cause abortive medications to be more effective. Unlike abortive medication, preventive medicine should be taken every day, whether you have a headache or not. You may need to take preventive medications daily for at least four to six weeks before you feel the full effect of the medication. Do not abruptly (suddenly) stop taking a preventive medication. Talk to your health care provider first. Many of these medications must be slowly discontinued over time to avoid disturbing side effects.

Virtually all medications used to treat headaches are also used to treat other conditions. Don’t be confused by terms such as “anti-seizure” or “anti-depressant,” among other names. The main purpose of these medications is to treat your headache.

• Beta-blockers – These medications work by stabilizing blood vessels; thus, minimizing size changes and limiting stimulation of the surrounding nerves. Also, beta-blockers can stop the effects that neurotransmitters can have on blood vessels. Possible side effects include fatigue, light headedness, sleep interruption, decreased heart rate and sexual dysfunction. Some commonly used beta-blockers for headache treatment include propranolol (Inderal, Inderal LA), nadolol (Corgard), bystolic (nebivolol), atenolol (Tenormin) and metroprolol (Lopressor, Toprol XL).

• Botox (botulinum) – Botulinum is a naturally-occurring toxin. When given by subcutaneous injection in small doses, it can provide health benefits that include prevention of chronic headache. Botulinum is given on an outpatient basis, so speak with your health care provider about this therapy. 

• Calcium channel blockers – Similar to beta-blockers, these medications help stabilize blood vessels. Potential side effects include constipation, light headedness (especially when standing up), low blood pressure, facial flushing and upset stomach. Examples include verapamil (Isoptin, Calan, Verelan, Covera) and nimodipine (Nimitop). 

• Dopamine reuptake inhibitors – Medications such as bupropion (Wellbutrin) increase the amount of dopamine available for your body to use. People with a history of seizures should not use this drug. Side effects include agitation, insomnia and upset stomach.

• Selective serotonin reuptake inhibitors (SSRI) – SSRIs increase the amount of serotonin available for your body to use. Potential side effects include drowsiness, constipation, insomnia, upset stomach, tremor and sexual dysfunction. SSRIs used for headache treatment include fluoxetine (Prozac), paroxetine (Paxil),setraline (Zoloft), citalopram (Celexa) and escitalopram (Lexapro).

• Serotonin and norepinephrine reuptake inhibitors (SNRI) – SNRIs such as venlafaxine (Effexor XR) and duloxetine (Cymbalta) increase the amount of the serotonin and norepinephrine available for your body to use. In addition to causing the same side effects as SSRIs, these medications can also cause dry eyes or dry mouth. 

• Specific serotonergic/noradrenergic – Medications such as mirtazapine (Remeron) cause your body to release increased amounts of serotonin and norepinephrine and stop the effects of histamine. Possible side effects include excessive sleepiness, constipation, dry mouth and increased appetite. 

• Tricyclic antidepressants – These medications alter the amount of serotonin and norepinephrine available for your body to use. They can also stop the effects of histamine (histamine release can result in swelling of blood vessels and contribute to pain). Side effects may include drowsiness, upset stomach, dry mouth, dry eyes, increased appetite, constipation and sexual dysfunction. Examples include amitriptyline (Elavil), protriptyline (Vivactil), doxepine (Sinequan), desipramine (Norpramine), imipramine (Tofranil), nortriptyline (Pamelor), trimipramine (Surmontil) and amitriptyline/chlordiazepoxid (Limbitrol).

Neurotransmitter Modulators

Other neurotransmitters besides serotonin and norepinephrine may be involved in causing headaches. Thus, medications that help properly regulate other neurotransmitters can often help in headache relief. These drugs include:

• Gabapentin (Neurontin) and pregabalin (Lyrica) – These two medications are structurally related. Their exact mechanism of action is not known, but they can be useful for a variety of types of pain. Drowsiness is the most common side effect. 

• Lidocaine patches – Lidocaine is an anesthetic that disrupts a nerve’s ability to send pain signals. Lidocaine patches can be cut into smaller sizes and applied to a hairless area such as the forehead or neck. People typically apply a patch for 12 hours, and then remove it for 12 hours before using another patch. Side effects are uncommon.

• Lithium – Lithium is normally used for cluster headaches. The exact mechanism of action is not known. Drink plenty of water while taking lithium and eat a consistent amount of salt-containing foods. You will need to have lithium blood levels drawn on a regular basis. Ask your health care provider about your blood test schedule. Possible side effects include thirst, upset stomach, fatigue, frequent urination and tremor. Examples include lithium (Eskalith) and sustained release lithium (Eskalith CR, Lithobid, Lithotabs).

• Topiramate (Topamax) – This medication is FDA-approved for the prevention of migraine. On-going research is examining topiramate for chronic headaches. Its mechanism of action is unknown, although topiramate appears to affect neurotransmitters, primarily GABA. Drowsiness, fatigue, upset stomach, tremor and memory difficulties may occur. 

• Valproic acid (Depakote) – Depakote increases the amount of GABA (gamma aminobutyric acid) available. Side effects may include upset stomach, drowsiness and liver effects. Most people have their blood drawn every two to 12 months to make sure your liver is not harmed. Three out of 100 women and a lower number of men may have hair loss. Take a daily vitamin containing zinc and selenium to help reduce this problem. Hair growth will return after the Depakote is stopped. Depakote ER (extended-release) is a new formulation. If you are prescribed Depakote, always check your medication bottle carefully to make sure you receive the correct Depakote tablet.