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Headache Medications: 2000
Lawrence Robbins, M.D.
Posted Oct 1999

This guide is the author’s opinions; prescribing should be individualized, in conjunction with more complete medical references such as the PDR. Many of the listed medications do not have an FDA indication for headache.

The following is based upon Dr. Robbins’ 2 books:

Management of Headache and Headache Medications
2nd edition (2000)
Springer-Verlag |
ISBN: 98944-7
(Reviewed as the top book for physicians on headache)
To order: 1-800-SPRINGER – approximately $ 50.00

Headache Help
2nd edition (2000)
At: Barnes & Noble, Borders – approximately $ 11.00

Dr. Lawrence Robbins has directed the Robbins Headache Clinic since 1986. Any of this material may be copied for your use. This guide is only the opinion of the author and does not represent "standard consensus" treatment. Many listed drugs do not have an FDA indication for headache.

Table 1: First Line Migraine Abortive Medications

  1. Sumatriptan (Imitrex): This is the ‘gold standard’ and most effective migraine abortive. The nasal spray of Imitrex is available at a very low dose, 5 mg., or the usual dose, 20 mg. One nasal spray is approximately equal to one 50 mg. tablet. We use one nasal spray every three to four hours as needed, two per day at most. The nasal spray is very well tolerated, but can give a bad taste in the mouth. This can be alleviated by keeping the head upright during administration of the spray and by utilizing juice or a carbonated beverage at the same time as taking the spray. The usual oral dose is one 50 mg. tablet q 2-3  hours, 4 per day at most. The SQ (6 mg.) Imitrex is the most effective migraine abortive for more severe, faster onset migraines.
  2. Maxalt: Very similar to Imitrex. Maxalt is very effective for migraine headaches. The usual dose is 10 mg. of the tablets or the Maxalt MLT rapidly disintegrating tablets, which are placed on the tongue. These rapidly disintegrating tablets have a pleasant taste. Side effects are similar to those of Imitrex. Maxalt is very well tolerated. Certain patients tolerate one of these triptans better than another and it is worthwhile to try several in an individual patient. While some patients utilize the 5 mg. tablet, 10 mg. is well tolerated and more effective. The MLT form may be taken without water, which is an advantage.
  3. Amerge: The usual dose is 2.5 mg. every three to four hours as needed, two or three in a day at most. Amerge is the "kinder, gentler, smoother" triptan. Amerge takes longer to work, up to two hours, but has a long half-life. With a half or one tablet of Amerge, most patients will not have more than minimal side effects. It is better tolerated that the other triptans, but somewhat less effective than Imitrex. Amerge is good for long lasting headaches or headaches of slow, rambling onset. Amerge can also be used as a preventive medication for menstrual migraine. If triptans are used as preventive medications, Amerge may be a good choice.
  4. Zomig: Zomig, 2.5 mg. or 5 mg., is another in the growing list of triptans. The usual dose is 5 mg. every three to four hours, as needed, two per day at most. Zomig has the same general tolerability and efficacy profile as the others. Again, if patients do not tolerate one triptan, it is often worthwhile to try another because they may be able to tolerate another version.
  5. Migranal Nasal Spray: Definitely not nearly as effective as the triptans. Migranal Nasal Spray is dihydroergotamine (DHE). This has been available since 1945 in one form or another with remarkably few serious side effects in all of that time. The usual dose is one spray in each nostril and you can repeat it, and often do need to repeat it, in 15 or 20 minutes. That would be the maximum for the day, which is two sprays in each nostril. Migranal is relatively well tolerated. As with the triptans, tightness in muscles, a flushing feeling, or slight chest heaviness can occur. Nasal stuffiness is relatively common with Migranal. Since DHE is primarily a venoconstrictor and is only a mild arterial constrictor, Migranal may be safer in the population with risk factors for cardiac disease. Migranal may also be useful for menstrual migraines, as it has a fairly long duration of action. The older (compounded) version, DHE nasal spray, works as well as Migranal and is less expensive. The compounded DHE should be refrigerated, however.
  6. Excedrin (Excedrin Migraine): Useful as an over-the-counter preparation with aspirin, caffeine, and acetaminophen. Anxiety from the caffeine or nausea from the aspirin is common. One or two pills every 3 hours as needed are effective for many patients with mild or moderate migraines. Aspirin Free Excedrin is also available, but is less effective. This contains acetaminophen plus caffeine. Rebound may occur with overuse.
  7. Naproxen (Anaprox, Naprelan, Aleve): Useful in younger patients, occasionally helpful for menstrual migraine. Naprelan is an outstanding long-acting form of Naproxen, available in 375 mg. and 500 mg. Nonsedating, but very frequent GI upset. The usual dose is 500 mg. with food or Tums to start, then may repeat in one hour (if no severe nausea), and then in 3 or 4 hours. Three per day at most. OTC as Aleve (2 Aleve approx. = 1 Anaprox ). Adding caffeine increases efficacy. Naproxen may be used at the same time as a triptan.
  8. Ibuprofen: Over-the-counter, and approved for children. Liquid Advil is available. Not as effective as Anaprox. Occasionally useful in menstrual migraine. GI side effects are common. The usual dose is 400 to 800 mg., every three hours, limiting the total dose to 2,400 mg. per day. Combining with caffeine may be helpful. The short half-life is a drawback. May be used with triptans, even at the same time.
  9. Midrin: Effective, safe and used in children. Fatigue is common. Contains a vasoconstrictor, a nonaddicting sedative, and acetaminophen. Usual dose is one or two caps to start, then one every hour as needed, five or six per day at most. May be combined with caffeine for increased efficacy. Generally well tolerated. Generic may not work as well. After many years, remains an outstanding abortive, but not as effective as triptans (Imitrex, Maxalt, Amerge).
  10. Fiorinal, Fioricet, Esgic, Phrenilin:Fiorinal contains ASA, butalbital, and caffeine; Fioricet, Phrenilin and Esgic replace the ASA with acetaminophen. Generics of these compounds do not work well. These are addicting, but very effective for many patients. Dosage is one or two pills every 3 hours, with a limit of 30 or 40 pills per month at most. Fiorinal or Fioricet with codeine (#3) adds 30 mg. of codeine, and is more effective than plain Fiorinal or Fioricet. Esgic Plus adds additional acetaminophen to Esgic. Phrenilin contains no aspirin or caffeine, and is very useful at night, or in those with GI upset.
    See Table 12-a for ingredients of butalbital medications.
  11. Eletriptan (Relpax):Another triptan tablet, with similar efficacy as sumatriptan.

Table 2: Second Line Abortive Migraine Medications

  1. Ergots: Vasoconstrictors, with many side effects, but usually effective. Nausea and anxiety are common with ergotamine compounds. Cafergot adds caffeine to the ergotamine. Only generic Cafergot or Cafergot PB is available. Suppositories are more effective than pills. Rebound headaches are common with overuse of ergots. Use with caution after age 40, particularly with cardiac risk factors. Ergomar SL tabs are back on the market.
  2. DHE: Effective as an IV or IM injection, and occasionally as a nasal spray. DHE is safe and well tolerated. Nausea, leg cramps, and burning at the injection side are common. IV DHE is very effective in the office or emergency room. One mg. IM or IV is the usual dose, but this may be titrated up or down. Migranal is now available as the DHE Nasal Spray (See Table 1).
  3. Ketorolac (Toradol): The injections are much more effective than the pills. Patients may use the injections, 60 mg. per 2 cc at home. The syringes have changed, where Toradol is now available in vials, which the patient must draw up into the syringe. These have the advantage over the pre-filled syringes in that we can use a smaller gauge and shorter needle than was previously available. The usual dose is 60 mg., which may be repeated in 1 hour if necessary. Nausea or GI pain may occur. Ketorolac is nonaddicting and does not usually cause sedation. Limit to 3 per week due to possible nephrotoxicity.
  4. Corticosteroids: Cortisone is often the most effective therapy for severe, prolonged migraine. Dexamethasone (Decadron) or Prednisone are the usual oral forms, and are dosed at 4 mg. of Decadron or 20 mg. of Prednisone, ½ or 1 every 4 to 6 hours, as needed. Three tablets a month is the usual maximum. These are very helpful for menstrual migraine. The small doses limit side effects, but nausea, anxiety, fatigue and insomnia are seen. IV or IM steroids are very effective as well.
  5. Stadol Nasal Spray: This is a last-resort-type medication, as it may produce severe cognitive side effects. One spray in one nostril should be given only every three to four hours as needed. One spray is actually one mg. of butorphanol, which is a powerful narcotic. Stadol is actually a mixed agonist-antagonist. Stadol is much more addicting that was previously thought, and should not be used for daily headaches except in very rare circumstances. However, it is a good parenteral form of a narcotic that is not an injection. Cost is a problem, as each bottle is expensive and you only receive 11 sprays or so out of a bottle.
  6. Narcotics: Fiorinal with codeine, vicoprofen, hydrocodone, oxycodone, meperidine, etc. PO or IM, these are often the best of the ‘last resort’ approaches. IM, they are usually combined with an antiemetic. While addiction is a potential problem, the difference between dependency and addiction is crucial to understand. Ultram is a milder newer analgesic, with relatively few side effects. Vicoprofen combines 7.5 mg. of hydrocodone with 200 mg. ibuprofen; it is more effective than the other hydrocodone preparations because of the addition of ibuprofen, and generally is well tolerated.

Table 3: Antiemetic Medication

  1. Promethazine (Phenergan): Mild but effective for most patients. Very sedating. Low incidence of extrapyramidal side effects. Available as pills, suppositories and oral lozenges (formulated by compounding pharmacists). Used for children and adults.
  2. Prochlorperazine (Compazine): Very effective but high incidence of extrapyramidal side effects. Anxiety, sedation and agitation are common. Given intravenously, it may stop the migraine pain as well as the nausea. Pills, long-acting spansules, and suppositories are available.
  3. Metolclopramide (Reglan): Mild, but well tolerated, commonly used prior to IV DHE. Fatigue or anxiety occur but are not usually severe. Five to 10 mg. are given PO, IM or IV.
  4. Trimethobenzamide (Tigan): Well tolerated, useful in children and adults. Pills, suppositories or oral lozenges may be used (lozenges formulated by compounding pharmacists).
  5. Chlorpromazine (Thorazine): Extremely effective but with increased side effects, particularly sedation. The suppositories often prevent an ER trip by sedating the patient and stopping the nausea. Used with patients where other antiemetics have failed.
  6. Zofran:4 or 8 mg. PO, very effective with few side effects. Very expensive. Not sedating. Zofran is extremely useful for patients who need to keep functioning and not be sedated with an antiemetic. Most patients who use Zofran also utilize another less expensive antiemetic for other times.

Table 4: Information that Patients Need to Know Prior to Starting Prevention Medication

  1. The realistic goals of the medications are to decrease the tension headache severity by 70%, not to completely eliminate the headaches. It is always wonderful when the headaches are 90% to 100% improved, but the idea is to minimize medication. Most patients need to be willing to settle for moderate improvement.
  2. Patients must be willing to change medication, if necessary. They need to know that what is effective for someone else may not work for them. Trial and error may be needed to find the best preventive approach for that person.
  3. The preventive medications may take weeks to become effective. The doses often need to be adjusted, and thus patience will be necessary with these medications. The physician needs to be available for phone consultations pertaining to the headaches and medicine.
  4. Most preventive medications are utilized in medicine for another purpose. It is best if patients are informed, for instance, that Elavil is also used for depression, usually in much higher doses. Patients should be told why we are utilizing Evavil, and that it is not because they are depressed.
  5. Side effects are possible with any medication, and the patient has to be prepared to endure mild side effects in order to achieve results. We cannot simply stop medication and switch to another because of very mild side effects. Most patients are willing to put up with mild, annoying side effects.
  6. In the long run, preventive medications are only effective for approximately 50% of patients.

Table 5: First Line Preventive Medications for Migraine

  1. Valproate (Depakote): This seizure medication is becoming increasingly popular for migraine prevention. Usually well tolerated in the lower doses utilized for headaches. Liver functions need to be monitored in the beginning of treatment. Side effects include lethargy, GI upset, depression, memory difficulties, weight gain and alopecia. Dosage ranges from 250 to 2,000 mg. per day, in divided doses. The average dose is 1,000 mg. per day. Levels need to be checked for toxicity on the higher doses. The efficacy has now been established with double-blinded studies. Depakote is also one of the main "mood stabilizers" for bipolar (manic-depression).
  2. Propranolol (Inderal): Effective. Long-acting (LA) capsules may be dosed once per day. Occasionally, effective for daily headaches. Sedation, diarrhea, lower GI upset and weight gain are common. Very useful in combination with amitriptyline. Dosage begins with LA 60 mg., and is usually kept between 60 and 160 mg. per day. Other ß-blockers can also be effective, such as metoprolol and atenolol. Some of these are easier to work with than propranolol because they are in scored tablets, and metoprolol and atenolol have less respiratory effects.
  3. Naproxen (Naprosyn, Naprelan, Anaprox): Useful in younger patients, once a day dosing. Sometimes helpful for daily headaches. Particularly useful for menstrual migraine. nonsedating, but frequent GI upset. Effective as an abortive, and may be combined with other first line preventive medications. The usual dose is 500 or 550 mg. once a day, but this may be pushed to twice a day. OTC as Aleve. Other anti-inflammatories, such as Oruvail, Voltaren or Cataflam, can be utilized for prevention of migraine. As with all anti-inflammatories, GI side effects increase as people age, and so we use these much more in the younger population. The COX-2 inhibitors (Vioxx, Celebrex) will be very useful. These COX-2 inhibitors are useful abortively for pain, and may prove helpful in preventing headaches as well. They greatly decrease the GI risk.
  4. Verapamil: Reasonably effective for migraine, once a day dosing with the slow release (SR) tablets. Usually nonsedating, and weight gain is uncommon. Occasionally helpful for daily headaches. May be combined with other first line medications, particularly amitriptyline or naproxen. Constipation is common. Starting dose is ½ of a 240 mg. SR pill, increasing quickly to one 240 mg. pill per day. May be pushed to 240 mg. twice a day, or decreased to 120 mg. or 180 mg. per day.
  5. Amitriptyline (Elavil): Effective, inexpensive and also useful for daily headaches and insomnia. Use in low doses, at night. Sedation, weight gain, dry mouth and constipation are common. Starting dose is 10 mg., working up to 25 or 50 mg.; can be pushed up to 200 mg., or decreased to 5 mg. Other tricyclic antidepressants such as Doxepin, and protriptyline can be effective for migraine. Nortriptyline is similar to amitriptyline, with somewhat fewer side effects. These are generally used more for daily tension-type headaches. Protriptyline is one of the only older antidepressants that does not cause weight gain. However, anticholinergic side effects are increased with protriptyline.

Table 6: Second Line Migraine Preventive Therapy

  1. Polypharmacy: Two first line medications are used together. The combination of two preventives is more effective than one drug alone. Depakote is often combined with an antidepressant. Amitriptyline is often combined with propranolol, particularly if the tachycardia of the amitriptyline needs to be offset by a ß-blocker. This combination is the most commonly used one for "mixed" headaches (migraine plus chronic daily headaches). The NSAIDs may be combined with any of the other first line preventive medications. Thus, naproxen is often given with amitriptyline, propranolol or verapamil. Naproxen or other NSAIDs are employed simultaneously as preventive and abortive medication.
  2. Methysergide (Sansert): Extremely effective, but with more side effects than the other first line medications. Nausea, leg cramps and dizziness are common. Screening for the very rare fibrosis must be done, and the drug should be stopped for 1 month, every 5 or 6 months. Dosage is one to four pills per day, with food; try to attain the least possible dose.
  3. Neurontin: Neurontin (gabapentin) is an anti-seizure medication that has been demonstrated to be useful in migraine and tension headache prophylaxis. Capsules are available in 100 mg., 300 mg. and 400 mg. sizes. The usual dose for headache prevention is 600 to 1800 mg. per day. In a recently completed large study on migraine, doses ranged around 2,300 mg. per day. Sedation and dizziness can be a problem; however, Neurontin does not appear to cause end-organ damage, and weight gain is relatively minimal. Neurontin can be used as an adjunct to other first line preventive medications. Some patients do well with very low doses (200 or 300 mg. per day).

Table 7: Preventive Medication: When to Proceed Quickly with Two Preventives at One Time

  1. With most patients, we utilize one prevention medication at a time, in low doses, slowly raising the dose as needed. Most of the patients appreciate the approach, and are perfectly willing to wait for the medication to work.
  2. At times, patients may become extremely frustrated with the headaches, and they desire quick results. When these patients suffer from moderate or severe CDH, with bothersome migraines, it is justified to push ahead at a faster rate with a preventive approach. For instance, amitriptyline and verapamil, or amitriptyline and propranolol may be initiated at the same time. Alternatively, doses may be increased very quickly. The IV DHE repetitive protocol may be utilized, with one or two preventive medications instituted concurrently. The initial amount of preventive medication utilized for a patient depends upon the severity of the headaches and the frustration level of the patient.
  3. Patients with new onset of severe headaches, which are usually daily headaches plus migraine, are often extremely upset and frustrated with the pain. In this situation, pushing preventive medication at a faster pace is justified.

Table 8: Third Line Migraine Prevention ("End of the Line")

  1. Long-acting opioids (methadone, Oxycontin, Kadian, MS-Contin): In a very small select group of severe headache patients, particularly with severe, refractive, chronic daily headaches and migraines, long-acting opioids have some demonstrated utility. Methadone may work because of its antagonism on NMDA. Methadone is relatively well-tolerated, but sedation and constipation are limiting factors. Doses need to be kept low, from 5 mg. to 20 mg. per day. Morphine is available as MS-Contin or the once a day Kadian. This is occasionally helpful as well, but not as useful as methadone. Oxycontin is a long-acting oxycodone without the acetaminophen or aspirin. Oxycontin can also be useful, but is more expensive than methadone and tends to have more tolerance associated with it. May be combined (in low doses) with stimulants.
  2. Repetitive IV DHE Therapy: Helpful for patients with frequent migraine, severe daily headache, status migraine, and cluster migraine. Weeks of headache improvement are often seen. IV DHE is useful in patients withdrawing from analgesics. The protocol can be done in the office or hospital. In the office, the first dose, ½ mg. is given, and if it is well tolerated, the subsequent doses are 1 mg. Three or four doses are given in the office, and up to nine in the hospital. Side effects include nausea, heat flashes, muscle contraction headache, leg cramps, diarrhea, and GI pain. The IV DHE is usually well tolerated and effective. After the DHE, patients are continued on prevention medication.
  3. Stimulants: (Dextroamphetamine, Methylphenidate, Phentermine): Occasionally useful as a "last resort" therapy. Phentermine is also a possibility and can be an adjunct to other medications. Recently, it was discovered by French scientists that phentermine actually has significant MAO inhibitor activity which may explain its utility in pain. Phentermine is activating and can cause insomnia. However, it can also help decrease appetite, which is its primary use, and decreases sedation in patients with chronic fatigue. Dexedrine and Ritalin may be used in combination with long-acting opioids. Addiction is a risk.
  4. Phenelzine (Nardil): The MAO inhibitor (MAOI) is a powerful migraine and daily headache preventive medication. Phenelzine may be used alone, or in combination with amitriptyline, verapamil or propranolol. Phenelzine is very helpful for depression, anxiety and panic attacks. The risk of a hypertensive crisis is small, but is a major drawback to the MAOIs. Dietary restrictions render MAOIs difficult for the patient. Side effects include insomnia and weight gain, both of which are often major problems. Dry mouth, fatigue, constipation and cognitive effects may also occur. Patients need to be aware of the symptoms of hypertensive reactions. The usual dose is 45 mg. each night (3 of the 15 mg. tablets). This is adjusted up or down, and the range varies from one to five tablets per day. One other major drawback is that the triptans cannot be used with MAOIs.
  5. Daily Triptans: In some patients with chronic daily headache and frequent migraines, the only medication that is useful is a low dose daily triptan. There are more and more people around the United States on these daily triptans for long periods of time. Long-term side effects are unknown at this time. Particularly well-suited to this type of approach would be the long-acting ones, such as Amerge (naratriptan). Imitrex or Maxalt have been successfully used in some of these patients.

Table 9: "Natural" Headache Herbs/Supplements

  1. Feverfew: Feverfew has been demonstrated to be effective in some patients for prevention of migraine headache. The problem with many herbal supplements is quality control, and certain farms consistently have better quality than others. The parthenolide content varies widely from farm to farm. The usual dose is 2 capsules each morning.
  2. Magnesium Oxide: 500 mg. per day as a preventive; however, GI side effects may limit use. Do not take with calcium, as the magnesium will not be absorbed.
  3. Vitamin B2: 400 mg. per day has been utilized in at least one blinded study, with effect on milder migraines. B6 and B12 may also play a preventive role.
  4. Long Chain Fatty Acids (Omega-3, Omega-6 fatty acids): These may play a role in headache prevention, as well as (possibly) useful for anxiety, depression and heart disease. We usually recommend Flaxseed oil, 1000 mg. , 1 or 2 per day.

Table 10: Treatment of Menstrual Migraine
The abortive therapy follows the general abortive therapy for migraine. Cortisone (Prednisone, Decadron) is very effective for many women; it is utilized in very limited amounts. The severe intensity of menstrual migraines often dictates stronger abortive measures. Triptans (particularly Imitrex SQ) are particularly useful.

Preventive Treatment:

  1. NSAIDs (Naproxen, etc.): Effective for many women and usually well tolerated. These are started 3 days prior to the expected onset of the headache. Many NSAIDs have been utilized, including naproxen, ibuprofen, flurbiprofen, meclofenamate sodium, etc. GI upset is common.
  2. Ergotamine derivatives: The usual forms of ergots utilized include: ergotamine tartrate, ergonovine, DHE and methysergide. These are started 1 to 3 days prior to the onset of the headache. Ergots are poorly tolerated, with frequent GI upset and nausea. Ergotamine rebound may occur, but it is unusual when ergots are used for menstrual migraine.
  3. Hormonal approaches: Tamoxifen (Nolvadex) is sometimes utilized for seven to fourteen days at 10 mg. per day. Estrogen has been used, but is questionably effective. Occasionally, the birth control pill, even on a cyclic basis, will reduce headaches. If used continuously (no break), it may also occasionally be effective. The birth control pill, however, can also increase migraines.
  4. Triptans: Amerge (naratriptan) is a long-acting, smooth, well-tolerated triptan. Its utility in menstrual migraine is being investigated. The usual dose would be 2.5 mg. once or twice a day for three to five days around the time that the menstrual migraine would occur. Occasionally, sumatriptan, which is shorter acting than naratriptan, has been used for this purpose. Rizatriptan (Maxalt) may also be useful in this regard.

Table 11: First Line Tension Headache Abortive Medications

  1. Acetaminophen, Aspirin: These are the staple of OTC pain relief; acetaminophen is much less effective for headache, but better tolerated. These need to be limited, so as to avoid the rebound situation.
  2. Ibuprofen (Motrin): Helpful for migraine and tension headache. Useful in children, and a liquid form is available. GI upset is relatively common, but ibuprofen is more effective for headache than acetaminophen. Adding caffeine can increase efficacy.
  3. Caffeine: Caffeine beverages or tablets (100 mg.) are helpful for migraine and tension headache, either alone or as an adjunct to analgesics. Caffeine added to other abortives enhances their effectiveness and decreases drowsiness. For example, Midrin plus caffeine is an effective combination. Caffeine must be limited so as to avoid "rebound" headaches.
  4. Caffeine-aspirin combinations: Excedrin Migraine has 65 mg. caffeine, 250 mg. of aspirin, and 250 mg. of acetaminophen; this is a very effective OTC preparation, but overuse leads to rebound headaches. Anacin contains much less caffeine (32 mg.). Aspirin Free Excedrin is a very useful combination of acetaminophen and caffeine.
  5. Naproxen (Anaprox, Aleve (OTC), Naprelan): Useful in younger patients, nonsedating, but very frequent GI upset. The usual dose is one 500 mg. tablet with food, which may be repeated up to a maximum of three per day. If used on a daily basis, two per day should be the limit. Adding caffeine can increase efficacy. Naprelan is an excellent long-acting form of naproxen, available in 375 mg. and 500 mg. One Aleve=220 mg.
  6. Cox-2 inhibitors (Vioxx, Celebrex): These are useful for some headache patients, with significantly less GI side effects. Adding in caffeine may enhance efficacy. The usual dose is 12.5 or 25 mg. of Vioxx, once or twice per day "as needed". Vioxx has been useful for preventing and aborting pain.
  7. Midrin: Effective, safe, and used in children as well as adults. Primarily a migraine abortive, Midrin is also very helpful for tension headache. The usual dose is one or two per day to start, then one every hour as needed, five or six per day at most. May be combined with caffeine for increased efficacy. Sedation and light-headedness may occur.
  8. Ultram: 50 mg. tablets, 1 or 2 every four hours, relatively few side effects but sedation, nausea, and dizziness may occur. Addiction uncommon but is occasionally seen. Need to limit to 4 per day, 10 per week. Generally well tolerated.
  9. Ketoprofen: NSAID now available OTC. Most patients require 3 or 4 of the low strength OTC tablets. Adding caffeine can increase efficacy. Some GI side effects, as with other NSAIDs.

Table 12: Second Line Tension Headache Abortive Medications

  1. Butalbital compounds: Effective but habit forming. Fiorinal, Esgic, Esgic Plus, Fioricet, Axotal, and Phrenilin are the primary butalbital compounds. Generic butalbital preparations do not work as well as brand names. Sedation or euphoria is common. Strict limits need to be set for daily and monthly use. If used daily, one or two is the usual limit.
    See Table 12-a for ingredients of butalbital compounds.
  2. Narcotics: Codeine, hydrocodone, and propoxyphene are commonly utilized. These are a last resort, should be limited per month, and generally should not be used on a daily basis. These need to be discontinued if patients use them to alleviate stress, depression, fatigue or anxiety. Vicoprofen combines 200 mg. ibuprofen with 7.5 mg hydrocodone, and is generally more effective than Vicodin.
  3. Sedatives: Most are benzodiazepines, such as diazepam (Valium) and clonazepam (Klonopin). Chlordiazepoxide (Librium) is also useful. Sedation is common. Because they are habit forming, these need to be monitored with a monthly limit. They are a last resort, not a first choice. Addiction is always the major drawback.
  4. Triptans: While triptans are generally utilized for migraine and cluster headaches, the triptans can be useful for tension headaches as well, particularly the more severe tension headaches. There are some patients who only do well with a triptan with any of their headaches, such as Imitrex, Amerge, Zomig or Maxalt. In migraine patients, triptans often work for their "lesser" headaches.

Table 12-a: Butalbital (Fiorinal) Compounds
Fiorinal (Butalbital 50 mg / Aspirin 325 mg / Caffeine 40 mg.): 1 or 2 every 3 hours prn; 6 a day maximum. Habit forming; the aspirin may cause nausea. The most effective of the butalbital class.

Fioricet or Esgic (Butalbital 50 mg / Acetaminophen 325 mg / Caffeine 40 mg / Esgic Plus has 500 mg. of acetaminophen): 1 or 2 every 3 hours prn; 6 a day maximum. Less nausea than with fiorinal, but less effective.

Phrenilin (Butalbital 50 mg / Acetaminophen 325 mg / Phrenilin Forte has 650 mg of acetaminophen): 1 or 2 every 3 hours prn; 6 a day maximum. Less effective than the other butalbitals; good for use at night (no caffeine), less nausea.

Fiorinal with codeine (30 mg) / Fioricet with codeine (30 mg.): 1 every 3 hours prn; 4 a day maximum. The codeine helps but increases the side effects (nausea).

Table 13: First Line Chronic Daily Headache (CDH) Prevention Medication

  1. Valproate (Depakote): Effective for daily headache and migraine; the dose varies widely, from 250 to 2,500 mg. per day. GI upset, fatigue, weight gain and alopecia may occur. Usually well tolerated in low doses. Need to wait at least 4 weeks before abandoning valproate. One of the most widely used and effective preventives for migraine and CDH. The average dose is 1000 mg. per day, but many patients do well on 250 or 500 mg. once daily.
  2. Amitriptyline (Elavil): Effective and inexpensive. Helpful for migraines and daily headache. Sedation, dizziness, dry mouth, weight gain, and constipation are common. Important to begin with only 10 mg., as many patients cannot tolerate more than 10 mg. Average dose is 25 to 75 mg. The weight gain is a major drawback.
  3. SSRI’s (Prozac, etc.): Fewer side effects than amitriptyline, but not as effective. Nausea, anxiety, sexual dysfunction, insomnia are common. Weight gain may occur but is infrequent. Helpful for migraine in some patients. Begin with low doses. Expensive. All of the SSRI’s have been useful for preventing chronic daily headache and to a lesser extent for migraine. Considering tolerability, these are often the best choice for chronic daily headache. Prozac, Zoloft, Paxil and Celexa are all reviewed later in the SSRI section.
  4. Protriptyline (Vivactil): Effective and nonsedating. Weight gain does not occur. Dry mouth, constipation, dizziness are common. Used in the morning, as insomnia is a common side effect. May be used in the morning with a sedating tricyclic at night. Usual dose is 5 to 15 mg. per day (lower than for depression). The only tricyclic that tends not to cause weight gain.
  5. Nortriptyline (Pamelor): Better tolerated than amitriptyline, but less effective. Side effects are similar to amitriptyline, but less severe. Useful in children, adolescents and the elderly. Occasionally helpful in migraine. Usual dose is 25 to 75 mg. per day.
  6. Doxepin (Sinequan): Very similar to amitriptyline; more effective than nortriptyline, but with increased side effects. Begin with very low doses (10 mg. each night), as many patients cannot tolerate more than this amount. Usual dose is 25 to 75 mg. per day.
  7. NSAID’s: Not as effective as antidepressants for chronic daily headache, but without the cognitive side effects. GI side effects are common, however. Hepatic and renal blood tests need to be monitored. NSAID’s are used more frequently in younger patients. Ibuprofen is available over the counter. Naproxen (Naprosyn, Naprelan, Aleve, Anaprox) is more effective than ibuprofen. Flurbiprofen (Ansaid), diclofenac sodium (Voltaren), and ketoprofen (Orudis, Oruvail) are also utilized. As always, attempt to use the minimum effective dose. The COX-2 inhibitors (Celebrex, Vioxx) may be useful without the GI side effects. Vioxx has been helpful as a pain preventive, and as an abortive for acute pain.
  8. Neurontin: See Section in Table 6: Second Line Migraine Preventive Therapy. Neurontin is safe, and may be used (in low doses) in older patients, with no liver or GI toxicity.

Table 14: Second Line CDH Preventive Medication

  1. ß-blockers: Occasionally useful for daily headache and very effective for migraine. Often combined with tricyclics or anti-inflammatories. Propranolol (Inderal) and nadolol (Corgard) are commonly used. Fatigue, depression, lower GI cramps and weight gain may occur. Doses are similar to those used for migraine (generally low doses are used).
  2. Muscle relaxants: Safe but only mildly effective; some patients do respond well to these. Fatigue is a prominent side effect. Skelaxin is very mild, non-sedating, well tolerated. Zanaflex may cause fatigue, but can help prevent migraine and chronic daily headache. Cyclobenzaprine (Flexeril) is one of the most effective, but may cause severe fatigue. Orphenadrine (Norflex) is effective for some patients. It is best to utilize nonaddicting muscle relaxants.
  3. Calcium channel antagonists (Verapamil): Occasionally effective for daily headache as well as migraine and cluster. Verapamil (Calan, Isoptin, Covera HS, Veralan) is the most effective calcium blocker. The SR tablets allow once per day dosing. Constipation and allergic reactions (with a rash) are common. May be combined with tricyclics or anti-inflammatories.

Table 15: Third Line CDH Preventive Therapy

  1. Polypharmacy: Combinations of two of the first or second line preventives are often very effective. Tricyclics may be combined with NSAIDs or ß-blockers; NSAIDs may also be combined with ß-blockers or verapamil. Valproate (Depakote) may be combined with tricyclics, ß-blockers, or verapamil. The various preventive medications possess different mechanisms of action.
  2. Long-acting Opioids: See section in Table 8: Third Line Migraine Prevention Medication.
  3. Repetitive IV DHE: Four to nine injections of 1 mg. DHE are utilized over 2 to 4 days, either in the hospital or, preferably, as an outpatient. More effective for migraine, but daily headache often responds to DHE. DHE is useful in helping to withdraw patients off of analgesics. This is a safe but expensive therapy.
  4. Tranquilizers: More useful in patients with severe anxiety disorders. Occasionally effective for daily headache, but habit forming. Benzodiazepines or phenobarbital are the primary sedatives used for daily headache. Doses need to be minimized and patients must be carefully monitored. Alprazolam (Xanax), Clonazepam (Klonopin), and diazepam (Valium) are the usual benzodiazepines that are used.
  5. Amphetamines: Helpful for some patients as an "end of the line therapy". Methylphenidate (Ritalin) or Dextroamphetamine (Dexedrine) have been used. Tolerance may be a problem. Phentermine (used primarily for weight loss) is occasionally effective.
  6. MAO inhibitors (phenelzine): Phenelzine (Nardil) is a powerful medication for migraine and daily headache. Use is limited because of the dietary restrictions, weight gain and insomnia. Phenelzine is also effective for depression and anxiety. Combining phenelzine with tricyclics, ß-blockers, verapamil or NSAIDs often enhances the efficacy.
  7. The triptans (such as Amerge (naratriptan)) in low doses can be useful for prevention of daily headache. However, long-term side effects are not known.
  8. Botox injections: Still being tested, these may help decrease CDH or migraine for up to 4 months. Twelve injections of low dose (2 units each) Botox are done at one sitting; in low doses, this is very safe. Expensive. Botox relaxes (paralyzes) the muscles that were injected for 3 to 4 months.

Table 16: First Line Abortive Medications for Cluster Headache

  1. Oxygen: Very effective, with no side effects. May be combined with other abortives. Oxygen is worth trying for all patients willing to rent a tank; the usual dose is 8 liters/min., for 10 to 20 minutes as needed, with a mask, used sitting up and leaning slightly forward. 60% success rate.
  2. Sumatriptan (Imitrex) injection: The most effective cluster headache abortive medication. The injections often work within minutes, and cluster patients prefer this route of administration. However, patients may at times require two or three injections in a day. Chest heaviness or pressure, tingling or hot sensation, nausea, fatigue, etc. may occur.
  3. Sumatriptan (Imitrex) nasal spray: The 20 mg. nasal spray is convenient and easy to use. While not as effective or as fact acting as the injection, many patients do prefer this route. Side effects tend to be minimal, but a bad taste in the mouth is common. Cluster patients often require two, or at times, even three nasal sprays in a day. Many patients utilize nasal spray at times, and the injections at other times. Occasionally, the tablets of triptans are preferred by cluster patients.

Table 17: Quick Reference Guide: First Line Cluster Preventive Medication

  1. Cortisone: Very effective for cluster headache; is used primarily for episodic clusters. It is given for 1 or 2 weeks during the peak of the cluster series. Prednisone, Decadron, or injectable forms may be utilized. When used for short periods of time, side effects are minimal. A typical regimen is prednisone (20 mg.) or Decadron (4 mg.) once a day for 3 days, then one-half pill per day for 10 days, then stop. Additional cortisone may be given later in the cycle, when the clusters increase. Higher doses may be needed.
  2. Verapamil (Covera HS, Calan, Isoptin, Verelan): A well tolerated calcium channel blocker; effective in episodic and chronic cluster. One 240 mg. SR pill is taken once or twice per day. This is often initiated at the onset of the headaches, in conjunction with cortisone. Verapamil is then continued after the cortisone is stopped. Constipation is common. Because of its efficacy and a lack of side effects, verapamil is a mainstay of cluster prevention.
  3. Lithium: Very helpful for chronic cluster and, to a lesser degree, episodic cluster. Small doses, one to three of the 300 mg. tablets per day, are used for cluster headache. May be combined with verapamil and/or cortisone. Lithium is usually well tolerated in low doses; drowsiness, mood swings, nausea,tremor, and diarrhea may occur. Blood tests need to be done.

Table 18: Abortive Tension Headache Medications in Children (less than 11 years old)

  1. Acetaminophen: Well tolerated, safe, not as effective as ibuprofen or aspirin. Chewable tablets and liquid are available. The usual dose is 5 to 10 mg/kg per dose. Because of safety, acetaminophen is the usual primary abortive medication to utilize in children. The addition of caffeine may enhance the effectiveness.
  2. Ibuprofen: More effective than acetaminophen, but with occasional GI upset. Liquid Advil is available, which helps in younger children. Caffeine may enhance the effectiveness. The usual dose is 100 to 200 mg. Effective for migraine as well as tension headache.
  3. Caffeine: Either used by itself, or with an analgesic, caffeine is useful for tension and migraine headache. In children, soft drinks containing caffeine are helpful. Side effects are minimal when caffeine is used in very limited amounts.

Table 19: Abortive Migraine Medications in Children (less than 11 years old)

  1. Ibuprofen, Acetaminophen, Caffeine: Ibuprofen is effective and available as a liquid, but GI upset is relatively common. Acetaminophen is very safe, less effective than the other abortives, but easy to use, with liquid and chewable forms available. For children who are nauseated and cannot swallow oral medication, compounding pharmacists are able to formulate acetaminophen into a lozenge, to be kept in the mouth and absorbed by the buccal mucosa. This may be combined, in a lozenge, with an antiemetic such as Phenergan or Tigan. Caffeine decreases migraine pain in most children, and may be used alone, or in combination with other abortives.
  2. Naproxen (Naprosyn, Naprelan, Anaprox): Naproxen is an effective abortive that is nonsedating and is available as a liquid. GI side effects are very common, however. Adding small amounts of caffeine, such as in soft drinks, may enhance the effectiveness. Aleve (OTC) = 220 mg. naproxen.
  3. Midrin: These are very large capsules that consist of a combination of a nonaddicting sedative, acetaminophen, and a vasoconstrictor. The capsules may be taken apart, and the Midrin swallowed with applesauce or juice. Sedation is common, as is lightheadedness. GI upset, although not very frequent, occurs at times.
  4. Butalbital medications (Fioricet, Esgic, Phrenilin): One-half tablet to 1 tablet every 6-8 hours as needed. Sedating. See Table 12-a for a discussion of butalbital medications.

Table 20: Preventive Headache Medications in Children (less than 11 years old)

  1. Cyproheptadine (Periactin): Cyproheptadine is a safe and generally effective first line headache preventive therapy. Fatigue and weight gain may be a problem, but it is usually well tolerated. Cyproheptadine is not as useful after age 11. It may be dosed once a day, and a convenient liquid form is available.
  2. NSAIDs (ibuprofen, naproxen): Ibuprofen and naproxen are available as a liquid, and the lack of sedation renders these very helpful for daily use. GI side effects are relatively common, and when these are used on a long-term basis, regular blood tests for hepatic and renal functions need to be done. Ibuprofen and naproxen may be utilized as daily preventives or as abortives for both tension and migraine headaches. Both are available OTC.
  3. Propranolol (Inderal): Generally well tolerated, propranolol has been used for many years in children with migraine. Fatigue and decreased exercise tolerance may be a problem. With doses less than 60 mg. per day, we need to use propranolol twice per day, which is inconvenient for most children. Cyproheptadine or NSAIDs should usually be prescribed prior to propranolol.

Table 21: Abortive Headache Medications in Adolescents (11 years and older)

  1. At ages 11 and 12, the medications vary between those used for children and those for adults, depending upon weight and maturity. The NSAIDs (ibuprofen, naproxen), aspirin (with or without caffeine) and acetaminophen are most commonly utilized. Midrin is often used in adolescents. Triptans (Imitrex, Maxalt, Amerge) are being utilized with increasing frequency in adolescents. Many adolescents find the Imitrex nasal spray, or the Maxalt MLT (on the tongue) tablets useful at school. See earlier section on first line migraine abortive medications, plus Instructions for patients on Imitrex, Maxalt and Amerge.

Table 22: Headache Preventive Medications in Adolescents

  1. Anti-inflammatories: Frequent GI upset is seen, but the NSAIDs usually do not cause fatigue or other cognitive effects. Ibuprofen (Motrin) and naproxen (Naprosyn, Aleve, Naprelan and Anaprox) are the NSAIDs most frequently utilized. Liquid preparations are available for both of these. Doses need to be kept to a minimum; hepatic and renal functions should be monitored via regular blood tests.
  2. Depakote (Valproate): Useful for both migraine and CDH. Low doses (250 mg. b.i.d.) are used. GI side effects or sedation may occur. Blood tests are done occasionally.
  3. Antidepressants: Highly effective for migraine and daily headache. Nortriptyline (Pamelor, Aventyl), protriptyline (Vivactil), and amitriptyline (Elavil) are most commonly used. Usually well tolerated in low doses and safe for long term use. Cognitive side effects, dry mouth and dizziness are common. SSRI’s (Prozac, Zoloft, Paxil) are extremely useful.
  4. Beta Blockers: Effective for migraine, and occasionally for daily headache. Propranolol (Inderal) and nadolol (Corgard) are most commonly utilized. Beta blockers may decrease exercise tolerance, which is a problem in this age range. Cognitive side effects also limit the utility of beta blockers.
  5. Verapamil (Isoptin, Calan, Covera HS, Verelan): A calcium antagonist, effective for migraine, and occasionally, daily headache. Generally well tolerated, with constipation common. Convenient once per day dosing with the sustained release form.
  6. Feverfew (see section on natural headache herbs): This safe herb has been proven to help prevent headaches; the usual dose is 1 or 2 capsules each morning.

SSRI’s (Selective Serotonin Reuptake Inhibitors)
Chronic anxiety is a problem in approximately 60% of migraine patients. Dysthymia is seen in almost 20% of migraineurs. Migraineurs are 12 times more likely to have panic disorder at some point. The chronic anxiety or depression leads to a decreased quality of life in migraine patients. The selective serotonin reuptake inhibitors (SSRI's) have been very effective in combating anxiety and depression. They also are somewhat helpful in preventing migraine or tension headache. Large-scale studies have not revealed SSRI’s to be more than mildly helpful for preventing headaches. However, they continue to be widely used throughout the United States for headache patients because of positive effect on anxiety and depression. The low incidence of adverse reactions is another factor in the widespread use of SSRI’s.

The safety and efficacy of the major SSRI’s (Prozac/Zoloft/Paxil/Celexa) in treating anxiety or depression is well established. Although SSRI’s are not as effective as tricyclics (amitriptyline, nortriptyline, etc.) for pain, they have a very favorable side effect profile. The SSRI’s have much less of the dry mouth, constipation, weight gain and sedation seen with the tricyclics. SSRI’s are also a safer choice in the elderly, primarily due to tolerability, and the lack of cardiac side effects.

The major SSRI’s do differ somewhat in their side effect profile. Some patients do extremely well with one SSRI, but not with another. The most common side effects are: nausea, drowsiness or fatigue, dry mouth, anxiety, insomnia, decreased libido, impotence, asthenia, sweating, constipation, tremor, diarrhea and anorexia. Weight gain may be seen, but is far less than with tricyclics. Many of the side effects are dose related. Minimizing the dose can, for instance, decrease the sedation or sexual side effects. One key to minimizing side effects is to begin with low doses. Compliance is enhanced when the SSRI’s are slowly titrated. The initial anxiety seen with SSRI’s often abates if low enough doses are utilized.


  1. Start with very low doses. This minimizes sedation and anxiety and increases compliance.
  2. If patients are warned about the initial anxiety that may occur with SSRI’s, they are more likely to be compliant and stay on the medication.
  3. For most headache patients, lower doses are utilized than for severe depression.
  4. If one SSRI does not help or causes side effects, it is very often worthwhile to try another. Patients have widely differing responses to these medications.
  5. Slowly withdraw patients from Paxil and Zoloft in order to avoid the withdrawal syndrome.

Fluoxetine (Prozac): Prozac is available in10 mg., 20 mg., 40 mg. pulvules; 10 mg. scored tablets; liquid=20 mg./5 ml. Prozac is the prototype SSRI, having been used in 33 million patients in the United States. Prozac is a long-acting (elimination half-life=4 to 6 days, but the active metabolite, norfluoxetine, has an elimination half-life of 4 to 16 days) SSRI with a well-established track record. The long half-life is generally an advantage in avoiding the SSRI withdrawal syndrome. It is important to start with low doses of SSRI’s; 5 or 10 mg. of Prozac is a good starting point. Many patients report initial anxiety (or even panic) from SSRI’s, and if they are on a low enough dose, they are less likely to discontinue the medication. Patients can begin with ½ capsule of 10 mg. Prozac, or start with the liquid. Over 4 to 10 days, the dose may be raised to 10 or 20 mg. The effective dose for migraine or tension headache varies widely, from 5 mg. per day to 60 mg. (or more). Most patients are on 20 mg. daily. Milder tension-type headache often responds to low doses (10 or 20 mg). As is true with tricyclics, lower doses of SSRI’s are used for headache than for major depression.

Sertraline (Zoloft): Zoloft is available in 25 mg., 50 mg. and 100 mg. scored tablets. Zoloft is somewhat shorter-acting; elimination half-life=26 hours of the parent drug and 62 to 104 hours of the active metabolite. Because the half-life is shorter than with Prozac, occasionally patients are able to stop Zoloft for one or two days and alleviate the sexual side effects. However, with the shorter half-life, withdrawal syndrome is more common with Zoloft than with Prozac. I usually start with 25 mg., or ½ of a 25 mg. tablet, and slowly increase; the average antidepressant dose is 75 to 150 mg., but the usual headache dose is approximately 50 mg. While many patients are on 100 mg. or more for headaches, most patients are maintained on lower doses. The cost of the 50 mg. and 100 mg. tablets is approximately the same.

Paroxetine (Paxil): Paxil is conveniently available in 10, 20, 30 and 40 mg. tablets. The elimination half-life is 21 hours, with no active metabolite. Paxil is generally very well tolerated. Since it is short-acting, Paxil can be stopped for one or two days to alleviate sexual side effects; however, this does risk the SSRI withdrawal syndrome. I usually begin with ½ of a 10 mg. tablet and slowly increase to 10 or 20 mg.; some patients need more for depression. It is important to stop Paxil slowly in order to minimize withdrawal. Paxil (SSRI) withdrawal consists of one to several days (and occasionally longer) of flu-like symptoms, malaise, dizziness and asthenia. This often goes unreported to the physician. Managing the withdrawal can be difficult; at times, the addition of Prozac may help in weaning off of the short-acting SSRI.

Citalopram (Celexa): Celexa is available in 20 and 40 mg. tablets, which are scored. The mean terminal half-life is about 35 hours. Celexa has a clean profile in regard to cytochrome P450 enzymes. Celexa has been an outstanding antidepressant with a very good track record, and has relatively few side effects. Side effects are similar to the other SSRI’s. As always, we start with low doses, half of a 20 mg. tablet for four to six days, then progress to 20 mg. per day. Withdrawal symptoms have been exceedingly rare with Celexa. Celexa offers another useful option in the SSRI field.

Wellbutrin (bupropion): A number of miscellaneous antidepressants have been useful in treating headache patients. There are constantly new antidepressants coming on the market. Wellbutrin is actually an older antidepressant that is in its own class (aminoketone). It is unlike tricyclics or SSRI’s.

We primarily use Wellbutrin SR slow release tablets, available as 100 mg. and 150 mg. Wellbutrin is available in lower doses as immediate release. The usual dose is 100 or 150 mg. slow release tablets once per day. For moderate to severe depression, the doses are pushed to 300 mg. or more per day. Wellbutrin (bupropion) may work more via dopaminergic mechanisms that noradrenergic. However, as with many medications, mechanism of action is not entirely known. The advantages of Wellbutrin are that sedation, weight gain and sexual side effects are much lower than many of the other antidepressants. In fact, weight gain has been no more than placebo and the sexual side effects are exceedingly low. At higher doses, particularly at 300 mg. per day or more, people who are predisposed to seizures are at a slightly increased risk for seizure. This is dose related and is approximately .1% (1 out of 1,000) at 300 mg. per day, increasing to .4% at 400 mg. per day. In treating headache patients, we rarely use these levels.

Wellbutrin is also utilized for smoking cessation (under the name Zyban). While it is not as anxiolytic as certain other antidepressants, the general lack of sexual side effects and weight gain, render this a useful antidepressant for use in certain situations.

Remeron (mirtazipine): Remeron is available in 15 mg. and 30 mg. film coated tablets. Remeron enhances noradrenergic and serotonergic activity. Remeron is also an antagonist of histamine, which helps to explain its sedative effects. The usual dose is 30 mg. per day; however, we start with 15 mg. at night for a period of time before increasing to 30 mg. Somnolence is very common, but this is an advantage in agitated depressed patients with insomnia. Weight gain is seen in approximately 12% of patients, with increased appetite in 17%. The weight gain may be pronounced, however. Overall, Remeron has fewer side effects than the older tricyclics, and in certain patients is tolerated better than SSRI’s. While its primary use is in depression, for which it is a very effective medication, headache is sometimes improved with Remeron. We are awaiting further studies on this medication in headache patients.

Effexor (venlafaxine): Effexor is available in 25 mg., 37.5 mg., 50 mg., 75 mg. and 100 mg. tablets. The long-acting Effexor XR is available in 37.5 mg., 75 mg. and 150 mg. doses. Effexor has been an outstanding antidepressant with generally fewer side effects than many of the others. Effexor is basically an SSRI in low doses; at higher doses, norepinephrine, then dopamine, are affected. It is very well tolerated, with less weight gain and sexual side effects than many of the other antidepressants. Effexor has few interactions with cytochrome P450 enzymes, rendering it a fairly clean medication. We usually begin with 37.5 mg. and progress to 75 mg., with a usual dose in headache patients being 75 mg. or 150 mg. Studies on Effexor for headache are pending, but it is very useful in headache patients who have concurrent anxiety and depression. Sustained elevation in blood pressure occurs at higher doses, particularly 250 mg. per day or more. The lower doses have not increased blood pressure. While headache is a potential side effect to Effexor (and all of the others), it has been no more than placebo in studies. Nausea, constipation, somnolence, dry mouth, dizziness, insomnia and agitation have all been more than placebo in studies. However, if doses remain low, Effexor has been extremely well tolerated. While Effexor is less effective than tricyclic antidepressants for pain or headache, its efficacy in anxiety and depression, and its tolerability render it an extremely useful medication.

Clinical Pearls for Treating Headache Patients

  1. Legitimize the headache problem as a physical illness. Statements such as "headaches are just like asthma, diabetes or hypertension: a physical medical condition" go a long way toward establishing trust between the patient and physician. When we mention that it is a medical condition, primarily inherited, and that there is too little serotonin in the brain in people with headaches, patients respond exceedingly well to this. Once we have established this, the patients are much more amenable to addressing anxiety, depression, etc. with therapy or other means. However, if we focus on the patient’s stress, anxiety, depression, and psychological comorbidities, they are often turned off to the physician unless we do state that we are treating the headaches as a legitimate medical illness.
  2. We must try and achieve a balance between medication and headache; I tell the patients that we are trying to improve the headaches 50% to 90%, while minimizing medications.
  3. The initial history and physical is the best time to consider a differential list of medications, because at that point we have a good grasp of the patient’s comorbidities. If we list in the chart the other possibilities (in case our initial medications do not work), later we (or our partners) do not have to reconstruct the entire history with the patients.
  4. In choosing preventives, look at comorbidities, particularly: anxiety, depression, insomnia, gastritis, GERD, IBS, constipation, hypertension, asthma, and sensitivities or allergies to other drugs. These often determine which way to proceed with medication.
  5. Keep track of sensitivities and allergies to medications in a prominent place in the chart. If the patient has had severe reactions to two SSRI’s, a third is not a good choice. However, those reactions may not be readily apparent in the chart. If they are extremely fatigued on one ß-blocker, a second will probably not work for the long term.
  6. It helps to view chronic headache as a continuum or spectrum. The "in between" headaches may not fall neatly into the current tension or migraine categories. Whether these are severe tension or milder migraines, they often respond to the same medications.
  7. Start with low doses of medication, particularly with antidepressants and other preventives. Headache patients tend to be fairly somatic, and there is no need to push medicine very quickly. One exception to this is in patients with severe "new onset daily persistent headache"; these patients may be less patient.
  8. Keep a drug medication flow chart. Headache patients are constantly having medications stopped and re-started, and over ten years, a patient may have been on 50 different medications at various times. It is impossible to piece through forty progress notes trying to determine what the next best course of action is. A drug medication flow chart from the beginning helps immensely.
  9. When we place patients on antidepressants, we need to make it clear that we are trying to directly help their headache by increasing serotonin. We also state that we certainly hope this helps anxiety, depression, etc. Patients are often confused as to the reason why they are given an antidepressant. It helps if we make it clear that we are not trying to treat their headache by treating depression.
  10. Watch for soft bipolar signs in headache patients who have anxiety and depression. Bipolar disorder tends to be underdiagnosed, and the clinical stakes for missing it are enormous. Bipolar disorder, primarily mild and soft (Bipolar II or III), is seen in as many as 6% to 7% of migraineurs. While many of these patients will do well on an antidepressant, it is often necessary to add a mood stabilizer (Depakote, lithium, Tegretol, Neurontin).
  11. Many patients are frustrated by the lack of efficacy and/or side effects of daily preventives. Tell them that only 50% (at most) of patients achieve long-term relief with preventives. This helps them to realize they are in a big boat, and that it is not their fault.
  12. We need to stick with preventive medications for at least four weeks (or longer); if we abandon them too soon, we may not see the beneficial effect. However, few patients are willing to wait months for positive benefits from a medication.
  13. We cannot promise patients that their headaches will improve with psychotherapy (as it often does not), but coping with headaches and the stresses that headaches produce is often improved with therapy. Unfortunately, because of stigma, time and money, only a small minority of patients will actually go to a therapist. However those that do go will usually benefit.
  14. Patients with chronic daily headache may view the headache situation in black and white terms; they will come back for a return visit and state, "Well, I still have a headache everyday." They need to accept that if we have gone from moderate to severe headaches (7 on a scale of 1-10) to mild to moderate (4 on a scale of 1-10), that the situation is improved and we should not change all the medication. If the patients keep a headache chart or calendar, this may help. Patients need to be willing to accept 50% to 90% improvement in frequency and/or severity.
  15. While most patients are honest about analgesic use, some are embarrassed to tell us how much they are utilizing. Between OTC analgesics and herbal preparations, many patients are consuming larger quantities of medications than we realize.
  16. Weight gain is a major issue; even though a drug may be more effective, choosing one that avoids weight gain (in those prone to it) is more likely to lead to long term success. Fatigue is another major reason for patients abandoning a preventive medication.
  17. Do not confuse addiction with dependency; when treating chronic daily headache, dependency has to be accepted. Unfortunately, DSM-IV is inadequate in addressing prescription abuse.
  18. What to do when nothing works: Before "giving up" on a patient with severe, refractive chronic daily headache, consider "end of the line" strategies such as: MAOI’s, daily long-acting opioids (methadone, Kadian, Oxycontin, MS-Contin), stimulants (dextroamphetamine, methylphenidate, phentermine), IV DHE, daily triptans in limited amounts, daily IM DHE (or nasal), or combinations of approaches.
  19. Using a medication to establish a diagnosis may not be accurate. For instance, DHE or triptans have been effective for the pain of SAH or tumors.
  20. Acceptance of the chronic illness (headache) is a helpful state of mind for patients to achieve. Acceptance is different than resignation. Acceptance helps to ease anxiety ("isn’t there a cure; these must be curable").
  21. When patients feel that they can actively help their headaches ("self-efficacy"), by medication or biofeedback or other means, it improves their sense of well-being.


Non-Medication Strategies for Headache Patients
With migraine and chronic daily headache sufferers, we like to emphasize avoidance of triggers. The most common triggers are, in descending order: stress, weather changes, perimenstrually, missing meals, bright lights or sunlight, under sleeping, foods, perfume, cigarette smoke, after stress is over, over sleeping, exercise, and sexual activity. Headache patients, in general, do better with regular schedules, eating three or more meals per day and going to bed and awakening at the same time every day.

Exercise for 15 to 20 minutes per day (or more) is often helpful for headache patients; if patients will do the treadmill, bike, or walk on average 15 minutes per day, they will achieve 80% of the goals of exercise. Relaxation techniques such as biofeedback, deep breathing, and imaging can be helpful for daily headache patients, particularly where stress is a factor. Regarding stress, it is not so much "bad stress", but "daily hassles" that increase headaches. When patients are faced with overwhelming daily hassles, particularly when they cannot sleep well that night, headaches can be worse the next day.

Psychotherapy is extremely useful for many headache patients with regard to stress management, coping, life issues, family of origin issues, etc. Patients can often learn relaxation techniques from books or tapes that are readily available in bookstores, so that learning relaxation techniques often does not require extended visits to a therapist. If patients are willing and able to see a therapist, I have found that it is much more useful to see a regular psychotherapist about issues and stresses than purely doing biofeedback. However, even though we may recommend psychotherapy, it is crucial to legitimize the headaches as a physical condition; they are not a "psychological" problem, but rather a physical one that stress may exacerbate.

The following are the general food lists including the sources of caffeine that we have found useful in migraine patients:

Foods to Avoid, and Sources of Caffeine:
You may or may not be sensitive to any of the following foods. If a particular food is going to cause a headache, the headache will usually occur within three hours of eating. Also, the response to the foods may not be consistent. On one occasion, you may have a headache caused by a particular food; however, the next time you eat that same food, it is possible that a headache may not occur.

Foods that are Extremely Common Migraine Triggers (The Worst Offenders)

  • Monosodium Glutamate (MSG) – also labeled Autolyzed Yeast Extract, Hydrolyzed Vegetable Protein, or Natural Flavoring.
  • Possible sources of MSG include broths or stocks, seasonings, whey protein, soy extract, malt extract, caseinate, barley extract, textured soy protein, chicken or port or beef flavoring, smoke flavor, spices, carrageenan, meat tenderizer, seasoned salt, TV dinners, instant gravies, and some potato chips and dry-roasted nuts.
  • Red Wine
  • Beer
  • Chocolate
  • Citrus Fruits
  • Ripened, aged cheeses (Colby, Roquefort, Brie, Gruyere, cheddar, bleu, brick, mozzarella, Parmesan, boursalt, Romano) and processed cheese.
  • Less likely to trigger headache: cottage cheese, cream cheese, and American cheese.
  • Hot dogs, pepperoni, bologna, salami, sausage, canned or cured meats (bacon, ham), aged meats, or marinated meats.

While caffeine can help headaches, the overuse of caffeine may increase via rebound mechanisms. Some patients do not suffer rebound headaches from the ingestion of 500 mg. of caffeine per day, while others develop rebound headaches with as little as 30 mg. In general, I like to limit caffeine to 200 mg., or at most, 300 mg. per day.

The average 8 ounce cup of coffee has 75 to 125 mg. caffeine. Drip coffee is stronger than percolated, and instant is the weakest form. Depending on the size of the cup and its strength, instant coffee may contain from 40 to 150 mg., but is usually closer to 40 mg. Decaffeinated coffee contains from 2 to 5 mg. per cup. These calculations all depend upon the strength of the product and the brew.

Tea usually contains 30 to 50 mg. of caffeine per cup, and soft drinks average approximately 40 mg.

Chocolate contains 1 to 15 mg. of caffeine per ounce; however, cocoa has considerably more caffeine, up to 50 mg. for an 8 ounce serving.

Caffeine is available in both food products and as tablets or capsules. Caffeine tablets such as NoDoz, Tirend, and Vivarin are available, but I do not use the higher strength products.

When patients find that caffeine significantly decreases their headaches, I will occasionally utilize the pure caffeine tablets, with a dose of 1/2 of a 100 mg. pill (50 mg. total) every 3 to 4 hours as needed. At times, it is helpful to combine the caffeine with medications that do not contain caffeine, such as Midrin.

In whatever form that patients receive caffeine, whether in coffee, caffeine pills, or combination analgesics, it is necessary to limit the total amount of caffeine. The maximum amount of caffeine to take each day varies from person to person, depending upon their sleeping patterns, the presence of anxiety, and their sensitivity to possible rebound headaches.

Caffeine Sources
Limit caffeine to 200 mg. per day, or, at most, 300 mg. per day
Coffee: 8 ounces: average cup: 75-125 mg.
drip is stronger than percolated, which is stronger than instant
instant = 40-150 mg. per cup, usually closer to 40 mg.
decaf = 4 mg. per cup
Tea: 8 ounces: average cup: 30-50 mg.
Soft drinks: approximately 40 mg. per cup
Chocolate: 1-15 mg. per ounce
Cocoa – 50 mg. per 8 ounces
Caffeine tablets: (NoDoz, Vivarin, Tirend) = 100 mg. of caffeine
Caffeine is present in many analgesic medications, such as Excedrin Migraine (65 mg.), Anacin (32 mg.) and Vanquish (33 mg.)

Foods that Trigger Migraines Less Often (Moderate Offenders)
Alcohol (misc.): vodka is the least likely to cause a migraine
Fresh, hot, homemade yeast breads (once cooled, they are not a problem)
Nuts or seeds (any may trigger migraine)
Sour cream
Yogurt White wine
Yeast Extracts Soy sauce
Acidophilus milk Cocoa
Peanuts and peanut butter Buttermilk

Imitrex is currently the most effective migraine abortive medication. Side effects have, in general, been found to be minimal. Imitrex is effective for approximately 70% of patients. The gold standard in headache abortive treatment.

Imitrex is excellent for migraine patients who are not at risk for coronary artery disease (CAD). Tablets of Imitrex can be used in patients in their 50’s, 60’s and 70’s, but with caution, and only in those patients who have been screened for CAD. I do use tablets of Imitrex in-patients as young as 12 years old.

Imitrex comes in 25 mg. and 50 mg. tablets. As the tablets are expensive, it is more cost effective to use the 50 mg. tablets. Most patients require 50 mg. or 100 mg., but occasionally people will find 25 mg. to be effective. I start with 25 mg. every three to four hours to see how people will react to the drug. If they do not have adverse side effects, we have the patient take 50 mg., one or two as needed, every three to four hours, up to a maximum of 200 mg. per day, or four of the 50 mg. tablets.

Imitrex Nasal Spray is available in 5 mg. and 20 mg. sizes. Each unit dose is for one-time use only. Most patients need the 20 mg. spray. Side effects are similar, although there is more of a tendency to have stronger side effects with the injections.

Patients should limit the nasal spray to two 20 mg. sprays per day at most, separating them by at least two hours. We use only one spray and two tablets in a day at most. We consider one spray approximately equal to one tablet in efficacy.

The nasal spray is very easy to use. The instruction sheet for patients is easy to follow. Basically, they should keep their head in an upright position, close one nostril, insert the nozzle of the nasal spray into the open nostril, and press the blue plunger on the Imitrex. The nasal spray, of course, allows for much more convenient dosing than the injection. The nasal spray is usually sold in a box of six sprays at a time. A bad taste is by far the most common side effect. Keeping the head upright can help. Some patients have found that drinking a carbonated beverage prior to the spray can help.

Imitrex injections are available in the STAT dose injector form, which is simple to learn and comes in a convenient hard case. This carrying case fits into a purse and renders transportation of the injections (which many patients do carry around with them) very easy. The injections are dosed at one every three to four hours as needed, but limited to not more than two in a day at most. The tablets are limited to ten tablets per week, and the shots to four per week in general. There are exceptions where we will use Imitrex daily for periods of time, particularly with cluster headaches. The nasal spray is considered about equal to one injection. Recently, the older Imitrex injections became available again. Many patients preferred these, as they were easy to use without an "injector gun."

Side effects are milder with the tablets than with the injections. Many people will not have side effects with Imitrex tablets. With the injections, they do often feel of "rush" into their head. Feeling heat in the head or numbness is relatively common. Chest heaviness or pressure, or pressure in the throat is also common. This is rarely from cardiac origin. If chest heaviness is moderate or severe, or is associated with arm pain, the patient should not use it again prior to clearance with the physician. Nausea is also common, as is fatigue, but these side effects tend to be short lasting. Most side effects go away after 30 minutes. Occasionally patients will feel weak or dizzy. Tingling in the fingers or feet is occasionally seen, particularly with daily high dose usage of Imitrex. Again, the tablets are usually much better tolerated (and convenient).

The two serious side effects have been myocardial infarction and (possibly) stroke. Stroke has occurred in several cases, but it is unclear whether this was due to Imitrex or a random event. Over 14 million people have had Imitrex now, and Imitrex has been used to treat over 200 million migraines. The issue of myocardial infarction and coronary ischemia is very important with the use of Imitrex. Imitrex does decrease coronary artery blood flow by approximately 17% for one hour or so. These effects are more marked with the injections than with the tablets. Patients at any age should be screened for coronary artery disease at least by history, and patients over the age of 40 should possibly have some appropriate work-up. The tablets have only been associated with rare cardiac events (out of tens of millions of doses given). However, in studies investigating Imitrex tablets, patients who have coronary artery disease or who have ventricular arrhythmias can have some ischemia. While Imitrex has generally been a very safe medication, it is important to screen these patients. After moderate or severe chest symptoms, it is prudent to discontinue use.

The ergotamines should not be used in the same day as Imitrex, nor should Imitrex be used for 24 hours following any use of ergotamine. Pain medications or NSAIDs are all right to use in the same day or even at the same time as Imitrex. This may enhance efficacy in some patients. Antiemetics such as Phenergan, Reglan, Compazine, etc. are safe with Imitrex. Midrin, which is a mild vasoconstrictor, should not be used within eight hours of Imitrex. While all indications are that they are probably safe, Amerge (or other triptans) and Imitrex have not been cleared for use in the same day.

Imitrex absolutely should not be used during pregnancy and should not be used by a woman who is nursing.

Occasionally, Imitrex will be useful for preventing headache, particularly menstrual migraines. Sometimes we will use one tablet twice a day for three or four days for severe menstrual migraines. However, in general, Imitrex is too short-acting to be used as a preventive. Imitrex is also extremely effective in cluster headache and approximately 80% of cluster patients receive excellent relief from Imitrex. The longer-acting triptans, such as Amerge, may be better for prevention of headache.

Amerge is a smooth, long-acting triptan, extremely well tolerated. It is available in 1 mg. and 2.5 mg. strengths. In general, the side effects have been found to be minimal. Side effects are usually minimal, but include possible nausea, chest heaviness or pressure, pressure in the throat, shortness of breath, rash, tingling sensation, head sensation or heaviness, tiredness, drowsiness, dizziness, etc. Most of these symptoms have been minimal and actually are more common with Imitrex than with Amerge. The symptoms in general are short-lasting. They go away, but, if they are more than mild, Amerge should not be taken again. We are careful with Amerge or Imitrex in patients who have major risk factors for heart problems. Amerge should not be used in people with hardening of the arteries or who have had past heart attacks. However, in all of the studies and previous experience with Amerge, it has generally been a safe medication.

Amerge, 2.5 mg. may be taken one every three to four hours, as needed, two in a day at most. Most patients have only needed one tablet. However, 5 mg. or two tablets in 24 hours, is the most that we want to use. The tablets are generally limited to 10 tablets per week at most. The very first time you use it, try ½ tablet to see how you will react.

Amerge should not be taken in the same day as other ergotamines (such as Cafergot) and should not be taken in the same day as Imitrex, Migranal or Zomig. Pain medications (such as aspirin, ibuprofen, Fiorinal, Vicodin, Tylenol, etc.) may be used, even at the same time as Amerge. This can increase efficacy. Anti-nausea medications may also be used at the same time. Generally, there are relatively few interactions with medications and Amerge.

Amerge can take anywhere from 20 minutes to two hours to help. Because it can take awhile, we sometimes use Reglan or Propulsid with Amerge, to speed absorption.