Page last modified:
March 5, 2008
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Timothy C. Hain, MD, Chicago
IL..
Page last modified:
March 5, 2008
Migraines are recurrent headaches separated by symptom-free intervals and accompanied by nausea and light sensitivity. Migraines are often accompanied by visual symptoms and are relieved by sleep; furthermore there is usually a throbbing quality. More often than not there is a family history of migraine. Formal criteria have been defined. In general, there is sensitivity to various types of sensory inputs which may trigger headache -- light (photophobia), sound (sonophobia), smells (such as perfume), and motion -- persons with migraine are often prone to become motion-sick. Psychological testing shows unsurprisingly that people with an active migraine headache don't think as well as usual (Meyer JS et al, 2000).
Although
migraine headache is usually unilateral, opposite sides of the head are characteristically
affected during different attacks. About 20% of Migraine's are preceded by an "aura" (see picture on the right), meaning visual symptoms, dizziness,
numbness, or weakness. In fact, about 1% of the time, the aura may dominate
the migraine, and there may be minimal or no headache ! Migraine auras usually
last 5 to 60 min. Visual auras begin in central field of vision and move to
the periphery. Another common visual aura is a scotoma (black spot). There is
a genre of art called "migraine art",
based on migraine aura. There are also sensory auras -- they often move from
hand to arm to face and ipsilateral tongue. Presumably, any part of the brain
might have an aura. The possibilities are endless !
Visual aura mimics include AVM, TIA, retinal disease, and some focal seizures.
There are numerous defined variants of migraine.
Tension headaches are presently thought by some to be a milder type of migraine, although this is probably an oversimplification. Sometimes a tension headache is just a tension headache. They are usually described as a dull ache in the back of the head, over the ears, in the forehead or in a tight band round the neck. Like migraine as well as nearly any medical problem, tension headaches are made worse by stress.
Other medical problems such as brain tumors or aneurysms are rare in people with headache, but need to be considered, especially in headaches of recent onset.
WHO GETS MIGRAINE ? About 11 million Americans have significant problems with migraine headaches and about 10% of the population get migraines, at least occasionally (Stewart et al, 1994; Lipton et al, 2002). Women are especially likely to get migraine (3:1 female:male ratio, 4:1 during childbearing years). The age group between 30 and 45 has the peak incidence, roughly 25%. Women get more migraine than men because of hormonal fluctuations, and the incidence appears to be increasing in women recently (Rozen et al, 1999). About 4% of children have migraines.
WHAT CAUSES MIGRAINE ? Migraines are generally thought to be caused by a chemical abnormality in the brain due to a combination of familial tendency, trigger factors such as stress, sleep disturbance, hormonal fluctuations, and certain foods. While in the past Migraine was felt to be related to vasospasm, presently it is thought that the blood flow changes are not primary. Instead, it is felt that Migraine is related to abnormal sensitivity to sensory inputs (Goadsby PJ, 2001). Nevertheless, there is recent evidence in the other direction -- migraine is associated with a mutation in a gene that controls a potent vasoconstrictor (Tzourio et al, 2001)
Our most effective medications for migraine (ergots, triptans) manipulate a blood chemical called serotonin. Medications that manipulate another neurotransmitter (dopamine), are also often effective treatments for migraine although they have side effects and dopamine is unlikely to he a central problem (Mascia et al, 1998). Recently it has been proposed that a bacterial infection, Helicobacter pylori, is a cause of as much as 40% of migraine (Gasbarrini et al, 1998). Whether this will be borne out is unclear and this idea does not reflect the present consensus. Migraine does not appear to be related to allergy or immune disturbances in most instances.
HOW ARE MIGRAINES DIAGNOSED ? The diagnosis is made through identification of characteristic features of the headache and examination.
Patients with migraine typically have sensory amplification symptoms --
Interestly, patients with migraine are "wired differently" and have thicker sensory cortex than patients without migraine (DaSilva et al, 2007).
In most cases, no X-rays or blood tests are required to make the diagnosis, but in persons with severe and recent headaches, neurological findings, or complicated medical histories, the physician may recommend an MRI or CT scan (Silberstein, 2000). Imaging is generally not necessary if the examination is normal and the headache pattern is unchanged. Lumbar punctures are obtained when subarachnoid hemorrhage is suspected or meningitis. Migraine headaches are often misdiagnosed by patients themselves as sinus headaches. A recent study suggested that 88% of 2991 patients who had diagnosed themselves as having sinus headache, actually had migraine (Schreiber et al, 2004).
MRI scans may reveal white matter lesions in young persons with migraine. In fact, between 12-47% of patients with migraine have these, compared to 2-14% of controls (Evans and Olesen, 2003). When these are seen, it is the author of this review's policy to encourage the patient to consider use of migraine prophylactic medications (see following sections), and avoid vasoconstrictor medications such as "triptans". According to Evans, the clinical significance of these lesions in migraine is unclear. Possibilities include relationship to migraine, an incidental finding, other medical conditions, or comorbidity of other diseases. CADASIL should be suspected in migraine patients with a prolonged typical aura and white matter lesions. Mitochondrial myopathy, antiphospholipid antibodies, SLE, and MS should also be considered in this situation.
MR angiography can be used to diagnose vascular malformations. MR venography can be used for saggital sinus thrombosis. MR also may detect low-pressure type headaches, tumors, as well as the Chiari malformation. Fortunately all of these are rare.
Persons with prolonged auras (> 60 min) should get coagulopathy testing--to look for lupus antibody, anticardiolipin antibody, protein's C and S, factor V Leiden. However, this is a low-yield endeavor.
The best strategy seems to be adjust the intensity of treatment to the severity of ones migraine condition (stratified care). It doesn't work as well to start cautiously, and then escalate if the first treatment doesn't work (Lipton et al, 2000). There are (at least) 6 different ways to manage Migraine. In all instances, it is best to keep a "log" of headaches, such as a diary, in order to determine whether or not a particular treatment is effective.
1. Avoid trigger factors:
2. Simple non-drug treatment that should be tried first
3. Pain medications
4. Prophylactic medications: For those who have more than 2 severe headaches/month and in patients with complicated migraine (migraine with stroke-like features), a daily medication may be worth while. These are generally highly effective (about 75% effective), but do require daily regular use. These drugs fall into three major classes: anticonvulsants, antidepressants, and antihypertensives. Examples are: Amitriptyline (Elavil), Corgard, Depakote, Inderal, Nardil, Verapamil (Calan, Isoptin). These drugs seem to work via several pathways: some are beta-blockers (e.g. Inderal, Corguard), some are calcium channel blockers (e.g. verapamil), some work in mysterious ways (e.g. Depakote, Nardil, amitriptyline). More information about these is in the next section.
5. Acute, specific medications (also called "abortive" medication): For those who have severe but infrequent headache. Highly effective, especially Imitrex (sumatriptan). There are numerous others in the same family -- Zomig, Maxalt, and Axert, and Frova to name a few brand names. There are also older (cheaper) drugs, called ergots, that have similar effects but have more side effects -- examples of these types of drugs are: Cafergot, DHE, and Ergotamine. Drugs that are dopamine blockers include Metoclopramide and prochlorpromazine.
6. Nausea medications: For those with prominent nausea. Highly effective, but cause some major side effects. Examples are: Compazine, Phenergan, Reglan, Thorazine, Tigan. These drugs also have some utility as abortive agents, presumably because of their effects on the dopamine pathways. Droperidol is very effective in Migraine (Ashkenazi et al, 2003). but because of it's "black box warning" related to sudden death from cardiac side effects, we think it is best not used for a recurrent non life-threatening condition like migraine.
References:
Migraine prevention drugs
To use these drugs it is best to have a measure of effect. One way is to use a headache diary. Here we recommend a month/page style format, and a stoplight; color code - - red bad, yellow -- fair, green good. Another is to do it online -- see http://www.headachetest.com/.
General comments:
The author of this review usually starts patients with topamax, and proceeds on to try effexor, verapamil, propranolol and then amitriptyline. It is very unusual that headache control is not attained.
We would urge great caution in believing the migraine literature. In general, those that commonly publish articles about migraine treatment are funded by the drug industry. Drugs that might be particularly likely to have "slanted" literature are those that are expensive (which includes many) and in which there is no generic drug yet available. There are many of these medications used for migraine treatment.
In a recent review (Silberstein, 2000), medications for prevention were grouped into 5 categories: Group 1 are medications with proven efficacy and mild-moderate adverse events. Group 2 are medications with lower efficacy. Group 3 are medications based on opinion. Group 4 are medications with proven efficacy but serious potential side effects. Group 5 are medications proven to have limited or no efficacy.
Drugs (alphabetical).
Ace inhibitors (candesartin, lisinopril) Ineffective. ACE inhibitors are presently mainly used for hypertension, but they also have some slight utility for migraine prevention. (Ashenazi et al, 2003; Tronvik et al, 2003). The writer of this review considers these medications ineffective. These drugs are also expensive compared to verapamil, propranolol and especially amitriptyline.
amitriptyline (Elavil). Effective and inexpensive drug, with considerable side effects, used for prevention (Group 1). Usual dose is 50 mg at night but the starting dose is usually 10 mg. Some people do well with just 10 mg. Works very well, but takes 2-6 weeks to work. Amitriptyline doesn't lower the blood pressure. Dry mouth and sleepiness main side effects. Weight gain is also common. Elavil is very inexpensive ! Similar tricyclic type drugs include nortriptyline, doxepin and protriptyline. Amitriptyline is more likely to have serious side effects when used by people with heart block or urination problems or persons over the age of 60. Pregnancy is category D. We mainly use this drug when our favorites fail.
carbamazepine (Tegretol) is not effective as a preventive (group 5). A related anticonvulsant, oxcarbazepine (Trileptal) has had some limited success in treating refractory migraine with about a 50% response rate (two abstracts suggest this -- Johnson et al, 2002; Nett and Krusz, 2002). Oxcarbazepine is not FDA approved for this indication.
cyproheptadine (periactin) is a preventive medication mainly used in children. Weight gain is common.
Depakote (sodium valproate). Group 1. Effective but with many side effects. In fact, there are so many side effects that we generally avoid it. Used for prevention. Usual dose is 250, three times/day. Side effects include a prominant tremor, weight gain, and sometimes hair loss. Depakote also should not be used in women of childbearing age who are not using birth control as it is pregnancy category D. Some authors suggest that this drug is effective for persistent migraine aura (Rothrock, 1997). There are many possible reasons for it working and at this writing, it is not clear which one is correct (Cutrer et al, 1997).
Effexor (venlafaxine HCI), see below. We find this drug very effective.
Fluoxetine (Prozac). Group 1. Ineffective but perhaps worth a try anyway. This medication, a member of the SSRI family (which also includes Paxil, Zoloft, Celexa, Lexapro, and Luvox), is listed as a "group 1" medication for therapy (Silberstein, 2000). There is some evidence that another SSRI, paroxetine (Paxil) improves chronic daily headache (Langemark and Olesen, 1994; Foster and Bafaloukos, 1994). Not everyone agrees that there is good evidence that the SSRI's help (e.g. Goadsby, 2002)
Gabapentin (Neurontin). Group 1. Neurontin is not very potent for migraine, but it has so few side effects, that it may be worth a try anyway. This anticonvulsant is a prophylactic drug for treatment of migraine (Silberstein, 2000). Gabapentin (strangely enough) does not affect Gaba-b receptors or other commonly studied receptors. It may nevertheless increase glutamate-dependent GABA synthesis and it also binds to the calcium channel. Adverse effects include sleepiness, dizziness, fatigue and weight gain associated with increased appetite. . A newer version of Neurontin is "Lyrica". This is basically a far more expensive version of gabapentin with a few advantages. Pregnancy category C.
Inderal LA (propranolol, Group 1) and other beta-blockers such as timonol (group 1). Members in group 2 include atenolol, metaprolol and nadolol. Very effective and cheap drug, with moderate side effects, used for prevention. The usual dose is 60 mg LA in the evening. Works as well as Verapamil, but generally has more side effects. Pulse may be slowed. Has a mildly calming effect. Nadolol (Corgard) has a similar effect. Both Inderal and Corgard are non-selective beta blockers. More selective beta blockers include metoprolol (Lopressor, Toprol, dose 25-75 at bedtime) and Atenolol (Tenorman). These may have less side effects than the unselective beta blockers. In general, beta-blockers shouldn't be used by persons with asthma, depression, heart failure, diabetes, or taking allergy shots. All beta blockers have some risk of hair loss. This is fortunately rare. This is not an absolute prohibition and in some cases beta-blockers are helpful depending on the overall situation. Combined use of verapamil and beta-blockers should also, generally speaking, be avoided. Atenolol is pregnancy category D, while metoprolol, propranolol and nadolol are all pregnancy category C. The 'C' agents are preferable in women of childbearing age.
Lamotrigine (Lamictal). Effective but substantial side effects. This anticonulsant can be used in a similar way as Depakote (see above) to prevent migraine and migraine associated vertigo (Bisdorf, 2004).
Magnesium. Dietary supplements of magnesium as well as intravenous injections of magnesium have been reported to be effective in migraine (Peikert et al, 1996; Mauskop, 1998). It is presently considered a group-2 drug. Brain magnesium has a complicated relationship to migraine (Boska et al, 2002). Magnesium is usually taken as a dietary supplement, in combination with calcium. No prescription is necessary. Safety is unknown in pregnancy.
Memantine (Namenda). There are some very preliminary, uncontrolled studies suggesting that this drug in the usual doses for alzheimer's reduces headache frequency by about 50% (Charles et al, 2007; Peters et al, 2007). At this writing, we are trying this out in refractory patients. It is difficult to see why it would work.
Methysergide (Sansert):This drug is unavailable in the US as of 1/2003. Very effective but potentially dangerous. Taken in a dose of 2mg TID. Every 6 months, you MUST stop this medication for one month. There is a danger of poor circulation. This drug is a last resort. Some authors recommend getting a CT scan of the kidney area one year after initiating treatment.
NSAIDS (non-steroidal anti-inflammatory drugs) are generally group 2. Effective but substantial side effects. Examples are aspirin, fenoprofen, flurbiprofen, ketoprofen, mefanamic acid, and naproxen. . Indomethacin is not effective for prevention (group 5) although perhaps effective as an abortive treatment. Naproxen is pregnancy category B, making it one of the safest and least expensive drugs in pregnancy. This entire group is under some suspicion of contributing to cardiovascular risk.
Oxcarbamazine (Trileptal) is not indicated for migraine, see comments above related to carbamazepine.
Pizotifen is a medication similar to cyproheptadine, with both antihistamine and anti-serotonin properties. The usual dose is 0.5 mg daily. It is not FDA approved in the USA.
Topiramate (Topamax). Very effective but expensive. Unlike most headache prevention medications, Topiramate often promotes weight loss, even with low doses, due to anorexia (loss of appetite). Typical doses are 25mg/day to 200 mg/d. In the author's clinical practice in Chicago, 50-100 mg is the usual target dose, as this amount seems to have the best combination of cost/benefit. Topiramate is expensive and in large doses has peculiar cognitive effects, such as trouble finding words (Mula et al, 2003). Topiramate is not a good drug for people whose job involves manipulating words (i.e. writers, speakers, attorneys). About 50% of patients develop tingling in hands/fingers on startup. This effect usually fades out in about 2 weeks. Peak effect doesn't occur till 3 months, so trials must be made over long periods. The author has encountered a few patients who became severely depressed on topiramate -- they were also on Effexor, so this may be a drug-drug interaction. On the positive side, small doses are usually side effect free. Also, topiramate does not affect blood pressure. Topiramate increases the blood levels of amitriptyline. Pregancy is category C at present (2006). The mechanism for this anticonvulsant drug may include pharmacological effects including enhancement of GABA, inhibition of glutamate receptors, sodium channels, and calcium channels. It also has a weak inhibition of carbonic anhydrase. Due to the combination of migraine and carbonic anhydrase activity, it may be the optimal drug for people who have both migraine and Meniere's disease.
Venlafaxine (Effexor). Used for prevention. This antidepressant medication, of the SNRI group, is very effective and has relatively few side effects. (Diamond, Pepper et al. 1998; Nascimento 1998; Adelman, Adelman et al. 2000; Bulut, Berilgen et al. 2004; Ozyalcin, Talu et al. 2005). We particularly favor this drug for the visual dependence symptom commonly seen in migraine. The usual dose is small -- varying between 12.5 mg and 75 mg/day. Venlafaxine increases the blood pressure, and is neutral in regards to weight. There have been occasional reports of the "serotonin syndrome" provoked by the combination of effexor and triptans (see abortives), as well as the "SSRI" family of antideprssants. It seems unlikely that this would occur when using the small doses typical for migraine prophylaxis (37.5 to 75 per day), but caution is advised. Other SNRI's, such as Cymbalta (duloxetine) are of unknown efficacy (Unpublished information from Eli Lilly, 2007). We have encountered withdrawall problems in persons who stop effexor in larger doses than this, but none with the lower doses used for migraine. We usually start persons with 1/2 of the smallest dose available.
References regarding Venlafaxine:
Verapamil (Calan ). (Group 2) Used for prevention. A very effective and inexpensive drug that takes about 2 weeks to work.We particularly favor this drug for persons who have high blood pressure, or who have nausea accompaning migraine. It is an excellent drug for "cyclic vomiting". Usual dose is 120 to 240mg per day, SR. SR means sustained release. It is a member of the L-channel calcium channel blocker family. Other calcium channel blockers are generally ineffective (i.e. nicardipine, nifedipine), but Diltiazem is a group 3 drug (possibly effective). About 50% of users develop mild constipation. Sometimes lowers blood pressure. About 1% of users develop palpitations (fluttering feeling in chest). It is usually best to stop taking this drug if you develop palpitations. Safe in patients with asthma, and especially good in patients who also have high blood pressure. Should start with dose mg roughly = weight of patient. Combined use of verapamil or other calcium channel blockers and beta-blockers should, in general, be avoided. Not for use in pregnancy (but it is category C). Verapamil is effective in hemiplegic migraine (Yu and Horowitz, 2003). Extremely large amounts of verapamil are sometimes used for Cluster headache. For this situation, heart EKG testing is recommended.
Flunarizine is a similar drug to verapamil, available in Europe. Flunarizine is at least as effective as propranolol (see later). Flunarizine is likely more effective than verapamil because it combines calcium channel and dopamine blocking activity in a single preparation (Afran et al, 1998).
Wellbutrin (buproprion) has been reported useful in small studies for migraine, cluster and chronic daily headaches. Wellbutrin has no clinically significant effect on serotonin neurotransmission. We have not had much success with this drug.
Zonegran, another anticonvulsant, may have some anti-migraine effects too. Like Topiramate, it is a carbonic anhydrase inhibitor (among other things). Zonegran may also be associated with weight loss. It is too early to say with this new drug whether it will have a role in migraine prevention.
Medications that are reportedly not effective in preventing migraine include acebutolol, clomipramine, clonazepam, clonidine, indomethacin, nicardipine, nifedipine, and pindolol (Silberstein, 2000).
Migraine abortive drugs
Imitrex (sumatriptan) is an example of a category of drugs called triptans. As a general comment, the triptans are terribly expensive but very effective. At this writing, this category includes sumatriptan, naratriptan, zolmitriptan, rizatriptan, almotriptan, frovatriptan and eletriptan. These drugs are all group-1 agents. These drugs are 5HT-1B and 1D (serotonin) receptor agonists. Some also affect 5HT-1F. Serotonin does a lot of things in the body and there are many receptors, presently ranging from 5HT1-7. Other drugs that affect serotonin are the SSRI and SNRI families of antidepressants and the "setron" family of antinauseants, such as ondansetron, which antagonize the 5HT-3 receptor. The FDA has advised caution when taking both triptans and SSRI/SNRI's together. We have never encountered problems, but nevertheless we suggest avoiding taking large amounts of triptans and SSRI/SNRI's together. This mainly is a difficulty when someone has two conditions - -major depression and migraine - -simultaneously.
Imitrex was first released as an injection given under the skin (subcutaneously) at time of headache. Imitrex is not recommended for patients < 18 years of age although several studies have been performed on adolescents with similar results to adults.
| Compound | Dose | Tmax | T 1/2 |
| Rizatriptan (Maxalt) | 10 | 1 | 2-2.5 |
| Eletriptan (Relpax) | 40 | 1-1.25 | 4-7 |
| Sumatriptan (Imitrex) | 100 | 2.5 | 2-2.5 |
| Zolmitriptan (zomig) | 2.5 | 2.5 | 3 |
| Almotriptan (Axert) | 12.5 | 2.5 | 3.6 |
| Naratriptan (Amerge) | 2.5 | 2-3 | 5-6 |
| Frovatriptan (Frova) | 2.5 | 2-4 | 25 |
| (modified from Matthew and Loder, 2005) | |||
Presently triptans are also available as a pill (50-100 mg is best for Imitrex), as a nasal spray and as a sublingual preparation (Maxalt and Zomig). The sublingual forms are generally preferred because of fast and effective action. Eletriptan, a recent addition, has a nasal form that is well suited to rapid treatment (Ashkenazi and Silberman, 2003), and both rizatriptan and eletriptan have a very rapid onset of action when taken orally.
A recent addition is frovatriptan (Frova) , which has a very long half-life (about 26 hours). Longer half-life drugs have less recurrences. The triptans are very effective for migraine (about 60-85% relief from active drug vs. 20-40% in placebo) but also very expensive (roughly $75/injection or squirt). There are now some agents which cost a little less -- Axert, for example, is about $10/dose. The triptans usually relieve migraine associated nausea as well as headache. These drugs are also reported somewhat effective for tension headache (Lipton et al, 2000).
Because of the high cost, some pharmacy programs limit quantities to about 8 uses/month. For the injection form, chest pain occurs in 3-5% of patients, usually from esophageal spasm. Myocardial infarctions, however, have rarely been reported after triptan use. For the nasal spray, a bitter taste in the mouth is the most common side effect (Ryan et al, 1997). Sumatriptan can be used up to twice/day. Surprisingly, sumatriptan is not generally effective in children (Hamalainen, 1997), although some reports suggest that the nasal spray may work.
Triptans shouldn't be used by persons with heart trouble or blocked arteries (Maasen, Vandenbrink et al, 1998). Triptans should not be used within 24 hours of using an "ergot" type medication (see below) or Sansert (no longer available). Use in hemiplegic or basilar migraine (i.e. migraines with stroke like symptoms) is generally contraindicated. In the author's practice, these drugs are also avoided in persons with MRI evidence of small infarcts, which is not at all uncommon in persons with severe migraine. Coadministration with MAO inhibitors is contraindicated (see preventive treatments). See table under "addictive medications" for guides for use. While triptans are generally effective in cluster headache, extreme caution is advised, because of the temptation to overuse this drug, and also the tendency for cluster to occur in persons with higher risks of heart attack.
Similar medications to sumatriptan (Imitrex) are zolmitriptan (Zomig), rizatriptan (Maxalt), and eletriptan (Relpax). Amerge (naratriptan) is a slower onset, more prolonged version. While triptans are not recomended for use in a preventive, "prophylactic" mode, nevertheless Amerge is sometimes used for several days in a row to prevent menstrual migraine. Frova is a very long half-life triptan. Axert (almotriptan) is also somewhat longer lasting. Relpax is one of the stronger ones (Sandrini, Farkkila et al. 2002; Farkkila, Olesen et al. 2003). Some pharmacy programs limit use of Zomig to 6 tablets/month of the 2.5 mg form, or 3 tablets of the 5 mg form, and Amerge to 9 tablets. It is generally felt that it is unreasonable to use triptans more often than every other day. Triptans can lead to rebound (withdrawal) headaches (Limmroth et al, 1998). Inappropriate use of medication including dependence is certainly possible and, because of it's high price, may impact health care spending significantly (Gaist et al, 1998)
An older similar medication, DHE (dihydroergotamine), also group 1, is less used because of greater incidence of side effects. DHE and other ergots are broader in their action than the triptans and this is probably the reason for their increased side effects vs. the triptans. Nevertheless, DHE is now been recent released as a nasal spray preparation (Migranal). DHE are contraindicated in patients with renal or hepatic insufficiency, coronary, cerebral or peripheral vascular disease, and uncontrolled hypertension. These agents are also contraindicated in women who are or may be become pregnant. Caution should be used with ergots in lactating women, in patients also receiving peripheral vasoconstrictors, 5-HT1 agonists, propranolol, nicotine and macrolide antibiotics (PCS, 1999).
Other ergots --
The following ergot medications often undergo shortages -- these very old drugs are so often unavailable on a world scale. For example, at ergotomaine was mysteriously unavailable when Imitrex was first introduced, and at the present time (2007) Midrin has mysteriously gone off the market. It may have something to do with economics - -drug companies profit much more from the triptans (which are patent protected and extremely costly) than the ergot medications (which are not patent protected).
Ergotamine tartrate (Wigraine) SL or suppository. This is obviously an "ergot" type medication too. Take at time of headache, repeat in 30 minutes if not effective. Wait 3 days before using again. Should NOT be used by persons with heart trouble or poor circulation. Coldness and tingling in the legs suggest a need to stop treatment. Otherwise, contraindications are similar to DHE (see above). Ergotamine is rarely used, being replaced by Imitrex.
Cafergot. This is another ergot preparation, a group 2. It is used at time of headache. Same dose and precautions as Ergotamine tartrate. Suppositories are more effective than the oral dose (maximum 2/day).
Isometheptane (Midrin). This is a group-2 drug, also considered an "ergot" type medication. Take at time of headache, repeat in 30 minutes, up to maximum of 5. Wait 3 days before using again. Same precautions as ergotamine tartrate above. Midrin is not commonly prescribed at this writing.
As basic research suggests that these medications inhibit firing in trigeminal pain pathways via 5HT1B and D receptors (Goadsby and Hoskin, 1998), in theory at least, this group might also relieve other types of head pain such as sinus headache, tension headache, and toothache. Generally, it is not used for these purposes, and a good response to a "triptan" is considered a reasonable indication that the patient has a migraine.
Naproxen (Alleve 220 mg) and Ibuprofen (Motrin 200 or 400 mg). These medications are "non-steroidals". There are many others -- there is no reason to suspect that they vary in any significant way other than side effects. . Non-steroidals or "NSAID" medications are both useful for pain at the time of headache, and may also help on a daily basis. Main problems with them are stomach irritation and diarrhea. Don't take large amounts as these drugs can damage the kidney and liver too. Take with food. Aspirin may work as well. Cost for one of the older type NSAID's is about 0.20 $/day.
Droperidol has been reported as an effective acute treatment for migraine (Silberstein et al, 2003). Because droperidol has been associated with occasional life-threatening side effects, however, we do not recommend it for this purpose.
Steroids, according to Silberstein (2000), are not effective acute therapies for migraine. Nevertheless, they are often used in a short course to "break" a severe bout of migraine or cluster headache. This suggests they may be effective subacute treatment.
References:
ADDICTION TO HEADACHE MEDICATIONS
One is physically addicted when one takes a medication daily, and suffers withdrawal symptoms unrelated to the primary purpose of the drug, when one attempts to stop. Certain common patterns of drug use are generally considered addictive. For example, daily use of narcotics or use of sedative medications during the day usually indicates a physical addiction.
Narcotic drugs are often abused. In a recent study of migraine treatment in which daily narcotics were prescribed, there was evidence for dose violations (taking more than prescribed), multisourcing, lost prescriptions in about 50% of persons on narcotics (Saper et al, 2004). Diversion of drugs is also a significant concern.
While few people want to be addicted to drugs, from time to time, these agents are needed to keep patients comfortable and productive. In this situation, there should be regular physician supervision and consideration of other approaches than the addictive medication.
If one wishes to stop an addictive medication, one must usually "wean" off. In general, this means cutting down the dose by a significant amount (say by 1/2), every week, until it is entirely stopped. Going "cold turkey" with addictive medications is usually a bad idea.
Narcotics include Tylenol #3, anything with codeine or hydrocodone, Darvocet, Darvon, Demerol, Vicodin, Percodan, Roxanal, Stadol, and many others. Drug dependence is characterized by repetitive use of a substance that results in problems in three or more areas of life such as : 1). Development of tolerance 2). Development of withdrawal 3). use of substance in larger amounts or for longer periods than intended 4). unsuccessful efforts to cut down on use of substance 5). spending a great deal of time in activities necessary to obtain substance 6). giving up social, occupational or recreational activities because of drug use 7) continuing to use substance despite physical or psychological problems associated with use.
Sedatives or drugs containing sedatives (Fiorinal, Fioricet, Valium, Ativan, Xanax, Klonapin, Equinil). Addiction consists of either daily excessive use (e.g. 5 Fiorinals/day), or significant withdrawal symptoms unrelated to the primary indication for the drug -- for example, unable to sleep after stopping Ativan, Valium or Xanax. Barbituate overuse can be treated with phenobarbital which allows a slow taper.
While not generally used for headache, amphetamines such as Dexadrine and Ritalin, and of course alcohol are also addictive.
Ergot drugs and Triptan drugs(DHE, ergotamine, any drug with "ergot" in the name, and anything with "triptan" in the name). The main problem here is "rebound" headaches. Recommendations for MAXIMUM use of medications follow.
| Medication | Maximum Recommended Use |
| Caffeine | 2 treatments/week |
| Codeine | 2 treatment days/week |
| Oxycodone (i.e. Percocet) | 2 treatment days/week |
| Butlbital (i.e. Fiorinal) | 2 treatment days/week |
| Proproxyphene (i.e. Darvon) | 2 treatment days/week |
| Butorphanol (i.e. Stadol) | 2 treatment days/week |
| Ergotamine tartrate | 8 treatment days/month. Maintain 4 day gap between treatment days |
| Sumatriptan | 6 treatment days/month or 2 treatment days/week |
Adapted from table 6 in: Solomon G, Cady R, Klapper J, Ryan R. National Headache Foundation: Standards of care for treating headache in primary care practice. Cleveland Clin. J. Med 64/7, 1997, 373-383
We do not recommend that you stop prescription medications without the permission of your doctor. However, certain medications can trigger headaches. Note that some medications in the same category that cause headache, may relieve headache. There are far too many medications that cause Migraine to list here, however the most common ones are listed.
Migraine headaches often evolve or transform into daily headaches, and this pattern has been termed the "analgesic rebound headache". Common features are thought to be:
Some authors suggest that in addition there is tolerance to analgesic medication, and efficacy of usually effective medication is compromised by ongoing consumption of
ediate relief medications. Whether rebound can occur from sumatriptan is unknown at this writing (1997). However, many authors feel that rebound can occur from ergot medications, so it does seem likely that sumatriptan shares this problem. Treatment involves withdrawal of analgesic medication. This sometimes must be done during a hospital setting.
Reference: Seminars in Headache Medicine, Analgesic Rebound Headache, Vol #2, #3, Sept 1997.
(c) 2002-2007 Timothy C. Hain, MD, all rights reserved
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