4
The
Pharmacologic Treatment of Migraine
For the past two years our increasing knowledge of mi- graine’s biogenesis has been paralleled by an explosion of new therapies unprecedented in their biologic selectivity and clinical effectiveness. While these medications provide us with a potent arsenal of weaponry for combating mi- graine, all possess at least some imperfections, and their inappropriate use may make a bad situation worse. In this chapter, we will discuss the issues of acute migraine treatment, prevention of migraine attacks and suppression of chronic migraine, emphasizing the use of medications.
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Despite the advances that have been made, pharmaco- logic treatment of migraine remains a process of educated trial and error. Come to one of one of our headache clin- ics, and you will find after a few weeks that although their personalities may vary dramatically, virtually all migraine patients offer one of surprisingly few histories in describing their headache syndromes. Despite the sim- ilarities in the histories provided by migraineurs, there is no one abortive or prophylactic drug that is universally effective for all patients. Presumably this reflects the het- erogeneous nature of migraine’s underlying biology; it well may be that there are dozens, hundreds or even thousands of genetic permutations that yield these rela- tively few clinical presentations, and each of those ge- netic polymorphisms may produce a different type of neurochemical abnormality. The resulting biologic vari- ation implies that only some proportion of migraineurs will respond to a drug that possesses a relatively specific mechanism of action, acting only to modify a certain type neurochemical abnormality.
What are the different subtypes of migraine? The ma- jority of migraineurs have migraine without aura, but a significant minority (again, approximately 20%) have at least occasional aura with their attacks; a tiny percentage report migraine attacks that predominantly involve aura only. In terms of headache frequency, there are those pa- tients who experience less than 15 days of headache per month (episodic migraine), those who experience 15 or more headache days per month but not daily headache (frequent episodic migraine) and those whose headaches are daily (chronic daily headache/chronic migraine); the last group is subdivided into those who are aggravating their
chronic daily headache (CDH) headache syndrome through overuse of acute medications and those who are not.
Drug therapy for migraine is divided into treatment that is abortive (ie, for acute headache only) versus treat- ment that is prophylactic (i.e., intended for prevention of attacks).
Abortive Drug Therapy
Almost all migraineurs who experience at least occa- sional attacks of moderate or severe headache are candi- dates for treatment with an abortive agent. Some general caveats for the use of abortive drug therapy follow.
1. Use a therapeutic dose at the appropriate time: An ad- equate dose of aspirin or acetaminophen (say, 975 mg, especially taken in conjunction with a caffeinated bever- age) administered early in a migraine attack may be more effective than a “powerful” opioid (narcotic) taken too late. When patients tell us that “simple” analgesics have failed in the past, we are careful to ask them what dos- age was used and at what point in the attack the med- ication was taken. Especially with over-the-counter (OTC) medications, the “recommended” doses often are insufficient to terminate acute migraine.
2. Match drug to headache intensity: There is no sin- gle drug that is ideal for the treatment of migraine head- ache regardless of pain intensity. Some agents will work only-or at least consistently-if taken when the headache is mild to moderate in intensity, and others (e.g., in- jectable sumatriptan) ironically may have little effect on
early headache but relieve excruciating head pain com- pletely. Evidence is rapidly accumulating to suggest that the oral triptans (see Appendix 3) are most effective—
and most consistently effective—when taken early in an attack, when the pain is still relatively mild.
3. Treat early: This caveat serves to some extent as a corollary to #1 and #2. As an attack progresses, the pain pathways within the central nervous system become sensitized, resulting in reduced drug effectiveness and a higher incidence of drug-related side effects. If you have mild headaches that never progress, it is reasonable to have a different medication for that headache. However, if your attack is generally disabling, never “step up” to the most effective drug: treat with that agent early on.
4. Use the appropriate formulation: Use the appropri- ate formulation. It makes no sense to take an oral med- ication for acute migraine if you are experiencing asso- ciated nausea and vomiting; that situation calls for medication that is administered intranasally, rectally, subcutaneously (i.e., injection under the skin) or in some other fashion that will enable the drug to be absorbed by the body and do its job. If the nausea is experienced some time after the attack begins, the pills will probably suf- fice; if these symptoms are experienced early in the at- tack, then the agent will never be absorbed and it is doubtful that it will be effective.
5. Even when vomiting is not a problem, the oral administration of acute migraine medication may be complicated by erratic gastrointestinal absorption; acute migraine frequently produces gastric paresis (i.e., de- layed stomach emptying), resulting in impaired absorp-
tion. A way to overcome this obstacle is to take caffeine along with any other orally administered medication; a more expensive alternative is to administer oral meto- clopramide (Reglan), like caffeine an agent that promotes gastric emptying, about 20 minutes before taking another oral drug intended for acute migraine treatment. The newer migraine agents; triptans, all reduce nausea and vomiting in parallel with reduction in headache.
6. Avoid overuse: We will explore the issue of anal- gesic overuse headache in detail later in this chapter, but for now, medication intended for the acute treatment of migraine actually may promote headache if it is overused. Along with this, overuse of certain analgesics rapidly may lead to tolerance, wherein the pain killing effect of the drug progressively decreases with continued use. Tolerance may provoke a vicious cycle, enticing the patient to take more and more of an analgesic to obtain less and less pain relief and may lead to physical and psychological drug addition.
The abortive medications commonly used for migraine are listed and briefly described in Appendix 3. When you receive a prescription for such medication, be sure you understand how and when it is to be used, what side ef- fects you may anticipate and what to do should the drug prove ineffective. To ensure that you do not receive a pre- scription for an abortive medication that might cause a serious side effect or interact adversely with other med- ications you are taking, provide your physician with a complete medical history (emphasizing any problems you may have had with blood pressure, heart disease, di-
abetes or gastrointestinal disorder such as peptic ulcer disease). Also, be sure to provide a complete listing of your medications and their current dosages.
The ideal abortive agent for headache is one that is inexpensive, easy to administer, exerts its therapeutic ef- fect rapidly, invariably terminates the headache com- pletely, does so without conveying side effects, is asso- ciated with a 0% chance of early headache recurrence and possesses no potential for producing analgesic overuse headache. Needless to say, no such agent yet exists, but in designing an acute headache treatment strategy, this is the ideal for which we should strive.
Prophylactic Therapy
The question of when to begin a course of daily pro- phylactic therapy for prevention or suppression of mi- graine remains something of a moving target. As our understanding of migraine grows and the number and effectiveness of the abortive agents available increase, more and more patients who in the past might have been appropriate candidates for prophylactic therapy now can treat their headache attacks with abortive therapy alone.
The following represent some situations wherein pro- phylactic therapy strongly should be considered:
1. An established history of migraine, with headaches now occurring more days than not (regardless of head- ache intensity).
2. Attacks of migraine occurring at least monthly that are functionally disabling despite optimal self-adminis- tered abortive therapy.
3. Menstrual migraine of the “status migrainosus” type (i.e., menstrually associated migraine that typically lasts for days).
4. The migraineur holds a job (eg, airline pilot) or there is some other circumstance wherein severe migraine attacks must be kept to an absolute minimum.
In our clinics, the first of these is by far the most fre- quently encountered indication for prophylactic ther- apy. When migraineurs are experiencing fifteen or more days of headache per month, their head pain signaling pathways within the peripheral and central nervous systems are becoming biologically sensitized and, in essence, setting them up for more and more headache;
put simply, headache begets headache. The more sen- sitized the migraineur becomes (as evidenced by steadily increasing headache frequency and pervasive- ness), the more refractory to treatment intervention that patient becomes. Once a patient reaches the clinical swampland we term chronic daily headache (CDH), ex- trication can be extremely difficult; recent evidence sug- gests that patients who experience CDH for six months or more are much less likely to respond to prophylac- tic medication than patients with CDH of less than six months’ duration.
As we did for abortive therapy, let us offer you some general guidelines for maximizing the effectiveness of prophylactic therapy.
1. With many of the prophylactic medications em- ployed, you will need to start with a low (and probably ineffective) dose and then build up that dose sequentially
to a therapeutic level. Understand that there is almost al- ways a latency between onset of therapy and onset of a positive treatment response, and that latency will be in- creased if you must “start low, and go slow” with your dose. Remember, too, that drug side effects tend to be most common during the initial weeks of therapy, the very time when you are least likely to note any im- provement. It is easy to give up at this point. Don’t! or at least call your doctor before you do.
2. Rarely will a prophylactic therapy be so effective as to stop all headache attacks. Be sure you have appro- priate abortive medication on hand to treat “break- through” attacks, and treat those attacks aggressively; a prolonged, severe attack will only sensitize you further and prolong the treatment process. Be sure, however, that the abortive medication you use is compatible with the prophylactic medication you are taking.
3. Avoid sabotaging your prophylactic therapy by keeping a “dirty brain.” With your physician’s assistance, attempt to minimize the number of other brain-active medications you are taking on a daily basis. In addition, avoid precipitating analgesic overuse headache through overzealous use of your abortive agents; while the sci- entific basis for this has yet to be well established, there is a prevailing conviction amongst most headache physi- cians that patients with analgesic overuse are much less likely to respond positively to a given prophylactic medication.
4. Again, this is a process of educated trial and er- ror. There currently exists on the market no prophylac- tic agent that has greater than a 50% chance of reducing
your “headache days per month” by 50% or more. Given the problem with prolonged therapeutic latency (see #1) and the side effects so common with these drugs, the search for an effective prophylactic agent can be pro- longed and highly frustrating for all parties involved.
Hang in there! The vast majority of patients who give it their all will find a prophylactic drug that is effective for them.
5. Now for the good news: Very few migraineurs require chronic, indefinite prophylactic therapy. Pro- phylactic therapy is intended to desensitize an inher- ently sensitive migrainous brain that, for whatever rea- son, has become yet more sensitized (as expressed clinically by increasing headache frequency). Once de- sensitization has occurred, the patient is headache-free or nearly so and this happy state has persisted for an ap- propriate length of time, it is appropriate (and in fact ad- visable) for your physician to taper you off the prophy- lactic medication and for you to treat such attacks that occur with abortive therapy only. In terms of desensiti- zation/stabilization with a prophylactic agent, how long is long enough? As with a somewhat similar question posed earlier in regards to analgesic overuse headache, the answer probably varies from person to person and drug to drug. In general, we like to see patients head- ache-free or nearly so for a period of at least three months before attempting to taper them off prophylac- tic therapy. Most patients who are stabilized for that pe- riod of time will enjoy a carry-over effect (i.e., remain rel- atively free of headache even without concomitant prophylactic therapy).
Menstrual Migraine
As indicated in Chapter III, menstrually associated mi- graine (MAM) is a migraine of a different color. If you have the type of MAM which involves a single headache attack that persists for days, you may wish to consider beginning a course of “miniprophylaxis” that starts shortly before the anticipated day of headache onset and is continued for a week or so. Miniprophylaxis for MAM is most effective in patients who can predict onset of menstrual flow and consistently can predict when their headaches will begin in relation to that date. This is eas- iest for women who take an oral contraceptive pill (OCP) that includes a placebo week. Options for mini-prophy- laxis of MAM include: an NSAID (eg, naproxen sodium), a triptan (sumatriptan, naratriptan or frovatriptan), mag- nesium supplementation, or elimination of menses via use of an active oral contraceptive pill throughout the month.
Analgesic Overuse Headache
With the possible exception of the nonsteroidal antiin- flammatory agents, such as naproxen, indomethacin, and ibuprofen, it appears that virtually any of the drugs used for acute treatment of migraine may aggravate headache if they are overused. There are two types of analgesic overuse headache (AOH): paroxysmal and chronic/
pervasive. With the paroxysmal type, patients often are awakened from sleep by headache, take the offending agent, experience temporary headache relief and then hours later develop another headache. Repeated admin-
istration of the offending agent may continue temporar- ily to relieve the headache, but the pain invariably recurs.
This type of AOH is easy to identify and understand; in essence, the patient is treating drug withdrawal headache by administrating the offending drug (much as a “hair of the dog” will relieve the headache of alcoholic hang- over). One tip-off that the paroxysmal form of AOH is in effect is the patient’s tendency to be awakened from sleep by a particularly severe headache; while asleep the pa- tient obviously is unable to sense the impending and in- creasing headache, and by the time the pain awakens him or her, it is typically intense. This type of AOH is easy to treat, and withdrawal from the offending agent typically produces dramatic improvement within just a few days.
If the withdrawal process is too miserable for the patient to endure at home, repeated intravenous administrations of dihydroergotamine (DHE) (see Appendix 3) or an- other, similar agent in clinic or during a brief hospital- ization will assist in the withdrawal process. Unfortu- nately, this type of AOH is rare and is caused by only a handful of agents. Of these, caffeine is the most common offender, followed by ergotamine tartrate and, ironically, the triptans.
The chronic/pervasive type of AOH is unfortunately far more prevalent and more insidious. With this head- ache syndrome, the sharp peaks and valleys of the parox- ysmal form are blunted. The patient has a chronic head- ache that may wax and wane in intensity but rarely vanishes entirely. Administration of the offending agent may offer some partial and temporary relief, but it is not uncommon for us to hear from patients that the medica- tion they are taking so often and on a daily basis “doesn’t
really help anymore” (so why do they continue to take it?!!?). The drugs that may induce this form of AOH range from simple analgesics such as acetaminophen to the po- tent opioids (narcotics). In one recent study, daily high dose administration of humble acetaminophen to labora- tory rats resulted in a loss of the drug’s pain-protective ef- fect within two weeks, and after that point, the drug pro- duced a biologic and anatomical change in the nervous systems of the animals that led to an acceleration of pain signaling. In other words, overuse of a medication as seem- ingly innocuous and freely available as acetaminophen is likely to be capable of reshaping our brains in a way that favors the promotion of headache. Treatment of this form of AOH is difficult. Clinical improvement following with- drawal from the offending agent may be delayed for weeks up to months, but such withdrawal is mandatory if the patient is to achieve any success in overcoming his or her chronic headache syndrome.
How much is too much? No one knows for sure, and the answer likely varies from drug to drug and individ- ual to individual. As a rule of thumb, we recommend that patients restrict their use of a given abortive agent or class of agents two or three days per week, with a maximum of two therapeutic doses on those days. For acute head- ache treatment on the “off days,” we would suggest early intervention with an NSAID.
Drug Therapies
Drug therapies for migraine operate in one of two ways.
1. Prevention of attacks (prophylaxis).
2. Treatment of attacks once they have begun (abortive).
(Prophylactic) Therapy
Prophylactic therapy is considered for people whose headaches occur with sufficient frequency to justify use of daily medication. Some of the more commonly pre- scribed drugs included in this group are:
1. divalproex (Depakote): This is the newest of the FDA-approved prophylactic medications for migraine.
Long used for treatment of epilepsy, it can be of benefit to many patients with episodic or chronic migraine. The most common side effects are gastrointestinal discomfort and nausea; sedation, tremor, weight gain, and hair loss occur less frequently. Use of the single daily dose ex- tended release (ER) formulation administered at bedtime, appears to reduce many of these side effects. Inflamma- tion of the liver or pancreas and lowering of blood cell counts infrequently occur, and periodic blood testing is required to exclude those complications.
2. propranolol (Inderal) or other beta-blocking agents: These medications are presumed to act on blood vessels or brain serotonin receptors to prevent migraine attacks. Common side effects (especially with higher doses) include dizziness, lightheadedness, lethargy, and insomnia; depression or memory impairment also may occur. Some of these result from the drug’s effect of slow- ing the heart rate and lowering blood pressure. This ac- tion on the heart means they are sometimes contraindi- cated in patients with heart disease, and they typically should not be taken by individuals with asthma or dia- betes. The dose required for headache control varies widely from patient to patient, and a period of dosage adjustment may be required. It can be dangerous to stop
taking a beta-blocker suddenly after use for a prolonged period.
3. amitriptyline (Elavil) or other tricyclic antide- pressants: This medication is commonly used as an anti- depressant or to treat other types of chronic pain or to promote sleep. Serendipitously it was found to be useful for migraine prophylaxis and has become very popular for this indication. It is thought to work by a specific ef- fect on neurotransmitters within the brain, but its precise mechanism of action is not well understood. Initially, se- dation and dry mouth are common side effects, but these tend to improve with time. The drug may increase ap- petite, a side effect that tends to persist. It is particularly useful for patients with frequent headaches and sleep dis- turbance. Related medications within the same class, es- pecially nortriptyline (Pamelor), often are prescribed for migraine and may have less potential to cause sedation.
4. gabapentin (Neurontin): As with divalproex, this drug initially was developed to treat epilepsy but subse- quently was found to be effective in preventing migraine.
Side effects are relatively uncommon but may include se- dation, dizziness, and disequilibrium.
5. topiramate (Topamax): Yet another drug devel- oped for epilepsy that is effective for migraine preven- tion as well. Side effects include stomach irritation and impairment of memory and concentration . . . especially if too much is taken too soon. Tingling of the extremities is common (but not harmful) at higher doses. Weight loss of varying degrees occurs in many patients taking topi- ramate. There have been reports of acute visual impair- ment/glaucoma and of hyperthermia (elevated body temperature) secondary to impaired sweating in patients
taking topiramate. The former typically occurs within the first month or two of treatment, and the occurrence of uncharacteristically impaired vision in a patient taking topiramate should prompt an immediate call to his/her physician.
6. Verapamil (Calan) or other calcium channel blockers: Mechanism and site of action are uncertain. Side effects include constipation, nausea, and lightheaded- ness; transient hair loss occasionally may occur. Reason- ably effective for cluster headache, in migraine verapamil is less useful than the drugs previously described.
7. Nonsteroidal antiinflammatory agents (NSAIDs) (Anaprox, Aleve, Motrin, Advil, Indocin, naprosyn): This class of medications is used for many types of headaches, including migraine, and some patients seem to benefit from such therapy. All may be especially effective for mi- graine associated with menses. All may cause gastroin- testinal discomfort, and, less frequently, stomach in- flammation, bleeding, and ulcer formation; these side effects are less common with the newer, long-acting NSAIDs (e.g., Bextra) Chronic use may (rarely) cause sig- nificant injury to the kidneys.
8. SSRIs (selective serotonin reuptake inhibitors:
Prozac, Zoloft, Paxil, Celexa, Lexapro): While these drugs unquestionably are often of great help in treating de- pression or anxiety, their effectiveness in preventing headache is unproven. Most typically, migraine tran- siently may worsen when an SSRI is started and then sub- side back to its previous baseline. Common side effects include nausea, diarrhea, insomnia, restlessness, weight gain, and sexual dysfunction (egs, decreased libido, de- layed orgasm).
9. zonisamide (Zonegran): Another antiepileptic drug that currently is under investigation for its use in preventing migraine. Mechanism of action appears sim- ilar to that of topiramate, but zonisamide generally is eas- ier to tolerate.
10. Occipital nerve blocks: These blocks typically involve injection of a long-acting local anesthetic and a steroid antiinflammatory drug into the tissues sur- rounding the greater and lesser occipital nerves in their location at the base of the skull. Performed correctly, the procedure is safe, fairly painless, and often dramatically effective in relieving headache . . . especially when the patient has prominent associated neck pain and muscle spasm. Any benefit from the blocks is variable in dura- tion, ranging from hours to months.
11. Botulinum toxin (BOTOX): Injection into the muscles of the face and neck of small doses of the bacte- rial toxin that causes botulism appears to be a promising therapy for headache prophylaxis in some patients. The benefit of treatment with a single set of injection may per- sist for as long as 3 to 6 months. When the injections are performed correctly, and especially when the injections are confined to the face, side effects are rare; eyelid droop is the most common side effect, and it typically resolves within 1 to 2 weeks. At this writing, however, the effec- tiveness of BOTOX for migraine treatment remains un- proven, and controversy exists as to what represents the optimal dose and pattern of injection to be used. Many insurance carriers consequently will not underwrite the use of BOTOX for headache.
12. Chronic opioid therapy (methadone, Oxycon- tin CR, Duragesic patch): At some clinics and headache
centers, and in a highly selected subgroup of patients with chronic migraine who fail to respond to other, more conventional therapies, chronic daily administra- tion of a long-acting opioid may be used to suppress headache. Potential side effects of such treatment in- clude nausea, constipation, fatigue, physical addition (i.e., precipitation of the opioid withdrawal syndrome if the drug is stopped too rapidly), and psychological addiction (less common with methadone; more com- mon with Oxycontin CR). Such treatment should be con- sidered as a last-ditch effort at relieving the burden of disability imposed by migraine, and treatment should be initiated only when all parties involved are respon- sible and well informed.
If you are taking one of these prophylactic medica- tions, some general rules should be kept in mind:
1. Most of these drugs must be taken at doses that un- fortunately may produce side effects. Side effects tend to be maximal during the early phase of treatment and subsequently may subside or at least diminish. There is often a trade-off between side effects and beneficial prevention of migraine.
2. Despite being quite successful for many people in the prevention of headaches, these drugs are typically not useful during an acute attack.
3. Many of these drugs require several weeks of therapy before they become optimally effective. Coupled with the tendency for side effects to be maximal during this period, many patients give up and stop treatment pre- maturely (see #6).
4. None of these medications should be discontinued suddenly, as this may precipitate severe “rebound”
headache. If you choose to discontinue any of these medications after using them for a month or more, consult with your physician. A gradual taper can be initiated to insure your safety and comfort.
5. It is important to realize that many migraine medica- tions interact with other medicines (sometimes ad- versely). Check with your doctor before using other drugs (e.g., over-the-counter diet pills, cold medica- tions, or any prescription medications).
6. These drugs will not work if you do not take them.
Call your physician before stopping treatment; often a dosage adjustment or a few words of encouragement will carry you over the hump and to a positive treat- ment response.
Abortive Therapy
For some people, therapy aimed at stopping headaches once they have begun is more appropriate than daily administration of a preventative medication, and even when prophylactic medication is taken, “breakthrough”
headaches may occur and require acute treatment. As de- tailed in this chapter, two general rules must be kept in mind:
1. These medications should not be taken too frequently, as the risk of side effects may increase with dose. In addition, overuse of abortive agents may lead to anal- gesic overuse headache (also called rebound headache by some) (i.e., headaches caused by medication).
2. Aside from injectable sumatriptan or DHE, intranasal butorphanol and the opioids, you should take these medications as early as possible, at the first sign of headache. Do not wait to see what happens; as the headache progresses, it becomes much more difficult to treat effectively.
Some of the more commonly prescribed abortive med- ications include:
1. aspirin: Don’t laugh! A relatively high dose (i.e., four tablets at onset and then two tablets every four hours thereafter) is often very useful for acute migraine. As- pirin’s mechanism of action is not well understood, but its antiinflammatory properties, are thought to be par- tially responsible for its effectiveness. It also acts on cer- tain chemicals active in the pain pathways of the brain and body . The most common side effect is stomach up- set, and this may be lessened by taking aspirin with food or milk or by using a buffered/coated preparation. Ad- dition of caffeine (e.g,, coffee, tea, soda) may enhance the therapeutic response.
2. ergotamine tartrate (e.g., Cafergot): This medica- tion comes in a variety of forms. The oral preparation of- ten is combined with caffeine to increase absorption from the stomach. This is a potent medication which may con- strict blood vessels throughout the body, and its use in patients with high blood pressure or heart disease is not recommended. If taken too frequently, it can actually cause headaches or lead to decreased blood flow in the extremities. The most common acute side effect is nau- sea. Ergotamine tartrate is now rarely prescribed, having largely given way to the triptans.
3. Midrin: This is a combination medication con- taining isometheptene (which acts by constricting dilated cranial arteries), a mild sedative, and acetaminophen (Tylenol). This drug is less nauseating than the ergota- mines but unfortunately is often not as effective. The usual dose is one or two capsules immediately at head- ache onset, followed by one or two capsules every four hours, as needed. The effectiveness of this product has not been established by current standards.
4. naproxen sodium (Anaprox, Aleve): This non- steroidal antiinflammatory agent (NSAID) (see also the section on Prophylactic Therapy) is relatively fast acting and easy on the stomach and sometimes effective when taken early for acute migraine.
5. indomethacin (Indocin): This old-fashioned, in- expensive NSAID also can be quite effective when taken early in an attack. Its most common side effect is “heart- burn” which can be problematic.
6. dihydroergotamine (DHE): An ergot that is less nauseating than ergotamine tartrate and less prone than most other abortive agents to cause analgesic overuse headache. It is available in injectable and nasal spray for- mulations; the trade name for the latter is Migranal, and as with the other drugs listed thus far, it is more effec- tive when taken early in an attack, before pain is severe.
Injectable DHE is often very effective for acute, severe migraine which is refractory to other treatment.
The Triptans
These agents have revolutionized migraine treatment and generally are considered the drugs of choice for most migraines that are historically disabling. Do not mix dif-
ferent brands of triptans or triptans with ergots within a 24-hour period. You can mix forms of the same triptan within the 24-hour period (i.e., sumatriptan injection and tablets). Side effects include chest or neck tightness or tin- gling of the face or extremities.
1. sumatriptan (Imitrex): The prototype of the trip- tans, a family of abortive agents that resemble serotonin (a brain chemical active in migraine), act rapidly and are effective for many patients. Side effects include nausea, chest or neck tightness, and tingling in the face or ex- tremities. Early recurrent headache following initially successful treatment is common and may require ad- ministration of a second dose. However, treating early in the attack and with an adequate dose dramatically re- duces the likelihood of this occuring. Injectable (subcu- taneous), nasal and oral forms are available. The oral for- mulation is most effective when taken for acute headache while it is still of mild intensity, and the 100 mg tablet appears to be superior to the 50 mg for most patients when they treat early; a recently released oral formula- tion may be faster and perhaps more effective than “old”
Imitrex. The injectable formulation is for headache of moderate to severe intensity, for attacks which are severe at the onset, those awaking one from sleep which are se- vere when treated, or those with significant nausea and vomiting which will affect the absorption of tablets.
2. zolmitriptan (Zomig): The second of the triptans to become available. Similar to oral sumatriptan in ef- fectiveness and side-effect profile. Available in tablet and melt wafer forms, in 2.5 and 5 mg doses, and in a 5 mg nasal spray. The wafer form is convenient, but not faster or more effective than the tablet.
3. rizatriptan (Maxalt): Another oral triptan, simi- lar to sumatriptan and zolmitriptan. Available in tablet and melt oral formulations, in 5 mg and 10 mg doses.
The 5 mg dose should be used by individuals also tak- ing propranolol (Inderal). Again, the melt is convenient, but not more effective than the tablet.
4. almotriptan (Axert): Tablet formulation only (6.25 mg or 12.5 mg). Similar to oral sumatriptan, riza- triptan, zolmitriptan, and eletriptan.
5. eletriptan (Relpax): The latest (and likely last) of the triptans to have become available. Similar to the other
“fast-acting” oral triptans.
6. naratriptan (Amerge) and frovatriptan (Frova):
Naratriptan and frovatriptan differ from the other oral trip- tans in having a longer period to onset of therapeutic re- lief, less frequent side effects and a longer duration of ac- tion (as evidenced by somewhat lower rates of early recurrent headache). Available in tablet form only (nara- triptan: 1 mg and 2.5 mg doses; frovatriptan: 2.5 mg dose).
7. Stadol: A nasal spray that mimics opioid (“nar- cotic”) drugs. Sleepiness, dizziness, or nausea occurs commonly with its use. Potential for abuse is high.
8. steroids (prednisone, Decadron): Potent antiin- flammatory agents that are sometimes used to treat a per- sistent migraine attack (“status migrainosis”). Side effects are fairly rare with short-term use, but upset stomach, restlessness and insomnia may occur.
Other Medications for Acute Migraine
1. antiemetics: These are medications for nausea and vomiting, a common problem for many patients with
acute migraine. Nausea and vomiting can cause worsen- ing of the headache and, when severe, dehydration. The most commonly used agents in this group include promethezine (Phenergan) and prochlorperazine (Com- pazine). Both are available in oral and suppository forms and may have the additional effect of acting directly to reduce headache.
2. butalbital/caffeine/acetaminophen or aspirin (Fiorinal, Fioricet, Esgic, Phrenilin): This combination of a barbiturate, caffeine, and a “simple” analgesic can be effective for some patients with acute migraine headache, especially if taken when the pain is relatively mild. Each individual component has the potential to induce “re- bound” headache if taken too frequently, and use of these compound medications should be restricted to a maxi- mum of 2 to 3 days per week.
3. Oral opioids (“narcotics”) (hydrocodone [Lortab, Lorcet, Vicodin], oxycodone (Percodan, Perco- cet, Tylox, Oxycontin), codeine [Tylenol #3 or #4], meperi- dine [Demerol, Mepergan]): These drugs all may be ef- fective in “rescuing” one from acute, severe migraine headache but potential problems abound: side effects, in- ducement of analgesic overuse (“rebound”) headache, tachyphylaxis (i.e., rapidly developing tolerance to the pain-relieving property of the opioid), and physical or psychological addiction. Side-effects common to this class of drugs include nausea, euphoria, sedation, con- stipation, and pruritus (itching). In most cases, opioid use should be restricted to a maximum of 1 or 2 days per week.
4. caffeine: As previously mentioned, caffeine com- bined with another oral agent (for example, aspirin) may be very effective for acute migraine if used early. Re-
member, however, that chronic excessive use of caffeine may aggravate migraine.
“Alternative” Therapy
The Internet is rife with advertisements for therapies whose promoters insist will eradicate migraine in a safe and “natural” manner. Common to all: they are not free.
Rarely present: any scientific basis whatsoever to support their use. Some “alternative” therapies do at least make sense, and a few even possess a reasonably solid scien- tific basis.
1. Self-relaxation techniques: if migraine is a re- flection of a hypersensitive brain, then it follows that any intervention that “relaxes” the hair should have an ame- liorative effect on migraine. While this can be accom- plished through the administration of medications, there is more than one way to skin a migrainous cat. Biofeed- back training, self-hypnosis, massage, and meditation all are relaxation techniques that may induce brain “desen- sitization.” All have proven difficult to assess by the tra- ditional scientific method, and the consequent lack of incontrovertible proof of their efficacy has had the prag- matic effect of enabling insurers to deny payment.
2. Riboflavin (vitamin B2): Riboflavin taken in a dose of 400 mg daily has been demonstrated to reduce migraine attack frequency. The 400 mg strength may be hard to find but often is available in health food stores or nutrition centers. This therapy may take three to four months to become effective. Side effects are minimal. It may be helpful to take supplemental vitamin B6 in com-
bination with the B2, but do not exceed more than twice the RDA (recommended daily allowance).
3. Magnesium oxide (or, alternatively, magnesium diglycinate): Magnesium’s effectiveness as a therapy for migraine remains in some doubt. It appears to be most useful when given intravenously for an acute attack or when used as “miniprophylaxis” in menstrual migraine.
The dose usually recommended for migraine prevention is 400 mg taken once or twice a day in divided doses. Ini- tially begin taking one tablet a day with meals for the first week, and then increase to one tablet twice a day.
The most common side effect is gastrointestinal distur- bance (stomach upset, nausea, and/or diarrhea). If this occurs, decrease to 200 mg per day. If still present at 200 mg a day, then discontinue the medication.
4. Feverfew: Few data exist to support the effec- tiveness of this drug as a treatment for migraine. The dose usually recommended is 100 mg to 200 mg three times a day. Rarely, mouth ulcers have been reported, but oth- erwise feverfew is well tolerated. There is considerable variability in the constitution of most herbal medicines.
Feverfew comes in many different forms, and the tablet is the preferred. Look at the label to make sure that each tablet contains one whole leaf extract and at least 0.2%
parthenolide.
5. Petasites hybridus (“butterburr”) (fetadolex): An extract of the butterburr plant, this “natural COX-2 inhib- itor” was demonstrated in one study to reduce migraine attack frequency in over two-thirds of participating sub- jects (preparation⫽ Petadolex; dose ⫽ 75 mg twice daily).
The most common side effects of butterburr extract are gastrointestinal (nausea, abdominal pain, diarrhea).
These are only a few of the therapies commonly used in migraine. Never hesitate to ask your doctor about the medication or procedure you are using to treat your headaches or others you would like him/her to consider.
It is unrealistic to expect a rapid cure for a chronic problem. It probably has taken a long time for your head- aches to get where they are today. You must afford your- self and your doctor at least a measure of patience in learning what is required to treat your particular head- ache process.
