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What to do When Nothing Works
Posted Nov 1998

Many people have chronic migraines and/or chronic daily headaches severe enough to warrant daily preventive medications. Unfortunately, the usual preventive meds do not work for everybody; in fact, they are only successful for the long term in about half of all patients. We recently completed a study of 540 people with moderate or severe chronic daily headache, and only 46% found that daily preventive medications were very helpful for the long term. When the headaches are moderate to severe, people suffer due to the pain, with a greatly reduced quality of life.When quality of life is poor due to headaches, and the preventives are not helping, what are these people to do?

The usual 'first line' preventive meds include: Depakote, antidepressants(excluding maoi's), nsaids, beta blockers, and calcium blockers. Examples of these include: Elavil, Pamelor, Prozac, Zoloft, Paxil, Effexor, Serzone, Naprosyn, Oruvail, Inderal, Toprol, Tenormin, Corgard, Isoptin, Covera, verapamil, etc.

Neurontin is another (newer)commonly used preventive. Sansert(methysergide) is usually reserved for situations where the first line meds are not effective. What are the options when these 'usual' preventive meds either are not effective, or cannot be tolerated due to side effects?

The different headache doctors have varied approaches. There is no 'consensus' as to what approach is best in patients where the usual meds have not been effective. The following is my experience and opinion on some of the useful approaches; this is not meant to summarize 'general medical opinion' on treatment of refractive, severe headaches.

I currently utilize 6 main medication approaches in these patients:

  1. combining 2 first line daily preventives;
  2. daily long acting opioids;
  3. repetitive intravenous DHE(dihydroergotamine), in the office or the hospital;
  4. daily triptans or DHE at home;
  5. stimulants, and;
  6. monoamine oxidase inhibitors(maoi's).

Each of these has a role in certain people; unfortunately, at times, none of these will be successful. We are trying to improve the frequency and/or severity of the headaches by at least 50%, and improve quality of life. However, with these stronger approaches, we always need to balance side effects of the meds versus the headaches, and try not to overmedicate.

In treating headache, combining different mechanisms of action has often been effective. Depakote can be utilized with antidepressants, nsaid's with beta-blockers, Depakote with calcium channel blockers, etc. The problem with this approach is that as we increase medication, we also increase the likelihood of significant side effects. In deciding which medications to use with any individual person, we look at associated medical conditions. These include the presence or absence of stomach problems, anxiety, depression, insomnia, hypertension, etc. If a patient has significant insomnia and anxiety, we may use a tricyclic antidepressant in combination with one of the other 'first-line' preventive medications. The key with this approach is to keep doses low and not overmedicate.

I have published several studies on long-acting opioids such as methadone, oxycodone (Oxycontin), and long-acting morphine (MS Contin, Kadian). In my studies of over 330 patients who have been placed on these medications, only 13% to 15% did well long term. However, these were people who had failed on virtually every other headache regimen. For those 13% to 15% of patients, quality of life was significantly increased and headache pain was significantly decreased. This approach has some utility in a small group of patients.

Significant psychiatric problems or previous addiction renders long-acting opioids relatively unlikely to succeed in the long term. However, we have had a number of patients do well on low dose methadone or Oxycontin for years with the same dose. Side effects include fatigue, constipation, and nausea, among others. Withdrawal from these medications can be prolonged and severe.

Repetitive intravenous (IV) dihydroergotamine (DHE) has been effective therapy for stopping cycles of severe headache. This is usually accomplished in the hospital, but a few physicians have used this approach in an office outpatient setting. People receive three to nine injections of IV DHE over a period of time, usually spaced four to eight hours apart. This technique is useful in patients who have severe rebound headaches, and are being withdrawn off of analgesics. DHE has been proven to be a remarkably safe medication; since 1945, only a handful of serious side effects have been reported. The usual side effects include nausea, diarrhea, or leg cramps. These tend to be transient, and most patients experience virtually no side effects from DHE. Over weeks, the effects often wear out so that we are left with the patient's usual chronic daily headache problem.

Patients have occasionally utilized DHE injections intramuscularly (IM) at home. Migranal Nasal Spray on a daily basis is an option, but has been only mildly effective, with the injections providing much more benefit. Since the triptans have become available, particularly sumatriptan (Imitrex), naratriptan (Amerge), and rizatriptan (Maxalt), a few patients have utilized these on a daily basis. We recently completed a study of 59 such patients who had been taking daily triptans, usually one Imitrex 50 mg. tablet per day for at least six months. Most of the patients were on this regimen for 1 1/2 years. In our limited study, we did not find long-term side effects, but long-term sequelae of daily triptan use is not known. These are also costly medications. A small percentage of patients will experience rebound headaches from triptans, and then they are not utilized on a daily basis. While the long-term side effects of daily triptan use are not known, we do know the side effects of alternative medications that patients ingest. Many patients consume large amounts of analgesics (if they do not have an effective alternative). The stomach, liver, and kidney side effects of these are very well known. Future studies will have to be accomplished before we can assure people that daily triptan use does not have long-term problems associated with it.

For many decades, stimulants such as dextroamphetamine (Dexedrine) or methamphetamine (Desoxyn) have been used in very limited situations with end stage severe refractive daily headache patients. They are effective for some people, but do have side effects of anxiety, insomnia, and addiction. However, a few patients have been able to stay on a limited dose for the long term. I have utilized phentermine, a daily weight loss medication, in a limited number of patients. It is the same basic mechanism of action as the stronger stimulants or amphetamines. This class may provide some benefit, particularly for patients who tend to be extremely fatigued with moderate to severe chronic daily headaches that are resistive to all other approaches.

Monoamine oxidase inhibitors (maoi's) are powerful antidepressants that are very successful for depression and headaches. The usual medication in this class utilized in the United States is phenelzine (Nardil). Nardil is generally well tolerated but may cause insomnia, dizziness, and weight gain, among other side effects. The problem with this class of medications is the diet and medication restrictions because of the risk of a high blood pressure crisis. However, the serious side effects have been few in patients on limited amounts of these medications, particularly when responsible mature patients are selected. At times, maoi's will be combined with other 'first-line' medications such as Depakote, tricyclic antidepressants, beta-blockers, or calcium channel blockers. They cannot be used with ssri's and the triptans. DHE or Migranal Nasal Spray may be utilized with maoi's. Most patients who discontinue maoi's do so because of weight gain and/or insomnia.

The six approaches listed above constitute my basic approach with refractive headache patients. There are alternative approaches that may be useful. The real hope is that better preventive medications will come along for these large numbers of people who do not do well with the current ones. While great strides have been made in the 'as needed' abortive field, particularly with the triptans, we are lagging behind in developing new and better daily preventive medications.