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Sample Case: Analgesic Rebound Headache in a Patient
with Severe, Frequent Migraines and Severe Daily Headaches
Posted August 2000

Mark is a 23-year old man with a history, since age 5, of severe daily headaches and frequent migraines, once to twice per week. As with most patients with a history of severe headaches since early childhood, these are headaches that he inherited from both sides of his family. If both parents have had migraines, usually all of the children will have headaches. He has been refractive to the usual first line preventive medications, including tricyclic antidepressants, Prozac, verapamil, beta blockers, and NSAIDs. He takes 12 to 14 pills per day of an aspirin and caffeine combination. Mark has noticed that the headaches have increased in severity as his analgesic consumption has accelerated.

The usual migraine teachings need, of course, to be done with Mark: diet, not to miss meals, wear sunglasses outside, and to utilize ice packs where the headache hurts. I instruct Mark to watch his neck posture so that his cervical spine is in a neutral position; it is important to have students or office workers raise up the level of their desk so the neck is not as flexed. Utilizing a speaker phone, instead of bending the neck on the telephone, helps some patients avoid neck pain. Neck stretching exercises may help.

Relaxation or biofeedback is offered to Mark, as is a program of "headache-stress management," incorporating stress management techniques with, if applicable, psychotherapy or cognitive therapy. Some patients welcome a more holistic approach, and others wish to only use medication. Combining the two approaches is ideal.

Mark is in the analgesic rebound situation, with an increase in headaches from the aspirin and caffeine combination. His true headache pattern, or severity of his underlying migraines and daily headaches, is unknown at this point because of the rebound situation. It is a fallacy to pretend, in this rebound situation, that the offending drug being overused is the only cause of the headaches, because there was a reason why the patient took that drug in the first place. Once we stop the drug responsible for the rebound, and we are over the rebound situation, the true headache severity will be seen.

The severity of the underlying headaches is, in my experience, usually 25% to 75% less after the rebound headaches are stopped. However, a significant number of people do not appreciably decrease their headaches by stopping the analgesics, and the rebound headache situation does not actually apply to them.

The strategy with Mark is to withdraw the offending drug causing rebound, in this case an aspirin and caffeine preparation, and to institute effective preventive medication. We need to educate Mark as to the dangers of constantly "chasing" after the headaches all day. There are generally two manners in which the rebound drug may be withdrawn: all at once (cold turkey) or slowly. It is often necessary to simply throw away all of the offending medicine, for if it is in the house, the patient will take it. Mark’s situation is not as difficult as the situation with an addicting sedative or narcotic, because the withdrawal is usually milder with aspirin and caffeine. Many patients taking butalbital or narcotic preparations originally take the medication for daily headaches, and then increase their use as they realize that the medication helps stress, depression, anxiety, and gives them an "energy boost" for several hours.

Mark decides that he must stop the medication abruptly, because if it is in his apartment, he will take the aspirin and caffeine. I estimate that he is consuming the equivalent of 12 cups of coffee per day through the medication, and I urge him to not abruptly stop all of the caffeine. The caffeine withdrawal headache can be very severe, and many patients suffer through this withdrawal on weekends, when they abruptly decrease their caffeine. He agrees to consume several cups of coffee or cans of soda per day, so as not to immediately shut off the caffeine. Mark has been refractive to all of the first line preventive medications. It may be worthwhile to utilize one of the first line medications again, because when patients are in the analgesic rebound situation, they may be refractive to all medications used to prevent headaches. Medications that patients seemed resistant to are often effective after the analgesics are discontinued.

We decide to institute sodium valproate (Depakote). Later, if we need to, we could add another first line medication such as amitriptyline or propranolol. If we can keep Mark from overusing analgesics, the first line medications that were previously ineffective may indeed help. We begin with one Depakote, 250 mg. twice a day, with food. The plan will be to increase this dose to 1,000 or 2,000 mg. per day, if necessary. Many patients improve on as little as 250 or 500 mg. of Depakote. As with most preventives, at least 3 weeks needs to be allowed for the Depakote to work. A c.b.c. and an SMA need to be drawn at least once in the first month.

Along with using the Depakote, we stop the aspirin and caffeine. I ask Mark to continue some caffeine, the equivalent of three cups of coffee. If he simply stops all caffeine, a severe withdrawal migraine may ensure. I give Mark four injections of IV DHE, over 2 days, in the office. This can be accomplished in the office with much more convenience for the patient than the hospital. At the same time, we give Mark a long-acting triptan, Amerge.

Mark does well for the 2 days on DHE, but after this he begins to have severe daily headaches. We are now in the rebound situation; the Depakote has not had a chance to work, and his basic underlying headache pattern is also very severe. I give him four pills of Prednisone, 20 mg. each, to take one each day. The headaches are slightly improved over these 4 days. I speak with him frequently, and encourage him not to retreat back to the aspirin and caffeine. If patients understand the reason behind stopping pain medication, I find that they are much more likely to follow the program. I give him 10mg. prochlorperazine (Compazine) tablets or 25 mg. suppositories to help with the nausea of the migraines. He finds that Amerge helps. Antiemetic medication is very helpful in providing sedation, as well as in combating the nausea. Compazine is effective, but some patients become agitated or restless with this antiemetic. Promethazine (Phenergan), although more sedating and less effective, rarely creates anxiety.

Mark manages to stay off the aspirin and caffeine, but he begins to call for pain medications. Some patients, in this rebound situation, need a sedative to weather the withdrawal; in other patients we simply do not want to begin with pain medication or addicting sedative medication. If sedatives, such as diazepam (Valium), are given, they need to be limited, and given for only 1 to 3 weeks. I increase Mark’s Depakote to 500 mg. twice a day, and ask him to refrain from using pain medication. At the 3 week point, he has had a rough time, but the headaches are definitely less than when he was on the aspirin and caffeine. He is having mild to moderate daily headaches, and one migraine in the past week that was decreased with Amerge. Blood tests are normal; I usually do not test the level of valproate until we progress to 1,500 mg. per day.

The headaches remain tolerable, but after several months Mark has gained 8 pounds, is beginning to lose hair, and is very fatigued on the Depakote. All of these side effects are occasionally seen with Depakote. We decide to stop the Depakote, and see how he does with no preventive medication. As abortives, Mark has Amerge and Compazine, and we add Midrin as a milder abortive medication.

Soon after stopping Depakote, Mark begins to experience severe daily headaches once again. We now give him gabapentin (Neurontin), starting with 600 mg. per day in divided doses and slowly increasing to 1,800 mg. per day. Mark is fatigued on the Neurontin, but states that it does help the headache 30% to 40%. Amerge has now ceased to be effective and we give Mark Maxalt MLT 10 mg. He states that Maxalt was effective for his milder migraines, but it does not help the more severe ones. For a severe headache, we teach him how to use Imitrex injections. He finds that while he does have an initial rush of muscle tension from the injection into his head and neck, that it quickly abates, as does the headache. He now uses Maxalt for milder headaches and Imitrex injections for more severe headaches. He does not use more than one type of triptan in one day.

As usual, the migraines are more easily dealt with than are the chronic daily headaches. The Neurontin does help Mark, but it is limited. At this point, we still wish to avoid daily painkillers as to not end up in the rebound situation. However, if nothing else helps, long-acting opioids would be a remote consideration with Mark. These include methadone, Kadian, and Oxycontin, among others. With Mark, we add a nonsedating tricyclic, Vivactil, in a small dose, 5 mg. per day. Vivactil almost never causes weight gain, and fatigue is rare. The anticholinergic side effects, such as dry mouth, constipation, and blurred vision, may be severe. We start with one 5 mg. tablet of Vivactil each morning. Many patients cannot tolerate more than 5 to 10 mg. per day of Vivactil.

Mark reports that the headaches are not improved, and we push the Vivactil to 10 mg. per day. The headaches are slightly better on this regimen along with the Neurontin. Neurontin is one of the few medications that does not irritate the liver, but occasionally we do watch the blood tests for renal function, although serious side effects have been exceedingly rare. Methysergide (Sansert) would be a consideration with Mark, but we always try to avoid utilizing this medication, because of the small risk of fibrosis. Other considerations with Mark would be to retry other first-line preventive medication, such as tricyclics other than Vivactil, or SSRIs, or progress to something such as an MAOI (Nardil). The use of frequent or daily triptans, such as Amerge, Imitrex, Maxalt, or Zomig, is controversial. While this is an expensive approach, it does help some patients.

However, long-term side effects are not known. With Mark, we do want to avoid painkillers on a daily basis, and hold the line on medication, utilizing at present the Neurontin and Vivactil combination with Maxalt or Imitrex as abortive. We do not want him to slip back into the rebound headache situation.