Man With Incapacitating Daily Headaches

A 39-year-old man complains of severe daily headaches that he describes as throbbing and "burning," with a sensation of pressure. He rates the severity of his pain as 8 to 10 on a 10-point visual analog scale (VAS) in which 10 is the most severe. The mean duration of the headaches is 12 hours, and the mean frequency is 5 days per week. Between the episodes of severe headache, he has constant "minor" headaches that are not as severe (mean severity, 3 to 5 on a 10-point VAS). Within the past 5 months, he has never been totally free of headache. The patient’s headaches started during his 20s. At that time, they were very severe but not as frequent. The frequency of the headaches slowly increased over 2 to 3 years until they occurred on more than 15 days each month. For the past 7 years, he has had daily headaches, which have worsened and become disabling in the past 4 months. His treatment history is extensive; he has tried a variety of appropriate medications, but none have enabled him to control his headaches and to function normally. Preventative medications he has tried include verapamil(, fluoxetine(, paroxetine, amitriptyline(, divalproex, topiramate, and celecoxib. The abortive medications include several potent antimigraine agents (sumatriptan, almotriptan(, and zolmitriptan(). In addition, for pain relief, he has tried over-the-counter analgesics, oxycodone(, and propoxyphene. For the past 7 months, he has used butalbital-containing medications every day. A recent MRI scan and MR angiogram and results of a neurologic examination are all normal.

• Which clues in the history and clinical picture point to the diagnosis?
• How would you intervene to alleviate this patient’s disabling headaches?
• How would you institute effective preventative therapy?

Primary care doctor: This patient's headaches are of different types and have some unusual features (such as "burning"). This makes the clinical picture unclear. How would you arrive at a diagnosis?
Headache specialist: I suspect your patient has rebound headache, which is now termed "medication-overuse headache," according to the classification proposed by the International Headache Society in 2003.^1,2 The new classification provides valuable criteria regarding the type of medications and frequency of use associated with this kind of headache. According to the new classification, medication-overuse headache is diagnosed if:

• The patient is taking an ergotamine(, a triptan, an opioid, or a combination of various pain medications on more than 10 days per month (or simple analgesics on more than 15 days per month) for more than 3 consecutive months.
• The patient has chronic headaches that have worsened during the period of medication overuse.
• Discontinuation of the agent suspected to have caused medication-overuse headache results in noticeable improvement.¹
• Your patient's headaches have been getting worse while he has been taking butalbital-containing medications daily; this strongly suggests that he is experiencing medication- overuse headache.

Primary care doctor: This man tried various medications and even used a combination of several preventative medications and abortive medications. Yet the agents he tried-especially the triptans-did not help him. So how do you conclude that he has medication-overuse headache rather than some type of secondary headache?
Headache specialist: First, his normal MRI scan, MR angiogram, and neurologic examination results help rule out secondary headache. In cases such as this, it is important to perform all these studies, as well as a psychological evaluation, to avoid misdiagnosing secondary headache.
Also, a patient who is overusing pain medications- and in whom medication-overuse headache develops as a result-may simply not benefit from any kind of preventative treatment until the habituating medication is stopped. I believe this applies in this man.
Primary care doctor: What approach would you recommend at this point?
Headache specialist: I would recommend inpatient treatment. This is a very effective method of managing intractable headaches. First, a multidisciplinary approach can be employed that combines pharmacologic, nonpharmacologic, and educational strategies. Also, inpatient treatment allows the use of more "aggressive" therapies, which often require parenteral administration and dosing every 6 to 8 hours. Round-the-clock treatment is essential to break the existing headache cycle and is a very effective method of acute (abortive) treatment. It is very difficult to employ this type of therapy in an outpatient setting.
Primary care doctor: Should all patients with medication-overuse headache be hospitalized for treatment?
Headache specialist: Not necessarily. You need to consider what types of medications are being abused. It is also important to review the patient's treatment history and determine whether any previous treatment was successful. If it was, then you need to compare the previous headache pattern with the current headache problem to determine whether the headaches have worsened since that time.
In this man's case, the medications being overused contain a narcotic (butalbital). Thus, detoxification may require substitution therapy (eg, phenobarbital(). In addition, outpatient treatment has repeatedly failed. Both these facts support inpatient treatment.
Primary care doctor: What other criteria should be considered before making the decision to admit a patient with headache?
Headache specialist: There are several others (Table). It is always important to assess the current clinical presentation of the headache, as well as the patient's status. What type of headache is he or she experiencing? Consider inpatient treatment for different kinds of chronic headache, and for certain other types of headache, such as status migraine, which requires aggressive abortive treatment to resolve the pain.
The level of the patient's disability, which is usually a function of the frequency and severity of the headaches, is also a determining factor. Patients with severe associated nausea and/or vomiting may require admission because of dehydration and decreased functioning.
Another important consideration in the decision to hospitalize is the method of treatment that will be used. In addition to aggressive abortive treatment and detoxification therapy, initiation of certain types of preventative treatment (eg, monoamine oxidase inhibitors [MAOIs] or combination therapy with various agents) may require careful inpatient observation because of the possibility of drug interactions or reactions.
Primary care doctor: What does inpatient treatment entail?
Headache specialist:Treatment at an inpatient center typically involves:

• Detoxification therapy.
• Acute (reversal) therapy.
• Prophylactic therapy.
• Nonpharmacologic therapy.

Detoxification therapy is required for patients with medication-overuse headache to help them discontinue the habituating medications. To avoid possible withdrawal, especially for those who have been overusing narcoticcontaining medications (such as butalbital), substitution therapy may be needed.
Various agents are used in acute (reversal) pharmacotherapy. I frequently use the dihydroergotamine( (DHE) protocol (DHE mesylate, 0.5 mg, administered intravenously over 2 to 3 minutes in combination with ondansetron, every 8 hours for 3 days).³ I also use the NSAID ketorolac(, 30 mg (if the patient was not abusing it previously). The ketorolac is alternated with muscle relaxants (eg, IV orphenadrine(, 30 mg) and antiemetics. In some cases, I may use IV valproate(, 1000 mg as needed (not daily), as an abortive agent. If the patient complains of very severe headache and other abortive drugs are not effective, corticosteroids might be used (IM methylprednisolone(, 80 mg as needed [not daily]). For pain relief, IV methadone(, 10 mg, in combination with IV promethazine(, 50 mg as needed (not daily), may be given. Any pain medications previously abused by the patient are avoided. This type of intensive reversal treatment often allows patients to experience their first headache-free (or almost headache-free) interval-which increases their willingness to cooperate with further treatment.
Primary care doctor: The reversal treatment you describe differs from traditional outpatient treatment. What about preventative treatment? Is the prophylactic therapy instituted during inpatient treatment different from that used on an outpatient basis?
Headache specialist: Yes and no. Sometimes I use traditional preventative medications, such as ß-blockers, calcium channel blockers, divalproex, and topiramate(. Antidepressants are prescribed for many patients-with the tricyclic antidepressants (TCAs) as first choice. However, TCAs are prescribed only if the patient has never been treated with these agents or has had a previous positive experience with a TCA. For those patients who have had negative experiences with these antidepressants, another option must be explored. In such patients, the MAOI antidepressants, such as phenelzine( and isocarboxazid, are the "last resort."⁴
I prefer to initiate treatment with MAOIs in an inpatient setting because of the extensive list of associated contraindications, dietary limitations, and interactions with other medications. Inpatient initiation facilitates thorough patient education regarding medications and foods to avoid in order to prevent undesirable interactions and side effects.
Primary care doctor: You have mentioned nonpharmacologic interventions. Could you elaborate?
Headache specialist: Nonpharmacologic interventions are an important part of headache management. These include biofeedback training, stress management therapy, relaxation training, physical therapy, and psychological and/or psychiatric consultations. It is also important to review and challenge patients' diet and sleep habits. In general, I try to teach patients how to deal with pain, manage stress without pain medications, and use more appropriate coping strategies.^5,6.