RIVIERA BEACH, FL—Neurologists sometimes encounter patients with headaches that have not responded to prior treatment. These patients may be demoralized, and neurologists may be at a loss for a way to relieve their pain. Effective treatment is possible for many of these patients, according to Thomas N. Ward, MD, Emeritus Professor of Neurology at Dartmouth College in Hanover, New Hampshire. He described the process of differential diagnosis, as well as outpatient and inpatient therapeutic options for refractory headache, at the 44th Annual Meeting of the Southern Clinical Neurological Society.
Confirm the Diagnosis
When faced with a patient with refractory headache, a neurologist should first verify the diagnosis and rule out the possibility of secondary headache. These steps will improve the likelihood of a positive outcome. “If you follow the fundamentals and treat the type of headache it is, you usually get a pretty good result,” said Dr. Ward.
A patient with headache on 15 days per month or more has chronic daily headache. The duration of the headaches can provide the basis for a more specific diagnosis. Headaches of short duration (ie, less than four hours) may be symptoms of cluster headache, chronic paroxysmal hemicrania, hypnic headache, or trigeminal neuralgia. Headaches of long duration (ie, more than four hours) may indicate chronic migraine, chronic tension-type headache, hemicrania continua, or new daily persistent headache.
A patient with headache on 15 or more days per month, and for whom headaches on at least eight days per month meet the criteria of migraine, has chronic migraine. The two best-supported treatments for chronic migraine are topiramate and onabotulinumtoxinA. In patients with chronic migraine, what appears to be a tension-type headache may eventually declare its true nature and become a migraine headache with accompanying pounding and photophobia. What looks like a tension-type headache in a migraineur may respond to a triptan, said Dr. Ward.
Stop Medication Overuse
Medication overuse can confound the diagnosis and alter the headache itself. Many patients with refractory headache overuse medication but may fail to mention this to a neurologist. The overused medication may be a prescription or an over-the-counter drug such as ibuprofen, acetaminophen, or a combination that includes caffeine. Drugs with short half-lives appear to be particularly likely to cause medication overuse headache.
Some patients may be overusing opioids for their headache. “Opioids for headache are not a good idea,” said Dr. Ward. “Nothing good will come of it.” These drugs may cause central sensitization and reduce the efficacy of other headache remedies.
The risk of medication overuse headache increases if the patient uses combination analgesics, ergotamine, or triptans on 10 or more days per month, or simple analgesics on more than 15 days per month. “The clinical question I always ask patients is, ‘Are you taking more pills and having more headaches?’ If the answer is ‘yes,’ then they have medication overuse headache,” said Dr. Ward.
If patients stop taking the overused medication, they may have a withdrawal headache that is worse than their normal headache. Medication overuse headache usually resolves itself after the overuse is stopped, and bridge therapies such as steroids, nonsteroidal anti-inflammatory drugs, or dihydroergotamine may alleviate pain during withdrawal. “If you can get the patient over that hump, which can be several days of bad headache, they often do remarkably better,” said Dr. Ward.
Get Back to Basics
Taking a careful history is essential to successful treatment. “If you do not get the original history, you could miss the diagnosis,” said Dr. Ward. The neurologist must know about the mode of onset of the patient’s headache, and also know all about his or her prior headaches.
A patient with refractory headache should undergo a thorough head and neck examination, but physicians sometimes neglect to perform it. An MRI of the brain with gadolinium generally is warranted. About 90% of patients with low CSF pressure have pachymeningeal enhancement, which is visible on MRI performed with gadolinium, said Dr. Ward. Blood work, however, usually reveals little and appears normal. Sometimes thyroid tests, a Lyme test, a blood count, and a serum creatinine test are helpful, and a serum erythrocyte sedimentation rate test in those over age 50 is important to obtain.
Lumbar punctures may be underused, said Dr. Ward. Although it is uncommon, some patients present with high intracranial pressure, but without papilledema. The correct diagnosis can lead to effective treatment for these patients.
Effective treatment also is more likely when the neurologist gets to know the patient. He or she can use preventive medications to reduce the number of headache days. The literature suggests that successful preventive therapy should achieve a target of four headache days or fewer per month.
Neurologists also should treat the patient’s comorbid conditions, which often are psychiatric in people with refractory headache. It is unusual to see a patient with chronic migraine who does not have anxiety and depression, said Dr. Ward. Patients with refractory headache also may have phobias, bipolar disorder, or posttraumatic stress disorder, which is a significant confounder.
To Admit or Not to Admit?
A neurologist may have to decide whether to admit to the hospital a patient with chronic headache who is not doing well. First, the neurologist and patient should agree on a therapeutic target. Outpatient treatment works well if the patient is motivated and compliant and does not have confounding conditions. If the therapeutic target cannot be met through outpatient treatment, the neurologist should consider hospital admission. Insurance companies generally will cover three days of inpatient treatment, said Dr. Ward.
Neurologists have many options for inpatient treatment of refractory headache. Repetitive dihydroergotamine, known as the Raskin protocol, is highly effective if administered correctly. Dihydroergotamine should be given three times per day. “If you order it q. 8 h., the nurse will wake your patient up in the middle of the night, and waking up a patient with benign headaches is not a good idea,” said Dr. Ward. The dose must not be sufficient to cause nausea, because nauseating the patient can exacerbate headaches. “We usually premedicate with metoclopramide or prochlorperazine for nausea, but both of those drugs … also are good headache remedies.”
The Raskin protocol requires the withdrawal of other analgesics. The protocol typically lasts for three days, and most patients have good outcomes at this point. Extending the protocol to six or seven days may increase the number of patients with good outcomes. The success rate for the Raskin protocol is between 60% and 70%, said Dr. Ward. Patients who are pregnant or who have coronary artery disease should not receive dihydroergotamine, however.
Another option for inpatient treatment is IV chlorpromazine. The goal of this treatment is to induce a light sleep and maintain it for two or three days. The neurologist may start with a dose of 10 mg t.i.d. and monitor the patient’s response. The drug effectively suppresses narcotic withdrawal symptoms, so the neurologist may withdraw overused medications while the patient is asleep. Chlorpromazine may cause QT prolongation, so the patient should undergo cardiac monitoring. The drug also causes orthostatic hypotension, so patients should remain on bed rest and receive prophylaxis for deep venous thrombosis, said Dr. Ward.
IV valproate is an excellent choice if the patient has cardiac problems or bipolar disease, he added. The drug can be administered in a single dose of between 300 mg and 500 mg run in rapidly. “You can run in a whole loading dose in five or 10 minutes with virtually no side effects,” said Dr. Ward. Treatment can be administered b.i.d. or t.i.d. for two or three days. Pregnant patients should not receive valproate, however. Yet another option is IV magnesium, although the evidence for its efficacy is mostly anecdotal. A protocol of 1 to 2 g administered over 10 to 20 minutes, repeated several times per day, may be effective. It is advisable to monitor the patient’s serum magnesium levels to ensure that they do not become excessive. Magnesium may adversely affect fetal bone development, so neurologists should exercise caution when considering the drug for a pregnant patient. IV magnesium is “an excellent choice for hemiplegic migraine,” said Dr. Ward.
If the patient’s occipital nerves are tender, occipital nerve blockade may relieve pain. IV ketorolac, in 30-mg doses t.i.d. or q.i.d., may alleviate breakthrough headaches. Lidocaine patches can reduce back or neck pain for as long as 12 hours daily.
Abruptly withdrawing butalbital entails a risk of seizures and delirium. Neurologists may wish to administer phenobarbital in its place, as a single bedtime dose, while they are tapering or stopping butalbital. A 30-mg dose of phenobarbital may be substituted for every 100 mg of butalbital, said Dr. Ward.
Suggested Reading
Ford RG, Ford KT. Continuous intravenous dihydroergotamine in the treatment of intractable headache. Headache. 1997;37(3):129-136.
Lai TH, Wang SJ. Update of inpatient treatment for refractory chronic daily headache. Curr Pain Headache Rep. 2016;20(1):5.
Levin M. Opioids in headache. Headache. 2014;54(1):12-21.
Lipton RB, Silberstein SD, Saper JR, et al. Why headache treatment fails. Neurology. 2003;60(7):1064-1070.
