chronic daily headache

Chronic daily headache
By
Mario F P Peres

Historical note and nomenclature
There is sharp disagreement on the classification of frequent primary headache disorders, as well as on the appropriate use of the term chronic daily headache. When the Headache Classification Committee of the International Headache Society first defined the various headache disorders in 1988, the issue of frequent primary headaches was not addressed (Headache Classification Committee of the International Headache Society 1988). The term “chronic daily headache” refers to the broad group of frequent or daily headaches that last longer (more than 4 hours) than the brief headaches, such as cluster headache and chronic paroxysmal hemicrania. The only term in the 1988 IHS classification scheme that related at all to frequent primary headaches is chronic tension-type headache. Most patients who have IHS-defined chronic tension-type headache have an additional diagnosis, such as migraine with or without aura. Since these daily headaches often evolve from episodic migraine, it seems inappropriate to classify them as a form of tension-type headache.
The term “transformed migraine” or “evolutive migraine” was first proposed by Mathew and colleagues (Mathew et al 1982) and was operationalized and incorporated into the Silberstein criteria in 1996 (Silberstein et al 1996). Transformed migraine has also been called chronic migraine. The term chronic migraine is widely used today, and the last revision of the International Classification of Headache Disorders included the term, coded as 1.5.1, under complications of migraine 1.5 (Headache Classification Committee of the International Headache Society 2004).
Chronic daily headache is defined as headaches occurring more than 15 days a month and lasting at least 4 hours if untreated. Chronic daily headache is subdivided into 4 disorders: (1) chronic migraine, (2) chronic tension-type headache, (3) new daily persistent headache, and (4) hemicrania continua. Each of these disorders may occur with or without analgesic overuse. Secondary headache disorders (such as brain tumor or sinus disease) must be excluded.
The IHS criteria for chronic migraine differed from the 1996 Silberstein and Lipton criteria for transformed migraine. Its case definition comprises a migraine headache occurring for more than 15 days per month for more than 3 months, and does not require the transformation period from an episodic form. The problem is that when acute medication use in more than 10 days (for triptans, ergotamines and opioids) or 15 days (simple analgesics) a month for more than 3 months is associated, the diagnosis of “probable chronic migraine” (1.6.5) and “probable medication overuse headache” (8.2.7) have to be made until the acute medication overuse stops for 2 months and the headaches disappeared or reassumed its previous pattern. This is unethical and not practical because one should not propose only washout for patients with debilitating severe headaches but should start migraine prevention, which may induce a headache response. In the end, you may have the diagnosis of IHS 2004 “probable” chronic migraine or medication overuse for a long time. Moreover, for the medication overuse headache diagnosis due to analgesics, combination, and ergotamines, criteria A also states at least one of the following three [(1) bilateral pain, (2) non-throbbing type, (3) mild to moderate severity] has to be present. Criteria C indicates the headache appeared or worsened during the excessive intake of acute medication and criteria D, the headaches disappear or reassume its previous pattern. More studies are necessary in order to improve the diagnostic criteria for chronic migraine.
The International Headache Classification Committee has, therefore, worked out the more inclusive criteria for chronic migraine and MOH in a new appendix of the ICHD-2 (Headache Classification Committee 2006). It is now recommended that the medication-overuse headache diagnosis should no longer request improvement after discontinuation of medication overuse but should be given to patients if they have a primary headache plus ongoing medication overuse. The latter is defined as previously (ie, 10 days or more of intake of triptans, ergot alkaloids mixed analgesics, or opioids and 15 days or more of analgesics/NSAIDs or the combined use of more than 1 substance). If these new criteria for chronic migraine and medication-overuse headache prove useful in future testing, it should be included in a future revised version of ICHD-2.
For diagnostic and research purposes the Silberstein criteria are still considered the most appropriate for chronic daily headaches (Bigal et al 2002).
This chapter will focus on chronic migraine, which is the most common type of chronic daily headache seen by neurologists (Silberstein et al 1996). Other chronic headache disorders are covered in other clinical summaries.

Clinical manifestations
Chronic migraine occurs on a daily or near-daily basis. It is characterized by persisting pain (usually of mild to moderate intensity) that lasts at least 4 hours a day if untreated and is usually present for much or all of the day. When the headache pain is more severe (can occur daily or once every 2 weeks, for example), patients typically experience migrainous symptoms including throbbing pain, headache exacerbation with physical activity, associated nausea, vomiting, phonophobia, and photophobia. The evolution of this condition from an episodic disorder distinguishes chronic migraine from new daily persistent headache (daily headache from onset). The chronic migraine patient usually has episodic migraine that increases in frequency, losing some of its migrainous feature as it becomes a daily or near-daily condition. It may also evolve from tension-type headache, but at some point it must manifest full-blown migraine features. New daily persistent headache and hemicrania continua should be excluded.

Table 1. Revised International Headache Society criteria for chronic migraine

Appendix 1.5.1 Chronic migraine

A. Headache (tension-type or migraine) on >= 15 days per month for at least 3 months*

B. Occurring in a patient who has had at least five attacks fulfilling criteria for 1.1 Migraine without aura

C. On >= 8 days per month for at least 3 months headache has fulfilled C1 and/or C2 below, that is, has fulfilled criteria for pain and associated symptoms of migraine without aura


1. Has at least 2 of a through d:


(a) unilateral location


(b) pulsating quality


(c) moderate or severe pain intensity


(d) aggravation by or causing avoidance of routine physical activity (eg, walking or climbing stairs)


1a. Has at least one of a or b:


(a) nausea or vomiting


(b) photophobia and phonophobia


2. Treated and relieved by triptan(s) or ergot before the expected development of C1 above

D. No medication overuse† and not attributed to another causative disorder‡

(Headache Classification Committee et al 2006)

*Characterization of frequently recurring headache generally requires a headache diary to record information on pain and associated symptoms day-by-day for at least 1 month. (Sample diaries are available at http://www.i-h-s.org)

† Medication overuse as defined under 8.2 Medication-overuse headache.

‡History and physical and neurologic examinations do not suggest any of the disorders listed in groups 5 to 12, or history and physical and neurologic examinations do suggest such a disorder, but it is ruled out by appropriate investigations or such disorder is present but headache does not develop in close temporal relation to the disorder.

Chronic migraine is usually, but not always, accompanied by symptomatic medication overuse or rebound headaches. Medication-induced headache is characterized by any number of the following features: (1) gradually worsening headache; (2) increasing analgesic or triptan use; (3) a particularly strong headache when analgesics are discontinued; and (4) failure of preventive medication. Analgesic-overuse headaches may be accompanied by behavioral abnormalities and medication-seeking behavior. The following limits for defining medication use have been published (Table 3). In addition, the German Society for Migraine and Headache recommends limiting headache or antimigraine drugs to no more than 3 successive days or a maximum of 10 days per month (Haag et al 1999).
The International Classification of Headache Disorders divided the medication-overuse headaches (coded 8.2) into ergotamine-overuse headache (intake on 10 or more days per month on a regular basis for longer than 3 months), triptan-overuse headache (intake on 10 or more days per month on a regular basis for longer than 3 months), analgesic-overuse headache (intake on 15 or more days per month on a regular basis for longer than 3 months), opioid-overuse headache (intake on 10 or more days per month on a regular basis for longer than 3 months), combination medication-overuse headache (intake on 10 or more days per month on a regular basis for longer than 3 months) (Headache Classification Committee of the International Headache Society 2004).
Patients with chronic daily headache and chronic migraine often have comorbid disorders (Mathew 1993; Curioso et al 1999). This is logical, as major depression, dysthymia, bipolar disorders, and anxiety disorders are overrepresented among sufferers of episodic migraine (Breslau et al 1994). Moreover, these psychiatric disorders appear to be more common in chronic daily headache patients than in episodic migraineurs.
Peres and colleagues have shown a significant proportion of chronic migraine patients with fibromyalgia. Chronic fatigue was reported in the majority (86%) of chronic migraine patients; two thirds of sufferers fulfilled diagnostic criteria for chronic fatigue syndrome. Anxiety and depression scores correlated with fatigue intensity (Peres et al 2001b). In another study, clinical aspects and depression severity were analyzed in chronic migraine patients, it was found that moderate or severe depression, were present in 58.7% of the patients, severe depression was found in 25% and suicide thoughts in 5%. Some degree of depression appeared in 85.8% of patients. The BDI scores correlated with anxiety levels and pain intensity (p = 0.02) (Mercante et al 2005).
An interesting study looked at psychiatric comorbidity and muscle tenderness in patients with chronic migraine compared with chronic tension-type headache. Anxiety and depression were present in 80% of chronic migraine and in 63% of chronic tension-type headache women. No significant difference either in the personality profile or in the muscle tenderness between chronic migraine and chronic tension-type headache patients (Mongini et al 2005b). However, when psychiatric comorbidity was compared with muscle tenderness, using palpation tenderness scores calculated for the pericranial and cervical muscles in 459 patients, a positive correlation could be observed (Mongini et al 2005a). Psychiatric comorbidity and fibromyalgia are related. Muscle tenderness may share the pathogenesis and pathophysiology for this relationship.

Clinical vignette
A 45-year-old woman presented with chronic daily headache. In her teens, she developed menstrual migraine that was successfully treated with over-the-counter analgesics. In her 20s, the migraines occurred weekly, and she had several tension-type headaches each week, all of which could be controlled with over-the-counter medications. The patient improved during her first pregnancy at age 30, but shortly after delivery she developed severe migraines that could not be controlled by over-the-counter medications. She also continued to experience less severe migraines and tension-type headaches, for which over-the-counter medications remained effective. By the time she presented to her primary care physician, she was using over-the-counter medications on a daily basis. This fact, however, was not discussed, and only the uncontrolled headaches were mentioned. At first, these headaches responded well to a barbiturate-containing agent, which she continued to take during her second pregnancy. After delivery, her use of this agent accelerated, and by 6-months postpartum the patient was using it on a near-daily basis. She then entered a period of stability during which she used prescription and nonprescription medications daily. However, some of her more severe headaches were not adequately controlled by her medication, and she occasionally missed work. Several years before presentation, she developed increasingly severe headaches and rapidly accelerating medication use. On presentation, she was using approximately 6 over-the-counter caffeine-containing analgesics and 6 butalbital-containing analgesics a day, as well as 2 bottles of butorphanol during the week surrounding her menses. She received prescriptions from 2 different physicians, each of whom was only vaguely aware of the other's involvement. She was missing 3 days of work a month due to her headaches, and the quality of her work was slipping. She believed her employer was anticipating firing her.
On previous evaluation, she had 2 MRIs, a CT scan of the sinuses, and an electroencephalography, all of which were normal. Her previous physicians had tried several preventive agents, none of which were successful in relieving her headaches. Her neurologic examination was normal.
The patient was hospitalized, at which time all her symptomatic medication was discontinued, and she was placed on the Raskin protocol of repetitive intravenous dihydroergotamine (Raskin 1986). She received several doses of intramuscular phenobarbital for symptoms of withdrawal (from butalbital-containing compounds) and required several doses of intravenous chlorpromazine for severe headaches. She became headache-free 3 days after entering the hospital and was discharged on the fourth day. Discharge medications included nortriptyline 50 mg at bedtime, naproxen sodium 550 mg twice a day for moderate headaches, and dihydroergotamine 1 mg intramuscularly as needed for severe headache (limited to 2 days a week). Her headaches were poorly controlled initially, and oral prochlorperazine was prescribed as a rescue medication. The patient was having headache-free days 1 month after hospitalization and required dihydroergotamine only 1 day a week. Six months after hospitalization, she required naproxen sodium only 2 days a week and dihydroergotamine only twice a month.

Etiology
The etiology of migraine is discussed elsewhere. Medication overuse causes some, but not all, transformations from episodic migraine to transformed migraine. Transformation without medication overuse is thought to be caused by a particularly strong migraine tendency, a biological trigger such as a viral infection, or potentiation of migraine by stress, depression, or other psychological states. None of these beliefs have been proven. The only evidence for medication overuse as the cause of migraine transformation is the devolution of chronic migraine back to episodic migraine after detoxification, as demonstrated in a number of studies (Dichgans et al 1984; Diener et al 1989).

Pathogenesis and pathophysiology
The biological basis of migraine transformation is unknown. Possible mechanisms include:
(1) Sensitization of peripheral nociceptors from repeated activation. Substance P, calcitonin gene-related peptide, neurotrophins, kinins, prostaglandins, and nitric oxide are believed to be released during neurogenic inflammation and may, over time, sensitize peripheral nociception. Glutamate has been recently shown as an important mediator in central sensitization of chronic migraineurs; increase in cerebrospinal fluid glutamate levels was found in chronic migraine patients, and patients with fibromyalgia had even higher glutamate levels (Peres et al 2004).
(2) Enhanced responsiveness of the trigeminal nucleus caudalis due to central sensitization (ie, the second order trigeminal nucleus caudalis neuron may become hyperresponsive to afferent stimuli).
(3) Defective pain modulation from increased on-cell and decreased off-cell firing in the medulla, perhaps as an effect of chronic medication use (On- and off-cells are located in the rostroventral medulla and inhibit or facilitate nociception).
(4) Hypothalamic dysfunction has been implicated in chronic migraine pathophysiology (Peres et al 2001a). Abnormal melatonin levels were found in patients, confirming a chronobiologic dysregulation, probably due to a suprachiasmatic nuclei dysfunction.
(5) Spontaneous central pain as a result of a kindling phenomenon (Silberstein and Lipton 1997). Kindling has been observed in animal models of epilepsy and has been proposed for human progressive neural disorders such as epilepsy, depression, mania, and chronic migraine (Post and Silberstein 1994).
Platelet 5-HT2 receptors are upregulated in patients with transformed migraine (Srikiatkhachorn et al 1994). Such changes in the brain could be consistent with the last proposed mechanisms.

Epidemiology
In population-based surveys, primary chronic daily headache occurs in about 4% to 5% of the general population: United States 4.1% (Scher et al 1998), China 3.9% (Wang et al 2000), France 3.0% (Henry et al 2002), and Spain 4.7% (Castillo et al 1999). Population-based estimates for the 1-year period prevalence of chronic tension-type headache are 3% in Denmark (Rasmussen et al 1991), 2.2% in the United States (Scher et al 1998), 2.2% in Spain (Castillo et al 1999), and 2.7% in China (Wang et al 2000). The 1-year prevalence of chronic migraine is 1.3% in the United States (Scher et al 1998), 2.4% in Spain (Castillo et al 1999), and 1% in China (Wang et al 2000). It has been found that 0.5% of the population can be classified as having severe daily headache.
Quality of life of subjects with chronic daily headache in the general population was studied using the Short Form-36 in 89 patients compared to 89 healthy controls (Guitera et al 2002). There was a significant decrease in each health-related concept of the Short Form-36 as compared with healthy subjects. The highest decreases were seen for role physical, bodily pain, vitality, and social functioning. There was no significant difference in Short Form-36 scores in subjects with chronic tension-type headache as compared with chronic migraine. Chronic migraine patients showed lower values in each health-related concept when compared with patients with episodic migraine.
In specialty clinics, almost 80% of chronic daily headache patients have chronic migraine (Mathew 1993; Curioso et al 1999). In children, the characterization of frequent or chronic daily headache has been limited. A recent study noted that daily continuous headaches in children tend to be migrainous (Hershey et al 2001).

Prevention
Avoid analgesic overuse (rebound). To prevent the central changes that cause transformation, frequent migraine and tension-type headache should be treated aggressively with preventive medications, and a limit for dosage and frequency of dosing should be placed on all abortive medication. Migraine status and frequent headache should be treated early and in a manner that does not promote rebound. Patient education about the existence of chronic migraine is helpful. Biofeedback and other behavioral strategies for selected patients are useful to avoid analgesic overuse.

Differential diagnosis
Certain secondary headache disorders must be considered in chronic daily headache patients. These include mass lesions such as subdural hematoma, brain tumor, and sphenoid sinusitis. A toxic metabolic disturbance, such as anemia or hypothyroidism, or a medication-induced metabolic disturbance can cause daily headaches, although the typical history of gradual transformation from episodic migraine is generally not elicited. Posttraumatic headache and pseudotumor cerebri with or without papilledema often have clinical features similar to chronic migraine. Cervicogenic headache and greater occipital neuralgia have features of chronic daily headache. Among the primary headache disorders, new daily persistent headache is differentiated by its onset, hemicrania continua by its strict unilaterality and indomethacin-responsiveness, and chronic tension-type headache by its lack of migrainous features. The physician must recognize if medication overuse caused the transformation to chronic daily headache (transformed migraine) or if medication became overused after a chronic daily headache had already been set up (posttrauma, new daily persistent headache). In the later case, getting individuals out of analgesic rebound may not be enough to alleviate the chronic daily headache syndrome.

Diagnostic workup
There is no literature to support any particular diagnostic approach. Obtaining 1 MRI of the brain is reasonable, but this study should not be repeated unless there is a significant change in the neurologic examination or in the headache characteristics. A general panel of blood tests, including a complete blood count, electrolytes, kidney function tests, liver function tests, and possibly a sedimentation rate, is often obtained as a baseline and is used to exclude secondary causes of headache. An electrocardiogram is often obtained in patients who may eventually take vasoconstrictors (eg, triptans or dihydroergotamine). A lumbar puncture should always be performed in refractory cases since the diagnosis of idiopathic intracranial hypertension without papilledema can be present in 5% to 14% of patients with chronic daily headaches (Mathew et al 1996; Wang et al 1998; Quattrone et a 2001).

Prognosis and complications
The natural history of chronic daily headache and chronic migraine is unknown. Retrospective analysis suggests that rebound headache patients will experience periods of stable drug consumption and spells of increasing drug use, switching to more potent drugs to achieve equal therapeutic benefit. Detoxification for chronic daily headache with analgesic overuse has been studied at 3- to 12-months followup. Significant improvement occurred in 48% to 91% of patients (Silberstein and Lipton 1997). No data exist regarding the prognosis of chronic migraine without medication overuse. Saper has calculated that comprehensive treatment can result in a savings in work-related disability of $5145 per year ($138,915 per patient over the median 27 remaining years in the workforce) (Saper et al 1999). Complications (other than pain and disability) generally involve the sequelae of analgesic overuse such as gastritis, renal impairment, or physical dependency.

Management
Secondary headache disorders should be excluded and the patient reassured. A specific primary headache disorder should be diagnosed (eg, chronic migraine or chronic tension-type headache). Comorbid medical and psychiatric conditions and exacerbating factors, especially medication overuse, should be identified.
Most patients with chronic migraine who present to a neurologist's office are overusing symptomatic medication. The stoppage of this medication is the recognized treatment of transformed migraine. The type and amount of medication being overused will determine the setting in which detoxification can take place. Simple analgesics and small daily amounts of butalbital-containing compounds and narcotics can be stopped in an outpatient setting. If the patient is at risk for withdrawal, then an inpatient setting is warranted.
Withdrawal symptoms, including a severe headache accompanied by nausea, vomiting, agitation, restlessness, sleep disorder, and occasionally seizures, may occur and persist for as long as 2 weeks. Short-acting barbiturates and benzodiazepines are replaced by long-acting medications, which are tapered gradually to avoid a serious withdrawal syndrome. The “analgesic washout period” usually lasts 3 to 8 weeks, but it has been reported to last for as long as 6 months (Rapoport et al 1986; Warner 1998); once it is over, there is frequently considerable headache improvement.
Some patients are able to limit their symptomatic medication use after education alone. Another outpatient approach involves using a “transitional medication” to replace the overused medication and then subsequently weaning the patient off this transitional drug. A long-acting nonsteroidal agent or triptan can be substituted for the overused simple analgesic (eg, naproxen sodium or indomethacin); naratriptan is currently being studied as such a transitional agent. The patient can use this medication daily for approximately 1 week and then limit its use to avoid further analgesic overuse headache. Some clinicians use a short course of corticosteroids during outpatient detoxification (Bonuccelli et al 1996). A neuroleptic or other rescue medication may be necessary during outpatient detoxification.
Detoxification can be difficult and sometimes requires hospitalization. Diener and colleagues were able to detoxify only 1.5% of 200 patients on an outpatient basis (Diener et al 1988). In contrast, Hering and Steiner successfully used outpatient detoxification in 37 of 46 patients who were taking simple analgesics or ergotamine (Hering and Steiner 1991). The detoxification can last up to 2 weeks. Two studies by Raskin as well as Silberstein and colleagues have shown that the detoxification process can be enhanced and shortened and the patient's symptoms made more tolerable by the use of repetitive intravenous dihydroergotamine coadministered with metoclopramide, which helps control nausea and is also an effective antimigraine drug in its own right (Raskin 1986; Silberstein et al 1990). Patients who are not candidates for dihydroergotamine or are truly intolerant of the drug may require repetitive intravenous neuroleptics or corticosteroids. One study suggests that repetitive intravenous diphenhydramine is effective (Swidan et al 1999). Inpatient treatment is also effective for patients with severe chronic daily headache who are not overusing analgesics.
In addition to detoxification (if necessary), the general treatment strategies used for migraine should be applied to patients with chronic migraine. The physician should encourage regular sleep, exercise, and meal schedules. Treatment of a comorbid psychiatric illness is often necessary before the chronic daily headache comes under control. Behavioral methods include pain management, supportive psychotherapy, stress management, biofeedback, relaxation techniques, and cognitive therapy. Given the overall lack of evidence for the existence of most putative headache triggers, trigger avoidance should only be encouraged if a headache calendar has repeatedly demonstrated a temporal association between a potential trigger and a severe exacerbation of the daily headache. At the time of the detoxification, a new nonrebounding abortive and headache regime should be established that specifically defines which agents can be used (including dosage and frequency) and in what headache situations. For example, patients should be encouraged not to treat mild headaches and only treat moderate headaches 3 to 5 days per week.
Most preventive agents used for chronic daily headache have been studied for use in episodic migraine but have not been extensively evaluated in chronic migraine or chronic daily headache. Antidepressants are attractive agents for use in chronic daily headache (ie, transformed migraine, chronic tension-type headache, and new daily persistent headache), since many patients have comorbid depression or anxiety. The most widely used antidepressants are nortriptyline, amitriptyline, doxepin, and fluoxetine, but they have not been studied extensively and little data are available for its recommendation. Phenelzine, a monoamine oxidase inhibitor, was found to be highly effective in one small case series (Turkewitz et al 1992), but risks and side effects have limited its use. Promising drugs for chronic migraine and psychiatric comorbidity are the SNRIs, venlafaxine and duloxetine, but studies are necessary to confirm this hypothesis. Beta-blockers that are effective for migraine are used for chronic daily headache. Anecdotal evidence supports the use of the calcium channel blockers (verapamil, diltiazem, and nifedipine). Divalproex sodium is an important drug in migraine prophylaxis, even for patients who have failed other agents; however, efficacy studies have shown mixed results in chronic daily headache (Mathew and Ali 1991; Vijayan and Spillane 1995). Doses lower than those used for treatment of epilepsy (ie, 250 mg twice a day) may be sufficient. Divalproex sodium is an especially useful agent in patients who have comorbid epilepsy and manic-depressive illness and, possibly, anxiety disorders. Another recent study on divalproex sodium in the long-term treatment of chronic daily headache showed that 75% of 642 patients had at least a 50% reduction in headache frequency (Freitag et al 2001). Methysergide, the first FDA-approved migraine prophylactic drug, is used for patients with refractory chronic migraine, despite the risk of fibrotic complications. Although monotherapy is preferred, it is sometimes necessary to combine preventive medications. Patients with daily headaches must understand that preventive medications will not be fully effective until 3 to 6 weeks after the overused medication has been eliminated.
An open-label trial of tizanidine in the prophylaxis of chronic daily headache provided preliminary support for the efficacy of this medication (Saper et al 2001). The starting dose was half of a 4 mg tablet at bedtime and titrating upward slowly over 4 weeks, to either the maximum tolerated dose or a maximum daily dose of 18 mg, divided over 3 doses per day.
Recent new therapeutic options include topiramate and botulinum toxin type A. Topiramate should be slowly titrated starting with 25 mg, weekly increasing 25 mg, reaching 100 mg. Higher doses can be used. Topiramate induces weight loss, improving patients adherence to treatment. A recent study showed topiramate in the median dose of 100 mg was effective in reducing migraine days in chronic migraine patients and also relieved their anxiety and depression scores (Peres et al 2005). Botulinum toxin type A might be an alternative for chronic migraine prevention.
Since melatonin is decreased in chronic migraine patients, its supplementation may play a role in the preventive treatment, particularly in those with insomnia or other comorbid conditions.