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9 Articles in Volume 8, Issue #4
Chronic Daily Headache
Confidentiality, Choice, and the Question of Autonomy
Head and Neck: Temporal Arteritis and Temporal Tendonitis Co-morbidity
Laser Acupuncture as a Pain Relief Modality
Long-term Therapy Using Short Acting Opioids for Chronic Non-cancer Pain
New Daily Persistent Headache (NDPH)
Opioids in Patients with Renal or Hepatic Dysfunction
Pain Management and Terminal Illness
The Biopsychosocial Approach

Chronic Daily Headache

An overview of the four types of chronic headaches: chronic migraine, chronic tension-type headache, new daily persistent headache, and hemicrania continua.

Chronic daily headache (CDH) is a disorder that is distressing for patients and frustrating for clinicians. The reasons why some patients may be predisposed to having chronic daily headache are not entirely clear. We now know of certain predicting factors that may indicate the likelihood of chronicity for migraine patients. Although the etiology is still not clear, current theories suggest that trigeminal pathway and brainstem are highly involved in initiating and maintaining chronicity of headache. Several studies, using newer imaging technology, already show some interesting and promising results. It is very likely that CDH, like migraine headache, is a neurovascular disorder.

Since the mechanisms underlying CDH are still not well understood, the treatment choices are open to debate. There are both pharmacologic and non-pharmacologic treatment options available to patients. As more studies on CDH are conducted, eventually we will have a better understanding of CDH. At present, it is important for clinicians to keep in mind that CDH is a disabling disease, and that promptly recognizing and treating pa-tients with headache—as early as possible—can prevent chronicity in many cases.

What would you do for a 40-year-old patient complaining of 6 months of persistent headache? The patient reports he has had a headache almost everyday; he describes it as pulsating, unilateral, and aggravated by activity. What if his headache is unilateral without side-shifting but with ipsilateral lacrimation and ptosis? What if the headache is bilateral? What if his daily headache seems to occur without any preceding events and there is no past medical history of headache? Would the diagnosis be different? More importantly, would your option of treatment for this patient be different? Discussion on answers to some of these questions will be presented in this article.

Prevalence

Chronic headache is a common disorder even though it is still not well understood. The overall worldwide prevalence is approximately 4%, and the female to male ratio is close to two to one. A population-based survey from 1998 to 2000 showed that 4.1% of Americans, 4.35% of Greeks, 3.9% of elderly Chinese, and 4.7% of Spaniards had primary chronic daily headaches.1 There are two peaks of age-related prevalence: 20-24 years of age and those above the age of 64 (8% for both).2

Definition/Classification

The latest diagnostic criteria for CDH were published by the International Headache Society in 2004. According to these criteria, primary chronic daily headache (CDH) is defined as headache that occurs for more than 15 days a month and has no structural or infectious causes.

CDH is further divided into four subtypes3:

  1. Chronic tension-type headache (approximately in 2-3% of the population)
  2. Chronic migraine (~2%)
  3. New daily persistent headache (~0.2%)
  4. Hemicrania continua (very rare)

Figure 1 presents a diagnostic flow diagram for classifying chronic daily headache. The most common type of headache that a clinician encounters in practice is either chronic tension-type headache or chronic migraine. These patients usually have a history of previous episodic tension, migraine headaches, or both.

Figure 1. Classification of Chronic Daily Headache

New daily persistent headache (NDPH) is a new subtype recently created to describe headaches that suddenly appear one day and the patient distinctly remembers the onset. These patients usually do not have a previous history of headache. To date, we still don’t know much about the epidemiology, pathogenesis, or treatment of NDPH. [Editor’s note: see Dr. Steven Singer’s article “New Daily Persistent Headache” in this issue for a discussion of NDPH and the latest findings.]

Hemicrania continua is a rare headache disorder that is now more frequently recognized and treated by headache clinics. It is a continuous one-sided headache (sometimes with autonomic features like tearing and rhinorrhea) that completely resolves with the administration of indomethacin. It is so perfectly treatable that this condition should be considered in every CDH patient. An adequate trial of oral indomethacin over several days should be given if a CDH patient has only one-sided symptoms and is not responding to other treatment. The dose can be increased from 25mg bid to a maximum of 300mg per day.4 A single IM shot of 50mg indomethacin (the so-called Indotest) can also be used effectively.5

Risk Factors and Chronicity

Epidemiological studies have shown that migraine has a higher prevalence in households with lower socio-economic status.6 This could either be a cause factor or an effect. Having many migraines could lead to poorer health status and lower academic and social achievement since they can be quite debilitating. Who therefore has a higher risk of having CDH? Although there are limited data on the natural course of CDH, a few risk factors for CDH have been identified.

The risk factors that have been found to be associated with CDH include female gender, white race, lower educational level, being previously married (e.g. divorced, widowed, or separated), and obesity.7 Conversely, the factors associated with remission are non-whites, higher education level, and being currently married. These risk factors were identified by Scher et al who surveyed 55,255 potential cases and controls in the Baltimore, Philadelphia, and Atlanta metropolitan areas between 1997 and 1999.7 Scher et al collected information on gender, age, height, weight, current marital status, highest educational level, and race—as well as duration of CDH, pre-CDH frequency, and the speed of onset of CDH. The authors followed up with 798 controls and 1134 cases of patients who were able to provide their headache frequency. The one-year incidence of new-onset CDH was reported at 3%.9 This study found that the likelihood of remission increased with age for women but not for men—suggesting that the natural history of CDH might be different in men and women.7 This likelihood may be explained by the fact that the majority of women stop having migraines after menopause.

Scher et al also found that controls with higher headache frequency, obesity, or arthritis were all more likely to have new-onset CDH at follow-up.7 Moreover, the risk of new-onset CDH was significantly higher in control subjects with more than two headaches per month.7 It is therefore important for clinicians to promptly treat patients with frequent headaches to prevent progression to CDH. Scher et al, also reported that 16% of CDH subjects reported continuous headaches.7 Patients who had continuous headaches were often older and had experienced CDH for a longer duration. The authors hypothesized that “if there is such a thing as a progressive headache syndrome, then continuous headache may represent a later stage of the disorder.”7

So is there such a thing as progressive headache syndrome? Are certain patients with headache predisposed to chronicity? The question can be partly answered by the study of Spierings et al.8 They interviewed 258 patients of which 230 had known onset of their daily headaches. 22% (51/230) had daily headaches from the time of onset and 78% (179/230) initially had intermittent headaches. Of the latter 179 patients, 81% (145/179) developed daily headaches gradually and 19% had an abrupt transition into daily headaches. It took an average of 10.7 years for the 145 patients to develop daily headaches from intermittent headache. The severity of initial headaches varied among the 145 patients: 33% experienced mild headache while 67% suffered from severe headache. The patients with severe headaches experienced more nausea and vomiting than the ones with mild headache. However, regardless of the severity of initially intermittent headaches, these patients eventually developed the same daily headache.

In addition, of the 145 patients who gradually developed daily headaches, 69 were followed up to obtain more information on their transition of headaches. 33% (23/69) continued to have daily headaches whereas 67% (46/69) were having a recurrence of intermittent headaches. Of the patients with recurring intermittent headaches, 74% (34/46) were experiencing migraine and 26% (12/46) were experiencing tension-type headache. Of the 34 migraine patients, 88% (30/46) also initially had migraine, but 12% (4/34) originally had tension-type headache. Of the 12 patients who currently experienced tension-type headache, only 25% (3/12) had tension-type headache originally, and 75% (9/12) had migraine initially.8

The transition into daily headaches has been recognized since the 1980s, but it is difficult to determine who would eventually develop daily headaches. It is also difficult to determine whether people with certain headache types are more predisposed to chronicity. Patients with episodic migraine or tension-type headache ultimately develop the same daily headache and, when daily headaches become intermittent again, they seem to reassume the initial headaches.8 The specific risk factors for each subtypes of CDH are still not specified and more studies need to be done in the future to answer this question.

Pathogenesis

Current theories of episodic migraine headache clearly indicate that it is a neurovascular disorder. Migraine is now considered the result of dysfunction within the brainstem that induces changes in blood vessels within the pain-producing intracranial meningeal structures.9 The exact nature of this dysfunction is still not clear. Current theories propose that “the local vasodilation of intracranial extracerebral blood vessels and a consequent stimulation of surrounding trigeminal sensory nervous pain pathways is the key mechanism underlying the generation of headache pain associated with migraine.”9 The activation of the trigeminal pathway stimulates the release of pro-inflammatory mediators that results in sterile inflammation in the perivascular area. The release of vasoactive sensory neuropeptides like calcitonin gene-related peptide (CGRP) results in activation of the pain pathway.9 In addition to CGRP, the levels of nitrite, neurokinin A (NKA), prostaglandin E2 (PGE2), and 6 keto PGF1 alpha are elevated during the migraine attack and decrease after the end of attacks.10 Once the pathway is activated by the neuropeptides, the pain signals are sent up by activated trigeminal nerves to the central neurons in the brainstem trigeminal sensory nuclei. These signals are then relayed to higher centers where pain is perceived.

There is both central and peripheral sensitization during episodic migraines. Several MRI studies have demonstrated that a migraineur who is not currently having headache has a state of neuronal hyperexcitability in the cerebral cortex—especially in the occipital cortex.11 This finding explains the susceptibility of the migrainous brain to headaches. A frequent finding in migraine is the presence of high signal deep white matter foci on brain MRI—the clinical significance of which is still up for debate.12 In addition to MRI, PET scanning for patients with acute migraine headaches demonstrates activation of the contralateral pons—even after the pain has been aborted by medications.11

In addition to the trigeminal nervous pathway and brainstem, the hypothalamus plays a prominent role in certain headache disorders. Hypothalamus in-volvement can explain some of the autonomic behaviors seen with headaches: yawning, sweating, aggressive behavior, tearing, rhinorrhea, etc. These behaviors are more commonly seen in trigeminal autonomic cephalalgias (a new name given to cluster headaches and similar headaches). Studies using functional neuroimaging with PET and anatomical imaging with voxel-based morphometry have identified “the posterior hypothalamic grey matter as the key area for the basic defect in cluster headache.”13 The hypothalamus can also activate the trigeminal vascular pathway and thus generate a headache.

Do these theories that explain episodic headache also apply to CDH? Currently it is believed that CDH is also a neurovascular disorder that occurs due to an alteration in serotonergic and monoamingergic pathways to the brainstem and hypothalamus.11 We know that there is central and peripheral sensitization of the nervous system in episodic migraine. We postulate that a mechanism similar to kindling occurs in patients with frequent episodic headache resulting in a constant state of sensitization and, therefore, persistent headaches.

There is limited imaging data demonstrating that CDH is a neurovascular disorder. In 2004, Nagesh et al took high-resolution MRI images of 17 CDH patients, 10 episodic migraine patients, and 15 controls with a 3 telsa MRI system.14 There was a significant decrease in deoxyhemoglobin and hence persistent activation of red nucleus (RN) and substantia nigra (SN) in CDH compared to controls and episodic migraine groups. However, there was no significant difference between the controls and episodic migraine groups.14

Aurora et al assessed the excitability of the cortex by the magnetic suppression of perceptual accuracy (MSPA) profiles using transcranial magnetic stimulation in 25 chronic migraine patients.15 Ten of these 25 patients were studied with (18F-FDG PET) scans. MPSA demonstrated decreased inhibition in chronic migraine compared to controls and episodic migraine. PET evaluation in ten subjects demonstrated increased cerebral metabolism in areas of the brainstem compared to the global flow. Certain areas in the medial frontal, parietal, as well as the somatosensory cortex, also showed decreased cerebral metabolism. This study concluded that “chronic migrain-eurs are characterized by reduced visual suppression that correlates with high cortical excitability.”15 The brainstem activation and inhibition in certain areas of the cortex were observed in a cohort of these subjects suggesting “a potential dysfunction in the inhibitory pathways.”15 The cause of the activation is still unknown. How the brainstem changes during the progression of CDH and in response to treatment needs to be investigated.

Pharmacological Management

There are two types of treatment—acute abortive treatment and preventive treatment.

Acute Treatment. Abortive treatment aims at relieving symptoms immediately. If a CDH patient has an acute episode of migraine, triptans or ergots can be used. However, they are not very effective in controlling chronic headache. The role of serotonin agonists (i.e. triptans or ergots) is not clearly understood in the management of CDH. Triptans (e.g. sumatriptan) are serotonergic agonists that selectively inhibit vasodilation through 5-HT1B receptors expressed in intracranial arteries and inhibit neurogenic inflammation in the dural vessels.9 At the present time, these agents are only warranted for short-term management during exacerbation of headache.

Chronic tension-type headache can be effectively managed with analgesics such as NSAIDs. For hemicrania continua, prompt resolution of the headache with a trial of indomethacin 50mg 3 times a day, for 48 hours, will establish the diagnosis. These agents should not be used as long-term treatment, since doing so may prolong CDH.16 It is important to limit the use of acute medication to 2-3 days per week.17

Clinicians need to reevaluate the treatment protocol if a patient constantly seeks medications and, perhaps, institute preventive treatment instead.

Preventive treatment. Preventive treatment is the usual approach to CDH and is quite effective in controlling chronic headache. The primary goal of preventive treatment is to reduce the frequency, severity, and duration of headaches. Preventive treatment involves taking daily medication for 3-6 months or longer. Choice of prevention treatment should be based on the concomitant or co-morbid conditions. Regardless of the type of medications, as a general rule medication should start at minimum dose and be adjusted slowly until efficacy is achieved or side effects are reported. To date, only amitriptyline, fluoxetine, gabapentin, tizanidine, topiramate and botulinum toxin type A (BoNTA) have been evaluated as “prophylactic treatment of CDH in randomized, double-blind, placebo-controlled, or active comparator-controlled trials.”18

Currently, many physicians consider antidepressants as the primary choice for the treatment of CDH since they have been studied most extensively. Several double-blind, placebo-controlled studies were summarized in the review by Redillas and Solomon.16 Tricyclic antidepressants (TCAs) potentiate the action of 5-HT and norepinephrine (NE) by inhibiting their reuptake into the CNS. The review noted the study by Gobel et al in 1994 on 24 chronic tension-type head-ache patients indicated a decrease in headache duration by 30% after a six-week amitriptyline treatment regimen.16 The review also noted that Bendsten et al in 1996 compared amitriptyline and citalopram against placebo in 34 patients and reported that amitriptyline was effective in decreasing headache frequency and duration but that citalopram had no effect.16 Selective serotonin reuptake inhibitors (SSRIs) inhibit 5-HT, NE, and platelet 5-HT uptake. The review noted that the study by Saper et al indicated an increase in headache-free days in 40% of CDH patients on fluoxetine, and there was at least 50% improvement from baseline in overall headache status.16 The review also noted Foster and Bafaloukos reported improvement in headache in an open-label study of 60 CDH patients treated with paroxetine. In this study, 44 patients reported a decrease in headache frequency by at least 50%.16

If antidepressants are not effective, anticonvulsants can be used. Muscle relaxants or antianxiety agents can also be used as a part of a treatment regimen if muscle spasm or anxiety is co-morbid. One interesting, atypical preventive medication that has been studied for CDH is botulinum toxin (BoNTA). In a placebo-controlled study consisting of over 1000 patients followed for up to 11 months, there is a statistically significant difference (p=.038) in headache-free days at day 180 between BoNTA (10 headache-free) and placebo (6.7 days).18 The study concluded that BoNTA was safe, well-tolerated, and effective in reducing the frequency of headaches.

Occasionally, outpatient treatment may fail thus necessitating inpatient admission for intractable headache. Intravenous dihydroergotamine (DHE) can be used to break the cycle of CDH.16 Opioids can be used as a treatment of last resort when all other treatment options fail. The pros and cons of daily opioid therapy should be carefully discussed with the patient. However, opioids are still under-used, rather than over-used, in headache management. Clinicians need to be care-ul, but not afraid, when using opioids.

 

A summary of medications used for CDH is presented in Table 1.

The time between headache onset and treatment may be a factor contributing to treatment response. It is therefore important for physicians to be aware of CDH and treat it early. Unger pointed out that many patients delay medical treatment for their chronic headaches for 11 to 20 years from onset.2 The reason for the delay is either lack of physician understanding regarding headaches (in 46% of patients being surveyed), a false belief that no treatment was effective (in 31% of patients), or a false belief that no medications were available to ease CDH (in 20% of patients).2

Table 1. Medications for CDH
  CM* CTTH NDPH HC
1st Choice Antidepressants (TCA, SSRI) Antidepressants (TCA, SSRI) Antidepressants (TCA, SSRI) Indomethacin
2nd Choice Anticonvulsants (Valproate, Gabapentin, Topiramate) Anticonvulsants (Valproate, Gabapentin, Topiramate) Anticonvulsants (Valproate, Gabapentin, Topiramate)  
Add-on in muscle
tension or spasticity
Muscle relaxants (Botox, Tizanidine, Baclofen) Muscle relaxants (Botox, Tizanidine, Baclofen) Muscle relaxants (Botox, Tizanidine, Baclofen)  
Add-on in anxiety Antianxieties Antianxieties Antianxieties  
Acute relief IV DHE IV DHE IV DHE  
In refractive headache Opioids Opioids Opioids  
Alternative** Biofeedback, Acupunture Biofeedback, Acupunture Biofeedback, Acupunture  
*CM–chronic migraine. CTTH–chronic tension-type headache. NDPH–new daily persistent headache. HC–hemicrania continua.
**The confirmation of effectiveness of alternative treatments such as acupuncture and biofeedback still requires more research.

Treating CDH patients can be challenging, particularly if the headaches are complicated by analgesic overuse. Often, patients take over-the-counter analgesics. Excessive use of these medications may result in “refractoriness to treatment, perpetuation of the headaches, and a transformation from a pattern of intermittent migraine to one of CDH.”17 In addition to preventive treatment, the overuse of medication must always be curtailed.

Non-pharmacological Management

Alternative and complementary therapies such as acupuncture and biofeedback have been studied for CDH, but, due to the lack of standardization of techniques and lack of double-blind, placebo-controlled studies, no consensus has been reached regarding their effectiveness. In 2005, Coeytaux et al compared medical management with medical management plus 10 acupuncture treatments in a randomized, controlled trial of 74 CDH patients.19 This was the first randomized, controlled trial to evaluate the efficacy of acupuncture as an adjunct treatment for CDH. In this study, the Headache Impact Test showed an improvement of 3.0 points in the medical management plus acupuncture group. The Short Form 36 Health Survey showed an increase of more than 8 points on the role limitations due to physical problems, social functioning, and general mental health domains. In addition, patients who received acupuncture were 3.7 times more likely to report less suffering from headaches at 6 weeks.19 The strengths of this study include “the high follow-up rate (96%) for the primary analysis and the use of validated and clinically pertinent outcome measures and broad inclusion criteria.”19 On the other hand, the weakness of this study is the potential of significant bias. The study was not blinded and the outcomes were relatively subjective. In addition, this randomized, controlled trial has its limitation in that the investigator did not isolate acupuncture as the single causal variable.

Interestingly, in 1985, a controlled cross-over trial (acupuncture vs. placebo acupuncture) conducted in Denmark20 compared the effect of traditional acupuncture to placebo acupuncture in 18 patients with chronic tension headache (mean disease duration 15 years). Each patient was treated with acupuncture as well as with placebo acupuncture in “a cross- over design following randomization.”20 Each period of treatment was composed of six treatments. The result showed that pain reduction was 31% in the acupuncture group which was significantly more pain-relief than the placebo acupuncture group.20

The FDA has determined that biofeedback and other non-pharmacologic treatments for episodic migraine have grade A evidence (that is, proven to be highly effective by double blind control randomized trials). Grazzi et al (2002) compared pharmacologic therapy alone and pharmacologic therapy combined with biofeedback-assisted relaxation in sixty-one consecutive patients with transformed migraine and analgesic overuse in an inpatient setting.21 All patients were followed prospectively for three years. The levels of improvement immediately following treatment and for one year thereafter were similar.21 However, at year three, groups receiving combined treatment had fewer days of headache, reduced analgesic use and less relapse.21 This study suggested a combination of pharmacologic and behavioral treatment was more effective than drug therapy alone in the long-term management of transformed migraine with analgesic overuse. Confirmation of these findings, as well as generalization to other forms of behavioral and cognitive-behavioral treatment, is still required.

The knowledge gained from episodic headache patients is a good indication that a multimodal team approach to CDH—by offering both pharmacological and non-pharmacological options—has the best likelihood of success.

Disability

Unfortunately, CDH is not only common but also disabling for patients. Studies on quality of life in CDH showed that patients were greatly affected by this disease. Using the generic instrument Short Form-36 (SF-36), Guitera et al conducted a case-control study analyzing the quality of life in CDH patients in Spain by randomly selecting 89 CDH subjects.22 Also included were 89 healthy controls and 89 otherwise healthy subjects with episodic migraine as controls to those with chronic migraine.22 In this study, individuals were scored in eight areas: physical functioning, role physical, bodily pain, general health, vitality, social functioning role, emotional, and mental health. The SF-36 scores were then adjusted for co-morbid conditions. The results indicated that CDH subjects had lower scores in each section of the SF-36 as compared with healthy subjects. The lowest scores were in the role of physical, bodily pain, vitality, and social functioning.22 Chronic migraineurs also had lower scores in each section when compared with patients with episodic migraine. The lowest scores were in general health, vitality, and mental health.22 There was no significant difference in SF-36 scores between subjects with chronic tension-type headache and those with chronic migraine.22 Guitera et al observed that quality of life seemed to be “affected more by the chronicity than by the intensity of pain.”22

A study on the same subject of disability in CDH patients by D’Amico et al used the Migraine Disability Assessment Score (MIDAS) in its validated Italian version to study the quality of life and disability in Italian CDH patients.23 The result showed chronic migraine patients were impaired in everyday tasks including domestic, workplace, and social activities. Among the 150 chronic migraine patients studied, 39% of them reported work lost, 53% reported work reduced by 50% or more, 69% reported household work lost, 71% reported household work reduced by 50% or more, and 83% reported family, social, and leisure activities lost.23

Conclusion

Chronic daily headache (CDH) is a poorly understood headache type which is very disabling. It is more common than was previously thought. Continuing studies on the pathophysiology, contributing factors, and treatments are all important for a better understanding CDH. With exciting neuroimaging data, it appears probable that in the near future a patient with headache will be classified and confirmed for a certain headache on the basis of imaging.

“Continuing studies on the pathophysiology, contributing factors, and treatments are all important for a better understanding CDH.”

We do not know if the current treatment regimen relieves CDH patients from headache permanently or only temporarily (i.e., whether the headache comes back when the medication was stopped). It is also unknown if there are separate risk factors for each subtype of CDH and if the medications have different effectiveness on different subtypes of CDH. Further studies should be done to find factors contributing to the treatment responses and to look for the effective medications based on how the pain duration, frequency, and severity are influenced. More importantly, in order to improve the care of CDH patients, clinicians should be more aware of patients’ suffering from chronic headache. Prompt recognition and treatment of CDH is better than delayed treatment from both the clinicians’ and the patients’ perspective.

Last updated on: February 23, 2015
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