Chronic Daily Headache

Chronic daily or near daily headaches (CDH) are arbitrarily defined as headaches occurring more than 15 days/month or 180 days/year.

Chronic tension-type headache (CTTH) is the only chronic daily headache included in the International Headache Society (IHS) Classification. Clinical experience has clearly shown that CTTH is only one type of CDH and that there are other types of daily or near daily headaches, which are more disabling.

Although the IHS headache classification has greatly enhanced the precision of diagnosis of migraine and cluster headache, its application in chronic headaches has been less than satisfactory. The main deficiencies of the IHS classification in this regard are as follows:

a.. It is based purely on individual attacks of headaches and does not consider the natural history and evolution of primary headache disorders over a period of time.

b.. The significant clinical relationship between migraine and tension-type headache is inadequately appreciated and totally ignored in the classification.

c.. Even though tension-type headache and cluster headache are classified as episodic and chronic varieties, no mention is made of chronic varieties of migraine.

There is ample evidence to indicate that patients with CDH are a heterogeneous group, which can be subdivided into various categories. Approximately 20% of CDH are primary (daily from the onset), whereas the majority, 80%, is transformed from intermittent headache. Table 1 shows an attempted broad classification of chronic daily headache (CDH).

Approximately 35% to 40 % of patients who seek treatment at the headache centers suffer from daily or near-daily headache. All those patients have headaches for more than 15 days a month or 180 days a year, which puts them in the category of chronic tension-type headache (CTTH) according to the IHS criteria. 1 Are they all chronic tension-type sufferers? The majority require more than two, often three or four, diagnoses. Even though migraine is the most common diagnosis, only 1/4 of those with a migraine diagnosis has it as the only diagnosis. Seventy-five percent of migraine patients has coexistent chronic tension-type headache (CTTH), drug-induced headache or both. Ninety-six percent of patients diagnosed as having migraine with aura also suffers from migraine without aura. More than 1/3 of patients (37.7%) attending the clinic suffer from chronic daily headache (CDH) (chronic cluster headache excluded), which is not included as a separate entity in the IHS classification. Pure CTTH formed only a small minority of CDH, whereas 86.6% of CDH had migraine as one of the diagnoses. Drug-induced headache was a prominent or second or third diagnosis.

The majority of patients seeking treatment in headache clinics have transformed migraine (TM). The headaches in these patients are more severe and more disabling, as reported in the epidemiological study of frequent headaches.

A recent report by Scher et al indicate an overall prevalence of frequent headaches (more than 15 days/1 month) to be 4.2% in the population. In that survey, based on telephone interviews with a set of questions, CTTH was found to be 1.7 times more common than TM (CTTH 53%, TM 31%). Sixteen percent of those with frequent headache could not be easily classified as either CTTH or TM. The investigators feel that 16%, which could not be classified, had many features resembling TM. Scher et at found that TM is characterized by more severe pains and higher levels of disability than CTTH. This fact accounts for the higher percentage of patients with TM seen in the headache centers. Epidemiology of TM IS similar to that of episodic migraine because of 1) gender ration is 2.4:1, 2) inverse relation with low educational level.

Epidemiology of CTTH has features in common with migraine and episodic tension-type of headache (ETTH). Gender ratio is intermediate. The relationship with educational level resemble migraine, not ETTH. CTTH patients reported severe pain twice that as ETTH and missed work five times than that of ETTH. Disability profile of CTTH is similar to migraine. A recent survey by Russell et at has shown significantly increased familial risk of CTTH parents, siblings and children of CTTH patients have 2.1 to 3.9 fold significantly increased risk of CTTH compared to general population, again resembling migraine.

Castillo et al reported that in Spain the prevalence of CDH in the general population is 4.7% of which, 2.3% have CTTH and 2.4% TM. Medication overuse was found to be prevalent in 41% of TM patients and 18% of the CTTH, indicating that TM patients have more severe pain requiring more medications.

Chronic tension-type headache is defined in the IHS classification, and the criteria for its diagnosis include an average headache frequency of at least 15 days per month (180 days per year) for 6 months, and the ruling out of any organic or structural cause for headache. The headache has a pressing or tightening quality, is usually of mind or moderate severity (may inhibit but does not prohibit activities), has a bilateral location, and is not aggravated by physical activity. At least two of these pain characteristics must be met. There is no vomiting. One of the following, namely nausea, photophobia, or phonophobia, may be present.

Two clinical types of chronic tension-type headache may be recognized: those associated with pericranial muscle tenderness, increased EMG level, or a combination of both factors; and those not associated with pericranial muscle tenderness with a normal EMG level. Patients with muscle tenderness show tenderness in the cervical muscles as well as the pericranial muscles. However, muscle tenderness is not a specific phenomenon for CTTH, as it is also seen in patients with episodic migraine and TM.

Episodic tension-type headache sometimes transforms into the chronic variety, whereas, in many others the headaches are chronic from the onset, with no subsequent change in character. The essential difference between this type of headache and transformed migraine is the absence of history of episodic migraine and the absence of clear-cut exacerbations with migrainous features.

There is a great deal of evidence now to suggest that tension-type headache in migraineurs and chronic tension-type headache may be different from episodic tension-type headaches. Tension-type headache in migraineurs are frequent, severe and of longer duration compared to non-migraineurs. They are associated with more photophobia, phonophobia and nausea than tension-type headache in non-migraineurs. Only migraineurs have episodes of "tension-type" headaches precipitated by alcohol, aged cheese, chocolate and physical activity. 10"Tension-type headache" in migraineurs respond to agents like sumatriptan. Sumatriptan, has a significant effect in chronic tension-type headache. On the other hand, sumatriptan has no clinically relevant effect in the treatment of episodic tension-type headache.

Recent data from the "Spectrum Study" which examined the spectrum of headaches experienced by patients originally diagnosed as IHS migraine, migrainous headache, and episodic tension-type headache , clearly indicate that all these categories of patients exhibit a spectrum of headaches comprising of IHS migraine, migrainous headache and tension-type headache.

The above observation plus the epidemiological data on CTTH make a strong argument to consider tension-type headache in migraineurs and chronic tension-type headache, with their features in common with migraine, as different from episodic tension-type headache.

The term "transformed migraine" was first introduced in 1987 by Mathew et al. to describe a common, daily or near-daily headache condition that constituted 77% of CDH patients seen at the Houston Headache Clinic. In two separate series Manzoni et al. reported that 71% and 75%, respectively, of their patients transformed their headaches into a chronic daily pattern from a distinct episodic pattern. Solomon et al. also recognized chronic daily headaches and mentioned that the majority of their 100 cases transformed from episodic migraine, even through actual percentages were not given.

Typically the patient describes a history of distinct attacks of migraine with or without aura starting in the teens or early twenties, which eventually becomes more frequent. In addition, the patient develops interparoxysmal tension-type headache, which also becomes more frequent, eventually leading to a daily or near-daily headache. Women in this group may show definite exacerbations of their migraine perimenstrually. Many of the headaches retain certain characteristics of migraine, whereas others are indistinguishable from CTTH. Patients may suffer from a migraine one day and a tension-type headache the next day. Periods of prolonged, persistent and continuous headache lasting for many weeks may occur in many. In representative sample of 184 patients reported by Saper et al, mean number of headache days was 23 days/month, with 46% reporting daily headaches. Daily headache can be intermittent for a few hours per day or continuous. A single episode of prolonged headache period, a relapsing remitting course, a relapsing progressive course or a chronic progressive course can occur.

Manzoni et al. analyzed the evolutionary pattern of transformed migraine . The majority maintained migraine attacks in addition to developing tension-type headache daily or nearly daily. Others lost the temporal profile of migraine, but developed continuous headache with many migrainous features. It has been suggested to subdivide transformed migraine into (a) migraine with interparoxysmal headache and (b) chronic migraine to accommodate these two presentations. In general, the transformed migraine group showed higher incidence of family history of headache, more neurologic and gastrointestinal symptoms, aggravation during menstruation, relief during pregnancy, compared with other forms of chronic daily headaches, particularly CTTH. Table IV compares the clinical characteristics of transformed migraine and CTH.

Table II. Comparison of Clinical Characteristics of Transformed Migraine and Chronic Tension-type Headache

Transformed migraine	Chronic tension-type
Headache >15 days/month >180 days/year	Headache >15/month >180/year
Previous history of distinct mi8graine attacks	No history of distinct migraine attacks
Increased incidence of headache in the family	Positive family history less prominent
Retains migrainous characters to a significant degree, intermittently or continuously	Migrainous features absent or very insignificant
Increased neurologic and gastrointestinal symptoms	Neurologic and gastrointestinal gastrointestinal symptoms minimal
Menstrual aggravation	No particular aggravation during menstruation
More relief during pregnancy	Less relief during pregnancy
Excessive intake of analgesics	Excessive intake of analgesics
Responds to antimigraine therapy	Response to antimigraine therapy occurs, but less striking
Behavioral and psychological factors prominent	Behavioral and psychological factors prominent
More disabling	Less disabling
Seeks medical help more often	Seeks medical help less often-more lapsed consultations

Approximately in 70% of cases, the transformation from episodic headache to CDH is gradual, whereas it is sudden in about 30%. Factors aiding sudden transformation include, trauma to the head and neck, flue like illness, aseptic meningitis, surgical interventions, myelography, epidural injections, and medical illnesses. In many cases the aiding factors are not known.

Table V lists the suspected risk factors for development of transformed migraine and chronic daily headache, based on clinical observations.

Table III. Risk Factors for Chronic Daily Headache – Transformed Migraine Suspected Factors

Analgesic over-use ranged from 50-82% in clinic based samples of CDH, while community based surveys showed analgesic over-use in 30% of CDH patients compared to 10-12% of patients with episodic headache.

Recently Scher et al conducted a case control study of CDH (206 CDH and 507 controls) looking into risk factors. They looked at current and previous exposure to excess analgesics and reported that OTC medications containing caffeine may be a risk factor in developing CDH. They did not evaluate the role of butalbital / caffeine / analgesic combinations. Narcotics and NSAIDs were not found to be risk factors in this particular study. Aspirin was found to be protective.

It is not certain whether analgesic over-use is the cause of chronicity or whether it is a consequence.

Arguments in favor of analgesic over-use being a consequence of frequent headaches rather than a cause are that, a significant percentage of CDH patients do not over-use analgesics. In countries like India, where analgesic over-use is rare, CDH exists.

Scher et at reported other risk factors for CDH. Head injury was a very significant risk factor. Traumatic life events such as moving and relationship problems were also significant risk factors.

Silberstein et al field tested the proposed 1994 criteria for classification of daily or near-daily headache and produced a new proposal for transformed migraine diagnostic criteria26 (Table IX).

It is not uncommon to see patients who give a history of a fairly rapid onset of a persistent headache that continues on a daily basis. This is a primary variety of CDH. These patients do not have a history of previous migraine or tension – type headache, nor do they give a history of trauma or psychological stress. The patients may distinctly remember the "onset event" or the day or time when the headache started. Epstein –Barr virus-induced immune changes have been implicated as an etiologic factor. However, this hypothesis has not been confirmed. The disease is usually self-limiting, but it is not uncommon to see patients continuing to have daily headache for a long period of time. In these patients, follow-up observations have not been adequate to produce any reliable data as to the ultimate prognosis.

Excessive and daily use of immediate relief medications is seen in patients with CDH. Medication misuse headache has been variously referred to as "analgesic rebound headache" is a term, which is often used to characterize the headache perpetuating tendency when immediate relief medications are used in acute migraine.

There appears to be some confusion between the terms recurrence and rebound. Recurrence may be defined as the recurrence of the same headache, which was significantly relieved by an anti-migraine agent. Recurrence should occur with the expected natural duration of that migraine attack. Recurrence of the same headache may occur when 5-HT agonists are used in acute migraine.

Rebound Headache on the other hand can be defined as perpetuation of head pain in chronic headache suffers, caused by frequent and excessive use of immediate relief medication. It can also be defined as " a self-sustaining", rhythmic, headache-medication cycle characterized by daily or near daily headache and irresistible and predictable use of immediate relief medications as the only means of relieving headache attacks.

The most convincing evidence for analgesic-ergotamine rebound is the fact that mere discontinuation of these medications results in significant improvement. There is ample data in the literature to support the existence of analgesic/ergotamine rebound headache. Silverman et al36 reported that moderate or severe headache occurred in 52% of patients on caffeine withdrawal based on a double-blind cessation of caffeine consumption. In a survey of physicians engaged in the treatment of headache, more than 40% of the responds (174) indicated that analgesic rebound is present in at least 20% of their patients with headache.

Agents commonly associated with rebound in decreasing order include: Butalbital/aspirin/acetaminophen combinations, caffeine containing analgesic combinations, opioids and ergotamine

A number of clinical characteristics help us in identifying the occurrence of analgesic rebound headache in patients with primary headache disorders. The following are the clinical features of analgesic rebound;

Clinical evidence from various centers around the world points to the fact that rebound phenomenon alters the natural history of migraine.

There are few analogous phenomenon to rebound headache in medicine . These include worsening of nasal congestion by frequent use of decongestants, insomnia aggravated by sleeping pills, chronic constipation because of frequent laxative use and idiopathic edema caused by diuretics.

Analgesic rebound phenomenon is actually a paradoxical response. Those taking most medications experience most pain. The question then arises; is a high level of pain experience the cause of high analgesic consumption? Or is the overuse of analgesics due to certain psychological predispositions?. That leads to the question, is analgesic rebound headache due to addictive behavior?

There is no evidence of addictive personality in these patients . Sensation seeking behaviors are not high in these patients with chronic headache.

Pathogenesis is not clearly understood, although there is evidence to suggest involvement of 5-hydroxy tryptamine (5-HT) in the process. Hering et al reported reduction in whole blood 5-HT in patients with analgesic / headache, which was normalized, on discontinuing the analgesics. This rise in 5-HT level in the whole blood paralleled the improvement in headache frequency. Patients with analgesic induced headaches have lower basal content of platelet 5-HT, reduce 5_HT uptake ability when incubated with excess of the amine, and a greater density of 5-HT2 receptors on platelet membrane than in migrainous patients without analgesic reduced headache. These observations suggest that chronic analgesic overuse interferes with the intrinsic pain modulatory system by depletion of 5-HT and consequently up-regulation of its post synaptic receptors. Therefore, it is likely that analgesic induced headache is, at least partly, due to defective mechanisms of 5-HT uptake caused by analgesic use.

Alternation in the central pain modulation mechanism may account for perpetuation of headache. Recently, Welch et al reported deposition of iron in the periaqueductal gray (PAG) of the brain stem, indicating alternation in the functional physiology of that important pain control area in CDH.

Sicuteri postulated central opioid receptor impairment as an underlying mechanism for chronic headaches. Natural opioids play a vital role in regulating pain. Sicuteri pointed out the neurochemical and other similarities between chronic headaches and morphine abstinence syndrome. Both involve central serotonin and dopamine systems. Their prominent symptoms include headache, anhedonia, autonomic symptoms, and hypernociception. Intrinsic opioids act on the central nervous system to limit pain. Impairment of opioid system would lower the pain threshold in patients with chronic headache. Prolonged use of analgesics may lead to suppression of antinociceptive opioids, thus resulting in heightened pain sensitivity, if the drug use were to be discontinued.

As Lance et al postulated that further suppression or down regulation of an already partly suppressed or abnormal antinociceptive system due to excessive symptomatic medications is a possible explanation for analgesic rebound headache in migraine population. Alternations in the density and function of postsynaptic neuronal receptors as a result of chronic medication use may be another explanation for the refractory headache these patients develop (central sensitization and long-term plasticity).

A phenomenon akin to "kindling" seen in epilepsy may be operating in chronic headaches, also.

Activation of facilitatory nociceptive "on cells" in the ventral medulla as a result of excessive analgesic/narcotic use may be another explanation. "On cells" in the ventromedial medulla facilitate nociceptive reflex response such as tail flick response. "On cells" show increased firing during naloxone induced morphine withdrawal. Mechanisms such as this, even though not adequately understood, may give a physiological basis for drug analgesic induced headache.

The psychiatric comorbidity in CDH was assessed by Sandrini et al 0 in a series of 98 patients. DSM-III-R criteria was used to diagnose psychiatric conditions. Only 9.2% had no psychiatric diagnosis. Anxiety disorders were observed in 72.4%, mood disorders in 55.1%, combined anxiety and mood disorders in 46% and somatoform disorders in 3.1%. Of those with mood disorders, one-third suffered from major depression

Coexistence of migraine and idiopathic intracranial hypertension without papilledema may result in refractory chronic daily headache. A spinal tap to measure the CSF pressure in the only way to make a diagnosis of this condition. Headache characteristics of the two conditions may be very similar. In a refractory case of chronic daily headache with migrainous features, a spinal tap to rule out raised CSF is in order. Another comorbid neurological condition associated with chronic daily headache is sleep apnea

The two major factors that determine the prognosis of CDH are (1) analgesic rebound, and (2) comorbidity. The first step in the management of CDH is to determine the presence or absence of rebound phenomenon. A person suffering from headache despite consuming analgesics and ergotamine on a daily basis could fall into the category of drug-induced headache or analgesic rebound headache. Concomitant use of prophylactic medications in this situation is usually ineffective.

Behavioral, psychological, and disability aspects of CDH need to be considered when treating patients with this form of headache. A multimodality approach is essential for satisfactory results, and a combination of pharmacologic and behavioral interventions is necessary.

It is important to make as comprehensive a diagnosis as possible and attempt to recognize the subtype of CDH the patient is suffering from. Those with transformed migraine are significantly more responsive to treatment that those with CTTH. In all subtypes, the analgesic rebound has to be looked for.

The multimodality approach to treatment outlined above can be undertaken either as outpatients or inpatients.

Outpatient treatment is most suitable for highly motivated patients without serious comorbidities and who are not very high consumers of opioids/butalbital/tranquilizers containing analgesics. Out patient management will consist of (1) abrupt discontinuation for simple analgesics and triptans, (2) gradual taper of the butalbital/caffeine/opioid medications, (3) substituting naratriptan 2.5 mg bid or a nonsteroidal anti-inflammatory agent (NSAIDs) including COX2 inhabitants during the withdrawal period, (4) introduction of appropriate prophylactic pharmacotherapy, (5) treating break through headache with specific anti migraine drugs such as a triptan and (6) combining all the above with behavioral approaches and education.

Inpatient treatment is indicated in (1) those who fail out patient treatment, (2) those who consume very large quantities of opioids/butalbital/tranquilizers containing analgesics, (3) those with very significant psychological and behavioral comorbidities as well as medical comorbidities.

Essential differences in the inpatient approach are a more aggressive supervised withdrawal of offending medications, use of agents to reduce the effect of abrupt withdrawal, intravenous administration of medication around the clock to break the cycle of headache, initiating prophylaxis which often include rational combination of medications to treat comorbidities and adjusting the dosages. A hospital stay of 5-6 days is necessary in the majority of cases while it may extend to 10 or 15 days in more complicated cases.

Discontinuation of daily analgesics, narcotics, sedatives, caffeine and ergotamine is the first step. A rare patient with triptan induced rebound may also have to be taken off those medications, substituting with a triptan with low recurrence rate such as naratriptan.

Abrupt withdrawal of analgesics and narcotics is possible; however, it should be done under close supervision. Detoxification from opioids can be aided by using clonidine. Clonidine reduces the clinical symptoms of opioid withdrawal. Two #2 (0.2 mg) transdermal clonidine patches may be applied on the first day of withdrawal, to be changed after 1 week and discontinued after 2 weeks. Oral clonidine can be used after the first week.

In most transformed migraine patients, the daily headache cycle can be broken by repetitive intravenous administration of dihydroergotamine (DHE). A test dose of one thirst of a milliliter of DHE with 5 mg of metoclopramide or 10 mg of prochlorperazine may be used, followed by 0..5 mL of DHE with one of the antinausea medications every 6 hours for 48 to 72 hours. Some patients may require the therapy for a few additional days. Approximately 70% to 80% of patients do respond to DHE.

Diarrhea, leg cramps, and chest pain are seen as side effects in some patients. DHE is contraindicated in coronary and peripheral vascular disease.

In those who are unable to tolerate DHE or when it is contraindicated alternative intravenous medications are possible. These include chlorpromazine or prochlorperazine. In some patients, 12.5 mg of chlorpromazine given intravenously (piggy back) infused in 15 minutes every 6 hours for 2 days has been found to be effective. Orthostatic hypotension is a possible side effect, and precautions should be taken to prevent dizziness and syncope as a result of orthostatic hypotension.

Prochlorperazine at 5 to 10 mg given intravenously is also effective and can be repeated benztropine mesylate (Cogentin). Anecdotal reports also indicate the use of intravenous dexamethasone. Extrapyramidal dystonic reactions are possible side effects .. Although there are no controlled studies to prove its clinical efficacy, those who have prolonged migraine seem to respond to such therapy. It can be combined with DHE or prochlorperazine.

Recently intravenous valproate sodium has been found to be useful for status migrainosus and can be given to break the cycle of CDH. Five hundred milligrams of valproate sodium diluted in 50cc of I.V. saline given as fast drip or diluted in 20 ml N. saline as IV push are recommended. This can be repeated Q8H for 2 days.

Diener et al found that repeated subcutaneous injections of sumatriptan may be useful in breaking the cycle of TM. Because of the excellent tolerability of naratriptan, prolonged effect and very low recurrence rate, naratriptan tab 2.5 mg BID is being used during the withdrawal period.

Patients with transformed migraine may respond to antimigraine prophylactic agents effectively, provided detoxification from analgesic has been achieved already. The clinician may choose a prophylactic agent or a combination of prophylactic agents depending on the clinical diagnosis and comorbid factors. There is a place for rational copharmacy in the prophylactic treatment of CDH. For example, one can combine a primary antimigraine prophylactic agent, such as a – blocker, methysergide, or valporix sodium with agents that are effective for psychiatric comorbid conditions, such as depression or anxiety. A combination of antidepressants or antianxiety agents with antimigraine prophylactic agents is a rational way of approaching the treatment of persistent CDH.

combination of dexamethasone (4 mg intramuscularly) for 2 weeks followed by amitriptyline (50 mg per day) for 6 months. Acute exacerbations were treated with sumatriptan. They reported good response with this combination treatment. In a open study, divalproex sodium used prophylactically reduced the frequency and severity of transformed migraine.

Various medications such as MAOI inhibitors, stimulants, long-acting opioids, botulinum toxin type A, daily triptans, particularly naratriptan, daily DHE have been reported to be useful in very refractory cases.

Long-acting Opioids: Long-acting opioids such as OxyContin, fentanyl patch and Methadone may have a place intractable cases. However, long-term good control is obtained in only approximately 20-25% of cases (Saper et al 2000). They are safe and does not cause weight gain. However, the drawbacks of long-term opioids are sedation, constipation, nausea, potential dose escalation of doses and legal and regulatory issues for the physician. Short acting opioids should be avoided.

Patients with personality disorders such as borderline personality and those with severe insomnia may benefit from atypical antipsychotics such as olanzapine (Zyprexa), Quetiapine fumarate (Seroquel), and risperidone (Risperdal).

Concomitant behavioral intervention, including biofeedback therapy, individual cognitive behavioral therapy, family therapy, physical exercise, and dietary instructions, is imperative for successful management of patients with CDH. Details of these modes of treatment are beyond the scope of this chapter. Physical therapy (heat, massage, ultrasonography) to neck muscles may help partially. Selected application of trigger point injections may help as well.

Adequate instruction about the nature of the patient’s disorder and the ill effects of certain medications used in excessive and frequent quantities, particularly analgesics and narcotics, should be emphasized. The patients have to understand the fact that this disorder is biologic in nature, with neurochemical and physiologic changes producing the headache. They should also appreciate the fact that behavioral factors, such as anxiety, depression, inability to relax, and stress, influence this biology a great deal, making headaches more frequent, more severe, and more difficulty of manage. Every program that deals with CDH should have education as a part of the therapeutic program.

CDH is usually a prolonged problem occupying years of a person’s life, and none of the preventive medications are 100% effective. Adverse effects prevent prolonged use of many medications. Patients develop tachyphylaxis to many medications. Therefore, continuity of care with frequency follow-up and adequate physician/patient communication is essential for the long term.

TM/CDH are not primary psychiatric disorders, although comorbidities are important. Referral to a psychiatrist should not be an "end-of-the-road" referral. If a psychiatrist is consulted, the consultation should be in conjunction with the medical treatment. The physician who takes care of these patients have full control of all aspects of treatment, and the psychiatric treatment should only be an adjunct in the overall management.

A tertiary care headache center with facilities for inpatient and outpatient treatment is the most appropriate place for referral. Pain management clinics with emphasis on physical methods of treatment such as epidural blocks or heavy narcotics should be avoided.

A long-term follow-up study has looked at the prognosis for CDH. A group of 489 patients were followed for an average of 42 months (range, 18 to 72 months). Thirty-eight patients (8%) were lost to follow-up. Of the remaining 451 patients, 140 (31%) showed significant recurrence of headaches despite continuing efforts to use prophylactic medications, dietary control, behavioral treatment, and avoidance of analgesics, sedatives, and daily ergotamine. Most of these 140 patients continued to have periodic exacerbations of headache with episodes of status migrainous and low-grade daily headache. They continued to need some symptomatic medications or showed a tendency to use prescribed substitute medications such as isometheptene in excessive quantities. They were frequent visitors to the headache clinic compared with patients who showed improvement. In some, repeated hospitalizations were necessary. Ninety-two patients (20%) were unable to work, and the rest were relatively unproductive in their work. Many had to change jobs frequently because of absenteeism.

Pini et al evaluated 102 patients with chronic daily headache with analgesic rebound attending a headache center in Italy. They divided the group into those who underwent day hospital treatment program followed by prophylactic therapy and those who were given prophylactic therapy straight away. Both groups improved, with no difference with respect to hospital treatment or outpatient treatment. After four months of follow-up, 28% of patients reverted to daily analgesic use. These patients took barbiturate containing mixtures in higher percentages than other drugs. More patients who were treated as outpatients relapsed compared to those who were treated in the day hospital.

Overall, from the experience of many centers treating chronic daily headache patients, it appears that approximately one-third of patients show relapse of their daily headache and may have a tendency to go back to taking pain medications regularly unless they are supervised very carefully. In patients with their persistent, intractable chronic daily headache, the behavioral, psychological and neuroendocrine features are strikingly different from the CDH who show improvement. MMPI was abnormal in 100% of intractable cases. High scores and hypochondriasis, depression and hysteria (scores 1,2, and 3) were consistent and combinations of high scores of 6,7,8, and 9 were seen in 56% of those with intractable CDH. Among the parents of patients with intractable CDH, a high incidence of alcoholism was found. A high incidence of physical, emotional and sexual abuse was also found in this group when compared to those who were treated successfully. The Zung Depression Scale and the Beck Depression Inventory were also higher in the intractable group when compared to the improved group.

Therefore, it appears that there is a group of very persistent intractable chronic daily headache, which is resistant to all currently available forms of treatment. It may signify some permanent abnormalities in the pain control systems of the brain.

Episodic Headache	Chronic Daily Headache
OTC Meds 12%	30%
Prescription Meds 10%	30%