Risk Factors for Chronic Daily Headache

Transcription

1 Risk Factors for Chronic Daily Headache Ann I. Scher, PhD, Richard B. Lipton, MD, and Walter Stewart, PhD Address Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, 7201 Wisconsin Avenue, MSC 9205, Bethesda, MD , USA. Current Pain and Headache Reports 2002, 6: Current Science Inc. ISSN Copyright 2002 by Current Science Inc. There are many people who experience headaches that are independent of illness, injury, or hangover. Approximately 4% of the population suffer from headaches on a daily or near-daily basis. It is apparent that patients with chronic daily headache in community samples differ in important ways from patients with chronic daily headache in subspecialty clinics. In this manuscript, we review clinic-based data on risk factors for chronic daily headache and summarize the current data on the epidemiology of chronic daily headache. Introduction At least 70% [1] of the population experiences headaches unrelated to illness, injury, or hangover [2]. Although headaches occur once or twice monthly in most people, approximately 4% of the adult population suffers from headaches on a daily or almost daily basis (chronic daily headache) [3,4,5,6 8]. Studies based on such patients in headache subspecialty centers generally have reported high rates of medication use, depression, and disability [9 14]. The term transformed migraine was coined by Mathew et al. [10] and refers to the process by which episodic migraine may evolve into a daily or near-daily headache disorder. In recent years, a number of studies have described the epidemiology of chronic daily headache in non-clinical samples [3,4,5,6 8,15]; it has become apparent that patients with chronic daily headache (CDH) in community samples differ in important ways from patients with CDH in subspecialty care centers. Chronic daily headache usually is defined as headache of any type that occurs 15 or more days monthly for at least 6 months [16]. CDH is divided further into the long-duration ( 4 h/d) and shorter-duration variants. The primary subtypes of CDH of longer duration are chronic migraine (or transformed migraine), chronic tension-type headache, hemicrania continua, and new daily persistent headache [16]. Less common short-duration chronic headaches include chronic cluster headache, chronic paroxysmal hemicrania, and hypnic headache [16]. Until recently, the literature on CDH was limited to patient case series from tertiary headache referral centers. These patients are predominantly female and have a history of experiencing migraine headaches [10 12,17 19]. In chronic or transformed migraine, a patient with episodic migraine headache gradually experiences increasing frequency of headache, often coupled with decreased average severity until the headaches stabilize into a daily, usually continuous, pattern. Other clinical characteristics noted in these patients include sleep disturbances [18], dietary triggers for headache [18], hypertension [10,20], stressful or traumatic life events [20,21], and depression [10,20,22 24]. Although the biologic mechanisms of CDH are uncertain, several hypotheses have been proposed and are summarized briefly in this article. Detailed reviews of pathophysiologic mechanisms in CDH can be found in Srikiatkhachorn [25] and Silberstein [16]. Peripheral and Central Sensitization Injury to peripheral tissues or chronic nociceptive input may increase the sensitivity of nociception to produce peripheral sensitization [16,25]. During the migraine state, neuropeptides (substance P, calcitonin gene-related peptide, and neurokinin A) released from nerve fibers react with the blood vessel walls and produce a sterile inflammation [26]. It may be that repeated episodes of this neurogenic inflammation could chronically sensitize nociceptors, lowering the threshold for future attacks, and also lead to spontaneous activity and expansion of receptive fields of nociceptors [16,25]. Kindling Model The kindling model for epilepsy has been proposed as a model for non-epileptic progressive disorders such as mania and possibly headache transformation [27]. In this model, repeated brain stimulation on an intermittent basis may lead to a neuronal memory that culminates into a full-blown seizure. Perhaps recurrent, low-level electrical stimulation, as produced during a migraine attack, results in spontaneous headache episodes in a self-perpetuating cycle. Thus, according to this theory, undertreatment of pain may induce central

2 Risk Factors for Chronic Daily Headache Scher et al. 487 pain activation, and migraine prophylaxis may prevent the occurrence of episodes and block the process by which spontaneous pain activation arises [16,27]. Viral Trigger Although most patients in clinics with CDH report gradual onset of daily headache, some experience an abrupt onset. This syndrome is sometimes termed new daily persistent headache and some have speculated that there may be a viral trigger involved. Diaz-Mitoma et al. [28] found that 84% of patients with sudden-onset daily headaches (vs 25% of control subjects) showed evidence of active infection with the Epstein-Barr virus (EBV) [28]. As noted by the authors, this does not necessarily prove that EBV was active before the onset of CDH; latent EBV may have been re-activated secondary to the stress of chronic pain in these patients. Medication-induced Headache It often is noted that patients with CDH in subspecialty care overuse (by various definitions) abortive headache medication [10 14,20]. There is a widely held belief that analgesic or ergot overuse is involved in the onset or persistence of daily headache. There is weak evidence in support of this belief. The terms rebound headache, medication-induced headache, and withdrawal headache sometimes are used interchangeably to refer to the process by which frequent abortive medication use chronifies episodic headache, although these terms refer to different processes. The IHS criteria for headache induced by chronic substance use (IHS 8.2) (eg, medication-induced headache or medication-overuse headache) are as follows: daily use of a certain minimum dose for more than 3 months; the headache is chronic (15 or more d/ mo); and the headache disappears within 1 month after withdrawal of the substance. Criteria for withdrawal headache (IHS 8.4) are as follows: headache occurs after the use of a high daily dose for more than 3 months; headache occurs within hours after the elimination of the substance; headache is relieved by renewed intake of the substance; and the headache disappears within 14 days after withdrawal of the substance. There are no diagnostic criteria for rebound headache. Thus, although headache induced by chronic substance use may result from a different process (eg, suppression of endogenous, antinociceptive systems) than headache resulting from withdrawal (eg, caffeine-withdrawal headache) or rebound (eg, rebound vasodilation from ergotamine withdrawal), it is only possible to make these diagnoses after the substance is withdrawn and the headache disappears within a certain time period, according to IHS criteria. If high medication use can precipitate or maintain daily headache for some patients, patients who take pain medication regularly for non-headache conditions also should be at risk for CDH. Four studies that considered this question suggest that if there is such a risk, it is limited to patients with migraine. In a study involving 89 patients at a rheumatology clinic, there was no difference in headache frequency between those who took more than 14 analgesic tablets weekly and those who took fewer than 14 weekly [29]. In a study of 140 patients (mostly with degenerative musculoskeletal disease) who were taking non-opioid analgesics regularly, six (4.2%) had chronic headache, a prevalence similar to that seen in the general population [30]. Another study of patients in a rheumatology clinic (73% with rheumatoid arthritis) reported that eight of 105 (7.6%) of the patients with regular analgesic use had a history of CDH [31]. Because rheumatoid arthritis affects women disproportionally, this prevalence of CDH resembles that seen in the general population. However, in one prospective study of women who were taking opiates to reduce bowel motility after a colectomy for ulcerative colitis, those with daily opiate use were more likely to develop incident CDH (two of eight) than those who were not taking opiate daily (zero of 20) [32]. The difference was not statistically significant. These four patient studies provide no support for the theory that the frequent use of pain medication for a non-headache pain condition leads to CDH. Is it likely that caffeine as an adjuvant to analgesics or in the diet is a cause of CDH? Approximately 50% of habitual low-to-moderate caffeine consumers experience headache when caffeine is withdrawn [33]. Perhaps daily caffeine intake is involved in CDH by a cycle in which caffeine withdrawal triggers a new headache, which then leads to the consumption of more caffeine-containing medication or dietary caffeine until the headache occurs daily [34]. Presumably, withdrawal headache is a self-limiting process that generally resolves in days or weeks after cessation [35]. In addition, the headache disappears when the substance is resumed, according to the IHS criteria for withdrawal headache [36]. Therefore, it is not obvious how caffeine-withdrawal headache may apply to the more typical CDH sufferers in subspecialty clinics who often have a continuous headache. The primary justification for the belief that medication overuse is a cause rather than a consequence of frequent headache is the clinical experience that patients with CDH often notice a reduction in headache frequency or severity after withdrawal; however, this has never been demonstrated in a placebo-controlled trial. Moreover, patients often seek care when they are in their worst state and usually will improve without any clinical intervention. This process, known as regression towards the mean, often is observed in outcome studies, and mistakenly may be attributed to an intervention. A number of studies have been published that describe detoxification protocols for CDH, one of which has been reviewed in detail by Zed et al. [37 ] These studies were not designed to answer the question of whether medication overuse induces chronic headache, but are primarily case series describing the treatment of frequent headache in subspecialty practice. They were usually not controlled or blinded, and other therapeutic interventions (in addition

3 488 Chronic Daily Headache Table 1. Summary of selected medication withdrawal studies of chronic daily headache * Number of patients Days with headache Definition of Study Start End Follow-up Success treatment success Before After Krymchantowski and Barbosa [54] days N/A 96% 83% Katsarava et al. [55] months 97% Reduction in Ha frequency > 50% Smith [56] months 62% Ha < 15 d/mo N/A N/A Pringsheim and Howse [9] months 46% Reduction in Ha N/A N/A frequency > 50% Linton-Dahlof et al. [57] months 56% Reduction in Ha 90% 49% frequency > 50% Pini et al. [58] months 98% 55% Lake et al. [59] months 64% Average % reduction 93% 61% in days when Ha is severe and incapacitating Lu et al. [60] months 56% Ha < 15 d/mo N/A N/A Schnider et al. [61] years 50% Ha 8 days/month N/A N/A * Studies were included if success rate was based on post-treatment headache frequency and if the sample size was 50. Studies are ordered by the length of the follow-up. Calculated. Calculated by combining the results from 73 inpatients and 29 outpatients. Calculated based on days with headache of any severity. Ha headache. to withdrawal) usually were included. Thus, it is not possible to attribute treatment success solely to medication withdrawal. Furthermore, the natural history of CDH has not been considered. In general, there is no substantial support for the benefits of medication withdrawal in reducing headache frequency in patients with CDH. The belief of experts is the primary motivation behind the use of these protocols. Different outcome measures were used in these studies, with some defining success based on composite outcomes (eg, reduction in headache days times severity or reductions in headache frequency or medication use) [38,41], although others defined success based on frequency only (Table 1). Although CDH refers to frequent headache of any severity, reduction from daily severe headache to daily mild headache technically does not resolve CDH; however, it is clinically significant. Table 1 summarizes treatment results from a series of detoxification protocols. It is limited to studies that based success criteria solely on post-treatment headache frequency. For these patients, pre-treatment headache frequency ranged from 90% to 98% of days and post-treatment headache frequency ranged from 49% to 83% of days. Follow-up ranged from 1 month to 5 years. The remainder of this article focuses on demographic and other risk factors for CDH based on population-based studies. Risk Factors for Chronic Daily Headache Recent epidemiologic studies in Europe, the Far East, and the United States consistently show that approximately 4% of the adult population is affected by CDH (Table 2) [3 8]. In addition, a recent population-based, case-control study has examined potential risk factors for CDH by comparing characteristics of a case group with recent-onset ( 5 years) CDH to an episodic headache control group [15]. The results from these seven studies are synthesized below, with the caveat that some methodologic differences exist among the studies. Demographic factors Chronic daily headache affects more women than men by a factor of roughly 2:1 (Table 2). One exception is the Spanish study, which found a much higher female preponderance [4]. It is noteworthy that this female preponderance appears in the two studies that were based on elderly populations [5,6], suggesting that the increased prevalence of CDH in women relative to men persists even after the age of menopause, a finding that is consistent with the age-specific prevalence of migraine. The proportion of the population that experiences frequent headache appears to be relatively constant throughout the adult lifespan and possibly during childhood. For example, the prevalence of CDH in the elderly was roughly similar to that of younger adults (Table 2). Furthermore, there was no decrease in the older elderly compared with the younger elderly [5,6]. Although there are no epidemiologic studies of CDH in children, three school-based headache surveys that provided data on frequent headache [42 44] also suggested that CDH may be equally prevalent during childhood and adolescence. This relatively constant

4 Risk Factors for Chronic Daily Headache Scher et al. 489 Table 2. Prevalence of frequent headaches in the general and elderly populations Study, year Country Number of patients Prevalence, % Age range, y Total CTTH CM F:M Analgesic overuse *, % Case definition Castillo et al., 1999 [4] Hagen et al., 2000 [8] Lu et al., 2001 [7] Scher et al., 1998 [3] Prencipe et al., 2001 [6] Wang et al., 1999 [5 ] Spain /month, 4+h/day Norway 51, N/A N/A 1.6 N/A 15+/month Taiwan /month, 4+h/day United 13, N/A 15+/month States Italy /month China /month for 6+months * Analgesic overuse based on criteria from Silberstein et al. [53]. CM chronic migraine (transformed migraine); CTTH chronic tension-type headache; F:M female-to-male prevalence ratio. prevalence of CDH is in contrast with the pattern seen with episodic migraine [45] and, to a lesser extent, tension-type headache [46], both of which tend to become less prevalent with increasing age. Chronic daily headache was found to be inversely related to years of education [3,5,7,47]. In the case-control study in the United States, the odds ratio (OR) of CDH was almost three times as high in patients with less than a high school education compared with those who had graduated from college (OR=2.70; 2.12 to 3.45) [47]. Headache type Table 2 shows the prevalence of the most common forms of CDH: chronic tension-type headache and chronic migraine. In these six studies, the prevalence of chronic tension-type headache (1.4% to 2.7%) was similar or slightly higher than the prevalence of chronic migraine (1.0% to 1.7%). This is in contrast with patients with CDH in tertiary referral centers, who almost always have a history of migraine, which leads to the clinical impression that CDH is primarily a migraine-related disorder. This is consistent with the finding from the American study demonstrating that patients with migrainous CDH are more likely to consult physicians than patients with nonmigrainous CDH [3]. Chronic daily headache appears to be more common among those with migraine than those with non-migraine headache (8% vs 5%, OR = 1.6; 1.3 to 1.9) (unpublished data from Scher, et al.). Therefore, it is possible that migraine headache is a risk factor for CDH onset or is associated with a poorer prognosis (ie, longer duration) than nonmigrainous CDH. This result should be interpreted cautiously because headache classification in this study was based primarily on currently reported headache characteristics; longitudinal data are lacking. Medication use High medication use is less common in population-based samples of patients with CDH than in patients who consult subspecialty practices, with approximately one third (25% to 38%) overusing medication as defined based on criteria by Silberstein et al. (Table 1) [17]. Similar results were reported in the case-control study in the United States. In this study, 23% of the patients with CDH reported current daily medication use for headache [48]. This figure increased to 32% if daily medication use for non-headache pain was included. This study considered if specific pain medications were associated with CDH onset by comparing treatment patterns for headache and non-headache pain in the time before the onset of CDH for the patients, and an equivalent time period for the control subjects [48,49]. Results showed that CDH sufferers had higher caffeine consumption (dietary or combined analgesics) and were more likely to have used opioid analgesics for a non-headache pain condition than those in the control group. The finding that CDH sufferers were more likely to treat a non-headache pain condition with opioid analgesics supports the clinical impression that chronic headache often is comorbid with other chronic pain conditions [50]. Sleep-related factors Results from the case-control study revealed that patients with CDH were more likely to be habitual (daily) snorers than control subjects with episodic headache were [51]. Furthermore, this association was not explained by the usual cardiovascular factors associated with sleep-disordered breathing (eg, increased age, male gender, hypertension, body mass index), nor was it explained by other potentially confounding factors that could be associated with chronic headache and sleep disturbances (eg, caffeine consumption,

5 490 Chronic Daily Headache hypertension, depression). This suggests that if this association is causal, the effect of snoring on frequent headache is from a different mechanism than sleep apnea or hypopnea. In addition to and independent of snoring, patients were more likely than the control subjects to report sleep problems, being tired, and sleeping for short or long periods of time. Stressful life events Specific life changes were found to be associated with CDH onset in the case-control study [52]. Cases and control subjects were interviewed about the occurrence of specific life events (eg, moves, job changes, child-related changes, changes in marital status, deaths in the family or of close friends, and ongoing, extremely stressful life events) in the time before the onset of CDH until the present time. Events were divided into pre-cdh events and post-cdh events, with a randomly generated year comparable with CDH onset for the patients seen as the control subjects. Overall, cases reported more pre- CDH events than the control subjects (2.7 vs 2.0, P < 0.001, rank-sum test). There was no difference found for post-cdh events, strengthening a causal interpretation. Conclusions Chronic daily headache is surprisingly common, affecting one in 25 adults in several different population samples. CDH is more common in women than men and is inversely associated with educational level. Unlike the pattern seen for episodic migraine, the prevalence of CDH does not appear to decrease with age. Other identified associations include habitual snoring and the occurrence of specific stressful life events. Although high medication use is widely thought to be a factor in CDH pathogenesis, there is no experimental evidence supporting the existence of medication-induced chronic headache for any substance possibly other than caffeine. Because few of the patients with CDH in the population actually meet criteria for medication overuse, and medication overuse occurs without CDH, this factor is not necessary or sufficient to cause CDH. References and Recommended Reading Papers of particular interest, published recently, have been highlighted as: Of importance Of major importance 1. Rasmussen BK, Jensen R, Schroll M, Olesen J: Epidemiology of headache in a general population: a prevalence study. J Clin Epidemiol 1991, 44(11): Stewart WF, Lipton RB, Liberman J: Variation in migraine prevalence by race. Neurology 1996, 47(1): Scher AI, Stewart WF, Liberman J, Lipton RB: Prevalence of frequent headache in a population sample. Headache 1998, 38: Castillo J, Munoz P, Guitera V, Pascual J: Epidemiology of chronic daily headache in the general population. Headache 1999, 39: Wang SJ, Fuh JL, Lu SR, et al.: Chronic daily headache in Chinese elderly: prevalence, risk factors, and biannual follow-up. Neurology 2000, 2000(54): This was the first study to consider prognostic factors in communitybased patients with chronic daily headache. 6. Prencipe M, Casini AR, Ferretti C, et al.: Prevalence of headache in an elderly population: attack frequency, disability, and use of medication. J Neurol Neurosurg Psychiatry 2001, 70(3): Lu SR, Fuh JL, Chen WT, et al.: Chronic daily headache in Taipei, Taiwan: prevalence, follow-up, and outcome predictors. Cephalalgia 2001, 21(10): Hagen K, Zwart JA, Vatten L, et al.: Prevalence of migraine and non-migrainous headache: head-hunt, a large populationbased study. Cephalalgia 2000, 20(10): Pringsheim T, Howse D: In-patient treatment of chronic daily headache using dihydroergotamine: a long-term follow-up study. Can J Neurol Sci 1998, 25: Mathew NT, Reuveni U, Perez F: Transformed or evolutive migraine. Headache 1987, 27(2): Manzoni GC, Granella F, Sandrini G, et al.: Classification of chronic daily headache by International Headache Society criteria: limits and new proposals. Cephalalgia 1995, 15(1): Sandrini G, Manzoni GC, Zanferrari C, Nappi G: An epidemiologic approach to the nosography of chronic daily headache. Cephalalgia 1993, 13(suppl 12): Solomon S, Lipton RB, Newman LC: Clinical features of chronic daily headache. Headache 1992, 32(7): von Korff M, Galer BS, Stang P: Chronic use of symptomatic headache medications. Pain 1995, 62(2): Scher AI: A Case-Control Study of Chronic Daily Headache In the General Population [dissertation]. The Johns Hopkins University; Silberstein SD, Lipton RB: Chronic daily headache, including transformed migraine, chronic tension-type headache, and medication overuse. In In Wolff's Headache, edn 7. Edited by Silberstein SD, Lipton RB, Dalessio DJ. New York: Oxford University Press; 2001: Silberstein SD, Lipton RB, Sliwinski M: Classification of daily and near-daily headaches: field trial of revised IHS criteria. Neurology 1996, 47(4): Rothrock J, Patel M, Lyden P, Jackson C: Demographic and clinical characteristics of patients with episodic migraine versus chronic daily headache. Cephalalgia 1996, 16(1): Saper JR: Daily chronic headache. Compr Ther 1992, 18(5): Mathew NT, Stubits E, Nigam MP: Transformation of episodic migraine into daily headache: analysis of factors. Headache 1982, 22(2): De Benedittis G, Lorenzetti A, Pieri A: The role of stressful life events in the onset of chronic primary headache. Pain 1990, 40(1): Holroyd KA, Stensland M, Lipchik GL, et al.: Psychosocial correlates and impact of chronic tension-type headache. Headache 2000, 40: Juang KD, Wang SJ, Fuh JL, et al.: Comorbidity of depressive and anxiety disorders in chronic daily headache and its subtypes. Headache 2000, 40(10): Verri AP, Proietti CA, Galli C, et al.: Psychiatric comorbidity in chronic daily headache. Cephalalgia 1998, 21(suppl 18): Srikiatkhachorn A: Pathophysiology of chronic daily headache. Curr Pain Headache Rep 2001, 5(6): Moskowitz MA: Neurogenic inflammation in the pathophysiology and treatment of migraine. Neurology 1993, 43(6 suppl 3):S16 S20.

6 Risk Factors for Chronic Daily Headache Scher et al Post RM, Silberstein SD: Shared mechanisms in affective illness, epilepsy, and migraine. Neurology 1994, 44(10 suppl 7):S37 S Diaz-Mitoma F, Vanast WJ, Tyrrell DL: Increased frequency of Epstein-Barr virus excretion in patients with new daily persistent headaches. Lancet 1987, 1(8530): Lance F, Parkes C, Wilkinson M: Does analgesic abuse cause headaches de novo? [letter]. Headache 1988, 28(1): Bowdler I, Kilian J: The association between analgesic abuse and headache: coincidental or causal [letter]. Headache 1988, 28(7): Bahra A, Walsh M, Menon D, Goadsby PJ: Does chronic daily headache arise de novo in association with regular analgesic use [abstract]. Cephalalgia 2000, 20: Wilkinson SM, Becker WJ, Heine JA: Opiate use to control bowel motility may induce chronic daily headache in patients with migraine. Headache 2001, 41(3): Silverman K, Evans SM, Strain EC, Griffiths RR: Withdrawal syndrome after the double-blind cessation of caffeine consumption. N Engl J Med 1992, 327(16): Silberstein SD, Lipton RB: Chronic daily headache. In In Headache. Edited by Goadsby PJ, Silberstein SD. Boston: Butterworth-Heinemann; 1997: Griffiths RR, Evans SM, Heishman SJ, et al.: Low-dose caffeine physical dependence in humans. J Pharmacol Exp Ther 1990, 255(3): Headache Classification Committee of the International Headache Society: Classification and diagnostic criteria for headache disorders, cranial neuralgias, and facial pain. Cephalalgia 1988, 8 (suppl 7): Zed PJ, Loewen PS, Robinson G: Medication-induced headache: overview and systematic review of therapeutic approaches. Ann Pharmacother 1999, 33(1): Systemic review of medication-withdrawal protocols for chronic daily headache. 38. Silberstein SD, Silberstein JR: Chronic daily headache: long-term prognosis following inpatient treatment with repetitive IV DHE. Headache 1992, 32(9): Kudrow L: Paradoxical effects of frequent analgesic use. In In Headache: Physiopathologic and Clinical Concepts. Edited by Macdonald C. New York: Raven Press; Mathew NT, Kurman R, Perez F: Drug-induced refractory headache: clinical features and management. Headache 1990, 30(10): Diener HC, Gerber WD, Geiselhart S, et al.: Short- and long-term effects of withdrawal therapy in drug-induced headache. In In Drug-Induced Headache. Edited by Diener HC, Wilkinson M. Berlin: Springer-Verlag; 1988: Carlsson J: Prevalence of headache in schoolchildren: relation to family and school factors. Acta Paediatr 1996, 85(6): Egermark-Eriksson I: Prevalence of headache in Swedish schoolchildren: a questionnaire survey. Acta Paediatr Scandinavica 1982, 71(1): Rhee H: Prevalence and predictors of headaches in US adolescents. Headache 2000, 40(7): Scher AI, Stewart WF, Lipton RB: Migraine and headache: a meta-analytic approach. In In The Epidemiology of Pain. Edited by Crombie IK. Seattle: IASP Press; 1999: Schwartz BS, Stewart WF, Simon D, Lipton RB: Epidemiology of tension-type headache. JAMA 1998, 279(5 ): Scher AI, Lipton RB, Stewart WF: Natural history and prognostic factors for chronic daily headache: results from the Frequent Headache Epidemiology Study. Neurology 2002, 58(suppl 3):A Scher AI, Stewart WF, Lipton RB: Is analgesic use a risk factor for chronic daily headache? Neurology 2001, 56(8):A Scher AI, Lipton RB, Stewart WF: Is caffeine consumption a risk factor for chronic daily headache: results from the Frequent Headache Epidemiology Study (FRHE)[abstract]. Cephalalgia 2001, 21(4): Aaron LA, Buchwald D: A review of the evidence for overlap among unexplained clinical conditions. Ann Intern Med 2001, 134: Scher AI, Stewart WF, Lipton RB: Snoring and chronic daily headache: results from the Frequent Headache Epidemiology Study. Neurology 2002, 58(suppl 3):A Stewart WF, Scher AI, Lipton RB: The Frequent Headache Epidemiology study (FrHE): stressful life events and risk of chronic daily headache. Neurology 2001, 56(8):A138 A Silberstein SD, Lipton RB, Solomon S, Mathew NT: Classification of daily and near-daily headaches: proposed revisions to the IHS criteria. Headache 1994, 34(1): Krymchantowski AV, Barbosa JS: Prednisone as initial treatment of analgesic-induced daily headache. Cephalalgia 2000, 20: Katsarava Z, Fritsche G, Muessig M, et al.: Clinical features of withdrawal headache following overuse of triptans and other headache drugs. Neurology 2001, 57(9): Smith TR: Low-dose tizanidine with nonsteroidal antiinflammatory drugs for detoxification from analgesic rebound headache. Headache 2002, 42(3): Linton-Dahlof P, Linde M, Dahlof CGH: Withdrawal therapy improves chronic daily headache associated with long-term misuse of headache medication: a retrospective study. Cephalalgia 2000, 20: Pini LA, Bigarelli M, Vitale G, Sternieri E: Headaches associated with chronic use of analgesics: a therapeutic approach. Headache 1996, 36(7): Lake AE, Saper JR, Madden SF, Kreeger C: Comprehensive inpatient treatment for intractable migraine: a prospective long-term outcome study. Headache 1993, 33(2): Lu SR, Fuh JL, Juang KD, Wang SJ: Repetitive intravenous prochlorperazine treatment of patients with refractory chronic daily headache. Headache 2000, 40: Schnider P, Aull S, Baumgartner C, et al.: Long-term outcome of patients with headache and drug abuse after inpatient withdrawal: 5-year follow-up. Cephalalgia 1996, 16(7):