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Chronic Daily

Headache
An Evidence-Based and Systematic Approach
to a Challenging Problem

BY RASHMI B. HALKER, MD tonomic cephalalgia (TAC) characterized by severe
ERIC V. HASTRITER, MD orbital or temporal pain with accompanying cranial
DAVID W. DODICK, MD autonomic features such as nasal congestion or lacri-
mation. Cluster headache becomes chronic if attacks

I
ndividuals presenting with chronic daily occur for more than 1 year with remissions lasting
headache (CDH) are considered among the less than 1 month. Other TACs that may mimic
most difficult and labor-intensive patients CCH include chronic paroxysmal hemicrania
in a neurologist’s practice. However, when (CPH), short-lasting unilateral neuralgiform head-
treated successfully, they can be the most aches with conjunctival injection and tearing
rewarding. Successful treatment plans can be life- (SUNCT) syndrome, and short-lasting unilateral
changing for patients. Unfortunately, due to both neuralgiform headaches with autonomic symptoms
patient and physician-related factors, many individuals but without lacrimation and conjunctival injection
with CDH lapse from medical care and seek alternative (SUNA). These differ in terms of attack duration and
therapies, and some continue spiraling downward, fu- frequency, and have different therapeutic options
eled by medication misuse and overuse. (table 3).
CDH is not a diagnosis but the presence of head- Hypnic headache (HH) occurs usually in the el-
ache on at least 15 days/month for at least 3 months. derly exclusively during sleep. Patients typically
Patients with CDH need secondary etiologies ex- awaken with moderately intense and generalized
cluded through appropriate investigations before headache without associated symptoms that lasts less
establishing treatment programs. Table 1 lists sec- than 60 minutes. The headache tends to occur at
ondary causes of CDH to which the clinician must predictable times each night. In addition to lithium,
be alert. Imaging is frequently necessary to exclude melatonin, and indomethacin showing benefit, caf-
secondary causes, and in the majority of cases, MRI feine before bedtime can paradoxically be effective.
is superior to CT because of causes that are often
overlooked or not visible on head CT (table 2). In Long-duration CDH. Long-duration primary CDH
this article, we review primary CDH and discuss diagnoses include chronic migraine (CM), chronic
evidence-based treatment strategies. tension-type headache (CTTH), hemicrania con-
tinua (HC), and new daily persistent headache
PRIMARY CDH Short-duration CDH. Determining (NDPH). CTTH usually evolves from episodic
the usual duration (greater or less than 4 hours) of tension-type headache, and tricyclic antidepressants
individual headache episodes will refine the differen- with cognitive-behavioral measures are first-line
tial diagnosis in patients with primary CDH. The treatment options. HC is a continuous side-locked
prototypical short-lasting primary CDH (⬍4 hours) unilateral, moderately severe headache with exacer-
is chronic cluster headache (CCH), a trigeminal au- bations of severe pain lasting hours to days, with
cranial autonomic symptoms accompanying exacer-
From the Mayo Clinic Hospital, Phoenix, AZ. bations. By strict diagnostic criteria, patients experi-
Address correspondence and reprint requests to Dr. David W. ence substantial relief after a short therapeutic trial of
Dodick, Mayo Clinic Hospital, 5777 E Mayo Blvd., Phoenix, AZ
85054; Dodick.David@mayo.edu indomethacin (25–75 mg 3 times a day). NDPH re-
Author disclosures are provided at the end of the article. sembles CTTH in that it is typically bilateral, press-
Neurology® Clinical Practice 2011;76 (Suppl 2):S37–S43 ing or tightening in quality, mild to moderate in

Copyright © 2011 by AAN Enterprises, Inc. S37

can lead to this phenomenon. hypoxia. Synonyms for med- Arterial dissection ication overuse headache (MOH) include rebound. phe. of headache Headache attributable to cervical spine or head/neck myofascial pain disorders onset. Susceptible individuals Occipital neuralgia with preexisting episodic primary headache disor- Vascular ders. given treatment attempts for NDPH are Headache attributable to temporomandibular joint/dental pathology often less successful. Severe arterial hypertension drug-induced. Patients often pinpoint the Structural exact calendar date. parasitic) simple analgesics (taken ⬎15 days/month for ⬎3 Sinusitis (sphenoid sinusitis) months). or triptans can “transform” their Venous sinus thrombosis headache from episodic to daily. Carotid or vertebral artery dissections notypes resembling CM are not uncommon. carbon monoxide includes the following features: 1) headache fre- Thyroid disease quency increases over time. as well as combination analgesics. fungal. codeine. NDPH Ischemic stroke Cerebral venous sinus thrombosis Table 1 Causes of primary and secondary chronic daily headache Vasculitis Reversible cerebral vasoconstriction syndrome Primary chronic daily headaches Neoplastic disease Chronic migraine Parenchymal and extra-axial neoplasms (especially in the Chronic tension-type headache posterior fossa) New daily persistent headache Meningeal carcinomatosis Chronic cluster headache Pituitary tumor and hemorrhage Chronic paroxysmal hemicrania Metastatic brain tumors Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing Cervicomedullary lesions Hypnic headache Chiari malformation Hemicrania continua Foramen magnum meningioma Secondary chronic daily headaches Acoustic schwannoma Medication-related Infections Medication overuse headache Meningoencephalitis Medication-induced side effects Cerebritis and brain abscess Posttraumatic Other Headache attributable to head injury CSF leak (intracranial hypotension) Headache attributable to neck injury or whiplash Intracranial hypertension Disorders of intracranial pressure Idiopathic hypertrophic pachymeningitis Increased intracranial pressure (primary or secondary tumor. often the exact hour. “Successful treatment plans can be Table 2 Potential etiologies for headache that are often overlooked on head CT life-changing for patients” Vascular disease Saccular aneurysms intensity. However. or barbiturates). and may be associated with no more than one of photophobia. Cranial neuralgias Trigeminal neuralgia Medication overuse headache. opi- Ischemic or hemorrhagic stroke oids. Metabolic ergots. phonophobia. 2) patients often awaken S38 Neurology: Clinical Practice 76 (Suppl 2) February 15. particularly migraine and tension-type head- ache. frequent (⬎10 days/month). idiopathic intracranial hypertension. Ac- Infectious cording to the 2004 second edition of the ICHD-II. opioids. hydrocephalus) is an acute constant unremitting headache. ergotamine. Meningitis (tuberculosis. post–lumbar puncture headache) ing over less than 3 days. or analgesic-dependent headache. combination analgesics Giant cell arteritis (containing caffeine. develop- Decreased intracranial pressure (CSF leak with intracranial hypotension. Arteriovenous malformations (especially posterior fossa) ache Disorders (ICHD)–II criteria. a search for secondary causes is mandatory. and triptans (taken at least 10 days/month for ⬎3 months). 2011 . In NPDH. or Subdural hematoma daily use of simple analgesics.1 MOH Obstructive sleep apnea. near-daily. or mild nausea Subarachnoid hemorrhage according to International Classification of Head. hypercarbia.

The most pragmatic approach is ment plans. stopped. in 30% the transition can be stituted and tapered in patients using butalbital. begins with headache education. mean 15 1 60 withdrawal symptoms. 2011 S39 . SUNCT ⫽ short-lasting unilateral neuralgiform lactic and acute treatment establishment. and Neurology: Clinical Practice 76 (Suppl 2) February 15. and dependence dressing risk factors including poor sleep. and 6) headaches occur within predictable time frame after analgesic TREATMENT OPTIONS FOR CHRONIC MIGRAINE consumption. meeting criteria risk of tolerance. Lifestyle changes. and only after withdrawal of to be addressed. low abrupt. mean 11 30 1 Therapeutic goals in MOH are elimination of Preventive treatment of choice Indomethacin Lamotrigine Verapamil daily or near-daily acute medication use. in the absence of potential for renal. whereas opioids and butalbital-containing Most with CM have a history of episodic mi- analgesics should be tapered gradually. losing migrainous or auto- headache-related disability. hepatic. tified attack frequency (⬎4/month). lactic medications are being instituted. and prior history of episodic migraine as risk factors promoting CM. opioids. AND OTHER CHRONIC DAILY HEADACHE CM is Patients with CDH overusing analgesics must characterized by at least a 3-month history of head- discontinue or taper overused drugs because of the aches occurring ⬎15 days/month. Controlled epidemiologic studies have iden- doses of clonidine can help with withdrawal symp. 5) escalating doses of analgesics are required. Phenobarbi. ache can a diagnosis of CM be made. and initiating prophylactic therapy while minimizing many combination analgesics can be abruptly acute medications to 2 days/week. caffeine consumption. low education/socioeco- Chronic Headache nomic status. Treatment ache days per month and a past history of migraine. restoration of episodic headache pattern. the for migraine on ⬎8 days/month. mass index ⬎30). tic intervention is extraordinarily difficult in clinical mation that the headache may worsen before it practice. In long- headache with conjunctival injection and tearing. head injury. excessive 䡩 Renal. acute medications. and providing the patient with support has been shown to be effective without withdrawal of and close follow-up are important to successful treat. Practically. hepatic. including depression and anxiety. early with headache (despite this not being a feature and goals become decreasing daily headache inten- of original headache). can be sub. restoring patient’s functioning.1 However. dehydration. While appropriate prophy. habituation. min. 3) a proportion of attacks may sity. Simple analgesics. and begin resembling tension-type and providing acute treatment strategies for severe headache. Acute MO occurs in two-thirds of patients improves and that withdrawal symptoms can last with CM. and the use of prophylactic medications 2–10 days. including caffeine overused medications and the persistence of head- cessation. with reduced efficacy. need ble MOH can be made. however. and stress management strategies are important. it may be unrealistic to expect pain-free interval restoration. ergotamine. or corticosteroids) in limited doses Feature PH SUNCT Cluster (ⱕ2 treatment days per week) from drug classes Sex F:M 2:1 1:2 1:3 other than those being overused can help alleviate Attack duration. a long-acting barbiturate alternative. standing daily or continuous headache. di- hydroergotamine. a diagnosis of CM effects. and the possibility that medication overuse can confidently be made in a patient with ⬎15 head- (MO) may prevent optimal outcomes. and gastrointestinal side effects caffeine intake. improving quality of life. graine with gradual transition toward more frequent tal.3 • Headache at least 15 days per month for at least 3 months • Exclude secondary etiologies: MRI better than CT Aggressive approaches. symptomatic Table 3 Trigeminal autonomic cephalalgias (short-duration chronic daily headache disorders) analgesics (nonsteroidal anti-inflammatory drugs. including sharing infor. Comorbid MOH. involving pharmacologic • Medication overuse headache and nonpharmacologic options. 4) a lowered threshold for stress or exer- headaches. MO. withdrawing acute medications as the only therapeu- ting realistic expectations. reducing become nondescript. increased exercise. nomic features. ergots. and effective prophy- Abbreviation: PH ⫽ paroxysmal hemicrania. only a diagnosis of probable CM and proba- conditions. and dependence. lack of exercise. improved sleep hygiene. tion to precipitate headaches is present. headaches. Ad- 䡩 Risk of tolerance. Attack frequency. when CM is associated with of MO in perpetuating daily headache. and gastrointestinal side medication overuse. habituation. life stressors.2 Set. are often required to 䡩 Headaches transformed from episodic to daily treat CM (figure). specifically the role According to ICHD-II. snoring/sleep apnea/sleep disturbance. triptans. Avoiding identifiable triggers and 䡩 Simple or combination analgesics. obesity (body toms in opioid overuse. fe- male gender. or triptans regulating daily activities to a schedule can help.

which was significant treatment.1. days (6. p ⫽ 0.010) and a mean reduction from baseline of techniques. the largest properly ( p ⫽ 0. and have been given a grade A recom.1 ⫾ 6. disabling. placebo- eas that can aid in successful treatment of CDH. placebo-controlled. anxiety and depression are all nonpharmacologic ar.02) in a study conducted in Patients with migraine with frequent.1. A small-scale (n ⫽ 28) double-blind.5 ⫾ 7. 2011 .4 ⫾ 5. Similar data on MO were unavail- another condition.6 ⫾ 6.0) compared to mendation from the United States Headache Con. Re- networks.5 placebo (0. and cognitive-behavioral therapy allow ache frequency) in topiramate vs placebo-treated patients to exert control over otherwise automatic subjects was. physiologic responses that influence pain modula. Significant reduction clic antidepressants with stress management therapy in the mean monthly rate of migraine/migrainous was more efficacious than either alone. randomized. with or without acute medication overuse NSAID ⫽ nonsteroidal anti-inflammatory drug. topiramate in patients with CM.8 ⫾ 4. patients with or refractory headaches. S40 Neurology: Clinical Practice 76 (Suppl 2) February 15. avoiding drugs that may exacerbate days ( p ⫽ 0.7 ⫾ 6. but not in onabotulinumtoxinA. designed trials demonstrated the efficacy of these p ⫽ 0.3) was noted compared to migraine.6 Two larger. the European Union. respectively. While a number of prophylactic able from the US trial. In this study. The European trial responder rate of at conducted placebo-controlled trials in subjects least 50% reduction of migraine days was significant with CM have evaluated efficacy of topiramate and for topiramate (22% vs 0% p ⫽ 0.2 ⫾ 4.5 ⫾ 6. tion. Drug selection should be based on comor. Figure Approach to the patient with chronic migraine (CM).7 p ⫽ 0. placebo (4. compared to placebo with an increase of 0.8 bid conditions.012). benefit from prophylactic graine days by 3.1 days. double-blind. or with contraindications or acute MO reported mean monthly reduction in mi- overuse of acute analgesics. migraine days per month (5. biofeedback. controlled trial demonstrated low-dose topiramate Functional imaging studies have shown anxiety and (50 mg/day) may be effective in reducing headache attention to pain can inhibit central antinociceptive frequency in patients who had CM with MO. stress sponder rate (ⱖ50% improvement in monthly head- management.03). the US trial. but secondary analysis was medications have been evaluated for the treatment performed and showed a trend toward significance of primary CDH (table 4).059). Relaxation training.032) was observed in the sortium Guidelines and the American Academy of United States. 71% and 7%.7 whereas reduction in mean monthly Neurology Practice Parameter in the management of migraine days (⫺3. A recent randomized control trial involving 203 parallel-group clinical trials were performed with adults with CTTH demonstrated combining tricy.4 Well.8) compared to placebo (4.

other drug options should be considered.1%) receiving placebo showed at least a 50% re- Fluoxetine Small double-blind.2 onabotulinumtoxinA. was allowed using a modified follow-the-pain thought to act by facilitating the descending modula- approach.00001) and toxinA. ment (MIDAS) scores ( p ⬍ 0.0193).15 p ⫽ 0. p ⬍ 0. jects who had 1. 20- neck muscles using a fixed-site. tion of nociception within the trigeminal nucleus numtoxinA treatment significantly reduced mean caudalis and spinal dorsal horn by increasing the frequency of headache days (⫺8. but not specifically CM. administered which demonstrated superiority of amitriptyline at IM to 8 injection sites across 3 head and neck mus.384 patients with CM.009). vitality. One randomized open study in 49 subjects with graine episodes. and CTTH. headache duration ( p ⫽ 0. Seventy patients with CDH (29 with CM.13 Dosages increased up to abotulinumtoxinA as effective. Pooled analysis demonstrated onabotuli.11 After 12 weeks of treat- Topiramate Double-blind. and also. Treatment Evidence for use in CDH and CM Gabapentin was evaluated in patients with CDH Anticonvulsants (dose of 2. TM ⫽ transformed periority to placebo comparing overall headache in- migraine.8. Several other drugs have been evaluated for pro.4 onabotulinum. mean headache days per week ( p ⫽ 0. ⫺6. amount of synaptic amines. placebo-controlled phase followed by a 32-week Amitriptyline has been shown in clinical studies open-label phase enrolled 1. safe. most re- onabotulinumtoxinA in 31 sites across 7 head and cently in a double-blind.7 Gabapentin One double-blind.0127). Tizanidine Small double-blind.10 Several other efficacy variables (mi.14 Amitriptyline is cles.4%) receiving a stable dose of Amitriptyline Small open-label trial in TM 2. cumulative hours of headache on topiramate 75 mg/day. because sodium valproate in a prospective. doses of 20 mg fluoxetine).008). failed to show superiority of onabotulinumtoxinA over peak headache intensity ( p ⫽ 0. demonstrating su- Abbreviations: CDH ⫽ chronic daily headache. cial effects between the 2 medications were shown. placebo-controlled trials in CM ment. doses of 50 –100 mg at 8 weeks. double-blind.006). placebo-controlled trial in CDH Tizanidine was evaluated in a 134-subject Neurotoxins placebo-controlled single-blind study as adjunctive OnabotulinumtoxinA Double-blind. dex ( p ⫽ 0. migraine days. ⫺4.0020). 26 Antidepressants of 56 patients (46. by inhibiting cortical spreading depression. average headache intensity ( p ⫽ 0. placebo-controlled trial in CDH duction in 4-week migraine rate ( p ⫽ 0.12 headache-free days per week. in both groups. ache days with respect to baseline ( p ⬍ 0. placebo-controlled trial in CDH (baseline 4.001) and headache endogenous opiate receptors. Results showed significant improvements in significant reduction in Migraine Disability Assess- multiple headache symptom measures and demon. and overall quality of life. 2011 S41 . placebo-controlled trial. significant reduction in 30-day head- disability) were significant favoring onabotulinum. Two phase months. fixed-dose injection week parallel-track study involving 317 subjects paradigm. blind placebo-controlled trial with CDH (initial The PREEMPT clinical program confirmed on. Up to 40 additional units.0108).57 fewer headache 3 multicenter studies (PREEMPT 1 and 2) that each days per week compared with placebo-treated sub- had a 24-week. ran- these medications have demonstrated efficacy in sub. episodes (5.12 Efficacy of onabotulinumtoxinA in episodic migraine Fluoxetine was evaluated in a 64-subject double- and CTTH has therefore not been established. Sodium valproate jects with episodic migraine and given that CM is a and placebo were applied for 3 months to 40 and 30 Neurology: Clinical Practice 76 (Suppl 2) February 15. moderate or severe CM compared sodium valproate 750 mg/day to headache days. in rat models. No significant differences in benefi- psychological distress.5 (baseline Valproate Small placebo-controlled and comparator trials in CM 4. severe headache days per week ( p ⫽ Systematic series of exploratory controlled trials 0. placebo-controlled. double-blind. and proportion of patients with severe domization.2) in treatment group and 3. placebo-controlled trials in CM prophylactic treatment for CDH. and well.0025). 40 mg depending on patients’ response.1) in placebo group ( p ⫽ 0. However. CDH.400 mg of gabapentin per day and 5 of 31 patients (16. domized. highly disabling disorder with frequently unsatisfac- Table 4 Summary of evidence for prophylactic medications in undifferentiated chronic daily headache and chronic migraine tory treatment outcomes.0211). enhancing the action of toxinA. After 3 tolerated prophylaxis for adults with CM.16 Three months after ran- headache days.9 to be well-tolerated and effective as monotherapy for All patients received the minimum 155 units IM of prevention of migraine and other CDH. Additionally. CM ⫽ chronic migraine.6 placebo. and mean placebo in subjects with migraine. the median 4-week migraine rate was 2. 41 with phylactic treatment of undifferentiated primary CTTH) were studied for efficacy and tolerability of CDH.9 placebo.400 mg per day). parallel-group. fluoxetine subjects had 1.00001) were recorded strated improvement in patient functioning.

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Temporomandibular symptoms.com See also page S36 for other articles of interest related to headache. and chronic daily headaches in the population. www. Neurology Lipton et al. Chronic daily headache in adolescents: An 8-year follow-up study.If you liked this article. 2010. www. August 25.neurology. Clinical and prognostic subforms of new daily-persistent headache. 2009. February 3.neurology. www. Chronic daily headache in adolescence: A continuing problem.org Mack et al. November 4. 2010. migraine. www. 2009.org Charles et al. FDA Approves Botulinum A Toxin for Severe Chronic Migraine: Training on How and When To Use is Key. 2009. www.org Neurology Today Kurt Samson.. August 11. April 27. March 2. 2010. www. 2009. Neurology: Clinical Practice 76 (Suppl 2) February 15.neurology.org Wang et al. 2011 S43 .neurology. Experts Say.org Robbins et al.neurotodayonline. Chronic daily headache in adolescents: An 8-year follow-up study.neurology.neurology. you may be interested in . August 11.org Gonçalves et al.. Supplement on Chronic Migraine. www.

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