Introduction
Headache is an extraordinarily common and disabling condition that, despite widespread attention in both the scientific literature and popular media, is still poorly understood. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) studies identified headache as a “global public health concern” with an estimated 3 billion people worldwide experiencing a primary headache (migraine or tension-type headache [TTH]) in 2016. GBD studies found that more people worldwide experienced TTHs compared to other common headache types (1.89 billion compared to 1.04 billion migraineurs), though migraine was significantly more disabling, especially among women. Although some may consider headache as less disabling than chronic musculoskeletal pain because of the episodic nature of headache presentation, it is important to note that headache-related disability often extends beyond discrete head pain episodes as patients seek to limit exposure to potential headache triggers. Unlike chronic musculoskeletal pain, headache is difficult to assess because it can differ across a number of dimensions including pain intensity, duration of headache episodes, and frequency of headache episodes (whereas musculoskeletal pain is often assessed as a continuous phenomenon focusing primarily on pain intensity). Classification of headache is generally broken into two categories: primary and secondary headache. Primary headaches (those that develop through their own mechanisms) include migraine, tension-type, and trigeminal neuralgia headaches. Secondary headache includes headache that develops as a result another physical condition including head injury, vascular/nonvascular cranial disorders, substance use, and psychiatric disorders ( Fig. 2.1 ).
This chapter will describe the three primary headaches (because of their high prevalence) and their recommended treatments and will briefly touch on one of the more common secondary headaches (posttraumatic headache [PTH]: headache related to head or neck injury). Each section will also discuss headache assessment. Finally, this chapter will close with a discussion of Medication Overuse Headache , a subcategory of headache attributable to overuse of medication for headache control.
Primary Headaches
Migraine Headache
Migraine headaches may occur in up to 12% of the US population with significantly higher prevalence among women (18%) compared to men (6% ). Both episodic (<15 headache days per month) and chronic migraine (≥15 headache days per month) are significantly disabling and are more likely to occur in individuals with chronic musculoskeletal pain, asthma, and mood disorders. , According to the third edition of the International Classification of Headache Disorders (ICHD-3 ), migraine headache is characterized as headache lasting from 4 to 72 h (when untreated) during which nausea/vomiting and/or sensitivity to light or sound (photophobia, phonophobia) will occur. To be classified as migraine, headache must include at least two of the following characteristics: unilateral location, pulsating pain quality, moderate to severe intensity, and/or aggravation with activity. Migraine can be classified into two major “types” based on the presence or absence of aura symptoms (sensory, speech, motor, retinal, or head/neck pain symptoms). Although there is extensive extant studies of mechanistic differences between the two migraine types, there is little available information about how treatment could differ between the two groups (due to a paucity of comparative trials and the likelihood that many migraineurs experience both types of migraine ). ( Table 2.1 ).
| Core Features | Subtype Features | Duration |
|---|---|---|
| At least five attacks Duration between 4 and 72 h 2+ of these features:
| With aura : At least two headaches with fully reversible aura meeting three of the following:
| Headache on 15+ days/month for 3+ months |
At least one of the following:
| Hemiplegic migraine : Aura presents with fully reversible motor weakness, sensory and/or, speech symptoms | 8 days/month, headache meets criteria for either type of migraine |
Despite extensive study, there is still some debate on the underlying putative mechanisms that drive migraine headache. There is strong evidence supporting the roles of genetics/epigenetics, hormones, neurological factors, nutrition, and vascular changes, but the evolution of migraine across time and situations makes it difficult to specify general risk factors for migraine. Fortunately, the broad range of causal factors makes migraine headache one of the most widely researched forms of head pain, resulting in numerous available treatments and a robust body of research literature assessing the efficacy of these treatments.
Migraine headache is best assessed using a headache diary (described in detail below) and measures of headache-related disability. Self-report measures of disability allow a treatment provider to assess the impact that headache experience has on an individual’s functioning, in some cases with more precision than objective functional measures (i.e., functional capacity evaluation). Self-limiting and psychological disability are significant components of migraine experience. Migraineurs certainly limit activity (including socialization) during a migraine episode but may also do so between episodes in order to avoid environmental or stress-related triggers that may foster another headache. Thus, measures of self-reported disability are the most powerful tools for assessing the mechanisms and extent to which an individual with migraine is disabled by their headache. The Migraine Disability Assessment (MIDAS) questionnaire is perhaps the most commonly used self-report disability measure for migraine. MIDAS assesses disability across multiple life domains (school/work, housework, recreation) using five brief items asking patients to report the number of days over the last 3 months for which activity in a given domain was avoided or otherwise affected by headache. Total MIDAS scores correlate significantly with physician judgments about headache severity. ( Table2.2 ).
| Headache diary | Migraine disability assessment test MIDAS | Six-item headache impact test HIT-6 |
|---|---|---|
| Various formats available Assess: Headache frequency Episode intensity Episode duration Most common summary is headache days/month Can use headache index | 5 patient self-report items Assess # of days migraine affected various activities over the past 3 months 2 supplemental questions for providers Score = sum of days across the 5 patient self-report items | 6 patient self-report items Rate frequency of headache symptoms severity over the past 4 weeks Numeric rating scale (6,8,10,11,13 points per item) Score = sum of points across all 6 items |
Prophylactic treatments : Migraine prophylactic agents are highly researched but underutilized in migraineurs. These agents are designed to address biological trigger mechanisms for headache onset through various therapeutic channels including alteration of neurotransmitters, calcium channel blocking mechanisms, and direct action on peripheral and central pain networks. Although patients benefit from multiple options for migraine prophylaxis, which can be tailored to maximally benefit each individual migraineur, there is a paucity of comparative research that can be used to help providers choose which agents work best for certain types of migraine patients. Jackson and colleagues meta-analyzed 53 different studies of over 10 different migraine prophylactic agent types and found that most agents resulted in a clinically significant decrease in headache days. The authors found that drugs like amitriptyline (an atypical antidepressant) produced consistently strong migraine prevention outcomes, though there was limited evidence supporting amitriptyline as superior to other agents. They did note that tailored migraine prevention is supported by the available research, especially when tailoring is done to accommodate comorbid health conditions (e.g., prescribing beta-blockers for migraineurs with comorbid hypertension). Some have cautioned that treating providers should first consider FDA-recommended frontline agents for migraine prophylaxis (e.g., divalproex, topiramate, metoprolol, etc.) followed by amitriptyline as a second-line option.
Abortive treatments : While prophylactic agents are designed to prevent the onset of migraine headache, abortive medications are used to diminish and potentially stop migraine symptoms after the headache begins. Stopping migraine symptom cascade is more difficult than preventing onset, so outcomes of abortive treatments are likely less powerful than prophylactic outcomes. Unfortunately, because prophylactic agents are underutilized in migraine management, there is some evidence showing that migraine sufferers use abortive agents to control migraines at very high rates. For example, one study of prescription patterns for migraine from 1998 to 2006 found that anti-inflammatory analgesics were used (as an abortive agent) at much higher rates than prophylactic medications like triptans. As with prophylactic medication, abortive agents should be tailored to everyone’s headache presentation and clinical picture. Lucas recommends using simple analgesics to address mild migraine symptoms, and stronger medications should be used for more severe symptoms (including tailored responses to address cooccurring nausea and vomiting). Al-Quliti and Assaedi recommend distinguishing between nonspecific (analgesics, anti-inflammatory) and specific (ergots, triptans) abortive agents, with nonspecific agents recommended for children who can tolerate potential gastrointestinal side effects and specific agents like triptans recommended for more severe migraine when given early in migraine onset. Migraineurs use opioid medications at higher rates than the general public, and opioid medications are frequently used to address patients with severe migraine symptoms (even children and young adults), especially when these patients present for care in Emergency Departments. , Most abortive agents are more effective in terminating severe migraine compared to opioids, and prolonged opioid use can result in increased head pain (due to opioid-induced hyperalgesia), opioid dependence, and gastrointestinal symptoms. , , Generally, the evolving research literature warns against using opioid medications for headache control in any venue, and other treatment options are recommended. Finally, migraine treatment providers increasingly recommend botulinum toxin (e.g., BTX-A or Botox), a neurotoxic protein that can inhibit muscle spasms and hyperactivity, for the treatment of chronic migraine headache. Injection of BTX-A into pericranial muscles can significantly improve migraine headache and decrease reliance on medication for migraine control, which some investigators attribute to better control of muscle contraction migraine triggering. A recent study of BTX-A for chronic migraine found a median decrease of 3.5 headache days per month as well as decreased analgesic medication use for up to 9 months, though the investigation did not detect a significant improvement in headache-related disability in this small and possibly underpowered study. Larger controlled trials are needed to better affirm the short- and long-term benefits of botox for migraine.
Controversy: CGRP receptor antagonists and monoclonal antibodies : Recent studies have identified calcitonin gene–related peptide as a possible mechanism for episodic migraine. These studies gave rise to an evolving clinical trial landscape assessing the safety and efficacy of CGRP monoclonal antibodies as a potential treatment for these debilitating headache. As described by Moriarty and colleagues, CGRP is a neuropeptide with broad influence over multiple putative mechanisms of migraine including vasodilation and pain signaling pathways, and CGRP has been shown to upregulate during migraine headache events (cf. ). Experimental infusion of CGRP has been linked to migraine onset, cementing CGRP as a causal mechanism in migraine headache. Growing interest in CGRP as a causative factor in migraine led to the emergence of pharmacological interventions that block CGRP effects. Unfortunately, small-molecule CGRP antagonists, though effective, have been linked to liver toxicity, slowing development of these agents in migraine clinical trials. Attention has now turned to CGRP monoclonal antibodies (mAbs) as an effective and safe alternative due to the specificity of mAbs treatment targets and lower potential liver toxicity compared to small-molecule CGRP antagonists. To date, there are over 20 available CGRP monoclonal antibodies, studies of which have returned largely favorable outcomes. There is some equivocation in the extant body of available research at the time of this chapter regarding efficacy and safety of CGRP mAb (cf. ), and more research is likely needed to confirm their effectiveness compared to other migraine treatments.
Nonpharmacological migraine treatment : Numerous studies have confirmed both the benefit and safe side effect profile of nonpharmacological interventions (NPIs) for migraine, though these treatments are highly underutilized due to a lack of awareness among medical providers about the efficacy of these interventions and lack of availability of strong NPI in the treatment community. Foremost among migraine NPIs, cognitive and behavioral therapies (CBT) have the strongest level of support. CBT approaches to migraine management combine behavior change, migraine trigger management, cognitive therapies to address alarming cognitions about stress and headache, and relaxation strategies to reduce headache interference in functioning and improve quality of life. Once engaged with CBT, treatment retention rates are comparable to standard medical care, and patients report high levels of satisfaction with CBT-based migraine interventions. A meta-analysis of CBT for migraine found nine times greater odds of significant improvement in migraine for pediatric samples, and one of the largest studies of CBT for pediatric migraine to date found that the addition of CBT to amitriptyline doubled the improvement in headache days per months compared to amitriptyline alone. , Indeed, comparisons of pharmacological to NPIs for pediatric migraine conclude that CBT-based interventions should be a frontline option for children with migraine because of the minimal side effects and stronger outcomes for CBT in extant studies. Some CBT treatments will offer stress management and/or relaxation using biofeedback. Biofeedback is not a “type” of treatment for migraine but serves as a treatment adjunct, often using thermal or electromyographic sensors to help the patient identify and manage physiological stress. Decreased physical stress is associated with better headache outcomes, but there is some debate about the added benefit of biofeedback as an adjunct to behavioral relaxation training and concerns about patient retention for biofeedback-assisted relaxation. There is growing evidence that complementary and integrative health interventions like yoga and acupuncture are helpful for abortive migraine treatment, with preliminary outcomes showing decreased reliance on medication for migraine treatment with prolonged use of these interventions. Physical therapy can improve some migraine symptoms particularly in patients with cervical or temporomandibular pain. , Massage therapy is often offered as a migraine intervention, though the research on massage for migraine is not yet well-developed and the putative mechanisms of benefit for massage in migraine are unclear ( Fig. 2.2 ).
Conclusion : Migraine headaches represent one of the most prevalent and debilitating pain conditions worldwide. Although episodic migraine may occur at a lower frequency than chronic headache, both can be disabling at all times due to both headache experience and changes in behavior and function caused by concern about future headache episodes. Although research on the putative mechanisms of migraine is still developing, there are numerous treatment options available, many of which result in significant clinical improvement. Prophylactic and abortive medications can either prevent migraine onset or reduce episode duration, frequency or intensity, and NPIs (especially CBT) can significantly improve migraine with minimal side effects. Emerging treatments for migraine (e.g., CGRP mAb) offer great promise, though the research on these interventions is nascent.
Tension-Type Headache
Tension-type headache is one of the most common forms of headache with an estimated lifetime prevalence between 30% and 78% worldwide. The International Classification of Headache Disorders—Third Edition differentiates TTH from migraine based on an absence of nausea or vomiting and an absence of photophobia and phonophobia. TTH is diagnosed if duration of headache episodes ranges between 30 min and 7 days and two of the following characteristics are present: the headache pain is bilateral, of a pressing or pulsing quality, mild or moderate intensity, and/or not aggravated by physical activity. TTHs can be further differentiated based on the frequency of the headache. TTH occurring less than 1 day per month is considered infrequent episodic TTH , one to 14 days a month is frequent episodic , and 15 or more days per month for more than 3 months is considered chronic . Notably, there is some debate about the distinction between chronic TTH and migraine without aura, making treatment for chronic TTH somewhat difficult. When classifying TTH frequency, it is important to note that the headache episodes may change over time and repeated assessment of headache frequency is required to ensure appropriate classification ( Table 2.3 ).
| TTH Subtype | Frequency | Duration | Characteristics | Rule-Outs |
|---|---|---|---|---|
| Infrequent, episodic | 10 episodes < 1 day/month | 30 min to 7 days | Bilateral pressing or tightening mild to moderate | No nausea No vomiting Not worsened by activity |
| Frequent, episodic | 10 episodes 1-14 days/month for > 3 months | |||
| Chronic | Headache occurs ≥ 15 days/month | Hours to days unremitting | No more than one photo/phonophobia No moderate/severe nausea or vomiting |
TTH is a deceptive form of headache which presents with similar clinical characteristics to muscular pain, but the mechanisms that drive TTH are not purely muscular and likely involve a host of factors including central pain sensitization, peripheral excitability, muscle hyperalgesia, changes in neurotransmitters, and genetics and psychiatric comorbidities. , Neurophysiological studies of TTH have identified roles for brainstem hyperexcitability and generalized abnormality of neural excitability beyond cranial nerves, though an overview of these studies warned that extant neurophysiological TTH studies are methodologically weak. Attempts to experimentally induce TTH has shed some light on their underlying pathophysiology. Exposto and colleagues used a tooth clenching task to induce TTH and found that changes in pericranial tenderness did not predict headache onset, as expected based on some theories of TTH origin. Pain modulation profiles (which use information from conditioned pain modulation and temporal summation of pain to predict pain and response to pain treatment ) also failed to predict TTH onset leading the authors to suggest that pain modulation may be an effect of TTH instead of a cause. Unfortunately, TTH often cooccurs with migraine making mechanistic studies of TTH very difficult. Much more research is needed to further elucidate mechanisms specific to TTH.
TTH may be perpetuated and exacerbated through comorbid conditions like insomnia and myofascial pain syndromes that add considerable complexity to assessment and treatment. Sleep problems are highly prevalent among individuals with TTH, particularly those who fit criteria for chronic TTH. Jay and Barkin offer a nice description of the various pathways through which sleep difficulties influence TTH, noting disturbance in stage 4 sleep (which may be beneficially addressed with low-dose tricyclic antidepressants) and increased pain accompanying poor sleep that could worsen the impact of TTH. TTH is also associated with myofascial pain syndromes, characterized by regional pain experience and cranial, temporomandibular, sternal/clavicular, and trapezius trigger points. Myofascial pain may influence TTH through chronic muscle tension, posture changes, and temporomandibular joint dysfunction.
TTH assessment : Unlike migraine, there are few (if any) headache assessment instruments specific to TTH. Due to the variable and episodic nature of most TTH, the most recommended assessment tool is a comprehensive headache diary. There are numerous, publicly available options for headache diaries, most of which include a numeric rating scale of pain intensity, mechanisms to track headache frequency and duration, and fields for recording circumstantial factors that may affect headache including sleep, stress levels, and medication use. Various studies have found that headache diaries may outperform retrospective self-report of headache symptoms and that TTH-sufferers, especially children, are likely to overreport pain intensity using retrospective recall compared to prospective diary entries. Some warn, however, that retrospective report of headache does provide valuable information about headache experience, and the best approach for TTH assessment is to combine headache diaries and interviews. Despite their usefulness, there is concern that headache diaries may offer limited data about headache experience due to poor patient adherence to completing diary entries. One study found a high number of missing diary entries over a 30-day assessment period (15 mean missing entries) using a long-form paper diary and several recording or transcription errors in diary entries that affected data validity. However, the investigators found fewer omissions and errors on brief electronic headache diaries, suggesting that transition to now ubiquitous e-diaries for headache could improve their validity and utility.
Scoring and using headache diary data can be difficult. Most chronic pain conditions are meaningfully assessed and easily summarized using measures of pain intensity (cf. ), self-reported disability, functional quantification, and pain interference. Because of its episodic presentation, however, headache is a complex phenomenon to measure. Regular headache diaries assess the quality, frequency, duration, and intensity of headaches, but there is little guidance on how to weigh these dimensions of headache experience to produce a summary of headache pain. Some suggest that headache dimensions can be multiplied (e.g., frequency ∗ duration) resulting in a “headache index” (cf. ) or “headache ratio” (cf. ). Unfortunately, there are no extant studies supporting the use of these index varables and no data showing how headache index scores link to other meaningful clinical variables (e.g., psychiatric comorbidity). Most diaries will rely on either headache frequency or intensity without attempting to combine these metrics into a headache index.
Pharmacological treatment : Patients with TTH seek treatment at notably lower rates (16%) than migraineurs (56%; ), but when accounting for headache frequency (TTH is generally more frequent than migraine), TTH patients use pharmacological interventions at much higher rates. The broad array of factors contributing to TTH allows for a similarly broad scope of pharmacological interventions, though analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) are the most recommended and studied treatments. One meta-analysis of TTH analgesic studies found that NSAIDs and acetaminophen were significantly more effective for TTH management than placebo, and there were equivocal findings comparing NSAIDs to acetaminophen for acute TTH. The investigators found no significant difference in efficacy across different NSAID drugs, though they did note differences in adverse event profiles that may guide selection of some compounds (e.g., aspirin use was associated with higher risk of gastrointestinal complaints compared to ibuprofen). Fumal and Schoenen note that COX-2 inhibitors have shown some benefit for acute TTH management, though data comparing these compounds to NSAIDs are limited. Some suggest that adjuvant caffeine may increase the effectiveness of NSAIDs and simple analgesics. , Unfortunately, overreliance on analgesic medication is a significant concern for TTH patients. Schnider and colleagues studied analgesic use in a cohort of 80 TTH patients and found very high levels of use resulting in “considerable risk” for medication overuse headache (MOH) (described in more detail below).
Most TTH pharmacotherapy targets acute treatment of episodic headache, but there is an evolving literature on the prophylactic use of certain compounds for patients with chronic TTH. Most available research supports amitriptyline as the best frontline prophylactic agent for chronic TTH. , The success of amitriptyline and other tricyclic antidepressants and mirtazapine (a tetracyclic antidepression) in preventing chronic TTH may be due to alterations in central pain processing (cf. ), though this mechanism is not strongly addressed in extant research. Recent studies of prophylactic pharmacotherapy for chronic TTH found that almost all patients taking a prophylactic agent are taking amitriptyline, and over 70% in one study found it effective, though there are studies that found an insignificant change in TTH with amitriptyline (cf. ). Boz and colleagues compared prophylactic amitriptyline to the selective serotonin reuptake inhibitor sertraline and found that both agents significantly reduced TTH symptoms. However, outcomes associated with amitriptyline were noticeably superior to sertraline, further cementing amitriptyline as the best frontline prophylactic agent.
Nonpharmacological treatment : Many of the nonpharmacological treatments recommended for migraine are also recommended, and strongly supported, for TTH. CBT can significantly improve TTH through the same stress management and cognitive restructuring mechanisms that are effective in migraine studies. Holroyd and Stensland found that CBT interventions are just as effective as tricyclic medication for TTH, but found that CBT produced broader benefits than the medication that likely added to improved headache coping. Motoya and colleagues explored cognitive mechanisms through which CBT might benefit TTH in a small pilot sample and found that TTH patients who complete CBT report fewer catastrophic/alarming thoughts about their pain and decreased pain-related activity avoidance, both of which are likely to significantly improve disability. As is the case for migraine, complementary and integrative health approaches are receiving increasing attention in the management of TTH. One recent study tested acupuncture and massage for TTH and found that both treatments resulted in significant decrease in the frequency and intensity of tension headaches. Studies of chiropractic care for TTH offer some promising findings of decreased headache frequency though the research on chiropractic for headache is underdeveloped and nascent, and more research is needed to reliably conclude that chiropractic care is truly beneficial for TTH ( Fig. 2.3 ).
