Headache & Pain
Migraine: pathogenesis and pathophysiology
Nov. 18, 2022
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Psychological factors and their role in headache have been known for centuries and possibly millennia. In the past, it was believed that headache was caused by psychological factors; however, it is now recognized that headache is a complex biomedical disorder in which psychological factors can play a contributory, maintaining, and/or reactive role. The authors describe the interaction of psychophysiological factors with headache syndromes, the evidence for genetic and environmental factors, and novel forms of nonpharmacologic therapies for the patient with headache and psychological accompaniments. This update highlights research on psychological factors in headache-related disability and advances in cognitive behavioral treatments for headache.
• Although headache is almost always a biochemical disorder, psychological factors often play a contributory role in headache onset and/or a reactive role in headache maintenance.
• There is a high level of comorbidity between headache and psychiatric disorders such as depression and anxiety.
• It is hypothesized that psychiatric comorbidity is a risk factor for medication overuse, causing worsening headache frequency or chronic headaches.
• Because headache has a major impact on quality of life, psychological interventions such as psychotherapy and biofeedback are not only useful adjuncts to medication therapy, but also permit patients to be actively involved in managing their lifestyles.
The relationship between psychological factors and headaches has been observed for hundreds of years. The ancient Greeks and Romans were aware that emotional distress often triggered headaches, particularly migraine headaches. In 1743, Junkerius wrote that the primary cause of migraine is anger, especially when it is tacit and suppressed. In the 1880s, Breuer and Freud reported that many patients’ headache complaints disappeared after a cathartic experience or a state of improved emotional equilibrium had been reached (33).
The term "psychogenic" headache was introduced in the 1930s, when the field of psychosomatic medicine was developing. Psychogenic headache was considered to be "symbolic distress" relative to head function rather than distress originating in psychophysiologic mechanisms (83). Weiss and English stated that psychogenic headaches were "reflex headaches" in that they were caused by conscious or unconscious emotional stress (153). Headache improvement was noted following emotional releases (83).
Harold G Wolff, in summarizing his research regarding psychological factors in headache, wrote, "Since the human animal prides himself on 'using his head' it is perhaps not without meaning that his head should be the source of so much discomfort...the vast majority of discomforts and pains of the head...are accompaniments of resentments and dissatisfactions" (156). Because the head is commonly regarded as the portion of the body that controls consciousness, memory, talent, intellectual activity, cognition, and judgment, we begin to understand how the patient may use the complaint of headache as a means of expressing anxiety. To the layperson, the terms "head" and "brain" are often synonymous (83).
In the past, the terminology used by clinicians to describe psychological or psychogenic headache has often been vague and inadequate (23). In a survey conducted among physicians at a large medical center, numerous definitions were given for the term "psychogenic headache," with tension headaches, headaches with no organic basis, and headaches secondary to stress being the most frequent (103). Over time headache has been determined to be a medical rather than purely psychological disorder. It has been suggested that the term "psychogenic headache" should not be used, or used only when a peripheral pain-inducing mechanism is nonexistent (103). However, this often causes conflict when one tries to determine whether a patient's headache pain is "real" or "not real" (105). The patient's headache or complaint of head pain must always be approached as real. The emergence of the biopsychosocial model changed our view of headache incorporating the biological, psychological, and social variables that impact headache (12).
Headaches that had been primarily considered psychogenic have historically met the criteria for somatoform disorders. Somatoform disorders were characterized by physical symptoms for which no known organic findings or physiologic mechanisms could be identified and for which there was a strong presumption that the symptoms were linked to psychological factors (09). A somatoform disorder is different from a malingering or factitious disorder, in that a patient intentionally produces symptoms for the purpose of a specific gain. In the DSM-4-TR, somatoform disorders were subdivided into conversion disorder (loss of physical functioning that suggests a physical disorder), hypochondriasis (preoccupation with or the belief that one has a serious disease in spite of evidence to the contrary), somatization disorder (recurrent and multiple somatic complaints, often including headache), and somatoform pain disorder (preoccupation with pain without organic pathology). The publication of the American Psychiatric Association’s Diagnostic and Statistical Manual-5 (DSM-5) has resulted in substantial modifications to the conceptualization of somatization. The DSM-5 has removed the subdivisions of somatoform disorders and has categorized them under the umbrella term somatic symptom disorder (SSD). Another change to the DSM-5 criteria is that a diagnosis of somatic symptom disorder allows for symptoms that have a medical explanation. Thus, a cancer patient experiencing disproportionate and excessive thoughts, feelings, and behaviors related to their illness may qualify for a diagnosis of somatic symptom disorder (10). This consolidation of disorders was developed in part to facilitate use in nonpsychiatric settings. Thus, headache patients overly focused on headache symptoms could now be diagnosed with somatic symptom disorder, in addition to those patients whose headaches are obviously exacerbated or aggravated by psychological factors (09).
In 2013 the International Classification of Headache Disorders, 3rd edition, was released by the International Headache Society (71). Included was the heading of “12. Headache attributed to psychiatric disorder,” along with subheadings “12.1 Headache attributed to somatization disorder” and “12.2 Headache attributed to psychotic disorder.” When a headache disorder develops for the first time in close temporal association to a psychiatric disorder, it may be coded as a secondary headache that is attributable to that psychiatric disorder.
Secondary headache is defined as headaches that occur as a result of head traumas, whiplash, neck conditions, or rhinosinusitis and resolve in the majority of cases. However, in some cases, these headaches remain chronic. A study found that in those cases that remain chronic, the patients had significantly higher levels of psychological distress and neuroticism (86). Psychological distress was measured by the Hopkins Symptom Checklist-25. Neuroticism was defined as neurotic personality traits and symptoms of moodiness, nervousness, being easily irritated, lack of endurance, and feelings of guilt and worry, as measured by the Eysenck Personality Questionnaire.
When a preexisting headache syndrome is worsened in association with a psychiatric disorder, the patient can be diagnosed either with the preexisting headache disorder or as a headache attributed to the psychiatric disorder. The particular diagnosis of headache attributed to psychiatric disorder becomes definite only when headache resolves or improves after effective treatment or resolution of the psychiatric disorder. Criteria for these coded diagnoses are now available:
12.1 Headache attributed to somatization disorder
A. Headache, no typical characteristics known, fulfilling criterion C
1. History of many physical complaints beginning before the age of 30 that occur over a period of several years and result in treatment being sought and significant impairment in social, occupational, or other important areas of functioning
2. At least four pain symptoms, two nonpain gastrointestinal symptoms, one sexual or reproductive symptom, and one pseudoneurologic symptom
3. After appropriate investigation, each of these symptoms cannot be fully explained by a known general medical condition or the direct effects of a substance or medication; or, if there is a related medical condition, the complaints or impairment are in excess of what would be expected from the history, examination or laboratory findings
C. Headache is not attributed to another cause
12.2 Headache attributed to psychotic disorder
A. Headache, no typical characteristics known, fulfilling criteria C-E
In patients with headache disorder co-occurring with psychiatric disorders without any evidence of causal connection, both headache and a separate psychiatric diagnosis should be made (71). In the meantime, it must be recognized that there is an interplay between medical and psychological factors that makes it difficult to confidently identify pure psychogenic headaches.
Listed below are the various headache most often associated with psychological factors.
Tension-type headache. Tension-type headaches are the headaches seen most often in medical practice. Although organic factors are believed to be involved in most cases, most individuals who have tension-type headache also have associated emotional stress (106). Frequently, the fundamental psychic factors are unconscious, although patients are typically aware of their anxiety. The headache may be associated with insufficient coping strategies in the face of various degrees of psychological stress. Yucel and colleagues noted that, compared with healthy controls, patients with tension-type headaches were more likely to experience depressive thoughts and alexithymia (an inability to identify emotion) (158). Some studies suggest that subjects with tension-type headache are not more physiologically reactive to laboratory stressors. However, they may appraise and cope with stressful events in a different manner than headache-free controls. A study found that individuals with tension-type headache did not respond differently than control subjects to stressors (based on measures of EMG, heart rate, or subjective stress ratings) presented in the laboratory (57). However, diary questionnaires revealed that headache subjects experienced stressful events more frequently and rated these events as causing more stress than headache-free controls (57). Blomkvist and colleagues observed that patients with headache coped differently, depending on the nature of the headache; patients with tension-type headache are less likely to have social contacts or supports than patients with migraine (22). In addition, individuals with chronic tension-type headache tend to have higher levels of depression (158). Accumulating evidence suggests that tension-type headache sufferers report experiencing more everyday mild stressors, judge these stressors to have high impact, and use less successful strategies for coping with daily stressors (14). These individuals may also have greater pain sensitivity, reduced pain thresholds, and increased muscle tenderness (14).
Migraine headache. Migraine has been more intensely studied than any other form of headache. Many have theorized that specific personality traits (perfectionism, ambition, repressed anger, rigidity) are characteristic of migraine sufferers (155). Friedman reported that personality manifestations in migraine embraced a variety of primarily unconscious emotional factors, including hostility, identification with a family figure, a wish to remain in a position of dependency, or a means to gain love, affection, or attention (63). The notion that pathologic personality traits cause migraine, however, is controversial. It is noteworthy that no single personality pattern exists that could describe all migraine patients, and many patients with migraine are not compulsive, perfectionistic, or rigid (106).
Another study thoroughly examined the association between migraine and personality while controlling for a history of co-occurring psychiatric disorders (28). Migraine, defined according to the criteria developed by the International Headache Society (70), was significantly associated with neuroticism (measured by Eysenck's Personality Questionnaire), even when sex and history of major depression and anxiety disorders were controlled for (28). Breslau and Andreski found that over 25% of persons with migraine uncomplicated by psychiatric comorbidity scored in the highest quartile of neuroticism, suggesting that migraine headache may be comorbid with the anxious personality cluster (28). Saper and Lake were even more specific in their observation that patients with borderline personality disorder seem to have increased tendency towards migraine and severe headaches (126). Huber and Henrich compared migraineurs with healthy controls, using the Minnesota Multiphasic Personality Inventory and other questionnaires, to find that the migraineurs rated themselves as less calm, less capable of relaxing, more irritable, and more likely to respond to situations with a sense of internal stress, than the healthy controls (74). Kowacs and colleagues found that migraineurs, compared with both healthy subjects and subjects with nonneurologic chronic disease, had higher scores on scales assessing for depressive and anxiety disorders (85). In a study with women migraineurs, the results showed that stress, influenced by anxiety and depression, was a more powerful trigger for migraines than menstruation (107). A review study that cited 25 publications found that stress was the most common precipitation factor of a migraine attack (111). Longitudinal population-based studies by Breslau and colleagues revealed a high lifetime prevalence of major depression in subjects with migraine (29; 31). Similarly, most subjects with migraine and depression also have a history of at least one anxiety disorder. A study of 250 subjects comparing the psychological variables between acute and chronic migraine patients found that the variables responsible for headache chronicity were depression (odds ratio of 3.66) and lack of anger control (odds ratio of 5.04) among others (53). These studies indicate that the association between migraine and depression is most likely bidirectional (ie, each disorder increases the risk for development of the onset of the other disorder).
Conversion headache. There is often a delay in diagnosing conversion headache. The physician may believe that emotional factors are playing a role in headaches, but conversion headaches initially do not stand out in any remarkable way from other types of headaches. Patients will often deny any disturbing emotional relationships or events in their lives. This denial is the basis for the conversion reaction, as the patient unconsciously copes with psychological distress by “converting” the underlying conflict into a more manageable physical symptom. Most patients show a calm indifference to the pain. This affective indifference is often a valuable clue in diagnosing conversion headache (104).
Cluster headache. There is no clear evidence of the role of neuropsychological factors in cluster headache. A cross-sectional study compared cognitive and emotional functioning in individuals with episodic and chronic cluster headaches with healthy controls. The findings revealed that having cluster headaches was associated with worse working memory, mood disturbance, and increased rates of anxiety (145). One limitation of the study was its small sample size. The rates of depression and anxiety are highly variable due to rare nature of the headache and the time period in the headache cluster when the patients are assessed. In a large population-based cohort study, patients with cluster headaches were found to have 5.6 times greater odds of developing depression when compared to controls. Suicidal ideation was two to three times higher as compared to controls, but the actual act of suicide seems rare. Suicidal tendencies are more common in chronic and active than inactive cluster headache patients (128).
There is little doubt as to the negative impact and complications facing adults (61) and pediatric (117) headache sufferers alike. When psychological factors are at play, prognosis depends on the nature and severity of psychopathology, the patient's motivation toward treatment and recovery, and the skill of the practitioner. The date from American Registry for Migraine Research between February 2016 and June 2019 showed anxiety and depression were associated with migraine-related disability, reduced work productivity, and career success (108). Headache frequency, the number of headache days (HDs) per month, is associated with higher risk of anxiety and depression, severe disability, and lower quality of life. Irimia et al found the risk of anxiety is higher in patients having ≥ 3HDs, depression ≥ 19HDs, and very severe disability ≥ 10HDs per month (77). The longer duration, more frequent migraine attacks, and headache with substantial to severe impact were predictors of both disability and impairment in quality of life; in addition, comorbid psychiatric conditions were found to be a significant contributory factor (118). Other prognostic indicators include an insecure style of attachment along with depressive symptomatology, female sex, and number of headache days per month (125). A study by Carasco and Kroner-Herwig showed that children 9 to 15 years of age who suffered from weekly headaches and exhibited highly dysfunctional coping strategies (internalizing or externalizing symptoms, anxiety sensitivity, and somatosensory amplification) had reduced probability of headache remission (36). Furthermore, behavior disturbances among children and adolescents may also be a complication of headache. A large scale (n = 5393) survey of Finnish families with adolescent twins evaluated headache and externalizing behaviors, finding that adolescent “behavioral problems” could be considered a warning sign for worsening headache, and vice versa (149). A cross-sectional study of over 9000 children aged 4 to 17 years from the 2003 National Health Interview Survey concluded that children with frequent or severe headaches were 3.2 times more likely than children without frequent or severe headaches to have a high level of difficulties and 2.7 times more likely to have a high level of impairment, all of which was indicative of possible mental health difficulties. The authors determined that children with frequent or severe headaches were significantly more likely than those without frequent or severe headaches to exhibit high levels of emotional, conduct, inattention-hyperactivity, and peer problems. These children were significantly more likely than children without frequent or severe headaches to be upset or distressed by their difficulties and to have their difficulties interfere with home life, friendships, classroom learning, and leisure activities (140). Using various psychiatric rating scales, Mazzone and colleagues found differences between youth with tension and migraine headache in terms of the presence of behavioral and emotional difficulties (96).
A 32-year-old mother of three presented to the psychiatric emergency service with complaints of headache and numbness. She was a graduate student and was the sole parent of her three children. Over the past 6 months, she had begun a job in food delivery on top of her studies and parenting. Four months prior to presentation, she began to notice headaches, which became essentially daily headaches. The pain was holocephalic, pressure-like, and somewhat fluctuant through the day, although it worsened in the early morning and late afternoon hours. The headache was occasionally associated with feelings of fear, as well as malaise. She denied nausea, photophobia, and phonophobia, and did not notice worsening of the headache with exertion in particular. During one week, her mother visited and she noticed that the quantity and duration of headaches were significantly reduced that week.
She presented to psychiatry with complaints of excessive tension and concerns that she may have a brain tumor causing her symptoms. Neurologic consultation was requested.
Her past history was remarkable for episodic tension-type headaches as a teenager, but she was otherwise well. She had been using ibuprofen and acetaminophen for analgesia over the past 4 months. Her remaining history was noncontributory. Neurologic examination was completely normal, with pericranial tenderness noted on examination. Computerized tomography of the brain was entirely normal.
The patient was diagnosed with chronic tension-type headache with pericranial tenderness (IHS 2.3.1). She was reassured that neurologic examination and neuroimaging did not demonstrate any evidence of a brain tumor. Education about the importance of emotional and physical stressors on her headache syndrome was provided. It was explained that her life stressors were contributing to her headache. It was suggested that she ask family members to assist with parenting during times of excessive stress surrounding her studies and work. She agreed that awareness and acceptance of her limitations were important to improving her current health. She declined psychotherapy but agreed to pharmacotherapy with amitriptyline starting at 10 mg nightly, increasing up to 50 mg nightly over 4 weeks. One month later, her headache frequency was decreased to 14 days of the month, and the headache severity was improved.
The biological bases for headache are well documented and established. The role of psychological factors in headache, although widely accepted, remains complex and multifaceted. Research in this area, although limited, seems to indicate that psychological factors may act on the body through autonomic or hormonal pathways (psychophysiological reactions) or voluntary sensorimotor pathways (conversion reactions) (01).
Psychophysiological mechanisms involve the influence of prolonged or intense emotional states or chronically held attitudes on the body (01). These attitudes or emotions (either conscious or unconscious) bring about physiological changes to prepare for actions or consequences. Over time, the physiology accompanying these affects, attitudes, and defenses interacts with genetic vulnerabilities in the patient (01).
The contribution of both genetic and environmental factors in headache syndromes may eventually result in psychologically influenced headaches. For example, tension-type headaches may be influenced by excessive contraction of the cephalic musculature (physiological), a centrally mediated lowering of the pain threshold, and intramuscular vascular restriction (02). Psychological stress, including both major stressful events and daily hassles, can trigger headache and also increase the intensity of headache (150). Stress can increase sensitivity to pain and lower the pain threshold in sensory receptors, making individuals more prone to headache pain and intensity; furthermore, chronic stress has been found to increase pain sensitivity in both headache sufferers and healthy controls (37).
Tension-type headache and brain metabolites were investigated with proton magnetic resonance spectroscopy, which is a noninvasive method to quantify pain, and a correlation between low choline/creatine ratio in the primary somatosensory cortex and high trigger point count was found (99). Most clinicians would agree that tension-type headaches can be aggravated by psychological stress. In fact, stress and mental tension are the most prominent precipitating factors in tension-type headache (121; 127; 147). Experimental studies have also demonstrated that tension-type headaches can be induced by psychological stress (64; 69). Additional evidence for the link between psychological stress and tension-type headache syndromes is the efficacy of psychological and behavioral therapies in the treatment of tension-type headache syndromes, which can have similar treatment success as pharmacotherapy (72). However, the precise role of psychological factors in the creation, exacerbation, and continuation of tension-type headache syndromes remains unclear.
Central factors leading to exacerbation of tension-type headaches may occur through involuntary contractions of cephalic muscles, a loss of inhibition through supraspinal pathways, or supraspinal hypersensitivity to nociception (58; 97; 35). Evidence of increased pericranial tenderness has been found in patients with both episodic and chronic tension-type headache, which may suggest hypersensitivity mechanisms or a loss of normal inhibitory pathway functioning (80; 79). It has also been suggested that in patients with episodic migraine, the presence of anxious and depressive features may considerably increase levels of muscle tension in the head and neck, possibly contributing to transformation from episodic to chronic migraine (101).
Similarly, migraine headaches are primarily related to psychophysiological rather than strictly psychological mechanisms. Exacerbation of migraine at times of stress, more specifically during the "let-down" period, is well-documented (105). Although personality factors such as perfectionism, repressed hostility, and dependency are not specific to migraine, when genetic predispositions exist, one can readily observe how such personality factors become constant stressors and induce migraines in a susceptible individual.
The mechanism of conversion reactions involves the development of a symbolic physical reaction in the voluntary muscles or special senses in hopes of resolving unconscious conflicting impulses. Anxiety, instead of being consciously experienced, is converted into functional symptoms that usually symbolize underlying mental conflict. A key mechanism in the development of the conversion headache may be the identification with symptoms of a person with whom the patient has a close relationship, such as a child emulating their mother’s headache (104). Alternatively, complaints of headache are significantly associated with secondary complaints of anxiety or depression (66).
Studies have suggested that certain personality factors may predispose a person to headache. Therefore, personality factors should be considered in any thorough discussion of headache etiology. Personality profiles of patients with chronic tension-type headache demonstrate greater likelihood of harm avoidance behavior along with less evidence of self-directedness temperament (27). Relative to nonmedication-overuse headache participants, participants with medication-overuse headache reported greater headache-related disability, escape and avoidance responses indicative of fear of pain (like taking medications at the first sign of pain and ceasing activities at the first sign of pain), and use of combination medications for headache (109).
Patients with migraine demonstrate patterns of neuroticism and introversion scores when assessed by the Minnesota Multiphasic Personality Inventory relative to controls (74). Neuroticism scores rose with a greater weekly headache duration in migraineurs (74). The Minnesota Multiphasic Personality Inventory also rated migraineurs as less calm, less able to relax, and more likely to be irritable than controls (74). Perhaps as a result of these psychological differences, or due to the presence of headache, migraineurs are more likely to respond to their symptoms with internal tension in response to work-related or other stressors (74). Furthermore, certain personality characteristics could interact with a patient’s tendency to overuse medication for headache. Using the MMPI-2, patients who did not cease medication overuse following intervention showed higher scores on the neurotic triad, which includes an elevation on the depression, hypochondria, and hysteria scales (26).
Children with headache syndromes are not immune to psychological factors. Psychological profiles of 11- to 12-year-old children with migraine have demonstrated greater levels of internalization and somatic symptoms, in addition to a greater possibility of social and family difficulties relative to peers without headache syndromes (16). Children with tension-type headache also demonstrate more somatic symptoms and greater likelihood of family problems than peers without headache (16). A significant association has been observed between early somatic disorders and the persistence of idiopathic headache, as well as between the presence of psychiatric illness at the end of study follow-up and the persistence of headache in preschool-aged children (19). The same study concluded that “life events” were influential (though not to the point of statistical significance) in the evolution of headache in some of the study population.
Another potential factor in headache’s psychological and functional etiology is sleep disruption. Although the relationship between a sleep disorder and a headache syndrome is unclear and probably complex, changes in duration and sleep quality can affect headache syndromes (116). Petit and colleagues hypothesized that sleep deprivation-induced transcriptional changes may trigger migraine by reducing glycogen availability, which slows clearance of extracellular potassium and glutamate. Inadequate astrocytic glycogen turnover may be one of the mechanisms linking migraine, mood disorders, and sleep (115). Even “moderate” sleep problems have been associated with headache (odds ratio 3.60, 95% CI), with the association increasing as the sleep disturbance worsens (24). The association between headache and sleep disturbances is strongest for headaches that occur during the night or early morning, not including hypnic headache. Sleep fragmentation, insomnia, and hypersomnia all have a relationship to headache syndrome exacerbation (78).
Although the role of dietary factors in migraine is not well understood and may be overrated, some research suggests it may be important. Commonly reported migraine triggers include wine, cheese, chocolate, and processed meats (60). In a study using a large, nationally representative sample of women, the results found no differences in dietary intake among women with and without migraine. However, among normal-weight women, those with migraine had reduced dietary quality (55). Another study found that lower sodium intake was associated with a decreased risk of headache (07). Physical exercise has also been considered effective for treating migraine (84). The exact mechanism for this association is unknown. Additionally, obesity has been linked with the prevalence and frequency of migraine in both adults and youth (148).
Although the relationship of headache to psychological stress is more commonly reported, association with comorbid medical conditions has been postulated as a possible pathogen. In a large population of American adults, 88% of those subjects reporting a severe headache in the last 3 months also had another comorbid medical condition, compared with only 67% of those subjects not reporting recent severe headache. For males, the most commonly reported comorbid conditions were lower back pain (53%), neck pain (39%), and hypertension (31.7%). In females, the most common comorbid conditions were low back pain (51%), menopausal problems (51%), and neck pain (34%) (139).
Psychological factors and disorders are frequently comorbid with headache, including stress, depression, and anxiety. Other commonly reported psychiatric disorders include dysthymic disorder, panic disorder, somatoform disorders, and adjustment disorders (Headache Classification Subcommittee of the International Headache Society 2004).
Substantial comorbidity exists between headache and depression, although it is not always clear whether headache precedes or follows depression (136). Epidemiological work by Breslau and colleagues found a lifetime prevalence rate of major depression in 40.7% of patients with migraine and in 35.8% of patients with other severe headaches (32). Both of these percentages are more than three times higher than in controls. Bidirectionality of headache and depression, however, differed between the two groups. Migraine predicted first onset of depression and depression predicted first onset of migraine in patients with migraine, suggesting that migraine can lead to depression and depression can lead to migraine in these patients. Patients with severe headache differed in that the severe headache predicted first onset of depression but not the other way around, suggesting that for these patients, depression can occur as a reaction to migraine but not as a cause.
Migraine with major depressive disorder is frequently complicated by an anxiety disorder (135). It has been suggested that anxiety generally precedes the occurrence of the migraine and that migraine is followed by depression. Anxiety may appear as early as childhood and serves as a risk factor for developing migraine. Subsequently, after an individual begins to suffer with migraine, he or she is at risk for developing depression. A study by Seng and colleagues provided continuing evidence that anxiety and depression are not only migraine comorbidities but that among people with migraine, the presence of even relatively small elevations in levels of depression and anxiety are associated with higher migraine frequency and migraine-related disability (132). People with migraine who experience depressive symptoms are at a disproportionate risk for chronic migraine.
Due to the high comorbidity of depression and headache, it is important to recognize features of major depression in patients with headache syndromes. In such cases, concurrent treatment of depression should be attempted with antidepressants or psychotherapy. Whenever possible, treatment choices that may be beneficial for both conditions should be considered. In large-scale population-based studies, migraineurs were 2.2 to 4 times more likely to suffer depression, often felt to be a bidirectional association (32; 30). An article looking at patients with depression and migraine suggested that as little as a single day of behavioral training in psychological flexibility improved headache outcomes, and it called for further research to be done on the subject (50).
In a cross-sectional study of 199 individuals with head pain, there was a negative correlation between aspects of psychological flexibility when compared with head pain and depression (06). Aspects of psychological flexibility that were shown to be significant in coping with pain and depression included general acceptance, pain acceptance, and committed action.
Headache disorder is among the most common medical complaints worldwide. “Head pain” was the fifth leading cause of emergency department visits overall in the United States and was among the top 20 reasons for outpatient office visits (137). A 1-year prevalence of 26% for tension headache of 14% for migraine was estimated globally, higher among female and individuals aged between 20 and 50 years of age (65). The 2011 National Health Interview Survey interviewed 101,875 adults from 39,509 households and found that overall age-adjusted prevalence of severe headache or migraine in the previous 3 months among adults aged 18 or older was 16.6% (10.8% for males and 22.3% for females) (National Center for Health Statistics 2011). In Norway, comparing the time periods of 2017 to 2019 and 2006 to 2008, the 1-year prevalence of tension-type headache was 20.7% versus 15.9%, migraine was 11.1% versus 12.0%, and medication overuse headache was 0.3% versus 1.0% with high risk in young age, female, depression or anxiety (67). Since the declaration of COVID-19 as a pandemic, headache was the most common reported symptom in 32.3% of 906 healthcare workers, and depression, anxiety, stress, and PTSD were significantly associated with the presence of physical symptoms (39).
In children and young adults aged 7 to 21 years, tension-type headache occurs with a prevalence of 20% (25% for females and 14% for males). Over the past 4 decades, the incidence of migraine with aura in 7-year-old children has increased from 5.2 per 1000 person-years in 1974 to 41.3 per 1000 person-years in 2002. Likewise, the increase in the rates of migraine without aura was from 14.5 per 1000 person-years in 1974 to 91.9 in 2002. It is not yet clear if this large increase in incidence can be attributed to changes in children's lifestyles (15).
Finally, it is difficult to determine the number of instances in which psychological factors are primarily implicated in headache. Further complicating etiologic data are that no studies exist regarding the incidence or prevalence of conversion headache.
Although no specific psychological methods of prevention are known, many of the factors below have been observed to predict headache. Those factors should be prevented or mitigated. Aromaa and colleagues identified early life factors that predicted headache in a sample of children from 1443 families (17). They found that the mother’s assessment of poor feeding habits and poor health of the infant was predictive of childhood headache. Depression and sleeping difficulties in the toddler were strong predictors of later headache pathology. Other predictors included headache in the mother or other family member, and, in the child, travel sickness, nocturnal enuresis, concentration difficulties, behavioral problems, unusual tiredness, and high sociability further predicted childhood headache.
Risk factors in the adult include genetic predisposition to headaches, personality deficits (traditional "migraine personality" of repressed hostility, dependency, rigidity, perfectionism, and obsessive-compulsive behaviors), emotional instability, and exposure to numerous stressors (stressful occupation, stressful family life, involvement in many stressful activities). Waldie and Poulton differentiated migraine headache from tension-type headache psychological risk factors (151). Migraine appeared to be related to maternal headache, anxiety symptoms in childhood (and full anxiety disorders in adolescence), and stress reactivity personality traits by 18 years of age, whereas tension-type headache was significantly associated with neck or back injury in childhood. One of the most detrimental risk factors for tension-type headache is the presence of daily hassles or constant, trivial daily stressors (106). The perceived severity of minor daily hassles emerged as a significant predictor of headache frequency (56).
Posttraumatic stress may also be a risk factor or predictor of headache disorder. Symptoms of posttraumatic stress disorder are more frequently observed in patients with recurrent headaches than in the general population (47). Moreover, Sherman and colleagues found that posttraumatic stress disorder symptomatology was significantly associated with pain, disability, and coping difficulties (134). Clinical posttraumatic stress disorder was found in 25% of headache patients (both episodic migraine and chronic daily headache sufferers), which is significantly more than in the general population, where only approximately 8% develop posttraumatic stress disorder (112). Additionally, headache-related disability was significantly greater in patients with episodic migraine and posttraumatic stress disorder as compared to those without posttraumatic stress disorder. However, those with chronic daily headache did not show this difference, possibly due to higher baseline levels of disability.
Combat-related posttraumatic stress disorder, in particular, has been found in a large number of veterans returning from war and is related to higher incidences of headache. Afari and colleagues studied veterans at the VA San Diego Healthcare System and found that both posttraumatic stress disorder and physical injury are predictors of headache in veterans (03). These findings suggest the need for comprehensive treatments for headache and posttraumatic stress disorder.
Considerable research has highlighted the relationship between abuse and headache. The long-term health effects of childhood victimization and intimate partner violence are substantial (82; 49). For example, not only are abuse survivors at a higher risk for mental health problems, such as depression and posttraumatic stress disorder, but also for physical health issues (82). This is such a widespread problem that in 1995 the American Medical Association classified family violence as a “major public health problem” (08). Finestone and colleagues determined that women in a sexual abuse support group reported more pain and frequented doctors’ offices more often than a comparison group (59). In addition, research has associated abuse with headache. Specifically, Domino and Haber reported that 75% of patients with chronic headache were hospitalized compared to 25% of the nonabused sample (51). Chronic pain has a significant association with abuse history, and this leads not only to incredible healthcare costs, but significant losses in work productivity as well (34; 129).
It may not be surprising that significant mental and physical health concerns are associated with physical and sexual abuse, but the effects of emotional and verbal abuse are not as widely known. The effects of emotional abuse in childhood may be more long-lasting than other more obvious types of abuse (146). These effects may present not only in psychiatric sequelae but also in earlier-onset chronic daily headache and headache-related disability (143). This association with headache is maintained even when factors of depression and anxiety are taken into account.
Intimate partner violence in adulthood manifests itself in physical aggression, forced sexual intercourse and other forms of sexual abuse, psychological mistreatment, and controlling behavior (87). Living with intimate partner violence can yield outcomes associated with both somatic and psychological health concerns (49). Not only does intimate partner violence serve as a risk factor for increased headache and other types of chronic pain, but it is also correlated with factors such as breathing problems, lack of appetite, antidepressant use, sleep issues, and difficulty with concentrating and decision making (49). These additional symptoms are commonly noted in patients with headache and with or without a history of intimate partner violence, making the specific relationship difficult to decipher but nonetheless important to access in the headache population. Individuals who live with intimate partner violence are under chronic stress conditions that impact quality of life, limit daily activities, and decrease sense of well-being and self-confidence (68; 45; 75). Unfortunately, this population has also been associated with decreased social support, perhaps from the social isolation and sense of embarrassment experienced by victims. Furthermore, the intimate partner violence population is also at greater risk for substance use (42; 45). As such, it may be even more important to monitor the dangers of medication overuse headache in those with intimate partner violence. Taken together, these findings indicate a crucial need to identify not only a history of physical and sexual abuse, but also emotional and verbal abuse and neglect in the screening process of patients presenting with headache. Referral for coordinated psychological services is particularly important for such patients.
Conversion headaches should not be classified with headaches related to psychosis or delusional states or hypochondriasis. A conversion headache may be differentiated from the head pain described by the psychotic patient because the patient invariably displays other manifestations of psychosis (tangential thinking, hallucinations or delusions, loose associations, and asocial behaviors). The hypochondriacal patient will be noticeably anxious, not only about the headaches, but about many additional body functions that he or she fears are malfunctioning; the patient with conversion headache will usually only complain about headaches. Patients with somatization disorders also have numerous complaints affecting many organ systems (152).
Many patients with primarily psychological headaches are overly concerned about serious disease or brain tumors. Although most serious diseases associated with headache are rare, the physician must be alert to the possibility of headache-related brain tumors. A distinguishing feature of brain tumor headaches is the appearance of a headache that occurs for the first time in middle age or later, or the appearance of a new headache in a patient with chronic headache. In such cases, diagnostic tests, such as a contrast-enhanced CT scan or an MRI, are indicated.
It is important to consider psychiatric comorbidities in the face of a headache syndrome.
Medication overuse headache is a largely underdiagnosed health condition and is now the third most frequent type of headache (48). Medication overuse headache is defined as occurring when a headache sufferer experiences headache for 15 or more days per month and is overusing medication for pain (71). Additionally, in order to be considered a medication overuse headache, within 2 months of discontinuation of the overused medication, headache must revert to its previous episodic pattern (71). Although all medications prescribed for treatment of headache can cause medication overuse headache (44), the most commonly overused headache medications are triptans, opioids, and analgesics, or any combination, thereof (136).
The proportion of chronic daily headache sufferers in the general population who meet criteria for medication overuse headache is about 30% (136). A pilot study examining tertiary headache clinics reported that 85% of headache patients were overusing medication (88). Interestingly, Zeeberg and colleagues showed that 45% of patients with chronic daily headache and high medication use, treated for 2 months with medication withdrawal alone, showed significant improvement in their headaches (159). Peak prevalence for medication overuse headache in women is in their mid-50s, with 5% of women in this age range meeting the diagnostic criteria for medication overuse headache (43).
A study of French patients with either migraine or medication overuse headache indicated that those patients with medication overuse headache were more likely to suffer mood or anxiety disorders (120). In a case-control study, patients with medication overuse headache showed a high rate of emotion regulation difficulties, depression, and anxiety compared with healthy controls (98). However, it remains unclear if psychiatric comorbidity should be considered as a risk factor for the worsening of headache syndromes, or rather as a risk factor for medication overuse, which contributes to worsening of headache frequency and risk of chronic daily headache (120).
The most important part of headache diagnosis is the history. Four brief communication methods can help this process: empathy, patient education, elicitation of patient perspective, and attention to nonverbal communication (130). These brief communication strategies can be accomplished by clinicians in general, not just psychiatrists and psychologists. There is evidence that these techniques improve outcome, compliance, and patient satisfaction (130).
All patients with headache should receive a complete physical and neurologic examination, even if the headaches are believed to be psychogenic. Appropriate diagnostic studies, such as a CT scan, an EEG, or possibly an MRI, may be necessary to rule out organic causes or potential serious diseases. Most patients with headache have normal results.
If the provider feels that psychological influences are causing the headache, psychological testing may help confirm the hypothesis. The Minnesota Multiphasic Personality Inventory (MMPI-2, MMPI-2-RF) and the Millon Behavioral Medical Diagnostic (MBMD) are often useful in identifying and treating psychological factors in patients with headache. Patients with conversion headaches typically demonstrate a satisfied indifference in spite of bitter complaining, bizarre and dramatic descriptions of headache pain, and angry denial of any emotional difficulties (104).
Other measures may be used to detect specific levels of depression or anxiety. The Beck Depression Inventory provides a measure of the presence and degree of depression. The State-Trait Anxiety Inventory evaluates the presence of anxiety both at the time of assessment (state anxiety) and as an enduring personality construct (trait anxiety). The Migraine Disability Assessment Scale (MIDAS) identifies the impact of headache on functioning in a range of different areas. These tests may be helpful in detecting stress, anxiety, and tension associated with common headaches or in revealing anxiety associated with a conversion mechanism.
In young children, identification of idiopathic headache is challenged by the absence of a clear, clinical definition of the condition (18).
The complicated interplay of physiology, neurochemistry, and environment on headache lends itself perfectly to a multidisciplinary approach. In addition to providing headache evaluation, long-term treatment, and maintenance of gains, psychological services can also help prevent episodic headaches from becoming chronic by providing life management and coping skills (124). Various groups of patients with headache should be considered for referral for more focused psychological services. These include those with existing comorbid psychological disorders or self-disclosed history of trauma or abuse; those with limited coping mechanisms and/or support systems; patients who seek to gain control over their headaches outside of medications; and those who are treatment resistant or do not get anticipated benefits from medical/pharmacological treatment. The most efficacious treatments include relaxation, guided imagery, mindfulness meditation, biofeedback, and cognitive behavioral therapy. In addition, methods of psychoeducation, stress management, behavioral activation, and prevention offer skill sets that can be utilized long after the client discontinues therapy. Benefits of incorporating psychological care in the treatment plan of patients include improving patient self-efficacy as active members in their own care, streamlining the communication between physicians and patients, and providing patients with a thorough treatment plan that will address the far-reaching effects of headache on quality of life. Psychotherapy and biofeedback are appropriate supplements in not only the treatment of pain, but also in prevention, providing patients with an effective skill set to manage their lives and cope with pain (46). A study by Probyn and colleagues showed that self-management interventions such as CBT and mindfulness and educational components are more effective than usual care in reducing pain intensity, mood, and headache-related disability for migraine and tension-type headache sufferers (119). Thus, implementing behavioral medicine principles may not only help to supplement medical treatment in the short-term, but also in the long-term care of headache patients. Lipchik and colleagues provide a targeted review of empirically validated psychological intervention (94).
Not only do psychological factors figure prominently into the course and progression of headache disorder, but these factors also significantly impact the headache sufferers’ health-related quality of life. Health-related quality of life issues relate to the impact that health issues and treatments have on patients’ functioning and well-being, and should be considered in any thorough discussion of headache treatment. Health-related quality of life (HRQoL) is an aspect of overall quality of life that includes an individual’s health state and physical and mental health status (38). So, although the severity of headache symptoms is an important factor in HRQoL, psychological factors are also prominent in influencing HRQoL and headache-related disability (144). Headache-related disability is closely associated with HRQoL, yet it is also distinct. According to the World Health Organization, a disability is a restriction or lack of ability to perform an activity within the range considered normal for most people (157). Generally, improvements in health status equate to improved HRQoL and reduced headache-related disability (95). Psychotherapy and cognitive behavioral interventions aimed at promoting effective coping can improve quality of life across headache disorders.
Learning effective coping strategies can be considered an integral part of headache treatment and a key component in improved prognosis. Lake has identified several coping styles that are considered adaptive when managing headache pain (89). These include a balanced use of distraction and body awareness, proactive (as opposed to reactive) coping (in other words, making plans in advance on how to deal with different situations), balanced interpersonal discussions of pain, acceptance of having pain, and commitment to setting goals and engaging in activities, regardless of pain. In fact, research by Ciere and colleagues suggests that perceptions of goal hindrance and attainability because of headache may have a more negative effect on mood than headache per se (41). This suggests that helping patiets with headache to manage goal-oriented activities can have a beneficial effect on mood, even if goals have to be modified, thereby improving headache patients’ HRQoL and ultimately prognosis.
Certain patterns of perception and cognition such as catastrophizing, locus of control, self-efficacy, and explanatory style have emerged in the headache literature as having value for predicting outcome. Coping strategies directed at modifying these particular types of perceptions and cognitions are essential to improving both health-related quality of life and prognosis.
Catastrophizing is a psychological response to pain that has been associated with impaired functioning and reduced quality of life across a variety of chronic pain disorders (110). As might be expected, both anxiety and depression significantly impact headache sufferers’ health-related quality of life (91); however, catastrophizing was found to be an independent and stronger predictor of health-related quality of life than either anxiety or depression (73). Catastrophizing intensifies the possible negative impact of pain and exaggerates helplessness (73). This usually results in patients feeling powerless to participate actively in managing their pain (73). Bond and colleagues found that those who had clinical levels of catastrophizing had nearly 4-fold greater odds of having chronic migraine compared with those who did not have clinical levels of catastrophizing (25). Other variables associated with catastrophizing included higher BMI, longer migraine attack durations, greater headache-related impact, higher levels of cutaneous allodynia, lower headache-management efficacy, and more symptoms of depression and anxiety. Thus, catastrophizing can have considerable negative impact on various aspects of HRQoL and overall prognosis. Behavioral migraine management has been shown to decrease catastrophizing in patients with migraine and increase positive coping as compared to drug therapy alone (133).
Fear of pain, a concept closely associated to catastrophizing, was found to be a significant factor in headache-related disability among patients with migraine. Black and colleagues suggested that the early attention to and addressing of fear of pain may reduce the likelihood of headache chronification and disability (21).
Explanatory style is a habitual way of explaining life events. Holding a pessimistic explanatory style can predispose people to physical illness and lead to deficits, such as learned helplessness, passivity, depression, poor problem-solving skills, low self-esteem, poor immune functioning, and higher morbidity (114). The dimensions of explanatory style include stable versus unstable, global versus specific, and internal versus external. A study conducted by Dua showed that internal attribution for negative events, ie, attributing a negative event to personal causes, was the only explanatory style that predicted headache, and headache was the only physical health problem related to internal attribution (52). In considering work in mindfulness for chronic pain, it is of no surprise that detaching or taking pain less personally might be related to greater reduction in headache pain (90). Furthermore, the tendency to blame oneself for headache pain can cause physiological stress that can further exacerbate an existing headache condition.
Positive locus of control refers to the extent to which the patient believes that headache episodes and headache relief are controllable. Typically, this is broken down into three categories: internal, or the belief that headaches are influenced by personal actions; healthcare professional, or the belief that professionals influence headache pain and relief; and chance, or the belief that headaches are due to pure chance (123). A sense of personal self-efficacy, or confidence in one’s ability to take actions that prevent or manage headache episodes, enhances adaptation to headache pain (62). Headache patients with positive self-efficacy are more likely to actively work to prevent and manage pain, develop increased pain tolerance, divert attention away from pain rather than dwell on it, attribute bodily sensations to benign causes rather than worry about them, display fewer pain behaviors, and engage in greater levels of physical activity. Additionally, these patients are less likely to have psychological or stress responses that increase pain chronicity. Overall, it has been found that locus of control beliefs and perceived self-efficacy explain individual differences in headache disability above and beyond headache severity. Perceived loss of control may be the central experience that impacts quality of life for the headache patient, and psychotherapeutic interventions in this regard have been suggested (142).
Psychotherapy. Although different forms of psychotherapy can be used to help headache patients gain greater perspective on their headache condition, better manage stress that may be contributory, or learn more adaptive coping skills, cognitive behavioral therapy has been more well-researched in the treatment of headache than any other form of psychotherapy. Cognitive behavioral techniques can help patients change their feelings and achieve a greater sense of control by changing their thinking and coping strategies (81). Cognitive behavioral therapy has the advantage of effecting change in a relatively short period of time. Focusing on the thinking process enables interventions that can make the headache patient a more active participant in the treatment process. A study by Christiansen and associates found that a combination of 10 group therapy and 3 individual cognitive behavioral therapy sessions yielded both medical and psychological benefits – reducing headache frequency and intensity while also reducing catastrophizing (40).
Although cognitive behavioral therapy tends to be underutilized with pediatric headache populations, Ernst and colleagues, working with 10- to 17-year-olds, found that supplementing standard medical practice with cognitive behavioral therapy (8 weekly treatment sessions and two booster sessions) resulted in fewer headache days and improved quality of life (no or minimal disability) at the 1-year follow-up (54). These gains were superior to those made by a control group that received headache education.
Additional psychotherapeutic approaches have shown promise in working with headache patients. Acceptance and Commitment Therapy (ACT) is a mindfulness-based approach that encourages the observation and awareness of symptoms but reduces their impact by making a commitment to move forward rather than spending effort on cognitively disputing them (100; 50; 138)
Positive Psychology is more of a philosophy and evidence-based theoretical orientation than a formalized psychotherapeutic approach (131; 113). Rooted in cognitive behavioral therapy, it places an emphasis on strength-building by encouraging active steps toward well-being despite the presence of physical pain. Like Acceptance and Commitment Therapy, Positive Psychology places its focus elsewhere than the pain, while not rejecting the fact that headache is a part, but not the entirety, of one’s definition of self.
Biofeedback. Biofeedback is a process that enables an individual to learn how to change physiological activity to improve health and performance (20). Patients learn skills that enable them to directly alter physiological states. During training sessions, the feedback on the computer screen provides the patient with concrete evidence of internal changes, thus, supporting the direct relationship between thoughts, feelings, and behavior and the impact on the body. Both electromyographic biofeedback (which measures the electrical activity generated by a muscle or muscle group) and thermal biofeedback (which measures peripheral skin temperature as an indirect measure of peripheral blood flow) have shown significant efficacy in the treatment of patients with tension-type and migraine headaches (11). A study showed that biofeedback added to traditional pharmacological therapy reduced headache frequency and analgesic intake for medication overuse headache (122). Research provides convincing support of the effectiveness of biofeedback for various medical and psychological disorders (141). Emerging digital health technologies, including smartphones and wearable sensors, have provided new possibilities of administering biofeedback (76).
Additionally, patients with headache display a variety of irregular breathing patterns, such as very fast-paced or shallow breathing, supporting the need to train patients in diaphragmatic breathing. Each of these areas is targeted in biofeedback training, with a focus on the interplay between all physiological mechanisms and headache measures, such as frequency, intensity, and/or duration. Relaxation techniques and stress management are typically incorporated into biofeedback therapy. Biofeedback may also be used as an instrument-aided form of psychotherapy or relaxation therapy (02).
Relaxation. In randomized, controlled studies of relaxation training in children and adolescents suffering from recurrent tension-type headache, a therapist-administered relaxation approach was proven to be superior to self-help or school nurse–administered relaxation training approaches (92). Total headache activity, the number of headache days, peak headache intensity, and medication usage were significantly reduced after relaxation treatment within a 6- to 10-month follow-up period (92). Age-specific interventions are important given that children and adolescents experience an interaction between pain, depressive symptoms, and disability differently (93). Additionally, children with both episodic and chronic headache disorders who had at least two biofeedback therapy sessions were found to benefit significantly.
Meditation. Meditation, particularly mindfulness-based stress reduction (MBSR) programs, has gained attention in both headache and medical literature. Mindfulness-based stress reduction is a standardized 8-week mind/body intervention that teaches mindfulness meditation/yoga. Research has shown that mindfulness-based stress reduction is effective for chronic pain. A pilot randomized control trial showed that mindfulness-based stress reduction was safe and feasible for adults with migraines. Although the small sample size (19) did not provide power to detect statistically significant change, the interventions had a beneficial effect on headache duration, disability, self-efficacy, and mindfulness (154). In a study that examined incorporating mindfulness into treating pain with a special focus on headache, as well as in a literature review that studied potential physiological process in the brain that mediates effects of mindfulness on headache, preliminary findings suggest mindfulness may produce effects comparable to that of medication alone for patients with chronic migraine and medication overuse headache (13).
Onabotulinumtoxin A Injection. Onabotulinumtoxin A injection treatment of patients with both chronic migraine and major depressive disorder led to a significant reduction of disease severity of both chronic migraine and major depressive disorder in eight studies (04). Al-Hashel and colleagues treated patients with chronic migraine over 36 months with 155 units of onabotulinumtoxin A. They found improvement in quality of life in 81% patients and a reduction in symptoms of anxiety and depression (05).
Stephen D Silberstein MD
Dr. Silberstein, Director of the Jefferson Headache Center at Thomas Jefferson University, received consulting fees from Abbie, Curelator, Ipsen Therapeutics, Lundbeck Biopharmaceuticals, and Theranica for consulting. He is also the principal investigator for clinical trials conducted by Teva and Themaquil.See Profile
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