Headache and Psychiatric Comorbidity

November 1, 2004

Migraine affects approximately 12% of the population, and a high percentage of these patients have comorbid psychiatric disorders. Knowing more about the interaction between headache and psychiatric factors can assist in evaluating and treating these patients.

It is clear that comorbid factors are significant in the development and maintenance of headaches (Lipton and Silberstein, 1994). Originally coined by Feinstein (1970), the term comorbidity is used to refer to the greater than coincidental association of two conditions in the same individual. When the relationship between two disorders may be the result of pure chance, this is not considered to be comorbidity. It can be hypothesized that psychiatric factors and headaches may interact in three general ways: 1) etiologic, which would be extremely rare; 2) psychophysiologic or biobehavioral--in this case there is a real physiologic disorder that can be influenced by psychological factors (which is true of virtually any medical disorder); and 3) environmental or genetic risk factors that produce a brain state giving rise to both conditions (i.e., there may be some common biology underlying both conditions) (Puca, 2000; Sheftell and Atlas, in press). This last mechanism seems to be the most likely one underlying comorbidity of chronic headache and other medical disorders. Many have oversimplified the relationship between pain and psychiatric comorbidity, for example, viewing chronic pain as the cause of comorbid depression or pain itself as a form of somatic depression. However, the relationship is probably more complex and based upon common biologic mechanisms.

In this article, we will briefly look at psychiatric issues in migraine and chronic daily headache. Sufferers have daily or near daily headaches (>15 per month for more than four hours a day) not caused by other disorders. The most frequent subtype of this is transformed migraine, which is considered to be a complication of migraine. Patients with migraine and chronic daily headache seem to present multiple comorbid states (Puca, 2000; Sheftell and Atlas, 2002), which might suggest that these patients have a circular vulnerability between psychological conditions and chronic somatic pathologies. This vulnerability derives from both genetic and environmental factors and probably involves some neurotransmitter dysfunction pattern that produces the clinical variability.

Clinical Characteristics

Migraine is a common, chronic neurological disorder that affects 12% or more of the adult population in Western countries (Scher et al., 1999). It is a heterogeneous condition that results in a spectrum of disability within and among different subjects (Stewart et al., 1994). The disability of migraine can be severe and a considerable burden to the sufferer and to society. Despite significant disability, migraine is an under-recognized, under-diagnosed and under-treated condition (Stewart et al., 1994). Migraine results from altered neurochemical, electric and vascular changes in the nervous system (Goadsby, 2001; Lipton and Stewart, 1997), and although headache is the most common feature, migraine comprises more than just headache. The clinical manifestations of migraine are variable, across a broad spectrum of presentations (Moskowitz, 1990). See Figure 1 for migraine diagnostic criteria.

Transformed migraine is the most frequently seen headache syndrome at major tertiary care centers. This disorder has been variously called chronic, evolutive or mixed migraine. Patients with transformed migraine often have a past history of episodic migraine, reporting a process of transformation characterized by headaches that become more frequent over months to years with the associated symptoms becoming less severe (Sandrini et al., 1993). Patients then develop a pattern of chronic daily headache that phenomenologically may resemble that of chronic tension-type headache (few migraine symptoms), with some attacks of full-blown migraine superimposed. The second edition of the International Headache Society (IHS) classification provides criteria for chronic migraine, much stricter than the criteria for transformed migraine, which, in turn, are not included in the IHS classification (Headache Classification Subcommittee of the International Headache Society, 2004). Because most headache centers in the United States use the terms synonymously, in this article we refer to transformed migraine as defined in Figure 2.

Psychiatric Comorbidity

Migraine is an episodic disorder (<15 days per month) characterized by attacks of headache and associated symptoms. Association between migraine and a variety of psychiatric and somatic conditions has been reported in the literature since it was described as a discrete syndrome. The association between migraine, depression and anxiety has been consistently reported.

Breslau et al. (1991) found in a population study that, compared with controls, migraine sufferers are four to five times more likely to have affective disorders including dysthymia, major depression and bipolar disorder (Breslau and Davis, 1993). The same group also found that patients with migraine were three times more likely to develop depression, and patients with depression were also three times more likely to develop migraine than controls.

The same profile was found between migraine and panic disorder (PD), but patients with severe non-migraine headache did not show the same correlation: Non-migraine headache was predictive of psychiatric disorder, but the reverse was not true (Breslau et al., 2000; Merikangas, 1996; Moldin et al., 1993).

Stewart et al. (1989), in a population study examining headache occurrence and prevalence of PD, reported that male participants with PD were seven times more likely than those without the condition to report a migraine headache in the previous week. Furthermore, 9.5% of females and 5.5% of males with PD reported 25% of the total migraine headaches recorded in the one-week recall period.

Breslau et al. (2003) found a bidirectional association between depression and migraine. The researchers interviewed participants ages 25 to 55 with migraine (n=496), other headaches of comparable severity (n=151) and controls with no history of severe headaches (n=539). Participants were interviewed first in 1997, then reinterviewed in 1999. At baseline, major depression predicted the first-onset migraine during the two-year follow-up period (odds ratio=3.4); migraine at baseline predicted the first-onset major depression during the follow-up period (odds ratio=5.8). Prospective associations from major depression to severe headaches and vice versa were not significant.

In a population study, Patel et al. (in press) assessed the prevalence of major depression in individuals with migraine, probable migraine (a subtype of migraine missing just one migraine feature) and controls. The overall prevalence of major depression was 28.1% for migraine, 19.5% for probable migraine, 23.9% for migraine and probable migraine polled together, and 10.3% for the control group. The prevalence of major depression was elevated in all migraine groups compared to controls on both crude and adjusted (by age, sex, education) prevalence ratios.

Chronic Daily Headache and Comorbidity

Psychiatric issues are prominent among patients with more difficult headache problems, particularly chronic daily headache. Patients with chronic daily headache often present with a sense of emptiness, sadness and pain that may be visible even in their facial expressions. These symptoms might be common to both migraine and psychiatric disorders (American Psychiatric Association, 1995; Blumenthal and Rapoport, 2001), as shown in the Table.

Since transformed migraine, the most common form of chronic daily headache, evolves from migraine, one would expect a similar profile of psychiatric comorbidity. Studies have shown that depression occurs in 80% of patients with transformed migraine (Juang et al., 2000). The Minnesota Multiphasic Personality Inventory-2 (MMPI-2) was found to be abnormal in up to 61% of patients with primary chronic daily headache, compared with 12.2% of patients with episodic migraine (Cerbo et al., 2000; D'Amico et al., 2000; De Fidio et al., 2000). Comorbid depression often improved when the pain returned to episodic patterns.

A recent multicenter study was carried out in 10 Italian headache centers to investigate the prevalence of anxiety and depression in patients with chronic daily headache (De Fidio et al., 2000). The study investigated 219 patients. The results showed that anxiety and depression levels, in each group, were related to gender (females>males). Anxiety, but not depression, was related to the length of the chronification process. Anxiety and depression did not correlate with type of headache at onset. They concluded that chronification is a biological and psychological trait. The same group reported a triggering role of stress on the chronification process, suggesting that patients with transformed headache are characterized by a different way of reacting to stress.

Stewart et al. (2001) also suggested that stress, particularly environmental factors, may play a role on the pathophysiological mechanisms of chronic daily headache. They found that specific stressful life events, such as divorce, widowhood, separation and problems with children, were more likely to be associated with increased prevalence when compared to controls. The assessment of psychopathology in patients with chronic daily headache showed characteristic profiles of hypochondria, depression and hysteria scales of the revised version of the MMPI-2 (De Fidio et al., 2000).

Figure 3

> depicts possibilities for headache and psychiatric comorbidity, depending upon presence of disorders in Axis I to Axis III of the


. The left column shows headache accompanied by no Axis I or Axis II disorders. Treatment is very straightforward and only the headache with medication overuse, if present, must be treated. In the center column, headache is accompanied by major depression, but no Axis II disorder. Treatment is more complex but outcomes are fairly good with proper recognition and treatment of both conditions. In the right column, there are disorders on all three Axes, and the patient's treatment is most difficult with a less favorable prognosis. As one moves from left to right, patient's treatment becomes more complex and more challenging, showing the importance of recognizing the psychiatric comorbidity in such cases. Patients with disorders on all three axes with chronic daily headache and medication overuse (both over-the-counter and prescription analgesics, including mixed butalbital compounds, opiates/opioids and others) generally require intensive multidisciplinary treatment, including inpatient treatment. The latter treatment is generally best done on specialized headache units with pharmacologic and nonpharmacologic protocols.

A relationship to alcohol overuse, illicit drug use and chronic daily headache was reported by Mathew et al. (1982). They also reported the high frequency of sleep disturbances among patients with chronic daily headache.

Poor sleep is the most common complaint of many chronic daily headache sufferers. Drake et al. (1990) recorded nocturnal sleep in 10 patients with common migraine, 10 individuals with tension-type headache and 10 patients with chronic daily headache. Chronic daily headache was associated with reduced sleep, increased awakening, diminished slow-wave sleep, and rapid eye movement sleep that was decreased in amount and reduced in latency.

We recently conducted two studies assessing psychiatric comorbidities in several headache subgroups. In the first study, our sample consisted of 638 patients with chronic daily headache, broken down to 558 with transformed migraine, 69 with new daily persistent headache (i.e., sudden onset of chronic headache in the absence of secondary causes), six with chronic tension-type headache and five with hemicrania continua. We also studied 65 patients with chronic posttraumatic headache. Our control group consisted of 100 patients with episodic migraine (Bigal et al., 2002). We found the following positive associations between habits, comorbidity and chronic daily headache.

Habits. Patients with chronic daily headache have statistically significant higher levels of alcohol consumption. The highest level was observed in the new daily persistent headache group (p<0.01 against the other chronic daily headaches). A higher number of patients with chronic daily headache had the habit of smoking (p<0.05).

Self-evaluation of depressive symptoms. Patients with chronic daily headache felt depressed more frequently than migraine patients.

Self-evaluation of anxiety symptoms. All chronic daily headache groups reported higher levels of anxiety when compared to migraine patients (p<0.01).

Sleep profile. Patients with chronic daily headache had several sleep problems, contrasted with those with episodic headache, as shown in Figure 4. Overall, patients with chronic daily headache did not feel that they sleep well nor did they feel rested in the morning. Interestingly, patients with new daily persistent headache have a sleep profile similar to migraine and different from the other chronic daily headaches.

In the second study, we assessed the psychological profile of a large sample of patients with chronic daily headache seen in tertiary care (Bigal et al., 2003). We used a case-control design to study a group of 791 patients who fell into the following categories:

  • Transformed migraine with analgesic overuse (analgesic-rebound headache) (n=399)

  • Transformed migraine without analgesic overuse (n=158)

  • New daily persistent headache (n=69)

These groups were compared to two control groups:

  • Migraine (n=100)

  • Chronic posttraumatic headache (n=65)

All patients had their personality and psychopathology assessed by the MMPI-2. The occurrence of t-scores ≥65 and oe40 were analyzed by the two-sided Fischer's exact test. Analgesic-rebound headache and chronic migraine patient groups had a higher number of subjects with t-scores ≥65, when compared to the migraine group and when analyzing the following scales: scale 1 (hypochondrias), scale 2 (depression), scale 8 (schizophrenia) and scale 0 (social introversion). No differences were observed when comparing the new daily persistent headache and migraine groups. We concluded that:

  • Psychopathological factors are common in chronic daily headache patients, appearing in part to be a consequence of the chronification process;

  • Low scores in scale 9 (hypomania) might relate to the development of new daily persistent headache;

  • Different psychopathological profiles among the different subgroups of chronic daily headache do exist, and the MMPI-2 is reliable in identifying such patterns; and

  • Psychological assessment is an essential step in the evaluation and treatment of patients with chronic daily headache.Conclusions

Comorbidity is certainly a common finding in patients with migraine and other chronic headache syndromes. As with many other lifelong illnesses, conditions that control migraine and chronic daily headache are multidimensional, involving cognitive/emotional factors as well as biologic processes. The correct understanding of this mechanism, including the well-done assessment of the comorbid conditions presented by such patients, is key to implementing more effective interdisciplinary treatment. Intensity of treatment varies in terms of the complexity of illness, ranging all the way from intermittent migraine with no comorbidity to chronic daily headache with multiple comorbidities and medication overuse.


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