Address all correspondence to Dr. Kai-Dih Juang, Department of Psychiatry, Taipei Veterans General Hospital, Taipei, 11217, Taiwan.
Objective.—To investigate the frequency of depressive and anxiety disorders in patients with chronic daily headache.
Background.—There is a lack of data in the literature on the extent of psychiatric comorbidity in patients with different subtypes of chronic daily headache.
Methods.—We recruited consecutive patients with chronic daily headache seen in a headache clinic from November 1998 to December 1999. The subtypes of chronic daily headache were classified according to the criteria proposed by Silberstein et al. A psychiatrist evaluated the patients according to the structured Mini-International Neuropsychiatric Interview to assess the comorbidity of depressive and anxiety disorders.
Results.—Two hundred sixty-one patients with chronic daily headache were recruited. The mean age was 46 years, and 80% were women. Transformed migraine was diagnosed in 152 patients (58%) and chronic tension-type headache in 92 patients (35%). Seventy-eight percent of patients with transformed migraine had psychiatric comorbidity, including major depression (57%), dysthymia (11%), panic disorder (30%), and generalized anxiety disorder (8%). Sixty-four percent of patients with chronic tension-type headache had psychiatric diagnoses, including major depression (51%), dysthymia (8%), panic disorder (22%), and generalized anxiety disorder (1%). The frequency of anxiety disorders was significantly higher in patients with transformed migraine after controlling for age and sex (P= .02). Both depressive and anxiety disorders were significantly more frequent in women.
Conclusion.—Psychiatric comorbidity, especially major depression and panic disorders, was highly prevalent in patients with chronic daily headache seen in a headache clinic. These results demonstrate that women and patients with transformed migraine are at higher risk of psychiatric comorbidity.
Several large-scale community studies have confirmed the clinical impression that depressive and anxiety disorders are common in patients with headache.1,2 The term psychiatric comorbidity is now used to describe the association between psychiatric and headache disorders.3 Although chronic daily headache (CDH) is the predominant diagnosis in headache clinics and presents a major challenge to headache specialists,4 available data about psychiatric comorbidity in CDH are very limited. Previous studies have found a high percentage of depression, which was usually diagnosed by questionnaire rather than psychiatric interview, in patients with CDH.5 Even less is known about comorbidity with anxiety disorders in CDH.
Transformed migraine (TM) and chronic tension-type headache (CTTH) are the two most common subtypes of CDH.6,7 Since the conceptualization of TM, psychiatric problems have been thought to be one of the factors involved in the evolution from migraine to TM.5 However, the extent of psychiatric comorbidity in these subtypes of CDH has not been reported. The purpose of the present study was to assess the nature and extent of the comorbidity of depressive and anxiety disorders in CDH and its subtypes in a headache clinic.
PATIENTS AND METHODS
From November 1998 to December 1999, consecutive new outpatients visiting the headache clinic of Taipei Veterans General Hospital were included in this study. This hospital is one of two national medical centers in Taiwan and serves both citizens and veterans. Because most of the veterans in this hospital came from Mainland China in 1949 after the Civil War, they are older and predominantly men. The demographic data of these veterans were very different from the majority of our patients with headache, so we excluded them from the analysis. The National Health Insurance Program in Taiwan has no referral system, so all patients are self-referred.
At their initial visit to the headache clinic, all patients completed a structured headache questionnaire. A thorough headache history and neurologic examination were performed by a neurologist. Only those patients who had CDH (more than 15 headache days per month and more than 4 hours per day if untreated) at the initial visit were recruited.8 A subtype of CDH, including TM, CTTH, new daily persistent headache (NDPH), and hemicrania continua (HC), was diagnosed according to the revised criteria proposed by Silberstein et al.8
Psychiatric diagnosis was made by Mini-International Neuropsychiatric Interview (MINI) conducted by a board-certified psychiatrist who was unaware of the headache diagnoses. The MINI is a structured interview that focuses on mood and anxiety disorders. It is based on DSM-IV and ICD-10 diagnostic criteria and was shown to have high reliability with other more comprehensive structured interviews.9 Only depressive and anxiety disorders were investigated in this study. Depressive disorders included major depression and dysthymia; anxiety disorders included panic disorder, generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), and social phobia.
The Statistical Package for Social Sciences for Windows program was used for statistical analysis. Student t, chi-square, and one-way analysis-of-variance tests were used for comparisons when appropriate. Logistic regression analysis was used to control the influence of gender and age between groups. A P value of less than .05 was considered statistically significant.
A total of 435 consecutive new outpatients were recruited during the study period. One hundred four veterans were excluded. Of the 331 patients remaining, 261 (79%) had CDH, and these patients constituted the final sample. In this sample, there were 152 patients (58%) with TM, 92 (35%) with CTTH, 7 with NDPH, 5 with HC, and 5 with unclassified CDH. The demographic data and headache profiles of these patients are shown in Table 1.
The psychiatric comorbidities in CDH and its subtypes of these patients are shown in Table 2. Patients with TM had a higher frequency of depressive disorders than patients with CTTH, although the difference was not significant (70% versus 59%, P = .062). However, the comorbidity with anxiety disorders was significantly higher in TM than in CTTH (43% versus 25%, odds ratio [OR] = 2.2, P = .005). This difference remained significant after controlling for sex and age in logistic regression analysis (P = .02).
Gender was also a risk factor for both depressive and anxiety disorders in our patients with CDH. Women had a higher frequency of depressive (68% versus 42%, P<.0001, OR = 3.0) and anxiety disorders (39% versus 17%, P<.0001, OR = 3.2). The sex-specific frequency of depressive and anxiety disorders in patients with TM and CTTH is shown in the Figure 1. In patients with CTTH, the frequency of depressive disorders was significantly higher in women than in men (67% versus 36%, P = .007); the difference in the frequency of anxiety disorders between women and men was not significant (28% versus 16%, P = .223). In patients with TM, the frequency of anxiety disorders was significantly higher in women than in men (46% versus 21%, P = .041); the difference in the frequency of depressive disorders between women and men was not significant (72% versus 58%, P = .202).
The most important finding of this study is that depressive and anxiety disorders, major depression and panic disorder in particular, are very common in patients with CDH. Previous epidemiological surveys reported that in the general population in Taiwan, the prevalence of major depression was 0.8% and panic disorder was 0.2%.10,11 However, we found that more than half of our patients with CDH had concurrent major depression, and more than a quarter had panic disorder at the time they visited the headache clinic. The finding of a high frequency of panic disorder in patients with CDH has not been previously reported.
The comorbidity of panic disorder and migraine has been found in several large-scale community studies, with an OR ranging from 3 to 7.1,2,12 Many authors have suggested that a disturbance of the serotonergic system is a possible mechanism underlying the comorbidity of panic disorder and migraine.2,12,13 However, the overlapping symptoms of migraine and panic disorder may also account for the comorbidity.12 Several symptoms, such as dizziness, nausea, and vomiting, are common to both disorders. Because of the overlapping symptoms, the transdiagnostic effect makes the diagnosis of one disorder much easier if the other is also present.
Data from the previous studies of psychiatric comorbidity in CDH are summarized in Table 3. The frequency of major depression found in the present study of CDH is comparable to that found in the large-scale survey done by Mathew et al5 at a headache clinic in the United States. However, in studies conducted at European headache clinics, the frequency of depressive disorders was lower.14-16 This discrepancy may be explained by differences in the criteria for CDH used in these studies and the different populations that were served by these headache clinics. The only community-based study was our previous survey of geriatric subjects in Kinmen.17 A lower frequency of major depression (29%) was found in the Kinmen study of CDH. This finding suggests that a selection bias toward a higher frequency of depression may exist in hospital-based studies.
Table 3.—. Studies of Psychiatric Disorders in Patients With Chronic Daily Headache (CDH)
No. of CDH Cases
Mean Age, y
Criteria for Depression
Anxiety Disorders, %
TM indicates transformed migraine; CTTH, chronic tension-type headache; MMPI, Minnesota Multiphasic Personality Inventory; N/A, not available; SCID, structured interview for DSM-IIIR; MDD, major depressive disorder; GAD, generalized anxiety disorder; DYS, dysthymia; CIDI-c, Composite International Diagnostic Interview-core; HD, Hamilton Depression Scale; MINI, Mini-International Neuropsychiatric Interview.
Except for the present study, data about panic disorder can only be found in the study by Verri et al.14 The frequency of panic disorder was 4.5% in that study, similar to the frequency found in their control group of patients with low back pain. In contrast, we found that 26% of our patients with CDH had panic disorder. This discrepancy may be explained in part by the differences in the criteria for panic disorder used in the two studies. The criteria for panic disorder used in this study (ie, DSM-IV criteria) allowed a diagnosis of panic disorder in patients with less frequent attacks.18 The frequency of panic disorder should be higher in studies using the new criteria. However, the difference in the frequency of panic disorder in these two studies was too great to be explained by the change of criteria alone. In the study of the comorbidity between panic disorder and headache, the risk of panic disorder was even higher in patients with a duration of headache over 4 hours.12 The risk of panic disorder should be high in CDH. Further research is needed to assess whether there is comorbidity between CDH and panic disorder.
Compared with panic disorder, GAD was relatively infrequent in the present study. We found GAD in 5% of the patients with CDH, which is similar to the frequency found in the general population. DSM-IV criteria allow the diagnosis of GAD only in those whose anxiety is not limited or confined to depressive or other anxiety disorders.18 Therefore, the high frequency of major depression and panic disorder in our patients may have hampered the diagnosis of GAD in some of our patients. However, GAD was diagnosed in two thirds of the patients in the study by Verri et al. There may be some differences in the strategy for diagnosis of anxiety disorders between these two studies.
In our patients with CDH, the frequency of psychiatric comorbidity was higher in women, which is comparable with previous epidemiological studies. The frequency of major depression and panic disorder was 1.5 to 2 times higher in women in the general population.13 In addition, we also found that TM showed a higher comorbidity with anxiety disorders than CTTH, even after controlling for sex and age. A trend toward a higher comorbidity with depressive disorders in patients with TM than in patients with CTTH was also demonstrated. Although comorbidity with depressive and anxiety disorders is more likely to occur in patients with migraine than in patients with tension-type headache,10,11 the differences in the characteristics of psychiatric comorbidity between TM and CTTH may provide some clues to the nature of the differences between these two disorders. Evidence is accumulating that major depression and anxiety disorders, especially panic disorder, are related to serotonergic dysfunction. While migraine, but not tension-type headache, is associated with serotonergic systems, the higher frequency of major depression and panic disorder in patients with TM may indicate that TM is more akin to migraine than to tension-type headache.
Selection bias in a clinical setting is a limitation in this study. Patients with major depression and panic disorder tend to seek medical help and to disproportionately utilize the health care system. Therefore, the frequency of these disorders is higher in medical settings than in the general population.19 However, the frequency of major depression and panic disorder in this study was much higher than in general medical settings.19 It is unlikely that the high psychiatric comorbidity found in these studies is merely a reflection of selection bias.
In conclusion, the frequency of major depression and panic disorder in patients with CDH at our headache clinic was very high. Women had a higher risk of psychiatric comorbidity. Anxiety disorders were significantly more frequent in patients with TM than in those with CTTH. These findings should alert the clinicians to pay more attention not only to major depression but also to comorbid panic disorders when treating patients with CDH. In addition, our results may shed some light on the serotonin hypothesis of the pathogenesis of migraine, depression, and panic disorder. Based on the present data, a community-based study appears to be warranted.
Acknowledgment: This study was supported by a grant from Taipei VGH (VGH-321).