Background
Headache disorders are very common. In the Global Burden of Disease Study 2010 (GBD2010), tension-type headache (TTH) and migraine were found to be the second and third most prevalent disorders in the world [
1]. Additionally, the group of disorders characterised by headache recurring on ≥15 days/month affects 1.7–4 % of the world’s adult population [
2], many of them having medication-overuse headache (MOH) [
3]. Headache disorders are also disabling: in GBD2013, they were revealed as the third cause of disability worldwide [
4,
5], migraine and MOH being the substantial contributors. Also in GBD2013, depression and anxiety, both common psychiatric disorders, were ranked second and ninth highest causes of disability worldwide [
4].
Common disorders occur together (are comorbid) by chance. Depression and anxiety are comorbid with each other more than by chance [
6]. In addition, several studies point to a higher probability (2 to 4 times) of psychiatric disorders among people with migraine [
7‐
12]. Few studies have specifically considered TTH, although people with episodic TTH were found no more likely than controls to experience anxiety or mood disorders [
13], while those among a Chinese elderly population with chronic TTH were twice as likely to be suffering from depression [
14]. There is evidence associating psychiatric morbidity with medication overuse [
15], but no data on psychiatric comorbidity with MOH in the general population.
There are good reasons for wishing to establish whether or not there are associations between the common headache disorders and the common psychiatric disorders, all of them major contributors to public ill health and the burden of disability. The symptoms of comorbid illnesses are expected to summate synergistically. Comorbidities hinder management and negatively influence outcomes, more so when they are unrecognized. Comorbidity occurring more than by chance indicates that, where one disease occurs, the other should be looked for. It also suggests causal relationships or common aetiological factors, which should be elucidated.
The Eurolight project was an initiative supported by the European Commission Executive Agency for Health and Consumers (EHAC), and a partnership activity within the Global Campaign against Headache conducted by
Lifting The Burden (LTB), a UK-registered non-governmental organization in official relations with the World Health Organization. Eurolight gathered data on these disorders from over 9000 variously-selected adult participants in a questionnaire-based cross-sectional survey conducted in 10 countries in Europe [
16]. The survey included demographic enquiry and screened for headache, depression and anxiety, with diagnostic questions for migraine, TTH and MOH. We analysed the data for evidence of associations between depression and anxiety and headache type, by gender.
Discussion
The key findings were (1) a confirmation that anxiety in particular, but also depression, are comorbid more than is expected by chance with migraine, and (2) first clear evidence of similar but stronger relationships with pMOH. Anxiety but not depression was weakly comorbid with TTH.
Before we comment further on these findings, we need to recall the limitations of the Eurolight study: the full study was not entirely population-based, sampling methods differed between countries [
17], and participation rates were very low in some [
16]. We were selective here, analysing data only from samples drawn from the general population, but even so we cannot argue that the estimates of
prevalence that we made use of were reliable. Eurolight was a study of headache impact rather than prevalence [
16], and this is no doubt reflected in the reported migraine prevalence of 35.9 %, which is much higher than the global and European means [
1,
26] and only a little below that of TTH (39.4 %). The reported prevalence of pMOH (3.0 %) was also on the high side [
3]. It was not, of course, a purpose of this study to report prevalences of headache types, but we draw attention at the outset to this potential source of bias.
As for the prevalence estimates for psychiatric disorders, we found that depression affected about one adult in 20 (5.6 %), while anxiety was almost three times as common (14.3 %). Both disorders were more prevalent in females, but this gender association was much stronger with anxiety. Recent reviews have estimated the global prevalence of depression in the range 4.4–5.0 % [
27] and of anxiety in the range 4.8–10.9 % [
28], with national studies generally finding these disorders to be more prevalent in developed Western countries [
29,
30]. Therefore our estimates were in keeping with expectations, while towards their upper limits. It should be noted that HADS is a screening rather than diagnostic instrument for these disorders [
25], with a tendency to underestimate prevalence of both [
6]; we conclude, therefore, that levels of psychopathology in the sample, especially anxiety, were high. Depression and anxiety were highly comorbid with each other, as is invariably reported [
6,
31].
We found, also, comorbidity at levels greater than expected by chance between each psychiatric disorder and each of migraine and pMOH. This, almost certainly, is the explanation of the high levels of psychopathology in our sample, especially since, on the psychiatric side, the associations were stronger with anxiety. On the headache side, the associations were strongest with pMOH, but still strong with migraine. Only anxiety showed an association with TTH, and this was weak. Eurolight diagnosed only the most bothersome headache type in participants reporting more than one [
18,
22]; most people with both migraine and TTH would describe the former as more bothersome and not report the latter. While the prevalence of TTH might as a result be underestimated [
22], this could not have masked an association between depression and TTH uncomplicated by migraine.
Multiple studies have earlier found increased prevalences of depression and anxiety in people with migraine relative to those without headache [
12,
32‐
34]. Migraine and anxiety are clearly comorbid, and several studies have demonstrated, as we did, that this association is stronger than that between migraine and depression [
11,
35,
36]. However, relatively few population-based data exist on psychiatric comorbidity with TTH. Merikangas found no increased comorbidity between either depression or anxiety and TTH in a Swiss study [
7]; we were almost in agreement with her. On the other hand, the very large Norwegian HUNT study found that both migraine and non-migrainous headache (80 % of the latter being TTH) were comorbid with anxiety and depression (36).
For all headache types, these relationships became more pronounced with increasing headache frequency. The spectrum of highly-frequent headache (occurring on ≥15 days/month) includes chronic migraine, chronic TTH and MOH. Eurolight did not attempt to diagnose the first two, which cannot be done reliably in such surveys [
22], but we found strong associations with pMOH: ORs of 5.5 for depression and 7–10 (greater in males) for anxiety. Until now, no population-based studies have specifically assessed psychiatric comorbidity with MOH, although in clinical samples MOH patients frequently exhibit depression and anxiety [
37]. It has also been shown that depression and anxiety are risk factors for developing MOH in migraineurs [
38], so comorbidity is not surprising. Nevertheless, this study is the first to show it.
Most of these associations showed some evidence of a gender-relationship, being stronger in males. Although individual differences were not significant, the consistency is striking. Victor et al., in a US study, observed that males with migraine were more likely than females with migraine to report anxiety or depressive symptoms compared with the same gender without headache [
33]. However, a much earlier US study had found no gender difference in comorbidity between migraine and major depression or anxiety disorders [
39]. If such a difference should exist, we would presume that the socio-environmental and/or genetic factors explaining these comorbidities do not play exactly the same roles in males as in females.
On a clinical level, the importance of these associations is in how they might influence management. The key question is: should a physician treating a patient complaining of headache screen for comorbid psychiatric disorder? The data in the lower part of Table
3 indicate the probabilities of comorbid depression or anxiety by headache type, and are likely to be applicable to patients typically seen in primary care rather than those who have found their way to specialised clinics. A patient with migraine has a 19 % probability of comorbid anxiety, almost 7 % of depression and 5 % of both. These are certainly higher, but not dramatically so, than the 14.3, 5.6 and 3.8 % in the entire sample representative of the general population. On the other hand, comorbid psychiatric disorder, when present, adds to overall morbidity and, if not identified and itself treated, leads to unsuccessful headache management, or at least a poorer outcome. This suggests that, even in primary care where time is at a premium, there is a case for screening migraine patients with HADS. Against this it may be argued that, if anxiety – the more common comorbid disorder by a large margin – is actually secondary to the worrying headache symptoms that have brought the patient into a consultation, then treating the headache is the priority and perhaps all that is necessary. We have recently shown that interictal anxiety is an important component of the burden of migraine [
40]. In a patient with MOH, the probability of comorbid anxiety is almost 39 %, of depression 17 % and of both 14 %, which make the case for screening with HADS considerably more compelling. In TTH, the probabilities do not exceed those of the whole sample. In all cases, probabilities are higher in females than males, but this reflects the underlying prevalences of these disorders.
On a public-health level, our interest was more in how the effects of these comorbid disorders might summate. We assumed that a psychiatric disorder, when present, would add to overall morbidity and that this would be evident in the HALT analysis. We found, instead, that comorbid anxiety or depression did not add significantly to lost productive time attributable to headache. But there was a weak association – with all headache types, but most strongly pMOH – between lost productive time and the probability of depression or, less so, anxiety. We can speculate that this indicated cause: that comorbid anxiety and depression were at least in part the consequences of increasing lost productive time (or of the symptoms causing it), rather than due to underlying biological susceptibility. We have no further evidence in support of this idea.
While the Eurolight study had a number of methodological limitations, mentioned earlier, it also had several strengths. It was a European community-wide survey, sampling from ten countries [
17], of which we took six (from west, north, east, central and south Europe) that provided population-based data. It used a validated questionnaire (HARDSHIP) diagnosing headache types by applying modified ICHD-II criteria algorithmically [
19] and a widely accepted screening instrument (HADS) for psychiatric disorders [
25]. It is, for the time being, the only source of population-based gender-specific data on psychiatric comorbidity with TTH and MOH.
Acknowledgements
Part-funding for this study was received from the European Agency for Health and Consumers of the European Commission. Financial support was also provided by Lifting The Burden, a UK-registered non-governmental organization conducting the Global Campaign against Headache in official relations with the World Health Organization.
We are grateful to the members of the Eurolight Project External Evaluation Board: F Antonaci, H Kettinen, P Sàndor, J Schoenen; to the Eurolight Project’s Associated Partners: A MacGregor, G Mick, Asociacion Española de Pacientes con Cefalea, Migraine Action (UK), Migraine Association of Ireland, Nederlandse Vereniging van Hoofdpijnpatienten, European Headache Alliance, European Headache Federation, Lifting The Burden; and to the Eurolight Project’s Collaborating Partners: J Afra, M Allena, B Carugno, J-M Gérard, H Hauser, C Lucchina, G Nappi, Konventhospital Barmherzige Brüder (Linz, Austria), Neurology Group of the Spanish Society of Occupational Practitioners (AEMMT), Austrian Neurological Society (ÖGN), Finnish Migraine Association.
Competing interest
TJS, ZK and LJS are directors and trustees of Lifting The Burden. The authors declare that they have no competing interests.
Authors’ contributions
CL, CT and TJS conceived the idea for this analysis. CA was Eurolight project leader. CA, ZK, JML, CL, ML-M, DR, ERdlT and CT contributed to data acquisition. Analysis and data interpretation were performed by HT, TJS, CL, CT and LJS. The article was drafted by CL with input from TJS, CT and LJS. All authors reviewed and approved the final manuscript.