Open Access

Comorbidities of psychiatric and headache disorders in Nepal: implications from a nationwide population-based study

  • Ajay Risal1, 2,
  • Kedar Manandhar1, 2,
  • Are Holen1, 3,
  • Timothy J. Steiner1, 4 and
  • Mattias Linde1, 5Email author
The Journal of Headache and PainOfficial Journal of the "European Headache Federation" and of "Lifting The Burden - The Global Campaign against Headache"201617:45

https://doi.org/10.1186/s10194-016-0635-8

Received: 14 December 2015

Accepted: 12 April 2016

Published: 22 April 2016

Abstract

Background

Headache disorders, anxiety and depression – the major disorders of the brain – are highly comorbid in the western world. Whether this is so in South Asia has not been investigated, but the question is of public-health importance to countries in the region. We aimed to investigate associations, and their direction(s), between headache disorders (migraine, tension-type headache [TTH] and headache on ≥15 days/month) and psychiatric manifestations (anxiety, depression and neuroticism), and how these might affect quality of life (QoL).

Methods

In a nationwide, cross-sectional survey of the adult Nepalese population (N = 2100), trained interviewers applied: 1) a culturally-adapted version of the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire to diagnose headache disorders; 2) a validated Nepali version of the Hospital Anxiety and Depression Scale (HADS) to detect anxiety (HADS-A), depression (HADS-D) and comorbid anxiety and depression (HADS-cAD); 3) a validated Nepali version of the Eysenck Personality Questionnaire Revised Short Form-Neuroticism (EPQRS-N); and 4) the World Health Organization Quality of Life 8-question scale (WHOQOL-8). Associations with headache types were analysed using logistic regression for psychiatric caseness and linear regression for neuroticism. Adjustments were made for age, gender, household consumption, habitat, altitude and use of alcohol and marijuana.

Results

HADS-A was associated with any headache (p = 0.024), most strongly headache on ≥15 days/month (AOR = 3.2) followed by migraine (AOR = 1.7). HADS-cAD was also associated with any headache (p = 0.050, more strongly among females than males [p = 0.047]) and again most strongly with headache on ≥15 days/month (AOR = 2.7), then migraine (AOR = 2.3). Likewise, neuroticism was associated with any headache (p < 0.001), most strongly with headache on ≥15 days/month (B = 1.6), followed by migraine (B = 1.3). No associations were found between HADS-D and any headache type, or between TTH and any psychiatric manifestation. Psychiatric caseness of any sort, when comorbid with migraine or TTH, aggravated the negative impact on QoL (p < 0.001).

Conclusion

Headache disorders are highly comorbid with anxiety and show associations with neuroticism in Nepal, with negative consequences for QoL. These findings call for reciprocal awareness, and a holistic coordinated approach to management and in the health service. Care for common headache and common psychiatric disorders should be integrated in primary care.

Keywords

Anxiety Comorbidity Depression Headache disorders Holistic care Nepal Neuroticism Primary care Questionnaire South Asia Global campaign against headache

Background

The term “comorbidity” refers to the coexistence of any additional ailment in a person with an index disease [1]. Headache disorders such as migraine and tension-type headache (TTH) and psychiatric disorders such as anxiety and depression are all very common among general populations worldwide. Accordingly, some level of comorbidity between them will arise by chance. However, epidemiological studies over 25 years have consistently indicated that headache disorders and anxiety and depression are excessively comorbid [220], with bidirectional [6] or syndromal [7] associations. Although most such studies have selectively considered migraine [811], some have looked at TTH [12], “chronic daily headache” (CDH) [13] or headache in general [14]. Furthermore there are studies showing associations between headache disorders and neuroticism [21, 22], a personality trait closely interlinked with psychological distress [23].

Headache disorders, anxiety and depression are collectively viewed as the major disorders of the brain (MDBs) [24], each occupying a place among the top ten causes of disability in the world [25, 26]. From a public-health perspective, worrying consequences for overall disease burden arise from these disorders being comorbid. Firstly, comorbidity increases morbidity, perhaps synergistically. For example, headache associated with psychopathology has exaggerated effects on quality of life (QoL) and disability [23, 27, 28]. Secondly, comorbid disorders may be mutually aggravating. Again for example, comorbid psychiatric illnesses are risk factors for headache becoming chronic [29]. Thirdly, comorbid headache and psychiatric disorders pose significant management challenges: treatment of each may be hindered by the other, with worse outcomes likely and increased health-care liabilities [30]. Fourthly, there is the possibility of causal relationships, in either or both directions.

Most data on this subject come from the western world. However, MDBs appear to be prevalent and burdensome everywhere. The Global Burden of Disease Study 2013 (GBD2013) extrapolations to South Asia indicated that years of life lost to disability (YLDs) in this Region from these conditions were in line with global rankings [25]. Our study from Nepal, the only nationwide study in this region so far, showed high prevalences of both headache and psychiatric disorders, including a much higher prevalence of migraine than the global mean [31] and prevalences of anxiety above and of depression at the upper limit of their respective global ranges [32]. Both anxiety and depression correlated positively with neuroticism and negatively with QoL [32]. The probability of comorbidity between these disorders in Nepal, and the implications arising therefrom, are consequently matters of considerable public-health importance and of interest to health policy.

Therefore, our aims were to examine the extent to which the common headache disorders (migraine, TTH and the group of headache disorders characterised by headache occurring on ≥15 days/month) and psychiatric disorders (anxiety and depression) are comorbid in Nepal, a country with unique geocultural diversity [33], and to look also for associations between these headache disorders and neuroticism. Our objective was to establish the public-health implications of any associations discovered. Our purpose was to guide national health policy.

Methods

Ethics

This study was part of a research project addressing MDBs in Nepal [33], approved by the Nepal Health Research Council, the Institutional Review Committee of Kathmandu University School of Medical Sciences, Dhulikhel Hospital, and the Regional Committee for Health and Research Ethics in Central Norway. Informed consent was collected from all participants.

Study design and sampling

This was a cross-sectional study in which unannounced household visits were made during May 2013 by trained interviewers using structured questionnaires. In order to obtain a representative sample of the adult general population of the country, we used a multistage random cluster sampling technique to select households in all three physiographic divisions of Nepal, and, within each division, all five development regions (Far-Western, Mid-Western, Western, Central and Eastern). From each household, we randomly selected one adult aged 18–65 years. The details of the sampling and data collection procedures, including the steps taken to ensure a very high participation rate, have been published elsewhere [34].

Survey instrument

We used the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire [35], translated and culturally adapted for Nepal. It included demographic enquiry followed by modules assessing headache, psychiatric comorbidities, neuroticism and QoL.

All parts of the instrument, including these modules, were interviewer-administered.

Headache enquiry

The screening question asked “Did you have headache in the last 12 months?” Those who answered “no” were classified as headache-free and served as the reference group. Those responding “yes” were asked a series of diagnostic questions based on the International Classification of Headache Disorders (ICHD-3 beta) [36]. Participants reporting more than one headache type were requested to focus only on the most bothersome type in response to these questions. Diagnoses were made algorithmically. Participants with headache on ≥15 days/month were first separated; those who were also overusing acute or symptomatic medication for headache were diagnosed as probable MOH (pMOH), and the remainder as “other headache on ≥15 days/month”. To all other participants, the algorithm applied ICHD-3 beta criteria, with modifications, in the order: definite migraine, definite TTH, probable migraine, probable TTH. Any remaining cases were unclassifiable. In the subsequent analyses, definite and probable migraine were considered together as migraine, and definite and probable TTH as TTH. This procedure, and the necessary adaptations made to certain of the ICHD-3 beta criteria, have been described in detail earlier [31].

Assessment of psychiatric comorbidities

Imported as a module into the HARDSHIP questionnaire was a validated Nepali version of the Hospital Anxiety and Depression Scale (HADS) [37]. This scale consists of 14 items in two subscales, HADS-Anxiety and HADS-Depression, each with seven items [38]. Each item expresses the subjective experience of the respondent in the preceding week, and is rated 0–3 (3 indicating maximum symptom severity) so that the sum of each subscale has a potential range of 0–21. In accordance with the original description of HADS [38] and our validation of the Nepali version [37], a threshold of 11 on the respective subscale was taken to indicate caseness for anxiety or depression. Participants scoring above the threshold on only one subscale were regarded as cases of anxiety (HADS-A) only or depression (HADS-D) only; those scoring above 11 on both were regarded as cases of comorbid anxiety and depression (HADS-cAD).

Assessment of neuroticism

Also imported as a module into the HARDSHIP questionnaire was a similarly validated version of the Eysenck Personality Questionnaire Revised Short Form-Neuroticism (EPQRS-N) [39]. It has 12 questions, each with the response options “no” (scored 0) and “yes” (scored 1) to assess the degree of neuroticism in a respondent [40]: the sum of responses has a potential range of 0–12, with higher values indicating more neuroticism.

Assessment of quality of life

Finally imported into the HARDSHIP questionnaire was a culturally-adapted version of the World Health Organization Quality-of-Life 8-question scale WHOQOL-8 [41]. This consists of eight questions addressing perceived aspects of the respondent’s QoL in four principal domains: psychological, physical, social and environmental. Each question has five response options on a Likert scale, scored from 1 (worst) to 5 (best); the summed score has the potential range of 8–40, with higher scores indicating better QoL.

Statistical analysis

Analyses were carried out using IBM SPSS Statistics 21.

We used logistic regression analysis to examine associations between headache (all, and its different types: migraine, TTH or headache on ≥15 days/month) and psychiatric caseness (HADS-A, HADS-D or HADS-cAD). Both bivariate and multivariate analyses were undertaken with headache (or its types) as the independent variable; multivariate analyses were repeated with each of HADS-A, HADS-D and HADS-cAD as the independent variable. Odds ratios (ORs) with 95 % confidence intervals (CIs) are presented as the measure of association.

We used a general linear regression model (GLM) to identify associations between total neuroticism score and all headache or its types. The regression coefficient (B) represents the difference in neuroticism scores between participants with headache (or a headache type) and those with no headache (the reference category in both analyses).

In the logistic regression analyses as well as the GLM model, we adjusted for age (categorized 18–25, 26–35, 36–45, 46–55, 56–65 years), gender, annual household consumption (categorized ≤950, 950–1200, >1200 USD/year), habitat (urban versus rural), altitude (<2000 versus ≥2000 m) and the use of alcohol or marijuana (no versus yes). Potential interactions of headache types with demographic (age, gender) or environmental (habitat, altitude) factors in the associations with psychiatric caseness or total neuroticism score were tested by creating an interaction term (the product of the two independent variables: eg, age category*headache type) which was added to the regression model. If the interaction term reached statistical significance (p < 0.05), subgroup-specific results were derived.

We compared WHOQOL-8 scores among participants with each type of headache with or without psychiatric comorbidity, and among psychiatric cases with or without comorbid headache. We used Student’s t-test to compare differences in mean scores. We set p < 0.05 as the level of significance in all analyses.

Results

There were 2100 participants, with a participation rate of 99.6 % (males: 861 [41.0 %]; females: 1239 [59.0 %]; mean age 36.4 ± 12.8 years). The majority (1328; 63.2 %) were rural inhabitants, and over one fifth (470; 22.4 %) lived at an altitude of ≥2000 m. Well over one third (822; 39.1 %) were in the lowest category of annual household consumption. A detailed description of the sample characteristics has been reported previously [34].

Having any headache was significantly associated with HADS-A caseness (17.2 %) compared with having no headache (10.5 %; AOR 1.6; 95 % CI: 1.1–2.3; p = 0.024) (Table 1). In relation to headache types, the strongest association with HADS-A was observed for headache on ≥15 days/month (AOR 3.2) followed by migraine (AOR 1.7); there was no significant association between TTH and HADS-A (Table 1). No interaction effects were seen with any of the factors analysed.
Table 1

Logistic regression analysis showing association of headache disorders with anxiety (HADS-A)

Headache type

HADS-A caseness

p

n (%)a

OR [95 % CI]

AOR [95 % CI]

No headache (N = 306)

32 (10.5)

Reference

Any headache (N = 1794)

308 (17.2)

1.8 [1.2–2.6]

1.6 [1.1–2.3]

0.024

Migraine (N = 728)

134 (18.4)

1.9 [1.3–2.9]

1.7 [1.1–2.6]

0.013

Tension-type headache (N = 863)

121 (14.0)

1.4 [0.9–2.1]

1.3 [0.8–1.9]

0.29

Headache on ≥15 d/m (N = 161)

48 (29.8)

3.6 [2.2–5.9]

3.2 [1.9–5.4]

<0.001

aNumber (n) of cases with anxiety (HADS-A) and their proportion (%) among those (N) with the headache type; OR: odds ratio, AOR: adjusted odds ratio (adjusted for age, gender, annual household consumption, habitation, altitude and use of alcohol and marijuana), d/m: days/month

There were no significant associations between having headache and HADS-D caseness (Table 2).
Table 2

Logistic regression analysis showing association of headache disorders with depression (HADS-D)

Headache type

HADS-D caseness

p

n (%)a

OR [95 % CI]

AOR [95 % CI]

No headache (N = 306)

15 (4.9)

Reference

Any headache (N = 1794)

94 (5.2)

1.1 [0.6–1.9]

1.2 [0.6–2.0]

0.66

Migraine (N = 728)

44 (6.0)

1.3 [0.7–2.3]

1.3 [0.7–2.3]

0.49

Tension-type headache (N = 863)

36 (4.2)

0.8 [0.5–1.6]

0.9 [0.5–1.8]

0.91

Headache on ≥15 d/m (N = 161)

11 (6.8)

1.4 [0.6–3.2]

1.5 [0.6–3.4]

0.38

aNumber (n) of cases with depression (HADS-D) and their proportion (%) among those (N) with the headache type; OR: odds ratio, AOR: adjusted odds ratio (adjusted for age, gender, annual household consumption, habitation, altitude and use of alcohol and marijuana), d/m: days/month

Having any headache was significantly associated with HADS-cAD caseness (7.0 %) compared with having no headache (3.6 %; AOR 1.9; 95 % CI: 1.0–3.6; p = 0.050) (Table 3). Again the strongest association with HADS-cAD was seen for headache on ≥15 days/month (AOR 2.7) followed by migraine (AOR 2.3), and there was no significant association between TTH and HADS-cAD.
Table 3

Logistic regression analysis showing association of headache disorders with comorbid anxiety and depression (HADS-cAD)

Headache type

HADS-cAD caseness

p

n (%)a

OR [95 % CI]

AOR [95 % CI]

No headache (N = 306)

11 (3.6)

Reference

Any headache (N = 1794)

126 (7.0)

2.0 [1.1–3.8]

1.9 [1.0–3.6]

0.050

Migraine (N = 728)

64 (8.8)

2.6 [1.3–4.9]

2.3 [1.2–4.4]

0.016

Tension-type headache (N = 863)

42 (4.9)

1.4 [0.7–2.7]

1.4 [0.7–2.8]

0.34

Headache on ≥15 d/m (N = 161)

17 (10.6)

3.2 [1.4–6.9]

2.7 [1.2–6.1]

0.014

aNumber (n) of cases with comorbid anxiety and depression (HADS-cAD) and their proportion (%) among those (N) with the headache type; OR: odds ratio, AOR: adjusted odds ratio (adjusted for age, gender, annual household consumption, habitation, altitude and use of alcohol and marijuana), d/m: days/month

In tests for interaction, we found only a weakly significant effect of gender (p = 0.047) with any headache. A subgroup analysis, however, suggested that the association of any headache with HADS-cAD was specific to females (AOR 4.3 [95 % CI: 1.3–13.8] versus AOR 1.0 [95 % CI: 0.4–2.2] in males). Numbers were low in the reference group in these analyses. No significant interactions were seen with any of the headache types.

Linear regression analysis showed a significant association between all headache and neuroticism score (B = 0.9; 95 % CI: 0.5–1.2; p < 0.001). Among headache types, headache on ≥15 days/month showed the strongest association (B = 1.6; 95 % CI: 0.9–2.2; p < 0.001), followed by migraine (B = 1.3; 95 % CI: 0.8–1.7; p < 0.001); the association between TTH and neuroticism was weak, although significant (B = 0.4; 95 % CI: 0.02–0.8; p = 0.040). All these analyses were adjusted for age, gender, household consumption, habitation, altitude and use of alcohol and marijuana. Tests for interaction revealed no significant effects with regard to any headache. However, in relation to migraine, the association with neuroticism demonstrated some gender-specificity, being stronger among males (B = 1.9; 95 % CI: 1.3–2.5) than females (B = 0.8; 95 % CI: 0.1–1.4).

Tables 4 and 5 summarise the data from Tables 1, 2 and 3, presenting them from a clinical management perspective: what was the probability (expressed as a percentage and AOR) that a patient with either headache (of a specific type) or psychiatric disorder (as HADS caseness) had the other as a comorbid condition? HADS-A was the most prevalent HADS caseness comorbid with each of the headache types: a patient with headache on ≥15 days/month had almost 30 % probability (AOR 3.2) of also having HADS-A. Migraine was the most prevalent headache comorbid with each of HADS-A, HADS-D and HADS-cAD: a patient with HADS-cAD had 46.7 % probability (AOR 2.5) of also having migraine.
Table 4

Prevalence of psychiatric disorder among participants with headache, by headache type

Headache type

HADS-A caseness

(N = 340)

HADS-D caseness

(N = 109)

HADS-cAD caseness

(N = 137)

n (%)

AOR [95 % CI]

n (%)

AOR [95 % CI]

n (%)

AOR [95 % CI]

Migraine (N = 728)

134 (18.4)

1.7 [1.1–2.6]

44 (6.0)

1.3 [0.7–2.3]

64 (8.8)

2.3 [1.2–4.4]

Tension-type headache (N = 863)

121 (14.0)

1.3 [0.8–1.9]

36 (4.2)

0.9 [0.5–1.8]

42 (4.9)

1.4 [0.7–2.8]

Headache on ≥15 d/m (N = 161)

48 (29.8)

3.2 [1.9–5.4]

11 (6.8)

1.5 [0.6–3.4]

17 (10.6)

2.7 [1.2–6.1]

AOR: adjusted odds ratio (multivariate logistic regression analysis, using participants with no headache as reference and adjusted for age, gender, household consumption, habitation, altitude and use of alcohol and marijuana), d/m: days/month

Table 5

Prevalence of headache among participants with psychiatric disorder, by HADS caseness

HADS caseness

Migraine

(N = 728)

Tension-type headache

(N = 863)

Headache on ≥15 d/m

(N = 161)

n (%)

AOR [95 % CI]

n (%)

AOR [95 % CI]

n (%)

AOR [95 % CI]

HADS-A (N = 340)

134 (39.4)

1.8 [1.2–2.7]

121 (35.6)

1.2 [0.8–1.8]

48 (14.1)

3.2 [1.9–5.5]

HADS-D (N = 109)

44 (40.4)

1.3 [0.7–2.4]

36 (33.0)

0.9 [0.5–1.9]

11 (10.1)

1.1 [0.5–2.8]

HADS-cAD (N = 137)

64 (46.7)

2.5 [1.2–4.8]

42 (30.7)

1.4 [0.7–2.9]

17 (12.4)

2.8 [1.2–6.5]

AOR: adjusted odds ratio (multivariate logistic regression analysis, using participants with no psychiatric disorder as reference and adjusted for age, gender, household consumption, habitation, altitude and use of alcohol and marijuana), d/m: days/month

Tables 6 and 7 show how the effects of comorbid headache and HADS caseness interacted on QoL, being additive (reducing WHOQOL score) in almost all cases. The only exceptions were that the presence or absence of TTH made little difference to QoL in those with HADS-A or HADS-cAD. In general, the additive effects of comorbid HADS caseness were highly significant; those of HADS-cAD were strongest and those of HADS-A least strong. None of the effects of the headache types were significant although, apart from those of TTH, they were consistent; headache on ≥15 days/month had, numerically, the strongest effect (Table 7).
Table 6

Quality of life (WHOQOL scores) among participants with headache, by headache type, with and without comorbid psychiatric disorder

Headache type

WHOQOL score (mean ± SD)

HADS-A caseness

(N = 340)

HADS-D caseness

(N = 109)

HADS-cAD caseness

(N = 137)

Present

Absent

p*

Present

Absent

p*

Present

Absent

p*

Migraine (N = 728)

25.7 ± 4.1

26.9 ± 3.9

<0.001

24.6 ± 2.9

26.9 ± 3.9

<0.001

22.7 ± 3.6

27.1 ± 3.7

<0.001

Tension-type headache (N = 863)

27.2 ± 3.8

28.4 ± 3.7

<0.001

24.9 ± 3.2

28.4 ± 3.7

<0.001

24.4 ± 3.2

28.4 ± 3.6

<0.001

Headache on ≥15 d/m (N = 161)

25.1 ± 4.2

26.2 ± 3.9

0.10

24.0 ± 3.2

25.9 ± 4.1

0.11

21.6 ± 3.4

26.4 ± 3.8

<0.001

*Student’s t-test, d/m: days/month

Table 7

Quality of life (WHOQOL scores) among participants with HADS caseness, with and without comorbid headache

HADS caseness

WHOQOL score (mean ± SD)

Migraine

(N = 728)

Tension-type headache

(N = 863)

Headache on ≥15 d/m

(N = 161)

Present

Absent

p*

Present

Absent

p*

Present

Absent

p*

HADS-A (N = 340)

25.7 ± 4.1

26.5 ± 2.8

0.30

27.2 ± 3.8

26.5 ± 2.8

0.36

25.1 ± 4.2

26.5 ± 2.8

0.096

HADS-D (N = 109)

24.6 ± 2.9

26.5 ± 3.9

0.055

24.9 ± 3.2

26.5 ± 3.9

0.15

24.0 ± 3.2

26.5 ± 3.9

0.094

HADS-cAD (N = 137)

22.7 ± 3.6

24.2 ± 3.2

0.21

24.4 ± 3.2

24.2 ± 3.2

0.86

21.6 ± 3.4

24.2 ± 3.2

0.060

*Student’s t-test, d/m: days/month

Discussion

This is the first nationwide, population-based survey in any country of South Asia to explore the comorbidity of headache and psychiatric disorders, which are both highly prevalent in Nepal [31, 32]. Comorbidity occurred more than was expected by chance, at least with regard to migraine and headache on ≥15 days/month on the one hand, and HADS-A and HADS-cAD on the other, the associations thereby indicated (with AORs in the range 1.7–3.2) likely to be bidirectional. There were also significant associations between headache, especially headache occurring on ≥15 days/month, and neuroticism. There were no associations between any headache and HADS-D, and none between TTH and any HADS caseness. Additive and possibly synergistic effects of comorbid headache and HADS caseness were evident on QoL, highly significantly so when migraine or TTH was the index disorder and HADS caseness the comorbid disorder.

Before considering the implications of these findings, we would compare them with others as a test of veracity; but as we have noted, there are none from this Region. Outside South Asia, most studies exploring psychiatric associations with headache disorders have focused on migraine [311]. A Zürich cohort study first demonstrated strong relationships between migraine and both anxiety and depression [3], which were subsequently reported in the United States (US) [4, 9] and Canada [42]. Other US studies found that people with migraine had high levels of neuroticism [43, 44]. In Nepal, we found strong associations between migraine and HADS-A, HADS-cAD and neuroticism, but not HADS-D.

There is relatively little evidence regarding psychiatric associations with episodic TTH [45]. A large Swiss epidemiological study found no associations with depressive or anxiety disorders [7], and neither did we. Episodic TTH is usually a less painful disorder than migraine, and less troublesome since it lacks the range of associated symptoms that contribute to the burden of migraine [35]. Hence people with episodic TTH may not express the same extent of subjective emotional experiences as those with migraine [46].

People with chronic TTH, on the other hand, demonstrate strong psychiatric associations [47]: in the US, almost half had either a depressive or an anxiety disorder [48] while those in a Norwegian study had high levels of neuroticism [22]. We did not analyse chronic TTH specifically because it could not reliably be diagnosed by lay interviewers using a questionnaire [35], but among our participants with other headache on ≥15 days/month would have been some with this disorder. The category of headaches occurring on ≥15 days/month corresponds with what is elsewhere referred to as “CDH” [49], which has been associated with high frequencies of both depressive and anxiety symptoms [13, 50]. We found, in the Nepalese population, that headache on ≥15 days/month was associated with HADS-A, HADS-cAD and neuroticism, but not HADS-D.

Our findings, therefore, are not entirely in accord with others regarding depression. The explanation may be methodological. We found no association between HADS-D and any headache type, in line with French [27] and Norwegian studies [51] that also used HADS to establish psychiatric caseness. The studies from Switzerland [3], the US [4] and Canada [42], which found strong associations between depression and headache, instead used structured interviews based on Diagnostic and Statistical Manual (DSM) criteria [52]. A recent study from South Korea [53] obtained similar findings using the self-administered Patient Health Questionnnaire-9 (PHQ-9) [54], as did another US study [48] using the Beck Depression Inventory (BDI) [55]. Cultural factors determining how moods are expressed [56] may contribute: in many Asian countries, depression is often manifested somatically [57, 58], while HADS does not capture the somatic domains of depression so well [38]. HADS may therefore underestimate any association of depression alone with headache.

However, as was pointed out in a recent review [20] and revealed in the French study [27], depression in migraine rarely occurs alone but is almost always comorbid with anxiety. A stronger association of migraine with combined anxiety-depression than with either independently was seen in the early Zürich study [3], and similar findings in relation to the other headache types came later in Norway [51]. In our study, HADS-cAD occurred twice as often among all headache sufferers and those with migraine, and almost three times in those with headache on ≥15 days/month. Hence the association of headache with depression in our population, though not apparent in HADS-D, may have manifested in HADS-cAD. There was, however, a gender influence in this association: for any headache, the association with HADS-cAD appeared specific to females (AOR 4.3 versus 1.0 in males).

Summarising these arguments, we believe use of HADS – a screening rather than diagnostic instrument for depression – is valid among people with headache although it may underestimate caseness prevalence. We could not establish any association between headache disorders and HADS-D in Nepal, but this limitation should be taken into account.

We also note other limitations. It is a general limitation of cross-sectional studies that, while associations can be demonstrated, causality cannot. However, public-health purposes are served in the first instance by uncovering these relationships, which have important policy implications; subsequent research can investigate causation. It is a limitation of HADS that it cannot go beyond detecting caseness of anxiety or depression, which encompass heterogeneous mental disorders. This renders it difficult to identify and make provision in health-service planning for issues that might be related to particular types of these disorders. By a similar token, our headache diagnostic questionnaire captured episodic migraine and TTH, while all chronic cases were subsumed under headache on ≥15 days/month [35]. Comorbidities associated with these subtypes were likely to be different in view of their high-frequency, long-duration, intractable symptoms coupled with problems in management, but the prevalence of each would have been about 1 % or less. Categorically assessing these multiple types and subtypes would have been a cumbersome exercise requiring much greater investment. We believe that our approach, with simple validated interviewer-administered culturally-validated instruments, was a more practical option in a population with high illiteracy, and it best served our public-health purpose. Furthermore, our study had notable strengths: tried and tested methodology [3335, 59], large sample size, high participation rate and good representativeness of the diverse population of Nepal [33, 34].

Implications for Nepal

From the public-health perspective, there is reason for alarm in the high prevalences of these MDBs in Nepal. We found a clear negative impact on QoL in people with headache and comorbid psychiatric disorder. GBD2013 provides disability weights for these disorders [25], which, multiplied by prevalence, yield estimates of disability burden. Migraine, MOH, depression and anxiety are all in the top 20 causes of YLDs globally [25], while all seem to be more prevalent in Nepal than their respective global means [31, 32]. These facts, together with evidence of excessive comorbidity between headache disorders and anxiety, and indications of aggravated burden when they are comorbid, signal an urgent need for action backed by health policy. The global context is not good, either for headache, which is undertreated everywhere [60] (a failure that should not discourage attempts at remediation [26]), or for psychiatric disorders, for which only a minority of affected people receive adequate treatment in most countries around the world [61]. In Nepal, an underdeveloped country with multiple adversities [33], the challenges brought forward by these comorbid conditions are considerable; this resource-deficient country is not prepared to cope with them.

From the clinical perspective, patients with headache disorders can be expected to have an excess of psychiatric manifestations, and vice versa. Physicians in Nepal treating headache patients should be looking out among them for anxiety and depression as potentially aggravating comorbid factors likely to hinder management. Moreover, psychiatrists and others treating depression and anxiety can expect to encounter migraine and headache on ≥15 days/month at high levels. We summarise this as a need for reciprocal awareness.

We propose that a coordinated effort offers a solution from both perspectives – public-health and clinical. It requires training of health-care providers encountering headache patients to think beyond the somatic dimension: screening for both anxiety and depression, and collaborating with mental-health personnel in patient education on lifestyle, psychological treatment and behavioural strategies, may be appropriate options in addition to offering usual pharmacological interventions. This already happens to an extent in some cities where headache patients may be referred directly to psychiatrists, but these are a small minority. In the rural areas and in the high hills, such referrals are generally not possible. In these areas, and in the cities also, most headache care is and should be provided in primary care, for reasons related both to logistics and cost [60], as well as because it is feasible. In primary care is also where most depression and anxiety are encountered [62]. Bringing the management of common headache and common psychiatric disorders together under one primary-care roof, supported by educational initiatives and referral channels to specialist services, appears to be good health policy. We recommended its trial implementation in a circumscribed area as a first step, and enter a plea for urgency in this action.

Conclusion

Headache disorders, highly prevalent in Nepal, are excessively comorbid with anxiety and associated with neuroticism, and these relationships aggravate their negative impact on QoL. These findings call for reciprocal awareness, and a holistic coordinated approach to management and in the health service. Care for common headache and common psychiatric disorders should be integrated in primary care.

Abbreviations

AOR: 

adjusted odds ratio

BDI: 

Beck Depression Inventory

cAD: 

comorbid anxiety and depression

CI: 

confidence interval

CMD: 

common mental disorder

CDH: 

chronic daily headache

DSM: 

Diagnostic and Statistical manual of Mental disorders

EPQRS-N: 

Eysenck Personality Questionnaire Revised Short Form-Neuroticism

GBD: 

Global Burden of Disease

HADS: 

Hospital Anxiety and Depression Scale

HARDSHIP: 

Headache-Attributed Restriction Disability, Social Handicap and Impaired Participation

ICD: 

International Classification of Diseases

ICHD: 

International Classification of Headache Disorders

LAMI: 

low-and-middle-income

MDB: 

major disorders of the brain

NTNU: 

Norwegian University of Science and Technology

OR: 

odds ratio

PHQ: 

Patient Health Questionnaire

pMOH: 

probable medication-overuse headache

QoL: 

quality of life

SPSS: 

Statistical Package for Social Science

TTH: 

tension-type headache

US: 

United States

WHOQOL-8: 

World Health Organization Quality-of-Life 8-question scale

YLD: 

year of life lost to disability

Declarations

Acknowledgements

This project was funded by grants from Samarbeidsorganet, the Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology (NTNU). The study was a research collaboration between NTNU Department of Neuroscience, Kathmandu University School of Medical Sciences (KUSMS), and Lifting The Burden, a UK-registered non-governmental organization directing the Global Campaign against Headache in official relations with the World Health Organization. We thank Dhulikhel Hospital, Kathmandu University Hospital, for assistance and logistic support during the planning phase. We are grateful to Professor Grethe Albrektsen, Professor in Medical Statistics, Faculty of Medicine Department of Public Health and General Practice, NTNU, for advice in statistical analysis.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors’ Affiliations

(1)
Department of Neuroscience, Norwegian University of Science and Technology
(2)
Dhulikhel Hospital, Kathmandu University Hospital
(3)
Pain Unit, St Olavs University Hospital
(4)
Division of Brain Sciences, Imperial College London
(5)
Norwegian Advisory Unit on Headache, St Olavs University Hospital

References

  1. Feinstein AR (1970) The pre-therapeutic classification of co-morbidity in chronic disease. J Chronic Dis 23(7):455–468View ArticlePubMedGoogle Scholar
  2. Pompili M, Serafini G, Di Cosimo D, Dominici G, Innamorati M, Lester D, Forte A, Girardi N, De Filippis S, Tatarelli R, Martelletti P (2010) Psychiatric comorbidity and suicide risk in patients with chronic migraine. Neuropsychiatr Dis Treat 6:81–91View ArticlePubMedPubMed CentralGoogle Scholar
  3. Merikangas KR, Angst J, Isler H (1990) Migraine and psychopathology. Results of the Zürich cohort study of young adults. Arch Gen Psychiatry 47(9):849–853View ArticlePubMedGoogle Scholar
  4. Breslau N, Davis GC (1993) Migraine, physical health and psychiatric disorder: a prospective epidemiologic study in young adults. J Psychiatr Res 27(2):211–221View ArticlePubMedGoogle Scholar
  5. Lake AE 3rd, Rains JC, Penzien DB, Lipchik GL (2005) Headache and psychiatric comorbidity: historical context, clinical implications, and research relevance. Headache 45(5):493–506. doi:10.1111/j.1526-4610.2005.05101.x View ArticlePubMedGoogle Scholar
  6. Baskin SM, Smitherman TA (2009) Migraine and psychiatric disorders: comorbidities, mechanisms, and clinical applications. Neurol Sci 30(Suppl 1):S61–S65. doi:10.1007/s10072-009-0071-5 View ArticlePubMedGoogle Scholar
  7. Merikangas KR, Merikangas JR, Angst J (1993) Headache syndromes and psychiatric disorders: association and familial transmission. J Psychiatr Res 27(2):197–210View ArticlePubMedGoogle Scholar
  8. Merikangas KR, Stevens DE (1997) Comorbidity of migraine and psychiatric disorders. Neurol Clin 15(1):115–123View ArticlePubMedGoogle Scholar
  9. Breslau N, Lipton RB, Stewart WF, Schultz LR, Welch KM (2003) Comorbidity of migraine and depression: investigating potential etiology and prognosis. Neurology 60(8):1308–1312View ArticlePubMedGoogle Scholar
  10. Wang SJ, Chen PK, Fuh JL (2010) Comorbidities of migraine. Front Neurol 1:16. doi:10.3389/fneur.2010.00016 View ArticlePubMedPubMed CentralGoogle Scholar
  11. Buse DC, Silberstein SD, Manack AN, Papapetropoulos S, Lipton RB (2013) Psychiatric comorbidities of episodic and chronic migraine. J Neurol 260(8):1960–1969. doi:10.1007/s00415-012-6725-x View ArticlePubMedGoogle Scholar
  12. Puca F, Genco S, Prudenzano MP, Savarese M, Bussone G, D'Amico D, Cerbo R, Gala C, Coppola MT, Gallai V, Firenze C, Sarchielli P, Guazzelli M, Guidetti V, Manzoni G, Granella F, Muratorio A, Bonuccelli U, Nuti A, Nappi G, Sandrini G, Verri AP, Sicuteri F, Marabini S (1999) Psychiatric comorbidity and psychosocial stress in patients with tension-type headache from headache centers in Italy. The Italian Collaborative Group for the Study of Psychopathological Factors in Primary Headaches. Cephalalgia 19(3):159–164View ArticlePubMedGoogle Scholar
  13. Verri AP, Proietti Cecchini A, Galli C, Granella F, Sandrini G, Nappi G (1998) Psychiatric comorbidity in chronic daily headache. Cephalalgia 18(Suppl 21):45–49View ArticlePubMedGoogle Scholar
  14. Samaan Z, Farmer A, Craddock N, Jones L, Korszun A, Owen M, McGuffin P (2009) Migraine in recurrent depression: case–control study. Br J Psychiatry 194(4):350–354. doi:10.1192/bjp.bp.108.054049 View ArticlePubMedGoogle Scholar
  15. Breslau N, Davis GC, Schultz LR, Peterson EL (1994) Migraine and major depression: a longitudinal study. Headache 34(7):387–393View ArticlePubMedGoogle Scholar
  16. Holm JE, Penzien DB, Holroyd KA, Brown TA (1994) Headache and depression: confounding effects of transdiagnostic symptoms. Headache 34(7):418–423View ArticlePubMedGoogle Scholar
  17. Mitsikostas DD, Thomas AM (1999) Comorbidity of headache and depressive disorders. Cephalalgia 19(4):211–217View ArticlePubMedGoogle Scholar
  18. Lipton RB, Hamelsky SW, Kolodner KB, Steiner TJ, Stewart WF (2000) Migraine, quality of life, and depression: a population-based case–control study. Neurology 55(5):629–635View ArticlePubMedGoogle Scholar
  19. Smitherman TA, Penzien DB, Maizels M (2008) Anxiety disorders and migraine intractability and progression. Curr Pain Headache Rep 12(3):224–229View ArticlePubMedGoogle Scholar
  20. Smitherman TA, Kolivas ED, Bailey JR (2013) Panic disorder and migraine: comorbidity, mechanisms, and clinical implications. Headache 53(1):23–45. doi:10.1111/head.12004 View ArticlePubMedGoogle Scholar
  21. Rasmussen BK (1992) Migraine and tension-type headache in a general population: psychosocial factors. Int J Epidemiol 21(6):1138–1143View ArticlePubMedGoogle Scholar
  22. Aaseth K, Grande RB, Leiknes KA, Benth JS, Lundqvist C, Russell MB (2011) Personality traits and psychological distress in persons with chronic tension-type headache. The Akershus study of chronic headache. Acta Neurol Scand 124(6):375–382. doi:10.1111/j.1600-0404.2011.01490.x View ArticlePubMedGoogle Scholar
  23. Boye B, Lundin KE, Leganger S, Mokleby K, Jantschek G, Jantschek I, Kunzendorf S, Benninghoven D, Sharpe M, Wilhelmsen I, Blomhoff S, Malt UF, Jahnsen J (2008) The INSPIRE study: do personality traits predict general quality of life (Short form-36) in distressed patients with ulcerative colitis and Crohn's disease? Scand J Gastroenterol 43(12):1505–1513. doi:10.1080/00365520802321196 View ArticlePubMedGoogle Scholar
  24. Gustavsson A, Svensson M, Jacobi F, Allgulander C, Alonso J, Beghi E, Dodel R, Ekman M, Faravelli C, Fratiglioni L, Gannon B, Jones DH, Jennum P, Jordanova A, Jonsson L, Karampampa K, Knapp M, Kobelt G, Kurth T, Lieb R, Linde M, Ljungcrantz C, Maercker A, Melin B, Moscarelli M, Musayev A, Norwood F, Preisig M, Pugliatti M, Rehm J, Salvador-Carulla L, Schlehofer B, Simon R, Steinhausen HC, Stovner LJ, Vallat JM, Van den Bergh P, van Os J, Vos P, Xu W, Wittchen HU, Jonsson B, Olesen J (2011) Cost of disorders of the brain in Europe 2010. Eur Neuropsychopharmacol 21(10):718–779View ArticlePubMedGoogle Scholar
  25. Vos T, Barber RM, Bell B, Bertozzi-Villa A, Biryukov S, Bolliger I, Charlson F, Davis A, Degenhardt L, Dicker D, Duan L, Erskine H, Feigin VL, Ferrari AJ, Fitzmaurice C, Fleming T, Graetz N, Guinovart C, Haagsma J, Hansen GM, Hanson SW, Heuton KR, Higashi H, Kassebaum N, Kyu H, Laurie E, Liang X, Lofgren K, Lozano R, et al. (2015) Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 386(9995):743–800. doi:10.1016/s0140-6736(15)60692-4 View ArticleGoogle Scholar
  26. Steiner TJ, Birbeck GL, Jensen RH, Katsarava Z, Stovner LJ, Martelletti P (2015) Headache disorders are third cause of disability worldwide. J Headache Pain 16:58. doi:10.1186/s10194-015-0544-2 View ArticlePubMedPubMed CentralGoogle Scholar
  27. Lanteri-Minet M, Radat F, Chautard MH, Lucas C (2005) Anxiety and depression associated with migraine: influence on migraine subjects' disability and quality of life, and acute migraine management. Pain 118(3):319–326. doi:10.1016/j.pain.2005.09.010 View ArticlePubMedGoogle Scholar
  28. Beghi E, Allais G, Cortelli P, D'Amico D, De Simone R, d'Onofrio F, Genco S, Manzoni GC, Moschiano F, Tonini MC, Torelli P, Quartaroli M, Roncolato M, Salvi S, Bussone G (2007) Headache and anxiety-depressive disorder comorbidity: the HADAS study. Neurol Sci 28(Suppl 2):S217–S219. doi:10.1007/s10072-007-0780-6 View ArticlePubMedGoogle Scholar
  29. Gambini O, Islam L, Demartini B, Scarone S (2010) Psychiatric issues in patients with headaches. Neurol Sci 31(Suppl 1):S111–S113. doi:10.1007/s10072-010-0300-y View ArticlePubMedGoogle Scholar
  30. Pesa J, Lage MJ (2004) The medical costs of migraine and comorbid anxiety and depression. Headache 44(6):562–570. doi:10.1111/j.1526-4610.2004.446004.x View ArticlePubMedGoogle Scholar
  31. Manandhar K, Risal A, Steiner TJ, Holen A, Linde M (2015) The prevalence of primary headache disorders in Nepal: a nationwide population-based study. J Headache Pain 16(1):95. doi:10.1186/s10194-015-0580-y View ArticlePubMedPubMed CentralGoogle Scholar
  32. Risal A, Manandhar K, Linde M, Steiner TJ, Holen A (2016) Anxiety and depression in Nepal: Prevalence, comorbidity and associations. BMC Psychiatry 16(1):1–9. doi: 10.1186/s12888-016-0810-0.
  33. Risal A, Manandhar K, Steiner TJ, Holen A, Koju R, Linde M (2014) Estimating prevalence and burden of major disorders of the brain in Nepal: cultural, geographic, logistic and philosophical issues of methodology. J Headache Pain 15(1):51. doi:10.1186/1129-2377-15-51 View ArticlePubMedPubMed CentralGoogle Scholar
  34. Manandhar K, Risal A, Steiner TJ, Holen A, Koju R, Linde M (2014) Estimating the prevalence and burden of major disorders of the brain in Nepal: methodology of a nationwide population-based study. J Headache Pain 15(1):52. doi:10.1186/1129-2377-15-52 View ArticlePubMedPubMed CentralGoogle Scholar
  35. Steiner TJ, Gururaj G, Andree C, Katsarava Z, Ayzenberg I, Yu S-Y, Jumah MA, Tekle-Haimanot R, Birbeck GL, Herekar A, Linde M, Mbewe E, Manandhar K, Risal A, Jensen R, Queiroz LP, Scher AI, Wang S-J, Stovner LJ (2014) Diagnosis, prevalence estimation and burden measurement in population surveys of headache: presenting the HARDSHIP questionnaire. J Headache Pain 15:3View ArticlePubMedPubMed CentralGoogle Scholar
  36. Headache Classification Committee of the International Headache Society (2013) The international classification of headache disorders, 3rd edition (beta version). Cephalalgia 33(9):629–808. doi:10.1177/0333102413485658 View ArticleGoogle Scholar
  37. Risal A, Manandhar K, Linde M, Koju R, Steiner TJ, Holen A (2015) Reliability and Validity of a Nepali-language Version of the Hospital Anxiety and Depression Scale (HADS). Kathmandu Univ Med J 50(2):115–124Google Scholar
  38. Zigmond AS, Snaith RP (1983) The hospital anxiety and depression scale. Acta Psychiatr Scand 67(6):361–370View ArticlePubMedGoogle Scholar
  39. Manandhar K, Risal A, Linde M, Koju R, Steiner TJ, Holen A (2015) Measuring neuroticism in Nepali: Reliability and validity of the Neuroticism Subscale of the Eysenck Personality Questionnaire Kathmandu. Univ Med J 50(2):156–161Google Scholar
  40. Eysenck SBG, Eysenck HJ, Barrett P (1985) A revised version of the psychoticism scale. Person Individ Difl 6(1):21–29View ArticleGoogle Scholar
  41. The WHOQOL Group (1998) The World Health Organization Quality of Life assessment (WHOQOL): Development and general psychometric properties. Soc Sci Med 46:1569–1585View ArticleGoogle Scholar
  42. Jette N, Patten S, Williams J, Becker W, Wiebe S (2008) Comorbidity of migraine and psychiatric disorders--a national population-based study. Headache 48(4):501–516. doi:10.1111/j.1526-4610.2007.00993.x View ArticlePubMedGoogle Scholar
  43. Breslau N, Andreski P (1995) Migraine, personality, and psychiatric comorbidity. Headache 35(7):382–386View ArticlePubMedGoogle Scholar
  44. Breslau N, Chilcoat HD, Andreski P (1996) Further evidence on the link between migraine and neuroticism. Neurology 47(3):663–667View ArticlePubMedGoogle Scholar
  45. Semenov IA (2015) Tension-type headaches. Dis Mon 61(6):233–235. doi:10.1016/j.disamonth.2015.03.006 View ArticlePubMedGoogle Scholar
  46. Nicholson RA (2010) Chronic headache: the role of the psychologist. Curr Pain Headache Rep 14(1):47–54. doi:10.1007/s11916-009-0087-9 View ArticlePubMedPubMed CentralGoogle Scholar
  47. Heckman BD, Holroyd KA (2006) Tension-type headache and psychiatric comorbidity. Curr Pain Headache Rep 10(6):439–447View ArticlePubMedGoogle Scholar
  48. Holroyd KA, Stensland M, Lipchik GL, Hill KR, O'Donnell FS, Cordingley G (2000) Psychosocial correlates and impact of chronic tension-type headaches. Headache 40(1):3–16View ArticlePubMedPubMed CentralGoogle Scholar
  49. Murinova N, Krashin D (2015) Chronic daily headache. Phys Med Rehabil Clin N Am 26(2):375–389. doi:10.1016/j.pmr.2015.01.001 View ArticlePubMedGoogle Scholar
  50. Juang KD, Wang SJ, Fuh JL, Lu SR, Su TP (2000) Comorbidity of depressive and anxiety disorders in chronic daily headache and its subtypes. Headache 40(10):818–823View ArticlePubMedGoogle Scholar
  51. Zwart JA, Dyb G, Hagen K, Odegard KJ, Dahl AA, Bovim G, Stovner LJ (2003) Depression and anxiety disorders associated with headache frequency. The Nord-Trondelag Health Study. Eur J Neurol 10(2):147–152View ArticlePubMedGoogle Scholar
  52. American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders (4th ed., text rev.). doi:10.1176/appi.books.9780890423349.
  53. Oh K, Cho SJ, Chung YK, Kim JM, Chu MK (2014) Combination of anxiety and depression is associated with an increased headache frequency in migraineurs: a population-based study. BMC Neurol 14:238. doi:10.1186/s12883-014-0238-4 View ArticlePubMedPubMed CentralGoogle Scholar
  54. Kroenke K, Spitzer RL, Williams JB (2001) The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med 16(9):606–613View ArticlePubMedPubMed CentralGoogle Scholar
  55. Beck AT, Steer RA, Brown GK (1996) Manual for the Beck Depression Inventory-II. Psychological Corporation, San Antonio, TXGoogle Scholar
  56. Steel Z, Marnane C, Iranpour C, Chey T, Jackson JW, Patel V, Silove D (2014) The global prevalence of common mental disorders: a systematic review and meta-analysis 1980–2013. Int J Epidemiol 43(2):476–493. doi:10.1093/ije/dyu038 View ArticlePubMedPubMed CentralGoogle Scholar
  57. Yong N, Hu H, Fan X, Li X, Ran L, Qu Y, Wang Y, Tan G, Chen L, Zhou J (2012) Prevalence and risk factors for depression and anxiety among outpatient migraineurs in mainland China. J Headache Pain 13(4):303–310. doi:10.1007/s10194-012-0442-9 View ArticlePubMedPubMed CentralGoogle Scholar
  58. Shen YC, Zhang MY, Huang YQ, He YL, Liu ZR, Cheng H, Tsang A, Lee S, Kessler RC (2006) Twelve-month prevalence, severity, and unmet need for treatment of mental disorders in metropolitan China. Psychol Med 36(2):257–267. doi:10.1017/s0033291705006367 View ArticlePubMedGoogle Scholar
  59. Stovner LJ, Al Jumah M, Birbeck GL, Gururaj G, Jensen R, Katsarava Z, Queiroz LP, Scher AI, Tekle-Haimanot R, Wang SJ, Steiner TJ (2014) The methodology of population surveys of headache prevalence, burden and cost: Principles and recommendations from the Global Campaign against Headache. J Headache Pain 15(1):5. doi:10.1186/1129-2377-15-5 View ArticlePubMedPubMed CentralGoogle Scholar
  60. World Health Organization and Lifting The Burden (2011) Atlas of Headache Disorders and Resources in the World 2011. WHO, GenevaGoogle Scholar
  61. Kessler RC, Aguilar-Gaxiola S, Alonso J, Chatterji S, Lee S, Ormel J, Ustun TB, Wang PS (2009) The global burden of mental disorders: an update from the WHO World Mental Health (WMH) surveys. Epidemiol Psichiatr Soc 18(1):23–33View ArticlePubMedPubMed CentralGoogle Scholar
  62. Risal A (2011) Common mental disorders. Kathmandu Univ Med J (KUMJ) 9(35):213–217Google Scholar

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