An International Journal of Headache

doi:10.1111/j.1468-2982.2008.01644.x

Anxiety, stress and coping behaviours in primary care migraine

patients: results of the SMILE study
F Radat1, C Mekies2, G Graud3, D Valade4, E Vivs5, C Lucas6, J-M Joubert7 & M Lantri-Minet8
1

Department of Treatment of Chronic Pain Patients, Pellegrin University Teaching Hospital, Bordeaux, 2Private Neurologist, Toulouse,
Department of Neurology, Rangueil Hospital, Toulouse, 4Emergency Headache Centre, Lariboisire Hospital, Paris, 5General Practitioner,
Rivery, 6Neurological Clinic, Salengro Hospital, Lille, 7Schwarz Pharma France, Boulogne-Billancourt, and 8Department of Evaluation and
Treatment of Pain, Pasteur University Teaching Hospital, Nice, France
3

Radat F, Mekies C, Graud G, Valade D, Vivs E, Lucas C, Joubert J-M &

Lantri-Minet M. Anxiety, stress and coping behaviours in primary care migraine
patients: results of the SMILE study. Cephalalgia 2008; 28:11151125. London.
ISSN 0333-1024
The objectives of the SMILE study were to assess anxiety, stress, depression,
functional impact and coping behaviours in migraine patients consulting in
primary care in France. General practitioners (n = 1467) and 83 neurologists
included 5417 consulting migraine patients. Of these patients, 67% were found
anxious, of whom 59% were also depressive. Patients with both anxiety and
depressive dimensions showed a profile similar to that of chronic migraine
patients (severe attacks, poor treatment effectiveness and pronounced stress,
functional impact and maladaptive behaviours). A quantitative progression in
the levels of stress, maladaptive coping behaviours and functional impact was
noted from patients with neither dimension to those with both anxious and
depressive dimensions. Stress and maladaptive coping strategies were found to
be major determinants of anxiety. Anxious and depressive dimensions were
associated with elevated consumption of acute treatments for migraine and low
treatment effectiveness. Stress and anxiety should be looked for carefully in
migraine patients. Migraine, mood disorders, coping behaviours, medical management, primary care practice
Dr F. Radat, Centre Douleur Chronique, CHU Pellegrin, 33076 Bordeaux
Cedex, France. Tel. + 33 5 5679 8711, fax + 33 5 5679 5567, e-mail
francoise.radat@chu-bordeaux.fr Received 7 December 2007, accepted 22 March 2008

Introduction
Comorbidity of migraine with diverse psychiatric
conditions has long been recognized, especially
with major depression and anxiety disorders
(particularly panic and phobia) (1), and stress is
frequently considered to precipitate and exacerbate
migraine (2). Population-based cross-sectional
studies of prevalence of psychiatric disorders
among migraineurs have found increased risks of
generalized anxiety (3, 4), panic and major depressive disorders (37). A US population-based study
reported a 2.7-fold increase in the prevalence of
depression among migraine patients compared
with non-migraine controls (8), whereas a French
Blackwell Publishing Ltd Cephalalgia, 2008, 28, 11151125

nationwide postal survey found a 1.7-fold increase

in the prevalence of anxiety and depression (9).
Moreover, several works have indicated that psychiatric comorbidity may occur before migraine
onset (4, 10) and that it may constitute a risk factor
for the evolution from migraine to medication
overuse headache (11). On the other hand, recurrent
and intense pain may lead to anticipatory anxiety,
perceived loss of control and other behavioural or
cognitive risk factors for psychiatric syndromes.
Therefore, a bidirectional chronology may exist
between migraine and psychiatric disorders (5, 7).
Results from clinical samples of migraine patients
have confirmed that migraine patients more
often suffer from anxiety and depression than
1115

1116

F Radat et al.

non-migraine patients. Moreover, these studies

have shown that patients with chronic migraine
exhibit anxiety and depression more often than
those with episodic migraine (12).
Because they add to the burden that migraine
inflicts on patients (13, 14), taking psychiatric disorders into account is warranted for adequate
migraine evaluation and management and prevention of medication overuse. The objectives of
the SMILE study were to evaluate stress, anxiety
and depression in the population of migraine
patients consulting in primary care and to analyse
the potential relationship between anxiety and
migraine severity, stress, quality of life and effectiveness of acute migraine treatments. Since there is
a relationship in migraine patients between affective disorders (depression) and emotional adjustment (15), the adjustment strategies used to cope
with migraine and their relationship to anxiety and
stress were also assessed.

Methods
Study design, patient inclusion criteria
SMILE was an office-based, observational study
carried out in France by the opinion poll institute
TNS Healthcare from November 2005 to July 2006
among general practitioners (GPs) and neurologists.
Four thousand physicians were recruited by mail or
telephone from a physician database.
Each participating physician was to include, from
the date of start of the study, the first four patients
consulting for migraine who were aged 18 years
and not currently treated with a prophylactic treatment (because one of the study objectives was to
assess prospectively the effects of migraine prophylactic agents on the impact of migraine; these data
will be reported in a subsequent article). Patients
receiving anxiolytic or antidepressant therapies
were not excluded, in order to preserve the representativeness of the study population compared
with the population of migraine patients usually
consulting in private medical practice. Only
patients fulfilling the diagnostic criteria for strict or
probable migraine according to the International
Classification of Headache Disorders (ICHD-II)
were included (16).

Study questionnaires
Physicians completed a questionnaire about
personal demography and professional activity.
Patients completed a 50-item questionnaire about

socio-demography, ICHD-II migraine diagnostic

criteria, migraine history and impact on everyday
life, existence of affective disorders, stress, coping
strategies using psychometric tests (see below), the
treatments used for treatment of migraine attacks
and their perceived effectiveness.
French validated versions of psychometric scales
were used to assess affective disorders, migraine
functional impact and coping behaviour. Anxious
and depressive dimensions of affective disorders
were measured using the Hospital Anxiety and
Depression (HAD) scale (17, 18), originally
designed for the evaluation of anxiety and depression in patients hospitalized for somatic causes (17).
The French version of the HAD scale has been
validated in patients hospitalized in an internal
medicine department (19). Scores of 8 were considered to characterize anxiety and depression. This
threshold is associated with 82% sensitivity and
94% specificity for anxiety (19) and with 7078%
sensitivity and 6880% specificity for depression
(19, 20). Stress was assessed using the abridged
form (PSS4) of the original Perceived Stress Scale
questionnaire (21), the most widely used psychological instrument for measuring the perception of
stress. Functional impact of migraine was assessed
using an abridged version (MSQ4) of the original
Migraine-Specific Quality of life questionnaire
developed to allow easy use of the questionnaire in
general practice (22, 23). Maladaptive avoidance
coping strategy was evaluated using the behavioural disengagement subscale of the Brief Coping
with Problems Experienced (COPE) inventory (24
26). Brief COPE has been validated in a population
of breast cancer patients (27). Maladaptive pain
coping strategy was evaluated using the catastrophizing subscale of the Coping Strategies Questionnaire (CSQ) (28, 29). The French version of CSQ has
been validated in patients consulting for chronic
pain (30). No formal diagnosis of anxiety or depression was made by the study physicians.

Evaluation of acute treatment effectiveness

Effectiveness of the usual treatment of migraine
attacks was assessed using the set of four questions
designed by the French Society for the Study of
Migraine Headache (SFEMC) that enquires about
significant migraine relief 2 h after drug intake,
treatment tolerability, use of a single drug unit for
treatment of an attack, and rapid resumption of
normal social, family or professional activities (31).
A single No response to one of the four questions
characterized ineffective acute treatment. Triptans,
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Anxiety, stress and coping in migraine patients

aspirin combined with metoclopramide, and
ergotamine derivatives were considered specific
treatments of migraine. Paracetamol, non-steroidal
anti-inflammatory drugs, opioids and aspirin alone
were considered non-specific treatments.

Data analysis
The percentages of patients with anxious and/or
depressive dimensions were expressed as the relative proportions of patients exhibiting HAD anxiety
or depression scores of 8 (both scales spanning
the range of 021). The PSS4 score was the sum of
scores from 1 to 5 on the four items of the questionnaire (scale span 420). The MSQ4 score was the
mean of scores from 0 to 100 on the four items of
the questionnaire (scale span 0100; low scores corresponding to pronounced functional impact). The
Brief COPE avoidance score was the sum of scores
from 1 to 4 on the two items of the questionnaire
(scale span 28). The CSQ catastrophizing score was
the sum of scores from 1 to 4 on the four items of
the French version of the questionnaire (scale span
416) (30). Severity of treated attacks of migraine
was evaluated by the patients on a scale of 010.
Quantitative variables were described by the
mean and standard deviation (S.D.). Categorical
variables were described by the numbers and relative proportions in the relevant categories. Where
appropriate, differences between groups were compared by Students t-test (if the size of the groups to
be compared was > 30) for quantitative data or by
the Z-test for categorical data, with Bonferronis
adjustment to the significance level to allow for the
multiplicity of tests. Changes in psychometric
scores (stress, avoidance, catastrophizing) and
quality of life according to coexistence of an anxiety
dimension, alone or combined with depression,
were assessed by analysis of variance.
A principal-components analysis (PCA) followed
by mixed classification and hierarchical cluster
analysis was used to identify homogeneous groups
of migraine patients. Thirteen variables (sex, age,
migraine history duration, number of days with
headache per month, type of migraineepisodic or
chronicseverity of treated attacks, number of
medication units taken for an attack, treatment
effectiveness according to the SFEMC set of questions, PSS4 score, MSQ4 score, COPE avoidance
score, CSQ catastrophizing score, presence or
absence of mood disorderanxious or depressive
dimension alone, both, or neither anxious nor
depressive dimension) were entered in the PCA
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1117

analysis. From the factor analysis, eight main

factorial axes were retained for the subsequent
typology analysis.
Independent predictors of anxious dimension
were identified using logistic regression analysis
allowing for the effects of sex, age, migraine history
duration, number of days with headache per
month, severity of treated attacks, PSS4 score,
MSQ4 score, avoidance score, catastrophizing score,
and number of drug units taken for treatment of an
attack. Results of the regression analysis are given
as the odds ratios and 95% confidence intervals of
factors showing a statistically significant effect.
Only for demography and disease history have
patients characteristics been described separately
for patients consulting a GP and those consulting a
neurologist. Analyses of mood disorders were performed on the combined groups of study patients.
Statistical results were considered significant
or not significant (NS) at P < 0.05 or P > 0.05,
respectively.

Results
The 1618 physicians (39.9% of all physicians
recruited) who agreed to participate in the study
included a total of 6109 patients. After exclusion of
329 patients for incomplete data (one or more
missing questionnaires), of 17 patients who
returned blank questionnaires, and of 346 patients
not satisfying inclusion criteria [age < 18 years,
n = 4; non-migrainous according to International
Headache Society (IHS) criteria, n = 124; receiving
prophylactic treatment for migraine, n = 218], a total
of 5417 patients included by 1550 physicians (1467
GPs and 83 neurologists) remained for analysis.

Study populations of physicians and patients

Mean age of GPs (49.0 7.4 years), age class distribution and regional distribution were comparable to the national reference, whereas the men to
women ratio was slightly higher than the national
reference (82 vs. 76%; P < 0.01). Mean age of neurologists (47.0 8.3 years), age class distribution,
sex ratio and regional distribution were also generally comparable to the national reference. The mean
number of migraine patients seen in a month was
15.1 11.8 for GPs and 25.2 22.2 for neurologists
(P < 0.01).
Of the 5417 patients included in the study,
5169 (95%) consulted a GP and 248 (5%) a neurologist. Most of them (80%) were women (80% of
those consulting a GP; 83% of those consulting a

4.7 1.8
2.7 1.9
7.9 2.4
60.8 20.2
3.2 1.2
7.9 2.5
*P < 0.01 vs. patients with neither anxious nor depressive dimensions.
P < 0.01 vs. patients with anxious dimension alone.
The small differences in numbers of patients according to the psychometric test are due to incomplete records for some patients.

1599
1599
1584
1586
1597
1581
13.3 2.9*
10.9 2.6*
12.9 2.3*
40.9 17.3*
4.7 1.4*
10.9 2.5*
2013
2013
2001
1998
2009
2002
10.6 2.3*
4.7 1.9*
10.2 2.2*
51.2 18.4*
3.9 1.4*
9.5 2.5*
5224
5309
5352
5361
5399
5356

9.6 4.5
6.4 4.3
10.6 3.1
50.3 20.3
4.0 1.5
9.5 2.8

1415
1415
1400
1400
1411
1402

Patients with
both anxious and
depressive dimensions

Anxiety
Depression
Stress
Functional impact
Avoidance
Catastrophizing

According to the scores on the HAD scale, 66% of

patients were considered anxious, of whom 59%
were also depressive, and 31% were considered
neither anxious nor depressive (Table 1). Only 2%
were considered only depressive. As most depressive patients are also anxious, the small group of
patients with depressive dimension alone was not
detailed further. Twelve per cent of anxious
migraine patients had chronic migraine (9% of
migraine patients with anxiety alone vs. 15% of
those with both anxiety and depression; P < 0.01)
compared with only 5% of migraine patients with
neither anxiety nor depression (P < 0.01).
Mean anxiety and depression scores, as well as
mean scores for stress, migraine functional impact
and maladaptive coping strategies (avoidance, catastrophizing) in all evaluable patients and in the
different subgroups of patients with or without
mood disorders are presented in Table 1. Results
indicate that patients with anxious dimension, and
especially those with both anxious and depressive
dimensions, had significantly worse scores on all
psychometric tests for stress, functional impact and
maladaptive coping strategies than those with
neither anxious nor depressive dimensions.
The relationship between stress or coping strategies and mood disorders is depicted in Fig. 1. Stress
score increased progressively from the group of

Psychometric test

Anxious and depressive dimensions, stress and

coping strategies in study patients

Patients with
anxious dimension
alone

According to IHS criteria, 4922 patients (91%) had

strict migraine and 495 (9%) had probable migraine.
Intensity of migraine attacks was considered mild
by 3% of patients, moderate by 38% or severe by
66% (some patients had attacks of variable intensity). Mean number of days with headache per
month was 7.5 5.0 (range 131 days) and 517
patients (9%) had chronic migraine ( 15 days with
headache per month).

All evaluable
patients

Characteristics of migraine in study patients

Evaluable patients with assessable data on the relevant psychometric test

(N and score S.D.)

neurologist). Mean age was 41.4 12.4 years and

significantly greater (P < 0.01) for patients consulting a GP (41.6 12.3 years; fewer patients aged
1824 years) compared with those consulting a
neurologist (36.8 11.9 years; fewer patients aged
5564 years). Nevertheless, more patients consulting a neurologist had a long history duration of
migraine (> 10 years) compared with those consulting a GP (47 vs. 32%; P < 0.01). Overall, mean
migraine history duration was 10.9 9.6 years.

Patients with neither

anxious nor depressive
dimensions

F Radat et al.

Table 1 Patient anxious and depressive dimensions, stress, functional impact and coping strategies in consulting migraine patients as assessed using
psychometric tests

1118

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Stress

Catastrophizing

Avoidance

16
12.9

Mean score

14
12
10
8
6

10.2
7.9

P<0.01
10.9

9.5

7.9
P<0.01

4
2

P<0.01

3.2

3.9

4.7

0
Neither anxious
nor depressive
dimension

Anxious
dimension alone

Anxious and
depressive
dimensions

Figure 1 Increase in mean stress, avoidance and

catastrophizing scores in the Perceived Stress Scale (PSS) 4
questionnaire, disengagement subscale of the Brief Coping
with Problems Experienced (COPE) inventory and
catastrophizing subscale of the Coping Strategies
Questionnaire (CSQ) questionnaire, respectively, according
to the absence or existence of anxious dimension, alone or
combined with depressive dimension, in migraine patients
consulting in primary care. Statistical significance refers to
the progressive increase in each score in the three groups
of patients.

patients with neither anxious nor depressive

dimensions to the group of patients with anxious
dimension alone and then to the group of patients
with both anxious and depressive dimensions
(P < 0.01). Similarly, avoidance and catastrophizing
scores increased significantly from the group of
patients with neither anxious nor depressive
dimension to the group with both anxious and
depressive dimensions (both P < 0.01). Conversely,
MSQ4 score decreased progressively from the
group of patients with neither anxious nor depressive dimension to that with both psychiatric dimensions (P < 0.01) (Fig. 2).

Typology of consulting migraine patients

A total of 5067 migraine patients with assessable
data at the HAD, PSS4, MSQ4, Brief COPE inventory avoidance and CSQ catastrophizing scales
were included in the typology analysis. Four
homogeneous groups of migraine patients could be
discerned (Table 2).
Most patients in Group 1 (98%) exhibited both
anxious and depressive dimensions. They had a
medium migraine history duration, number of days
with migraine headache per month and severity of
migraine attacks. They used many drug units per
attack, often non-specific drugs with very poor
treatment effectiveness. These patients exhibited
Blackwell Publishing Ltd Cephalalgia, 2008, 28, 11151125

Mean score at the MSQ4 questionnaire

Anxiety, stress and coping in migraine patients

1119

80

60
60.8
51.2

P<0.01

40
40.9
20

0
Neither anxious
Anxious
nor depressive dimension alone
dimension

Anxious and
depressive
dimensions

Figure 2 Decrease in mean score of migraine impact on

everyday activities in the MSQ4 questionnaire according to
the absence or existence of anxious dimension, alone or
combined with depressive dimension, in migraine patients
consulting in primary care. Statistical significance refers to
the progressive decrease in MSQ4 score in the three
groups of patients. MSQ4, abridged version of the original
Migraine-Specific Quality of life (MSQ) questionnaire
(22, 23).

elevated stress scores, used pronounced maladaptive coping behaviours and experienced pronounced functional impact of migraine.
Most patients in Group 2 (92%) exhibited the
anxious dimension alone. Compared with patients
in Group 1, they used slightly fewer drug units per
attack with slightly better effectiveness, experienced
less stress and functional impact of migraine, and
used less maladaptive coping behaviours.
Most patients in Group 3 (98%) exhibited neither
anxious nor depressive dimension. They had
slightly less severe migraine attacks, used fewer
drug units per attack and less maladaptive coping
behaviours and experienced better treatment effectiveness, less stress and milder functional impact of
migraine.
Finally, all patients in Group 4 (100%) had
chronic migraine. More than half of them (58%)
showed both anxious and depressive dimensions.
They reported a slightly longer migraine history
duration, exhibited the highest number of days
with migraine headache per month and greatest
severity of migraine attacks. They took many drug
units per attack, mostly non-specific treatments and
seldom specific treatments and triptans, with very
poor treatment effectiveness. Like patients in Group
1, they showed a high level of stress, used pronounced maladaptive coping behaviours and experienced marked functional impact of migraine.

1120

F Radat et al.

Table 2 Typology of consulting migraine patients according to migraine characteristics and the existence of anxious or
depressive dimension or both, as determined by principal components analysis followed by mixed classification and
hierarchical cluster analysis (N = 5067 patients)
Group 1

Group 2

Group 3

Group 4

Number of patients (%)

1698 (34)

1369 (27)

1489 (29)

511 (10)

Migraine characteristics
Episodic/chronic (%)*
Severity of treated attacks
Number of days with migraine/month
Migraine history duration (years)
Consumption of drug units/attack
Use of non-specific treatments (%)*
Use of specific treatments (%)*
Including triptans (%)*
Treatment effectiveness (%)*

Episodic (100)
6.9
6.8
10.2
5.1
75
41
35
15

Episodic (100)
6.8
6.3
11.2
4.5
75
44
39
24

Episodic (100)
6.4
5.5
11.0
3.9
66
41
36
32

Chronic (100)
7.2
18.7
12.1
5.9
83
34
29
18

Patient psychiatric characteristics

Anxious dimension alone (%)*
Depressive dimension alone (%)*
Both anxious/depressive dimensions (%)*
Neither anxious/depressive dimension (%)*
PSS4 score
Brief COPE avoidance score
CSQ catastrophizing score
MSQ4 score

0
0
98
2
12.9
4.7
10.8
41.3

92
8
0
0
10.3
3.8
9.3
52.0

0
0
2
98
7.9
3.1
7.6
62.0

23
3
58
16
11.9
4.5
10.8
40.6

*Percentage of patients in each group.

Mean value.
PSS4, Perceived Stress Scale 4; COPE, Coping with Problems Experienced; CSQ, Coping Strategies Questionnaire; MSQ4,
Migraine-Specific Quality of life 4.
Table 3 Predictive factors of anxious dimension in migraine patients
Predictive factors

Odds ratio

95% confidence interval

Statistical significance P

PSS4 score*
Avoidance score
Catastrophizing score
Number of days with headache/month
Number of drug units taken/attack
Migraine history duration
MSQ4 score

1.64
1.15
1.10
1.04
1.04
1.01
0.99

1.58,
1.07,
1.05,
1.02,
1.01,
1.00,
0.99,

< 0.0001
0.0003
< 0.0001
0.0004
< 0.01
< 0.05
0.0005

1.70
1.25
1.14
1.06
1.06
1.02
1.00

*PSS4 indicates abridged form of the original Perceived Stress Scale questionnaire (21).
MSQ4 indicates abridged version of the original Migraine-Specific Quality of life (MSQ) questionnaire (22, 23).

Predictive factors of anxious dimension

Logistic regression analysis indicated that PSS4
score (P < 0.0001), avoidance score (P = 0.0003), catastrophizing score (P < 0.0001), number of days with
headache per month (P = 0.0004), number of drug
units taken for the treatment of an attack (P < 0.01)
and migraine history duration (P < 0.05) were positively associated with the anxious dimension. On
the other hand, a high MSQ4 score (P = 0.0005) was

found associated with a reduced risk of anxious

dimension (Table 3). The other factors studied (sex,
age, severity of attacks) were not found significantly predictive of the anxious dimension.

Medical management of migraine

Most patients stated that they used to take acute
treatments of migraine attacks (Table 4). As first-line
treatments of migraine attacks, most patients (61%)
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Anxiety, stress and coping in migraine patients

1121

Table 4 First-line acute treatments used by patients for a migraine attack

Patients who treated the attacks and with assessable data at the HAD scale
(N and % of patients)
All patients
who treated
the attacks

Patients with
anxious
dimension
alone

Patients with both

anxious and
depressive
dimensions

Patients with
neither anxious
nor depressive
dimensions

Any treatment

5417

93

1415

94*

2013

93

1599

92

Specific treatments
Triptans
Aspirin + metoclopramide
Ergotamines

5035

36
32
3
1

1415

35
31
3
1*

2013

32
28
3
1

1599

35
30
3
2

Non-specific treatments
Paracetamol
NSAIDs
Opioids
Aspirin alone

5035

61
20
18
16
7

1415

56
19
17
15
5*

2013

58
18
17
16*
7

1599

56
18
17
14
7

5035

24
74

1331

26**
7226**

1877

1626**
8326**

1471

34
64

5035

3.1 2.3

1331

3.0 2.1*

1877

3.4 2.5**,

1471

2.8 2.2

Treatment effectiveness
Yes
No
Number of first-line drug units
taken per attack (N and
mean S.D.)

*,**P < 0.05 and P < 0.01, respectively, vs. patients with neither anxious nor depressive dimensions.
,P < 0.05 and P < 0.01, respectively, vs. patients with anxious dimension alone.
NSAID, non-steroidal anti-inflammatory drug.

stated that they used non-specific treatments and

36% that they used specific treatments, with no
significant difference between patients with anxious
dimension alone, anxious and depressive dimensions, and neither anxious nor depressive dimensions. However, fewer patients with both anxious
and depressive dimensions used triptans, and more
of them used opioids.
The mean number of drug units (all pharmaceutical forms) taken for first-line treatment of an
attack was significantly higher for patients with
both anxious and depressive dimensions than those
with anxious dimension alone or with neither
anxious nor depressive dimensions (Table 4). The
mean number of drug units of specific treatments
taken for first-line treatment of an attack was
1.7 1.1 vs. 3.9 2.4 units for non-specific treatments (P < 0.01).
The total mean number of drug units taken for
the treatment of an entire migraine attack was
4.7 3.7 for all patients who treated the attacks,
3.9 3.4 for those with neither anxious nor depressive dimensions, 4.6 3.3 for those with anxious
dimension alone (P < 0.01 vs. patients with neither
anxious nor depressive dimensions) and 5.3 4.1
Blackwell Publishing Ltd Cephalalgia, 2008, 28, 11151125

for those with both anxious and depressive dimensions (P < 0.01 vs. patients with anxious dimension
alone and those with neither anxious nor depressive dimensions).
Treatment effectiveness determined using the
four-item SFEMC questionnaire was found good for
only 24% of all patients who treated the attacks.
Compared with patients with neither anxious nor
depressive dimensions, treatment effectiveness was
found good for significantly fewer patients with
anxious dimension alone or with both anxious and
depressive dimensions (Fig. 3 and Table 4). On
average, patients responding No to either question
of the SFEMC questionnaire exhibited a significantly higher score on the HAD anxiety scale
(Fig. 4).

Discussion
The results of the SMILE study indicate that 67% of
patients consulting for migraine are anxious, of
whom 59% are also depressiveworthy of note,
due to the rather low threshold selected for the
detection of anxiety and depression on the HAD
scale, the anxious and depressive dimensions

1122

F Radat et al.

100

Significant relief at 2 h
94

92

88*

80
% of patients

Single drug intake

Good tolerability

61
60
40

59

Resumption of activities

60

44*

54*

49

37*

42*

*: P<0.01 vs. Neither anxious

nor depressive
: P<0.01 vs. Anxious

33*
20
0
Anxious
Anxious and
Neither anxious
nor depressive dimension alone depressive
dimensions
dimension

Figure 3 Decrease in effectiveness of acute treatment of

migraine attacks according to the absence or existence of
anxious dimension, alone or combined with depressive
dimension, as assessed by the set of four questions
designed by the French Society for the Study of Migraine
Headache.

'Yes' response

Mean HAD anxiety score

16

12

10.2

9.1

'No' response

*
10.9

9.5

10.1

10.5

8.9

8.8

4
*: difference statistically significant between groups (P < 0.01)
0
Migraine relief
at 2 hours

Good
tolerability

Single drug
intake

Rapid
resumption of
activities

Figure 4 Mean score on the Hospital Anxiety and

Depression (HAD) anxiety scale according to the Yes or
No response in each question of the set of four questions
designed by the French Society for the Study of Migraine
Headache for the determination of effectiveness of an
acute treatment of migraine. Statistical significance refers
to the comparison of the groups of patients giving Yes or
No responses to each question of the set of four
questions.

detected in this study differ from generalized

anxiety disorder and major depressive disorder.
Furthermore, study results indicate that anxious
patients, especially those with both anxious and
depressive dimensions, exhibited higher levels of
stress and functional impact on everyday life and
used more maladaptive behaviours (avoidance,
catastrophizing) than migraine patients with
neither anxious nor depressive dimensions.
Moreover, in patients with episodic migraine,
the number of days with migraine per month,

consumption and ineffectiveness of acute treatments were found enhanced in case of coexisting
anxious dimension and especially if both anxious
and depressive dimensions were present. In
patients with episodic migraine and pronounced
psychiatric profile and stress, migraine severity and
functional impact were as marked as in those with
chronic migraine. Stress and maladaptive coping
strategies were found to be the major determinants
of the anxious dimension in migraine patients,
before the number of days per month with migraine
headaches.
Anxiety is known to be frequent among migraine
sufferers. The relationship between migraine, stress
and anxiety is indeed something of a vicious circle.
Migraine causes stress by the pain it generates
during attacks and, interictally, by the constant fear
of an impending attack. The difficulties migraine
patients have in managing stress may engender
exaggerated fear of attacks and maladjustment,
such as catastrophizing during attacks, avoidance
of any trigger factors between attacks and, in
the long run, chronic anxiety, withdrawal into
themselves and depression. Furthermore, anxiety
increases sensitivity to stress and aggravates the
perception of migraine symptoms, whereas stress is
known to be a precipitating factor of migraine
attacks. Finally, anticipation of attacks may promote
medication overuse by migraine patients, entailing
the risk of evolution to chronicity. In this complex
relationship between migraine and anxiety, it is
difficult to differentiate causes from effects. Detection of anxiety and stress in consulting migraine
patients appears, nevertheless, crucial to successful
management of migraine in clinical practice.
In the SMILE study, stress, anxious and depressive dimensions and migraine functional impact in
study patients were evaluated using classical psychometric tests, some of them in an abridged form
(PSS4, MSQ4) to be compatible with their use in the
primary care setting. The anxious and depressive
dimensions were measured using the HAD scale
with a threshold of 8 for the characterization of
both mood disorders, since this threshold has been
shown to afford optimal balance between sensitivity and specificity (32, 33). MSQ4 was used as an
estimate of migraine impact rather than frequency
and severity of headaches: although one item of
MSQ4 (feeling of being a burden to others) may
overlap to a certain extent with affective impact,
MSQ4 seemed a more comprehensive estimate of
the impact of headaches. Subscales of the Brief
COPE inventory (avoidance subscale) and CSQ
(catastrophizing subscale) were retained as the most
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Anxiety, stress and coping in migraine patients

relevant domains for the evaluation of maladaptive
adjustment in migraine patients. Catastrophizing
has been perceived as a tendency to exaggerate the
threat of pain and to feel hopeless about ones
ability to deal with pain experience. Catastrophizing in some ways is related to depression, but does
not overlap with it (34). Overall, catastrophizing
can be considered as a set of negative pain-related
cognitions (34) and to predict the life interference
attributed to headache (35). Concerning avoidance
coping strategies, they have been reported to be
associated with high degrees of headache intensity
(36). Several other coping strategies have been
described, but, in view of the limited number of
studies evaluating them, these strategies were considered less determinant for the study of migraine
outcomes. Effectiveness of acute treatments of
migraine was assessed using the SFEMC set of four
questions that has been recommended by the
French medical authorities (37).
One salient feature of the SMILE study is the
increasing intensity of stress and use of maladaptive coping strategies (avoidance, catastrophizing)
and quality of life impairment from migraine
patients with neither anxious nor depressive
dimensions to those with anxious dimension alone
and ultimately to those with both anxious and
depressive dimensions. The specific influence of the
depressive dimension in this progression is difficult
to establish, since the anxiety score also increased
from the group with anxious dimension alone to
that with both anxious and depressive dimensions.
Occurrence of signs of depression thus might characterize only a further step in the evolution of
psychiatric disorders in the natural development of
the disease.
Typology analysis identified four separate
groups of migraine patients: three groups with
episodic migraine (Group 1, patients with both
anxious and depressive dimensions; Group 2,
patients with anxious dimension alone; Group 3,
patients with no mood disorder) and one group
with chronic migraine (Group 4). Interestingly, the
group of patients with chronic migraine (those
generally considered as presenting the most pronounced impact on daily life) did not differ
notably from the group with both anxious and
depressive dimensions (Group 1) for stress, maladaptive coping strategies, functional impact on
daily life and ineffectiveness of acute treatments.
This suggests that a category of patients with episodic migraine characterized by both anxious and
depressive dimensions, emotional disturbances
and maladaptive coping strategies (Group 1) may
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1123

be at very high risk of becoming chronic migraine

patients. Prospective studies confirming this
hypothesis are required, all the more so since it is
of utmost importance to identify the specific risk
factors of transformation of episodic migraine
into chronic migraine (38). Such patients should
be identified in general medical practice and
should be prescribed a prophylactic treatment and
possibly a stress management therapy targeted at
maladaptive coping strategies. Since abridged
scales and questionnaires are now available that
can be easily used, systematic measurement of
anxiety, stress, avoidance and catastrophizing in
migraine might be advisable even in general
medical practice.
Among 10 putative predictive factors of anxiety,
logistic regression analysis identified PSS4, avoidance and catastrophizing scores as most closely
associated with anxious dimension, confirming the
relevance of using a stress appraisal model (39) for
understanding the emotional impact of migraine.
The efficacy of relaxation and stress management
therapies rests on the validity of this model. Relaxation therapies indeed demonstrated their efficacy
in reducing the disability associated with migraine
(40). Other identified significant factors contributed
only modestly to the prediction of anxious dimension (odds ratios of 0.991.04). Noteworthy, severity
of attacks does not feature in our list of significant
predictive factors. To our knowledge, there is only
limited information available in the medical literature concerning the relationship between severity of
migraine attacks and psychiatric comorbidity. Similarly to us, Mitsikostas and Thomas (41) have found
that anxiety and depression were not related to
severity of headaches in headache out-patients,
whereas there was a significant association with the
frequency and duration of attacks (41). Unfortunately, these analyses combined several types of
headache. Frequency of headache was not a parameter available in our study (it was not retained for
the study considering that it might be affected by
recollection bias), but the number of days with
headache in a month emerged as a significant predictive factor, although with a modest odds ratio
(1.04), notably lower than that for PSS4 score (1.64).
This study has some limitations. As regards study
methodology, SMILE was an open observational
study carried out among migraine patients consulting for migraine. That these patients may differ
from the general population of migraine patients is
reflected by the rather high reported number of
days with migraine headaches per month (7.5
days/month). The physicians recruited were aware

1124

F Radat et al.

of the study objectives. Those agreeing to participate were possibly those most interested in the
optimization of migraine management. However,
this may not have affected the validity of the
observed relationships between anxiety and
migraine. Some of the psychometric tests used were
abridged forms of the original tests, in order to
allow their use in the general practice setting.
Although not designed for the diagnosis of anxiety
and depression, the HAD scale was retained for its
easy and very widespread use and the existence of
a validated threshold allowing the identification
of patients with clinically significant anxiety or
depression. The data pertaining to acute treatment
of attacks were based on patients statements. As
regards study results, a weakness of the study may
be the difficulty in assessing the actual clinical
significance of the differences observed between
groups, some of which might be considered of
rather small magnitude. On the other hand, a
strength of the SMILE study is the very large
number of participating physicians and patients,
which reinforces the validity of the results.
The results of the SMILE study show an association between migraine and mood disorders, stress,
maladaptive coping strategies and impact on everyday life in patients seeking medical attention for
their headaches. This observation can in no way be
interpreted as a formal demonstration of a causal
relationship between migraine and anxiety and/or
depression. First, since most previous work that
assessed coping and catastrophizing referred to
pain or headaches in general, assigning study
results exclusively to a very specific condition such
as migraine may be an extrapolation to be viewed
with caution. Second, in interpreting study results,
one must bear in mind that study patients consulted specifically for migraine and may thus represent a particular category of migraine patients
having difficulties in managing their disease.
Anxiety in these patients may be a concomitant
disease or, for example, arise from the perceived
inefficacy of acute treatment of attacks, so that it is
difficult to establish firmly whether mood disorders
are the cause or the result of the relative ineffectiveness of acute treatment of migraine attacks in
anxious and depressive patients. A way of addressing this issue would be to determine, in a prospective study, whether or not mood disorders resolve
with effective treatment of migraine headaches and
whether they influence treatment efficacy. If so, this
would again emphasize the importance of assessing
anxiety and depression in migraine sufferers in
clinical practice.

In conclusion, the SMILE study has shown that a

large proportion of migraine patients consulting in
primary care present with anxious and depressive
dimensions. These patients experience notable
degrees of stress, pronounced functional impact of
migraine on their professional, family and social life
and exhibit maladaptive adjustment behaviours to
cope with the burden of migraine. Since stress and
maladaptive adjustment behaviours appear to
predict anxiety and to be positively related to the
functional impact of migraine, medication overuse
and poor effectiveness of acute treatments of
migraine, these dimensions should be looked for
carefully and taken into account for optimal management of migraine.

Acknowledgements
The authors thank Genevive Bonnelye (TNS Healthcare) for
managing the project, Sverine Ricard and Xavier Guillaume
(TNS Healthcare) for carrying out the study and statistical
work, and Jacques Legeai (Rdasciences-Sant) for his help
in writing the article.

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