Headache Medicine, v.2, n.1, p.5-9, jan./feb./mar. 2011 5
Disease progression to chronic migraine:
onset of symptoms of headaches, anxiety and
mood disorders
Progressão da doença em enxaqueca crônica: Análise do início dos
sintomas de cefaleia, ansiedade e humor
ABSTRACTABSTRACT
ABSTRACTABSTRACT
ABSTRACT
Background:Background:
Background:Background:
Background: Psychiatric conditions, mostly anxiety and mood
disorders, are common in patients with chronic migraine. There
has recently been extensive debate on migraine progression,
but little is known about the role of psychiatric disorders in this
respect.
Objective: Objective:
Objective: Objective:
Objective: In order to evaluate the role of psychiatric
disorders in migraine progression, we analyzed the temporal
profile of migraine, mood and anxiety disorders, and years
since onset of symptoms in chronic migraine (CM) patients.
Methods: Methods:
Methods: Methods:
Methods: Fifty CM patients diagnosed according to the
International Headache Society (2004) criteria were interviewed
and diagnosed for mental disorders using the Structured
Clinical Interview for DSM-IV (SCID-I/P).
Results:Results:
Results:Results:
Results: Anxiety
disorders preceded the onset of episodic migraine, which was
followed by depression and daily headaches.
Conclusions:Conclusions:
Conclusions:Conclusions:
Conclusions:
Psychiatric comorbidity evaluation in chronic migraine may
lead to better patient management and clinical outcomes.
Patients with a history of anxiety, episodic migraine, and
depression may be at risk of developing CM. Early treatment
of anxiety, mood disorders, and episodic migraine may prevent
disease progression to CM.
Keywords:Keywords:
Keywords:Keywords:
Keywords: Anxiety disorders; Mood disorders; Disease
progression; Comorbidity
ORIGINAL ARTICLEORIGINAL ARTICLE
ORIGINAL ARTICLEORIGINAL ARTICLE
ORIGINAL ARTICLE
Juliane P. P. Mercante
1,2
; Mario F. P. Peres
1
; Marcio A. Bernik
2
; Felipe Corchs
1,2
; Vera Z. Guendler
1,3
; Eliova Zukerman
1
1
Hospital Israelita Albert Einstein, Institute of Teaching and Research, São Paulo, SP, Brazil
2
Institute of Psychiatry, HCFMUSP, São Paulo, SP, Brazil
3
Universidde Federal de São Paulo –
UNIFESP – EPM, São Paulo, SP, Brazil
Mercante JP, Peres MF, Bernik MA, Corchs F, Guendler VZ, Zukerman E
Disease progression to chronic migraine: onset of symptoms of headaches,
anxiety and mood disorders. Headache Medicine. 2011;2(1):5-9
RESUMORESUMO
RESUMORESUMO
RESUMO
Introdução:Introdução:
Introdução:Introdução:
Introdução: Ansiedade e depressão são condições clínicas
comuns em pacientes com enxaqueca crônica. Um intenso
debate em relação ao processo de cronificação da enxaqueca
tem acontecido recentemente, mas pouca ênfase tem sido
dada a comorbidade psiquiátrica.
Objetivos:Objetivos:
Objetivos:Objetivos:
Objetivos: Para avaliar
o papel das comorbidades psiquiátricas na progressão da
enxaqueca, analisamos o perfil temporal de início dos sintomas
de humor, ansiedade e dor nos pacientes com enxaqueca
crônica.
Métodos: Métodos:
Métodos: Métodos:
Métodos: Cinquenta pacientes diagnosticados de
acordo com os critérios da Sociedade Internacional de Cefaleias
(2004) foram entrevistados e diagnosticados para transtornos
mentais de acordo com a entrevista estruturada para o DSM-
IV (SCID-I/P).
RR
RR
R
esultados:esultados:
esultados:esultados:
esultados: Transtornos de ansiedade prece-
deram o início das enxaquecas episódicas, que foram seguidas
pelo aparecimento pelos transtornos de humor e sequen-
cialmente a evoluçãoo/transformação para enxaqueca
crônica.
Conclusões:Conclusões:
Conclusões:Conclusões:
Conclusões: A avaliação das comorbidades
psiquiátricas na enxaqueca crônica podem levar a um melhor
diagnóstico e tratamento dos pacientes. Pacientes com história
de ansiedade, enxaqueca e depressão podem ter risco de
desenvolverem enxaqueca crónica. Tratamento precoce destas
condições podem previnir a ocorrência da enxaqueca crônica.
Descritores:Descritores:
Descritores:Descritores:
Descritores: Transtornos de ansiedade; Transtornos do
humor; Progressão da doença; Comorbidade
6 Headache Medicine, v.2, n.1, p.5-9, jan./feb./mar. 2011
INTRODUÇÃO
Migraine is a chronic and sometimes progressive
disorder characterized by recurrent episodes of headache
and associated symptoms. Chronic migraine (CM) is
debilitating and has a substantial impact on a patient's
life;
(1)
it has recently been added to the second revised
International Headache Society Classification (2004),
(2)
and redefined
(3)
under a broader concept of the disorder,
accepting as migraine headaches occurring more than 8
days a month (previously 15 days), for more than three
months. The diagnosis of medication overuse headache
must be excluded.
(4)
Chronic migraine has been shown to
be an early stage of chronification of transformed
migraine.
(5)
CM is common in the general population
(6)
and accounts for up to 60% of consultations at tertiary
headache centres.
(7)
Mental disorders are common conditions among
these patients and are associated with a high degree of
disability, low level of satisfaction, and low quality of life.
(8
)
Psychiatric comorbidities are also significant factors in the
development and maintenance of chronic headaches.
(9)
Some degree of depression is found in 85% of CM
patients, and severe depression in 25%.
(10)
Anxiety disorders
affect 75% of CM patients,
(11,12)
but anxiety and mood
disorders overlap in this condition.
(13)
CM is often difficult
to treat and its refractoriness has been attributed to
psychiatric comorbidity.
(14)
Mental disorders were also found to be more
common in migraine than in non-migraine individuals;
relative risk for major depressive disorders was 2.2%,
bipolar disorder 2.9%, generalized anxiety disorder 5.3%,
panic disorder 3.3%, simple phobia, 2.4%, and social
phobia, 2.0%.
(15)
Studies have consistently shown that
migraine with aura is more closely associated with
psychiatric comorbidity than migraine without aura.
(16)
Merikangas et al
(17)
observed that anxiety disorders
generally preceded migraine, followed by mood disorder
diagnoses, and postulated a syndromic relation between
migraine, anxiety and depression involving a range of
symptoms starting with anxiety (frequently in early
childhood), followed by migraines and depressive
episodes in adult life. CM has never been studied in this
context.
Recent evidence suggests that a subgroup of
migraine patients may have a clinically progressive
disorder,
(18-21)
but little emphasis has been given to the
putative role of psychiatric disorders in migraine
progression.
MERCANTE JP, PERES MF, BERNIK MA, CORCHS F, GUENDLER VZ, ZUKERMAN E
Our own study analyzed the years since onset of
anxiety-disorder symptoms, episodic migraine, mood
disorders, and daily headaches in chronic migraine
patients in order to evaluate the chronological relations
between these conditions. We predicted that CM would
be the next stage of disease progression after anxiety
disorders, episodic migraine and mood disorders had
set in.
METHODS
Fifty patients (forty women, ten men) were consecutively
diagnosed with chronic migraine in accordance with the
International Headache Society (2004)
(2)
criteria and
enrolled in the study. Their mean age was 41.1 ± 11.6
years (SD), range 23-65 years, most being caucasians
(45, 90%), with 4 black and 1 asian. Mean headache
frequency was 22.2 ± 2.7 days/month, mean headache
intensity (0-10 scale) was 8.1 ± 0.7. All patients had daily
headaches (more than 15 headache days/month). All
patients were enrolled at a tertiary headache centre in
Sao Paulo and interviewed using the Structured Clinical
Interview for DSM-IV SCID-I/P22;23 for psychiatric
assessment. Patients were asked about the onset of anxiety
symptoms and mood disorders using the standardized
SCID interview procedure. Questions about the onset of
symptoms of episodic and chronic migraine were asked
by the same SCID interviewer, and responses were
confirmed by the neurology team. We only included
responses with significant degree of confidence by both
patients and research team. The study protocol was
approved by the local Ethics Committee and all patients
gave written consent. We analyzed the onset of symptoms
in different groups; all patients had a history of daily
headaches and episodic migraine. We compared patients
with both anxiety and mood disorders (22 patients, 44%),
as well as patients with anxiety but not depression (16
patients, 32%), depression but not anxiety (6 patients,
12%), and no psychopathology (8 patients, 16%). A
Student t-test and Mann-Whitney rank sum test were used
to compare groups. Five percent was chosen as a
minimum level of statistical significance for two-sided tests.
Results were presented as mean ± standard deviation.
RESULTS
Forty-two patients (84%) met lifetime diagnostic criteria
for some mental disorder; 38 (76%) presented an anxiety
disorder; 25 (50%) presented a mood disorder; 22 (44%)
Headache Medicine, v.2, n.1, p.5-9, jan./feb./mar. 2011 7
DISEASE PROGRESSION TO CHRONIC MIGRAINE: ONSET OF SYMPTOMS OF HEADACHES, ANXIETY AND MOOD DISORDERS
presented both anxiety and mood disorder; 26 (52%)
presented generalized anxiety disorder; 3 (6%) presented
panic disorder, 2 (4%) obsessive-compulsive disorder, 3
(6%) posttraumatic stress disorder and 27 (54%) specific
or social phobia. Twenty-two (44%) presented major
depressive episode, 14 (28%) of them had a recent, and
17 (34%) patients had previous episodes. Two patients
met diagnostic criteria for dysthymic disorder, and 2 for
bipolar II disorder.
Patients with both anxiety and mood disorders,
episodic migraine, daily headaches onset and
comorbidities presented the following features: mean years
since onset of anxiety disorders was significantly earlier
than migraine (27.1 ± 16.9 vs. 20.5 ± 11.1 years since
onset, p=0.016), mood disorders (6.8 ± 1.9 years,
p<0.001) and daily headaches (4.6 ± 2.8 years,
p<0.001).
Migraine onset was significantly earlier than mood
disorder and daily headaches onset, p<0.001, as was
mood disorder onset compared to daily headaches onset
(p<0.01).
Anxiety disorders preceded the onset of episodic
migraine, which was followed by a mood disorder and
daily headaches (Figure 1).
In patients with anxiety but not mood disorders,
anxiety onset also preceded episodic migraine onset and
daily headaches onset (23.7 ± 17.4 vs. 21.6 ± 11.2,
p<0.01, vs. 5.5 ± 3.8, p<0.001). In patients with mood
disorders alone, episodic migraine preceded depression
symptoms (27.5 ± 8.2 vs. 4.2 ± 2.7, p<0.001). Mood
disorder onset also preceded daily headaches, but only
a trend toward significance was observed (4.2 ± 2.7 vs.
3.7 ± 2.8, p=0.054).
DISCUSSION
The findings of our study of the pattern of psychiatric
comorbidity symptoms and headaches in CM matched
those of Merikangas et al
(24)
who reported that anxiety
disorders preceded migraine, which preceded onset of
depression, but did not record daily headaches in young
adults aged 27-28 in Zurich (whereas the mean age of
our participants was 41.1 ± 11.6, range 23-65). Perhaps
the younger age of the Zurich population explains the
absence of daily headaches as a common symptom. We
also found that the last step in the symptom progression
from anxiety disorders to episodic migraine and mood
disorders may be migraine chronification and a daily
pattern. Even when anxiety patients without mood disorder
were compared with mood disorder patients without
anxiety, the same pattern was observed: anxiety preceded
episodic migraine onset in the former group, and episodic
migraine preceded mood disorders onset in the latter. The
small sample size of the latter may explain why depression
onset was not significantly different to daily headaches
onset, but a trend toward significance was found at
p=0.054.
CM may also be transformed to a wide spectrum of
symptoms, as elegantly reported by Bigal et al
(25)
who
suggested that the frequency of migraine attacks is high
in the early stages of migraine chronification, but the
frequency of nonmigraine headaches increases as the
illness progresses. Early descriptions of transformed
migraine mentioned anxiety and mood disorders as key
elements for developing daily headaches from episodic
migraines.
(26,27)
Our findings suggest that CM may be the result of a
combination of anxiety and mood disorder symptoms in
an episodic migraineur, but prospective studies are
required to draw causal inferences. In this context, CM
would be a truly neuropsychiatric condition. Another
possibility is that CM is a broader syndrome, involving
anxiety manifested frequently in early childhood,
adolescence or young adulthood, followed by episodic
migraines and then depressive disorders in adult life. There
may well be genetic predisposition for this disease
progression. Other comorbid conditions such as sleep
disorders, fibromyalgia, and other functional somatic
syndromes require further investigation to better define their
Figure 1. Mean onset age (years) of anxiety disorders, mood disorders,
episodic migraine and daily headaches. Profiling migraine and
comorbidities showed that mean ± SD onset age of anxiety disorders
was significantly lower than that of migraine (13.9 ± 13.7 (range 0-
44) vs. 20.9 ± 12.5 (range 4-54); onset of mood disorders (33.4 ±
10.1 (range 10-54); and CM (36.7 ± 11.3 (range 19-64). Mean onset
age of migraine was significantly lower than that of mood disorders
and CM, p<0.001, as it was for mood disorder onset compared to
daily headaches onset (p<0.01).
8 Headache Medicine, v.2, n.1, p.5-9, jan./feb./mar. 2011
role and level within a broader concept of disease
progression, which would hypothetically include these
syndromes.
Progression of symptoms in headache is common.
A longitudinal epidemiologic study found that 3% of
individuals with episodic headache (frequency from 2
to 104 days per year) progressed to chronic daily
headache (CDH, episode frequency >180 days per
year) in the course of a year.
(28)
The study concluded
that the incidence of CDH in subjects with episodic
headache is 3% per year. A one-year follow-up of 532
consecutive episodic migraine patients (<15 days per
month) found that 64 (14%) developed chronic daily
headache.
(29)
Despite its clinical relevance, the evidence of risk
factors for migraine progression is limited. The
prevalence of CDH has been reported to decrease
slightly with age and to be higher in women [odds ratio
(OR) = 1.65 (1.3 to 2.0)] and in divorced, separated,
or widowed individuals [OR = 1.50 (1.2 to 1.9)]. Social
risk factors have also been described: the risk of CDH in
individuals with less than high-school education was
threefold that of a college-educated sample [OR = 3.56
(2.3 to 5.6)].
(30)
CDH was also associated with a self-
reported diagnosis of arthritis [OR = 2.50 (1.9 to 3.3)],
diabetes [OR = 1.51 (1.01 to 2.3)],
(31)
previous head
trauma
(32
) and medication overuse.
(33)
Interestingly, the
highest risk factor described for development of CDH
was obesity [OR = 5.53 (1.4 to 21.8)].
(34)
A study
comparing 41 migraineurs with 41 medication overuse
headache (MOH) patients found that the latter showed
excess risk of suffering from mood and anxiety disorders
associated with use of psychoactive substances.
Psychiatric disorders occurred significantly more often
before rather than after the transformation from migraine
to medication overuse headache (MOH).
(35)
Most studies failed to explore one of the main issues
in migraine management: psychiatric comorbidity. Our
sample, although relatively small, showed a consistent
pattern of disease progression based on the onset of
symptoms described by patients. Recollection bias may
be present, but previous studies have utilized and validated
the same method.
(14)
The ideal methodology would be a
prospective study, but long term follow-up (decades) is
also very difficult.
This paper raises the possibility of early
pharmacological or non-pharmacological intervention for
adolescents or young adults with anxiety disorders in order
to prevent the future onset of migraine.
CONCLUSION
Psychiatric disorders, mostly anxiety and mood
disorders, are common in patients with CM. Anxiety
disorders may occur before the onset of episodic migraine
and be followed by depression and finally daily
headaches.
Psychiatric evaluation for CM patients may enhance
patient management and clinical outcomes. Even though
the present findings are limited by the cross-sectional
design of this study, the data suggests that anxiety disorders
may be an important risk factor for subsequent migraine
and that both anxiety and mood disorders play an
important role in migraine progression to CDH.
Therefore, early treatment of anxiety disorder and/
or episodic migraine may prevent long term
complications, such as depression and CM.
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Received: 10/8/2010
Accepted: 10/30/2010
Correspondence
DrDr
DrDr
Dr
. Mario F. Mario F
. Mario F. Mario F
. Mario F
ernando Pernando P
ernando Pernando P
ernando P
rieto Prieto P
rieto Prieto P
rieto P
ereseres
ereseres
eres
Al. Joaquim Eugenio de Lima, 881 cj 708
01403-001 – São Paulo, SP, Brazil
Tel. 55-11-8111-6662 – Fax. 55-11-3285-5726
marioperes@yahoo.com