Download Obsessive-Compulsive Disorder and Migraine With Medication

Headache
© 2009 the Authors
Journal compilation © 2009 American Headache Society
ISSN 0017-8748
doi: 10.1111/j.1526-4610.2009.01457.x
Published by Wiley Periodicals, Inc.
Research Submissions
Obsessive-Compulsive Disorder and Migraine With
Medication-Overuse Headache
Letizia Maria Cupini, MD, PhD; Marco De Murtas, MD; Cinzia Costa, MD, PhD; Maria Mancini, MD;
Paolo Eusebi, PhD; Paola Sarchielli, MD; Paolo Calabresi, MD
Objective.—A strong association has been demonstrated between migraine, particularly in the chronic form and with
medication overuse, and either major depression or various anxiety disorders. However, there has been less systematic research
on the links between migraine with medication-overuse headache (MOH) and obsessive-compulsive disorder (OCD). A
drug-seeking behavior shares with OCD the compulsive quality of the behavior. We investigated the relationship between OCD
and MOH in migraineurs.
Methods.—A structured questionnaire was administered to subjects with: episodic migraine (EM) (n = 30), chronic
migraine (CM) (n = 24), and MOH with a previous history of EM (n = 33) and 29 control subjects. Psychiatric diagnoses were
made by a senior psychiatrist blinded to the diagnosis of migraine. Psychiatric assessment of OCD illness was evaluated by
means of The Yale-Brown Obsessive Compulsive Scale (Y-BOCS).
Results.—In the subgroup of patients with MOH, psychiatric comorbidity (anxiety and mood disorders) was prevalent
compared with CM, EM, and controls (P < .0001). Subclinical OCD was significantly prevalent in MOH patients with respect
to other groups (P < .0002). Higher scores in Y-BOCS, as a measure of severity of obsessive-compulsive symptoms, were found
in both MOH and CM compared with controls and EM.
Conclusions.—The excess of psychiatric comorbidity in patients with MOH can be related either to medication overuse or
to chronification of headache. Among anxiety disorders, we observed a high rate of subclinical OCD. However, a direct link
between compulsive behavior and medication overuse cannot be established yet. OCD in MOH might be underdiagnosed and
undertreated.
Key words: episodic migraine, chronic migraine, medication-overuse headache, obsessive-compulsive disorder
(Headache 2009;••:••-••)
INTRODUCTION
Migraine is frequently associated with psychiatric
disorders and this association seems strongest in
major depression and anxiety disorders.1,2 Moreover,
a link between migraine and substance dependence
has been reported.1,2 As for other anxiety disorders,
an association between migraine and obsessivecompulsive disorder (OCD) has been investigated.3,4
Psychiatric comorbidity is higher in chronic migraine
(CM), particularly in the case of medication overuse,
rather than in episodic migraine (EM).1,5 Various
risk factors for migraine chronification have been
From the Ospedale S. Eugenio – Centro Cefalee, UOC Neurologia, Rome, Italy (L.M. Cupini); Ospedale S. Eugenio,
Roma – Servizio Psichiatrico Diagnosi e Cura, Rome, Italy
(M.D. Murtas); Clinica Neurologica, Perugia, Università degli
Studi di Perugia and IRCCS Fondazione S. Lucia, Roma, Italy
(C. Costa, M. Mancini, P. Sarchielli, and P. Calabresi); University of Perugia, Italy – Department of Economics, Finance and
Statistics, Perugia, Italy (P. Eusebi).
Address all correspondence to L.M. Cupini, Centro Cefalee,
U.O.C. Neurologia, Ospedale S. Eugenio, P.le dell’Umanesimo
10, 00144 Roma, Italy.
Accepted for publication March 11, 2009.
Conflict of Interest: None
1
2
hypothesized, but little is known about the causes and
mechanisms underlying CM and the occurrence of
medication overuse.6-11 Medication-overuse headache
(MOH) is a condition in which headaches become
increasingly frequent as a patient begins to use more
and more acute headache medications.6 The presence
of a comorbid psychiatric disorder and a greater risk
of suffering from substance-related disorders seem
to be more prevalent in MOH than in migraine
patients.11 Substance abuse behaviors have been
described in MOH patients.12 It was recently
observed that two-thirds of the MOH patients were
dependent on acute treatments for headaches according to the Diagnostic and Statistical Manual of
Mental Disorders (DSM)-IV criteria.13 Similarly, a
markedly enhanced substance need in chronic daily
headache patients with overuse of analgesics, compared with patients with episodic headaches, was
reported.14 Thus, it could be hypothesized that certain
behaviors and psychological states (ie, fear of headache, anticipatory anxiety, obsessional drug-taking
behaviors, and psychological drug dependence) are
particularly important in prompting and sustaining
the overuse of medication.15
A drug-seeking behavior shares the compulsive
quality of the behavior with OCD. An involvement
of the striato-thalamo-orbitofrontal circuit has
been postulated for both OCD and drug-seeking
behaviors.16-20 Interestingly, MOH has been recently
found to be associated with reversible metabolic
changes in some pain-processing structures and with
persistent orbito-frontal hypofunction, even after
withdrawal of analgesics.21
Thus, the objective of the present study was to
investigate whether there was a co-occurrence of
obsessive compulsive symptoms in migraine patients
with MOH. In particular, since subclinical OCD symptoms are relatively common in nonclinical populations
and share common neurobiological substrates with
clinical OCD,22-25 we have analyzed the occurrence of
subclinical OCD in episodic as well as CM and in
MOH.
SUBJECTS AND METHODS
Study subjects consisted of a series of consecutive
outpatients who complained of headache and were
examined at the outpatient Neurological Clinic of S.
Eugenio Hospital, Rome and the Neurological Clinic
of the University of Perugia. The study protocol was
approved by the local Ethics Committees and all
patients gave their written consent to the study. Interviews were performed using a standard questionnaire. We collected information on age, gender,
educational level, employment status, and headache
type. Data on headache frequency, severity, duration,
as well as data on the frequency and type of acute
headache drug use were collected from headache
diaries. Patients without clear documentation were
asked to complete headache diaries for at least 2
months. Thirty subjects suffering from EM, 24 from
CM, and 33 MOH patients (with a previous history of
EM whose headache had markedly worsened during
medication overuse) diagnosed according to the
International Classification of Headache Disorders
(ICHD)-IIR6,26,27 and 29 controls were recruited. In
fact, it has been shown in many studies that using
ICHD criteria, the reliability of diagnosis by different
observers is good and prospective studies have shown
that individuals in the general population can be classified appropriately using these same criteria.28 Controls were recruited among hospital staff members. A
clinical interview was performed to rule out that controls had a history of headaches. Overuse of headache
medication was defined as intake of any kind of
ergotamine, triptans, opioids, or combination analgesic medications on ⱖ10 days/month on a regular basis
for >3 months or intake of simple analgesics on ⱖ15
days/month on a regular basis for >3 months.26,27
At the time of study, the patients included were
not yet receiving headache preventive treatment nor
psychoactive treatment. Nevertheless, some of them
had been previously treated with tricyclic antidepressants or SSRI. However, this therapy had been discontinued at least 4 months before entering in the
study. All of them reported that they had not been
previously treated with either mood stabilizers or
antipsychotics.
Psychiatric Assessment.—Psychiatric diagnoses
were made by a senior psychiatrist blinded to the
diagnosis of headache. The psychiatric assessment
was based on a semi-structured interview (SCID-I)
and on the DSM-IV criteria.29 All patients were then
Headache
3
interviewed by means of the Yale-Brown Obsessive
Compulsive Scale (Y-BOCS)30 to identify types of
obsessions and compulsions and to quantify them.
The scale is used extensively in research and clinical
practice to both determine the severity of OCD and
to monitor improvement during treatment. This scale,
which measures obsessions separately from compulsions, specifically measures the severity of the symptoms of OCD without being biased towards the type
of obsessions or compulsions present. The scale is a
clinician-rated, 10-item scale, each item rated from 0
(no symptoms) to 40 (extreme symptoms). It includes
questions about the amount of time the patient
spends on obsessions, how much impairment or distress they experience, and how much resistance and
control they have over these thoughts. Furthermore,
the same types of questions are asked about compulsions (ie, time spent, interference, etc). The results can
be interpreted based on the score.22,30
If the patient met the full criteria for OCD
according to the OCD module of the SCID, then a
diagnosis of OCD was applied. If the patient met the
full criteria with the exception that the disability or
distress was judged to be below the diagnostic threshold, then a diagnosis of subclinical OCD was
applied.22
Statistical Analysis.—All statistics were calculated
using Statistics release: 6 (Statsoft Inc., Tulsa, OK,
USA).
Chi-square test and Fisher’s exact test were used
for frequency comparison of categorical variables.
Data of continuous variables were expressed as
mean ⫾ 2SD. Because of the normal distribution, we
applied 2-way ANOVA and the least significant difference test as post hoc analysis for age. Kruskal–
Wallis ANOVA by ranks was used to compare
independent variables with non-normal distribution
(frequency of headache, duration of headache,
Y-BOCS scale scores) among groups and between
one group and another.
Spearman rank order correlations (R) were calculated between scores of Y-BOCS and headache frequency and years of disease. P values less than .05
were considered significant.
RESULTS
Demographic and clinical characteristics of the
patient population are shown in Table 1.
There was a prevalence of females in all patient
groups with higher percentage values for the MOH
patient group (CM = 70.83%, MOH = 93.93%,
EM = 80.00%) compared with control subjects
Table 1.—Demographic and Clinical Features of Episodic Migraine (EM), Chronic Migraine (CM) and Medication-Overuse
Headache (MOH)
Characteristics
Age, years
Gender, %
Women
Men
Educational level
High school or less
College or degree
Employed and/or student
Nicotine dependence
Alcohol or illicit drug abuse or dependence
Headache frequency, d/mo
Duration of headache, years
EM
CM
MOH
Controls
37.4 ⫾ 4.6
39.4 ⫾ 12.03
43.9 ⫾ 11.2
37.7 ⫾ 11.5
<.048†
24
6
17
7
31
2
18
11
<.02‡
10 (33.3%)
20 (66.6%)
25 (83.3%)
8 (26.6%)
6 (20%)
5.3 ⫾ 2.6
18.3 ⫾ 8.0
7 (29.1%)
17 (70.8%)
17 (70.8%)
8 (33.3%)
7 (29.1%)
21.3 ⫾ 5.2
15.1 ⫾ 11.7
16 (48.4%)
17 (51.5%)
20 (60.6%)
11 (33.3%)
3 (9%)
21.6 ⫾ 5.2
23.3 ⫾ 14.4
20
9
23
12
0
(68.9%)
(31.0%)
(79.31%)
(41.3%)
(0%)
–
–
P
<.01§
<.04¶
n.s.
<.01‡‡
<.0001‡‡
<.056§§
Statistical significance:
†ANOVA test (F = 2.71); ‡chi-square value = 9.82; §chi-square value = 10.92; ¶chi-square value = 12.67; ††chi-square value = 10.99;
‡‡Kruskal–Wallis test (H = 58.81); §§Kruskal–Wallis test (H = 5.74).
4
Fig 1.—The histogram shows the psychiatric comorbidities in
episodic migraine (EM), chronic migraine (CM), medicationoveruse headache (MOH), and control subjects.
(62.06%) (Pearson chi-square = 9.8; df = 3; P < .021).
MOH patients were slightly older than subjects in the
other groups (ANOVA F = 2.70; P < .048). Post hoc
analysis showed that the difference in mean age was
significantly higher in MOH compared with EM
patients (P < .019) and control subjects (P < .013) but
not with CM patients.
A significant difference emerged among patient
groups in headache frequency (Kruskal–Wallis test:
H = 58.81, P = .0001). Post hoc analysis revealed no
significant difference between the MOH and CM
groups, whereas headache frequency values of both
chronic headache groups were significantly higher
than those of the EM group (P < .0001).
The duration of headache expressed in years was
greater in MOH patients than in the CM and EM
groups. Nevertheless, the difference reached a level of
statistical significance only between the MOH and
CM groups (Kruskal–Wallis test between the 2
groups: H = 4.64, P < .0278) (Table 1).
In the MOH group, 25 patients overused analgesics (76%), 1 patient overused ergot derivatives (3%),
4 patients overused triptans (12%), and 3 patients
overused a combination of acute medications (9%).
There was a significantly higher prevalence of psychiatric comorbidity (anxiety disorders and mood
disorders) in MOH patients with respect to the
other groups (Pearson chi-square = 65.34, df = 15,
P < .0001) (Fig. 1) (Table 2).
Concerning anxiety disorders, we observed that
subclinical OCD was significantly prevalent in MOH
patients with respect to the other groups (Pearson
chi-square = 19.88, df = 3, P < .0002) (Table 2). The
total Y-BOCS score in MOH ranged from 8 to 20.
Descriptive statistics of Y-BOCS scale scores of
patients and controls with OCD are shown in
Table 3.
A statistically significant difference emerged
between MOH and EM (Kruskal–Wallis test:
H = 4.74, P < .0295) and controls (Kruskal–Wallis test:
H = 8.47,P < .0036) but not between MOH and CM.In
fact, Y-BOCS values of the CM group were also significantly higher than those of the EM group and
controls (Kruskal–Wallis test: H = 9.42 and H = 14.33,
P < .0021 and P < .0002, respectively) (Fig. 2).
A weak but significant correlation between
Y-BOCS scores and headache frequency also
emerged, independently of headache type (Spearman
rank order correlation R = 0.24, P < .0227) (Fig. 3).
Conversely, there was no correlation between
Y-BOCS scores and years of disease. Interestingly, in
the subgroup of patients with CM there was more
likely a history of alcohol or illicit drug abuse or
dependence (Pearson chi-square = 10.39, df = 3,
P < .01), while there were no significant differences in
terms of nicotine dependence among groups. Headache frequency and years of disease were not significantly different in the subjects with subclinical OCD
vs non-OCD subjects. Subjects with subclinical OCD
were older than those without OCD in the CM
Fig 2.—The graph shows the trend of the mean Y-BOCS scores
in episodic migraine (EM), chronic migraine (CM),
medication-overuse headache (MOH), and control subjects.
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Table 2.—Psychiatric Comorbidities in Episodic Migraine (EM), Chronic Migraine (CM), Medication-Overuse Headache
(MOH), and Controls
EM (%)
(n = 30)
CM (%)
(n = 24)
MOH (%)
(n = 33)
Controls (%)
(n = 29)
All anxiety disorders
Subclinical OCD
Subclinical OCD plus depression
Subclinical OCD plus social phobia
Subclinical OCD plus panic disorder
GAD
Social phobia
Social phobia plus panic disorder
3 (10%)
3 (10%)
–
–
–
–
–
–
10
6
2
1
20 (61%)
12 (36%)
–
3 (9%)
1 (3%)
3 (9%)
–
1 (3%)
2 (7%)
2 (7%)
–
–
–
–
–
–
All mood disorders
Major depressive
Dysthymia
Bipolar disorder
Absence of psychiatric comorbidity
–
–
–
27 (90%)
(42%)
(25%)
(8%)
(4%)
–
–
1 (4%)
–
1 (4%)
–
1 (4%)
–
13 (54%)
9
5
3
1
4
(27%)
(15%)
(9%)
(3%)
(12%)
–
–
–
27 (93%)
GAD = generalized anxiety disorder; OCD = obsessive-compulsive disorder.
(47.33 ⫾ 7.97 vs 34.73 ⫾ 11.75) and control groups
(47.00 ⫾ 9.89 vs 37.11 ⫾ 11.48) but not in the MOH
(44.06 ⫾ 12.59 vs 43.88 ⫾ 10.19) and EM patient
groups (38.0 ⫾ 5.56 vs 37.11 ⫾ 11.48).
A prevalence of females was found in the MOH
and CM patient groups with subclinical OCD
(42.42% out of 48.46% and 33.30% out of 41.60% in
the two groups respectively). In the EM group,
10.00% out of 16.66% of the cases with subclinical
OCD was represented by males, whereas the only 2
patients with subclinical OCD (6.79% of the total
group) of control subjects were males.
No significant differences emerged regarding the
level of education, employment, or student status
between patients with subclinical OCD and those
without in all patient and control groups.
DISCUSSION
One of the major findings of this study is the
higher prevalence of psychiatric comorbidity (anxiety
and mood disorders) in the group of patients with
MOH compared with controls, EM, and CM. This
finding is in agreement with previous studies.1 Interestingly, among anxiety disorders we observed a
higher prevalence of subclinical OCD in MOH. Two
previous studies failed to provide univocal data on
the association between migraine and OCD.3,4 Since
both of these studies were population-based studies
Table 3.—Descriptive Statistics of Y-BOCS Scale Scores of Patients and Controls with OCD
Number of
patients
with OCD
Mean
EM
CM
MOH
3 of 30
9 of 24
16 of 33
Controls
2 of 29
+95% CI
Y-BOCS
minimum
score
Y-BOCS
maximum
score
10.71
8.52
11.37
14.71
15.03
14.87
10.00
5.00
8.00
20.00
16.00
20.00
2.65
30.01
1.00
3.00
Median
Standard
error
-95% CI
16.33
11.77
13.12
19.00
12.00
12.5
3.17
1.41
0.82
2.00
2.00
1.00
6
Fig 3.—The scatter-plot shows the correlation between headache frequency and the Yale-Brown obsessive compulsive scale
score.
of high methodological quality, the reasons for this
discrepancy remain unclear. However, none of these
two studies addressed the issue of OCD comorbidity
in a population of MOH subjects compared with
either EM or CM patients.
Obsessive-compulsive disorder is a chronic
anxiety disorder with a waxing and waning course.31
This clinically heterogeneous condition, like other
mental disorders, is often under-recognized, with an
apparently high rate of subthreshold, transient, and
misclassified cases of OCD.31 Moreover, OCD is associated with high rates of neuroses (depressive
episode, generalized anxiety disorder, agoraphobia or
panic disorder, social phobia, and specific phobia).31,32
A co-occurrence of alcohol dependence and drug
dependence has also been observed in OCD.32 In
addition, OCD, compared with other neurotic disorders, was also found associated with more marked
social and occupational impairment.32 Subclinical
OCD symptoms are relatively common in nonclinical
populations and share common neurobiological substrates with clinical OCD.33 The diagnosis of OCD is
considered definite if all required DSM-IV criteria
are met. A diagnosis of subclinical OCD is given if
characteristic OCD symptoms are present but the criterion of significant distress or impairment or of duration (>1 hour per day) is not met.22,33 Subclinical OCD
has been considered a syndrome distinct from OCD
which is also associated with significant impairments
in personal and interpersonal functions and in quality
of life.24 Moreover, previous studies dealing with
either neuropsychological characteristics or epidemiological features have shown that subclinical OCD
can be measured and analyzed in a reliable manner.22,23,33 We observed a co-occurrence of subclinical
OCD with other anxiety or mood disorders in both
CM and MOH. Although we found a higher prevalence of subclinical OCD in the MOH group compared with the other groups, it is worth noting that
subclinical OCD was also observed in CM and EM.
An interpretation of this latter finding could be that
subclinical OCD might play a role not only in MOH
but also contribute to the mechanisms leading to the
switch from EM and CM to MOH.
We observed a lower rate of psychiatric comorbidity in CM compared with MOH. Nevertheless, it is
important to screen for both mood and anxiety disorders in subjects with EM and CM. The observed high
rate of comorbidity between MOH and psychiatric
disorders might affect headache prognosis.
Medication-overuse headache is a major problem
that is often not effectively treated. Previous studies
tried to identify predictive factors with regard to the
outcome after withdrawal in patients with MOH.34
The comorbidity of OCD with MOH might account
for relapse. The propensity to relapse after sometimes
prolonged periods of withdrawal is a critical aspect of
drug seeking behavior.35
It is interesting to note that in a previous study on
the psychiatric comorbidity in MOH patients evolving
from episodic tension-type headache and migraine, a
high rate of obsessive-compulsive personality disorder
(OCPD) was observed in patients with preexisting
EM.36 However, although there is evidence that OCD
and OCPD are linked, the literature does not support
either one as a necessary or sufficient component of
the other. Thus, we cannot make any comparison
between our study and the previous one.36
In our study the sample had a prevalence of
MOH female subjects; accordingly, previous studies
also observed a higher prevalence of MOH in
females.37
Surprisingly, at variance with previous studies, in
the present study MOH patients had a lower rate of
Headache
alcohol and illicit drug dependence compared with
CM.11,12 Although our finding might reflect a bias
related to the sample studied, it cannot be excluded
that it represents the varied expression of vulnerability to substance dependence in some chronic
migraineurs.
Although MOH has been found to be associated
with behaviors of substance dependence,12 whether
overuse of headache medications represents a
subtype of substance dependence is still controversial.9,38 Moreover, the link between drug-dependent
behavior and compulsion is complex. It has been proposed that drug use is triggered to obtain specific
actions on brain reward circuits. After a certain
period, excessive drug intake can paradoxically
decrease the response of these reward circuits.39 Thus,
compulsive drug intake might develop in response to
such aberrant adaptive decreases in brain reward
systems. Similarly, we can speculate that in MOH the
trigger for excessive drug intake is initially represented by pain relief that is able, in turn, to activate
reward circuits. Then, compulsive drug use in headache patients no longer leads to the activation of
these brain reward systems but it rather paradoxically
facilitates pain sensitization mechanisms.The possible
link between compulsive drug use and MOH still
remains unclear and its mechanistic understanding
will require future multidisciplinary investigations.
Our study has several strengths, including the
diagnosis of headache by an experienced headache
specialist, psychiatric diagnosis by an experienced
psychiatrist and standardized data collection. Moreover, in the present study, we have used those clinical
instruments that, according to current literature, are
considered the appropriate measures to collect information with maximal reliability and validity.22,28-30,40
Several limitations, however, must be considered. We
studied a patient population from two specialized
headache centers, and therefore we cannot necessarily extend these results to other populations. This
could also explain the relatively high psychiatric
comorbidity rates we observed. We are aware that the
relatively limited number of subjects included in our
study cannot allow us to draw definitive conclusions,
in particular regarding negative findings. Our study
could be viewed as hypothesis generating; in fact,
7
studies of comorbidity are best conducted in representative samples of the general population. In addition, a longitudinal study might determine whether
one condition predisposes to the other or if each disorder predisposes to the other.
Further research on population-based samples is
needed to confirm the link between subclinical OCD
and MOH. Comparison studies are also needed in
different geographic areas, in individuals of different
socioeconomic groups, and in various racial/ethnic
groups and cultures.
REFERENCES
1. Radat F, Swendsen J. Psychiatric comorbidity in
migraine: A review. Cephalalgia. 2005;25:165-178.
2. Hamelsky SW, Lipton RB. Psychiatric comorbidity
of migraine. Headache. 2006;46:1327-1333.
3. Breslau N, Davis GC, Andreski P. Migraine, psychiatric disorders, and suicide attempts: An epidemiologic study of young adults. Psychiatry Res. 1991;
37:11-23.
4. Swartz KL, Pratt LA, Armenian HK, Lee LC, Eaton
WW. Mental disorders and the incidence of migraine
headaches in a community sample: Results from the
Baltimore Epidemiologic Catchment area follow-up
study. Arch Gen Psychiatry. 2000;57:945-950.
5. Baskin SM, Lipchik GL, Smitherman TA. Mood and
anxiety disorders in chronic headache. Headache.
2006;46(Suppl. 3):S76-S87.
6. Headache Classification Committee, Olesen J,
Bousser MG, et al. New appendix criteria open for a
broader concept of chronic migraine. Cephalalgia.
2006;26:742-746.
7. Bigal ME, Lipton RB. Modifiable risk factors for
migraine progression. Headache. 2006;46:1334-1343.
8. Peres MF, Sanchez del Rio M, Seabra ML, et al.
Hypothalamic involvement in chronic migraine. J
Neurol Neurosurg Psychiatry. 2001;71:747-751.
9. Calabresi P, Cupini LM. Medication-overuse headache: Similarities with drug addiction. Trends Pharmacol Sci. 2005;26:62-68.
10. Rainero I, Ferrero M, Rubino E, et al. Endocrine
function is altered in chronic migraine patients with
medication-overuse. Headache. 2006;46:597-603.
11. Radat F, Creac’h C, Swendsen JD, et al. Psychiatric
comorbidity in the evolution from migraine to medication overuse headache. Cephalalgia. 2005;25:519522.
8
12. Fuh JL, Wang SJ, Lu SR, Juang KD. Does medication overuse headache represent a behavior of
dependence? Pain. 2005;119:49-55.
13. Radat F, Creac’h C, Guegan-Massardier E, et al.
Behavioral dependence in patients with medication
overuse headache: A cross-sectional study in consulting patients using the DSM-IV criteria. Headache. 2008;48:1026-1036.
14. Ferrari A, Cicero AF, Bertolini A, Leone S,
Pasciullo G, Sternieri E. Need for analgesics/drugs
of abuse: A comparison between headache patients
and addicts by the Leeds Dependence Questionnaire (LDQ). Cephalalgia. 2006;26:187-193.
15. Saper JR, Hamel RL, Lake AE III. Medication
overuse headache (MOH) is a biobehavioural disorder. Cephalalgia. 2005;25:545-546.
16. Kalivas PW, Volkow ND. The neural basis of addiction: A pathology of motivation and choice. Am J
Psychiatry. 2005;162:1403-1413.
17. Volkow ND, Fowler JS. Addiction, a disease of compulsion and drive: Involvement of the orbitofrontal
cortex. Cereb Cortex. 2000;10:318-325.
18. Hyman SE, Malenka RC, Nestler EJ. Neural
mechanisms of addiction: The role of reward-related
learning and memory. Annu Rev Neurosci. 2006;29:
565-598.
19. Hyman SE, Malenka RC. Addiction and the brain:
The neurobiology of compulsion and its persistence.
Nat Rev Neurosci. 2001;2:695-703.
20. Remijnse PL, Nielen MM, van Balkom AJ, et al.
Reduced orbitofrontal-striatal activity on a reversal
learning task in obsessive-compulsive disorder. Arch
Gen Psychiatry. 2006;63:1225-1236.
21. Fumal A, Laureys S, Di Clemente L, et al. Orbitofrontal cortex involvement in chronic analgesicoveruse headache evolving from episodic migraine.
Brain. 2006;129:543-550.
22. Stein MB, Forde DR, Anderson G, Walker JR.
Obsessive-compulsive disorder in the community:
An epidemiologic survey with clinical reappraisal.
Am J Psychiatry. 1997;154:1120-1126.
23. Mataix-Cols D, Barrios M, Sànchez-Turet M, Vallejo
J, Junqué C. Reduced design fluency in subclinical
obsessive-compulsive subjects. J Neuropsychiatry
Clin Neurosci. 1999;11:395-397.
24. Grabe HJ, Meyer C, Hapke U, et al. Prevalence,
quality of life and psychosocial function in obsessivecompulsive disorder and subclinical obsessivecompulsive disorder in northern Germany. Eur Arch
Psychiatry Clin Neurosci. 2000;250:262-268.
25. Grabe HJ, Ruhrmann S, Ettelt S, et al. Familiality of
obsessive-compulsive disorder in nonclinical and
clinical subjects. Am J Psychiatry. 2006;163:19861992.
26. Headache Classification Committee of the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias
and facial pain, 2nd edition – 1st Revision ICHDIIR1. 2005. [WWW document], URL http://www.i-hs.org
27. Silberstein SD, Olesen J, Bousser MG, et al. On
behalf of the International Headache Society. The
international classification of Headache Disorders,
2nd Edition (ICHD-II)-revision of criteria for 8.2
Medication-overuse headache. Cephalalgia. 2005;
25:460-465.
28. Olesen J. The international classification of headache disorders. Headache. 2008;48:691-693.
29. American Psychiatric Association. Diagnostic and
Statistical Manual of Mental Disorders (4th edn)
(DSM-IV). Washington, DC: American Psychiatric
Association; 1994.
30. Goodman WK, Price LH, Rasmussen SA, et al. The
yale-brown obsessive compulsive scale. I. Development, use, and reliability. Arch Gen Psychiatry.
1989;46:1006-1011.
31. Jenike MA. Obsessive-compulsive disorder. N Engl
J Med. 2004;350:259-265.
32. Torres AR, Prince MJ, Bebbington PE, et al.
Obsessive-compulsive disorder: Prevalence, comorbidity, impact, and help-seeking in the British
National Psychiatric Morbidity Survey of 2000. Am J
Psychiatry. 2006;163:1978-1985.
33. Mataix-Cols D, Junqué C, Sànchez-Turet M, Vallejo
J, Verger K, Barrios M. Neuropsychological
functioning in a subclinical obsessive-compulsive
sample. Biol Psychiatry. 1999;45:898-904.
34. Katsarava Z, Muessig M, Dzagnidze A, Fritsche G,
Diener HC, Limmroth V. Medication overuse headache: Rates and predictors for relapse in a 4-year
prospective study. Cephalalgia. 2005;25:12-15.
35. Everitt BJ, Robbins TW. Neural systems of
reinforcement for drug addiction: From actions to
habits to compulsion. Nat Neurosci. 2005;8:14811489.
36. Atasoy HT, Atasoy N, Unal AE, Emre U, Sumer M.
Psychiatric comorbidity in medication overuse
headache patients with pre-existing headache type
of episodic tension-type headache. Eur J Pain.
2005;9:285-291.
Headache
37. Bigal ME, Rapoport AM, Sheftell FD, Tepper S,
Lipton R. The International Classification of
Headache Disorders revised criteria for chronic
migraine-field testing in a headache specialty clinic.
Cephalalgia. 2007;27:230-234.
38. Lake AE. Medication overuse headache: Biobehavioral issues and solutions. Headache. 2006;46(Suppl.
3):S88-S97.
9
39. Kenny PJ. Brain reward systems and compulsive
drug use. Trends Pharmacol Sci. 2007;28:135-141.
40. Skre I, Onstad S, Torgersen S, Kringlen E. High
interrater reliability for the Structured Clinical
Interview for DSM-III-R Axis I (SCID-I). Acta Psychiatr Scand. 1991;84:167-173.