Abstract
Introduction
Factors associated with the development of medication overuse (MO) are not fully understood. The aim of this article is to investigate whether patients diagnosed with migraine with and without MO differed in personality characteristics.
Methods
The study was a single-center observational study of patients with migraine, as defined by the International Classification of Headache Disorders III (ICHD-III). After written consent, patients were given access to an online survey. Scores obtained in the Severity of Dependence Scale (SDS) and NEO Five-Factor Inventory (NEO-FFI), namely openness to experience, conscientiousness, extraversion, agreeableness, and neuroticism, from both patients with and without MO were compared applying Mann–Whitney U-test.
Results
A total of 128 patients completed the survey, of which 46 (35.9%) were migraine patients with analgesic overuse. Patients with migraine and MO were significantly older (41.2 ± 8.6 vs. 37.5 ± 11.4, p = 0.015), while the percentage of female patients was equivalent between groups (73.3% vs. 86.4%, p = 0.068). Migraine patients with MO reported more frequent past or current visits to mental care providers (52.2% vs. 29.4%, p = 0.015). Scores obtained in the SDS were comparable between groups (2.8 ± 3.8 vs. 2.3 ± 2.9, p = 0.756). Patients with migraine without MO scored significantly higher on agreeableness (p = 0.016). No differences were observed between groups regarding the remaining personality characteristics.
Conclusions
Migraine patients with MO were significantly more likely to report past or current visits to mental health care providers compared to those without MO. Differences in personality traits were minimal, with only agreeableness being significantly higher in migraine patients without MO.
This is a visual representation of the abstract.
Introduction
Medication overuse headache (MOH) is a challenging, disabling, and mostly underdiagnosed condition.1–3 MOH occurs in patients who suffer from primary headaches, such as migraine or tension-type headaches, and use headache abortive medications too frequently. This analgesic overuse, counterintuitively, leads to a worsening of headache severity and frequency, contributing to chronification of pain.
MOH has a significant impact on quality of life. 1 The great majority of patients with MOH are young and working, having their productivity severely affected, which contributes to a high economic burden for the healthcare system. 4
To meet the diagnostic criteria for MOH in the most recent International Classification of Headache Disorders (ICHD) edition (International Classification of Headache Disorders III (ICHD-III)), patients must have headache on ≥15 days per month together with overuse of acute treatments for a pre-existing (usually primary) headache disorder (overuse being defined by thresholds that vary with medication class), both persisting for >3 months.5,6 In contrast, the term medication overuse (MO) refers specifically to the use of acute medications that surpass the defined thresholds. 6
According to previous studies, the prevalence of MOH in the general population ranges between 0.5% and 7.2%.1,7 Migraine is the most common risk factor associated with MO, affecting 78% of patients. Also, Bigal et al. 2 demonstrated that opiates and barbiturates confer a twofold risk of migraine chronification. Triptans increase the risk of chronic headaches mostly in people who have a high baseline frequency of migraine. 1
Multiple psychiatric disorders, namely anxiety, depression, and obsessive-compulsive disorder, are associated with MOH. 8–10 Some studies show that 40% of MOH patients met the criteria for depression and 58% met the criteria for anxiety. 1 Substance-related and addictive disorders are also known risk factors for MO, with overlapping pathophysiological mechanisms.
Personality might also be one psychological factor that influences the onset and maintenance of headaches. In a recent study, an age-matched cohort of episodic migraine patients (n = 94) and MOH patients (n = 94) were compared to a Danish normative sample (n = 1032). MOH females obtained significantly lower scores on extraversion (p < 0.01), openness (p < 0.01), and conscientiousness (p < 0.01) as compared to female patients with migraine. Compared to the normative sample, both headache groups showed a lower score on extraversion (p < 0.01).3,11
The aim of this article is to investigate whether patients with migraine with and without MO differed in personality characteristics.
Methods
Study design
Episodic migraine patients followed at the Headache Outpatient Clinic in a northern Portuguese tertiary hospital (Unidade Local de Saúde de Braga, Braga, Portugal) between January 2022 and June 2024 were asked to participate in the survey.
Information about the study was given by the attending neurologist at routine consultations at the Headache Clinic. After giving oral consent, written information was sent by e-mail, and patients were asked to give written consent, allowing them to access the survey. This study was approved by the local Ethics Committee.
Study population
Patients were eligible for participation if they were proficient in Portuguese, aged over 18 years old, and diagnosed with migraine according to the ICHD-III criteria. 5
Two groups of patients were created: patients with migraine with and without MO. MO was classified as ≥ 10 days per month for triptans, ergots and opioids; ≥ 15 days per month for simple analgesics (such as paracetamol or non-steroidal anti-inflammatory drugs); and ≥ 10 days per month for combinations of multiple drug classes. 6
Patients were included in the MO group if they met the criteria for MO at any time point during follow-up at the Headache Outpatient Clinic; hence both patients with current (active) and past (resolved) MO were considered.
Rating scales and questionnaires
Severity of dependence scale
The Severity of Dependence Scale (SDS) includes five items, each scored on a 4-point scale.12–14 The total score is obtained through the addition of the 5-item ratings so that the higher the score, the higher the level of dependence. The SDS was developed to measure the degree of dependence experienced by drug users, explicitly the psychological components of dependence, impaired control over addictive behavior, and anxiety driven by substance use.
Personality questionnaire
To assess the personality, we used the Portuguese version of the NEO Five-Factor Inventory (NEO-FFI). 15 The NEO-FFI was designed to assess the constellation of traits defined by the Five-Factor Theory of Personality: (1) openness, characterized by originality, curiosity, and ingenuity; (2) conscientiousness, which denotes orderliness, responsibility, and dependability; (3) extraversion, characterized by talkativeness, assertiveness, and energy; (4) agreeableness, that can also be seen as a combination of friendliness and compliance, and (5) neuroticism, the polar opposite of emotional stability.
Each trait is defined by 12 items that are answered on a 5-point Likert scale, ranging from “strongly agree” to “strongly disagree.” For each of the five personality descriptors, a raw score is calculated by adding the 12 items, the final score ranging between 0 and 48 points.
Statistics
Statistical analysis was performed using SPSS Version 29 for Windows (IBM, Armonk, NY).
Differences in continuous variables between groups were tested with the Mann–Whitney U-test, while the chi-square test was used when comparing categorical outcomes. Results are presented as mean and standard deviation (SD) or as numbers and percentages in brackets (%).
Statistical significance was set at p < 0.05.
Results
Baseline characteristics
A total of 128 patients completed the survey, of which 82 were migraine patients with no history of MO and 46 were migraine patients with MO. Demographic baseline characteristics are presented in Table 1.
Baseline characteristics of patients and severity of dependence scale scoring.
MO: medication overuse; SDS: Severity of Dependence Scale; SD: standard deviation.
* p-value < 0.05 is considered to be statistically significant.
Overall, the median age was 40 years (minimum: 18; maximum: 76) and 81.7% were female responders. Migraine patients with MO were older (median age: 41.2 years vs. 37.5 years, p = 0.015), but both groups had similar ages at the onset of headache disorder (median age: 19.8 years vs. 21.7 years, p = 0.396). No difference in gender distribution (percentage of males: 26.7% vs. 13.6%, p = 0.068) was observed between groups.
From our sample, 22 patients had comorbid pain conditions (e.g. fibromyalgia, neck pain, and low back pain), equally distributed between groups (12 individuals without MO and 10 with MO, p = 0.426).
Psychiatric comorbidities and substance dependence
Migraine patients with MO reported more frequently past or current visits to a psychiatrist or other mental care provider (percentage of patients: 52.2% vs. 29.4%, p = 0.015). In fact, a higher percentage of patients with MO had comorbid depression (30.2% vs. 12.9%, p = 0.024), while no difference was observed in the percentage of patients with anxiety (16.3% vs. 7.1%, p = 0.126).
In relation to substance dependency (other than headache abortive medications), no difference in the percentage of smokers was seen between groups (15.2% vs. 13.4%, p = 0.778). Following the same trend, the score obtained in the SDS was comparable between those with and without MO (2.8 ± 3.8 vs. 2.3 ± 2.9, p = 0.756) (Table 1).
Headache frequency and headache abortive medications
Overall, patients with migraine had a mean of 9.51 (± 6.75) days of pain in the previous month. Regarding headache frequency, no difference was found between those with and without MO (9.17 ± 5.90 days vs. 10.11 ± 8.05 days, p = 0.901).
Patients with migraine and MO consumed significantly more non-steroidal anti-inflammatory drugs (3.66 ± 3.01 tablets per week vs. 2.74 ± 3.31 tablets per week, p = 0.035), triptans (2.26 ± 3.00 tablets per week vs. 1.14 ± 1.71 tablets per week, p = 0.006), and ergotaminics (0.63 ± 1.54 tablets per week vs. 0.10 ± 0.41 tablets per week, p = 0.024). No difference was found in the consumption of opioid drugs (0.03 ± 0.18 tablets per week vs. 0.20 ± 0.95 tablets per week, p = 0.238) (Table 2).
Comparison of headache days, per month, and number of analgesics, per week.
MO: medication overuse; NSAIDs: non-steroidal anti-inflammatory drugs; SD: standard deviation.
* p-value < 0.05 is considered to be statistically significant.
Regarding preventive medication for migraine, a significantly higher percentage of patients with MO were using at least one preventive drug (both oral and CGRP monoclonal antibodies were considered), compared with those without MO (97.7% vs. 58.6%, p < 0.001).
Personality
Patients with migraine without MO scored statistically significantly higher on agreeableness when compared to the MO group (p = 0.016). No significant differences were observed between groups on the openness, conscientiousness, extraversion, and neuroticism traits (Table 3).
Scores of each of the five personality descriptors in NEO-FFI of migraine and MO patients.
MO: medication overuse; NEO-FFI: Neuroticism-Extraversion-Openness Five-Factor Inventory; SD: standard deviation.
* p-value < 0.05 is statistically significant.
Sex differences were also observed in the personality trait agreeableness, showing that the group of male patients with migraine and MO had a significantly lower score compared to the male patients with migraine without MO (7.083 ± 3.059 vs. 9.818 ± 2.272, p = 0.027). This was not the case for females, where no differences between groups were found (all p values > 0.05). Also, the remaining traits of personality showed no statistically significant differences between groups regardless of sex.
Supplemental Table 1 presents the results from the comparative analyses, when the groups are stratified by sex and (the presence or absence of) psychiatric comorbidities.
Discussion
A major finding of this study was that MO patients had a significantly greater burden of psychopathological comorbidities, namely comorbid depression. Sarchielli et al. 8 had previously shown that MO patients had a more complex profile of psychiatric comorbidities, including moderate/severe anxiety, depression, and obsessive-compulsive disturbances.
Previous studies have proposed that MO may, in fact, stem from a dependency-related behavior, including self-medication, anxiety in the face of an analgesic prescription shortage, and loss of control over the use of pain relievers. We found no such tendency in our cohort, with equivalent scores in SDS, in addition to an analogous percentage of smokers between groups.
In our sample of patients with migraine, those with and without MO did not significantly differ in the number of headache days per month. Notwithstanding, patients with MO reported taking significantly more simple headache abortive medications. These results may point to ineffective coping strategies in patients with migraine who develop MO, with the threshold for analgesic overuse possibly lowered by psychopathological comorbidities. Unlike other types of headache abortive medications, we found that the use of opioid analgesics is not superior in the group with medication overuse, which may be related to the fact that it is a drug generally less prescribed by the medical community and therefore less accessible.
Agreeableness is a personality trait that can be described as cooperative, polite, kind, and friendly. Accordingly, individuals who score high in agreeableness are more trusting, affectionate, and altruistic, and generally display more prosocial behaviors than others. 16 We propose that the lower agreeableness score is a consequence of headache-related disability, which causes headache patients in general to be less socially active than the general population. This can be both because of unwillingness to be with other people when in pain, especially in crowded and loud environments, but patients with migraine also frequently report withdrawal from social gatherings for fear of triggering an attack.
We did not find any between-group differences with respect to the trait neuroticism. Neuroticism is a core personality trait characterized by emotional instability, irritability, anxiety, self-doubt, depression, and other negative feelings. 16 This finding is particularly surprising, as a significantly greater percentage of MO patients reported past or current visits to a psychiatrist or other mental care provider. Needless to say, polarized psychological traits, such as high neuroticism, are not the only reason for patients to need psychological counseling. It may be that, despite their personality types, some patients develop inadequate coping strategies, leading to anxiety, depression, and, in the case of patients with migraine, analgesic overuse
That may, in fact, be the reason for the difference in agreeableness in patients with and without psychiatric comorbidities; the former might just have exhausted their strategies to manage and overcome problems, including headaches.
A major study investigating personality traits in migraine, conducted in Denmark, had already found differences between genders regarding the way pain was perceived and how males and females respond to it. Interestingly, Mose et al. concluded that females with MO displayed lower scores of extraversion, openness, and conscientiousness. They interpreted these findings taking into consideration gender impact on perception and response to pain, but these results should be further explored, as the number of males was very low in this study (total n = 41). 17
Indeed, the same holds true for our results, as the number of male responders was also low, as is usually the case in migraine clinical studies. Several of these studies have proven that women are more likely to experience most migraine-associated symptoms (namely nausea, vomiting, photophobia, phonophobia, and visual aura), in addition to more frequently requiring bed rest and experiencing a longer duration of impairment in function after a migraine attack compared to men. 17
Conducting a psychological assessment is a crucial first step in evaluating and treating patients with MO. A thorough explanation of the consequences of analgesic overuse and counseling on drug withdrawal should be addressed in every medical appointment.
Strengths and limitations
The questionnaire was easily accessible to the patients and completion was feasible, which made data collection very cost-effective and implementable in clinical practice. A full personality and psychopathological assessment, conducted by a psychologist/psychiatrist, would have been more thorough and reliable, but much more difficult to carry out during everyday clinical practice. The same principle holds true for a headache diary, a validated tool to assess headache frequency that requires patient adherence.
This is a cross-sectional study, which limits the ability to establish causal relationships between any personality trait and the development of medication overuse.
In our study, MO was a surrogate for MOH, although they are not truly interchangeable terms as MO can occur without increased headache frequency. It would have been interesting to assess a true MOH population prospectively to ascertain whether there are personality traits that make patients more likely to succeed in the withdrawal of overused medication.
External validity
Regarding reproducibility of our results in a primary care setting or even in the general population is difficult to appraise, as a patient's referral to our tertiary care clinic requires their condition to be refractory to multiple (at least two) oral preventives (or having intolerable side effects). In addition, our referral times are suboptimal, leaving patients unattended and unsupported, potentially predisposing them to MO. In any case, these refractory patients should be further investigated to identify modifiable risk factors and strategies to address the complex problem of MO.
Conclusion
MO is a common and disabling condition that remains an undiagnosed and under-recognized clinical entity despite being a proven risk factor for headache chronification. Our study indicates that patients with MO report a higher concurrence of psychopathological comorbidities. These can overburden patients with migraine, which end up resorting to MO, leading to poorer quality of life and possibly influencing personality, turning patients into less agreeable individuals.
MO based on our findings, it may be beneficial to screen episodic migraine patients with high attack frequencies for psychopathological traits to improve their management.
Future research should also explore whether appropriate behavioral treatments can improve outcomes in medication overuse or medication overuse management.
As for everyday clinical care, Portuguese patients with migraine could derive benefit from a multidisciplinary approach, including counseling by a dedicated psychotherapist. 9–11
Clinical implications
It is important to screen patients with episodic migraine and high attack frequency for psychopathological traits.
Future research should investigate whether or not appropriate behavioral treatment may improve medication overuse headache management.
Supplemental Material
sj-docx-1-rep-10.1177_25158163251318713 - Supplemental material
Supplemental material, sj-docx-1-rep-10.1177_25158163251318713 for Medication overuse in patients with migraine: Severity of dependence and personality characteristics by Sofia Alexandra Reis Marques, Matilde Silva Gomes, Andreia Ferreira, Lu챠Costa, Sofia Lopes, and Sara Dias Varanda in Cephalalgia Reports
Footnotes
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Ethical approval
This study was approved by the local Ethics Committee.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Patient consent
Oral and written consent were obtained from patients to enroll in the study.
Supplemental material
Supplemental material for this article is available online.
References
Supplementary Material
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