Abstract
Introduction
Medication overuse headache (MOH) is incurred by the excessive use of acute medications, including over-the-counter (OTC) treatments. This study aimed to characterize the burden, management, and treatment satisfaction of patients with migraine with or without MOH in Japan.
Methods
Data were derived from the Adelphi Migraine Disease Specific Programme (DSP)™, a cross-sectional survey conducted in Japan from August 2023 to February 2024. Physicians provided data for consecutive patients, including demographics, clinical characteristics, current treatment, OTC treatment usage, and treatment satisfaction. Patients voluntarily reported their symptom burden, migraine pain severity, and treatment satisfaction. Alignment between physician and patient regarding treatment satisfaction was assessed using Cohen’s weighted kappa statistics and multivariable regression models.
Results
Overall, 122 physicians provided data for 820 patients with migraine, 7.0% (n = 57) of whom had a diagnosis of MOH; 41.5% (n = 340) of patients self-reported data, with 3.2% (n = 11) having a diagnosis of MOH. Patients with MOH were more likely to experience chronic migraine (79%, n = 45), greater migraine frequency, and more severe migraine than those without MOH. Ninety percent of both groups received acute treatment. Patients with MOH were significantly more likely to receive preventive treatment than those without MOH (86% vs 56.6%, p < 0.001). OTC medication use was reported at 3.3% by physicians and 11.2% by patients. The alignment between physician and patient treatment satisfaction was low for acute treatment. The exploratory model analysis indicated that OTC use may have contributed to this misalignment.
Conclusion
Our study revealed that the alignment regarding treatment satisfaction with acute medications is low. OTC treatment usage may have inflated physician satisfaction with prescribed acute medications and caused a discrepancy regarding satisfaction of patients with MOH. To improve patient outcomes, it is essential to align drug effectiveness ratings between physicians and patients by enhancing communication and mutual understanding.
Keywords: Chronic migraine, Medication overuse headache, Migraine, Over-the-counter medication, Quality of life, Treatment patterns, Treatment satisfaction
Key Summary Points
| Why carry out this study? |
| Migraine-related medication overuse headache (MOH) is a complication affecting 2.3% of the general population in Japan and is often associated with chronic migraine |
| Early intervention is imperative to address MOH, with both physician and patient awareness key factors in reducing the prevalence of MOH |
| This study aimed to characterize the disease burden associated with MOH as well as alignment between physicians and patients regarding treatment satisfaction |
| What was learned from this study? |
| This study reported that the alignment on treatment satisfaction of acute treatment between physicians and patients was low, potentially because of using over-the-counter (OTC) treatment |
| To improve outcomes in patients with MOH, better communication between physicians and patients is essential, including careful assessment and monitoring of OTC use |
Introduction
Migraine is a neurological condition defined as recurrent headaches, often characterized by throbbing unilateral headache pain [1]. Migraine can be classified as either chronic or episodic, with chronic migraine considered more disabling and burdensome [2]. In Japan, the prevalence of migraine was estimated to be between 6.0 and 8.9% [3]. According to the Global Burden of Disease study, migraine is the second most common cause of disability worldwide [4, 5]. Migraine can lead to significant overall burden regarding health-related quality of life (HRQoL), including anxiety, depression, and increased activity impairment and decreased work productivity [6–8].
The primary goal of treatment is to relieve the symptomatic burden of migraine episodes and to prevent the transition from episodic migraine to chronic migraine [9]. Traditionally, acute treatments such as non-steroidal anti-inflammatory drugs (NSAIDs) are taken as soon as possible in response to a migraine attack [10]. In more severe cases of migraine, triptans are preferred and often prescribed together with preventative medications [11]. Since publication of clinical practice guidelines for headache disorders by the Japanese Society of Neurology in 2021 (Japanese only) [9], both acute and preventive treatment options have expanded. Lasmiditan, an oral 5-hydroxytryptamine (serotonin) receptor 1F (5-HT1F) agonist, was approved as an acute treatment in Japan in June 2022 [10, 12, 13]. Additionally, in early 2021, calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) targeting CGRP ligand or receptor were first introduced in Japan.
Chronic migraine is defined as headaches on ≥ 15 days per month, of which ≥ 8 are migraine-related headache days, for at least 3 months [1]. Ensuring a patient’s acute treatment is effective is an important factor to prevent migraine chronification [14]. Medication overuse headache (MOH) is defined as a headache that develops when a person uses either physician-prescribed acute medications or over-the-counter (OTC) headache medications excessively (> 10–15 days per month) for > 3 months [1, 15, 16]. Medications causing MOH include triptan, ergotamine, and NSAIDs, with different diagnostic criteria of overuse depending on the causative drug. In addition, MOH can be caused by multiple drug classes not individually overused. For example, when a combination of prescribed acute medications and OTC is used for > 10 days per month for > 3 months, the headache caused by those drugs can be diagnosed as MOH attributed to multiple drug classes not individually overused [1].
The prevalence of MOH in the general working population in Japan was reported to be around 2.3% [17]. However, MOH is often considered a complication of chronic migraine, with studies indicating a much higher prevalence of MOH among this population [18]. MOH and chronic migraine may interact with each other; patients who experience more frequent headaches may use their prescribed acute treatments and additional OTC medications more frequently, therefore increasing the likelihood of additional headaches caused by acute treatment overuse [19, 20].
For both the prevention and reduction of MOH, early intervention is imperative. Therefore, both physician and patient awareness is key. The widely accepted approach to MOH treatment is to ensure the patient is aware of MOH and acute treatment efficacy is optimized [21]. If further action is required, it is recommended to gradually withdraw acute treatment and administer preventative treatments instead [18, 21]. Management of MOH and chronic migraine requires the monitoring of headache days, overall disease burden, acute and OTC treatment usage, as well as treatment outcomes for both acute and preventive medications [9].
In summary, the most important clinical interventions to address the potential interaction between chronic migraine and MOH are: (1) consistently monitoring the efficacy of a patient’s acute and/ or OTC treatment, (2) accurately assessing overall migraine severity and number of headache days, and (3) ensuring equal awareness among physicians and patients so treatment goals and outcomes are aligned. However, a recent cross-sectional study of patients with migraine in Japan reported that physicians still have limited opportunities to discuss OTC use with their patients [22].
We hypothesize that the overall disease burden is greater, and treatment outcomes are worse in individual patients with migraine who currently have MOH. In addition, we hypothesize poor alignment between physicians and patients regarding treatment satisfaction as well as low physician awareness of the use of OTC treatment in addition to physician-prescribed treatments, both of which would indicate the existence of a physician-patient communication gap. To evaluate these hypotheses, it is necessary to use information obtained from both physicians and patients, but such reports have been limited to date.
The aim of this real-world cross-sectional study, using data from both physicians and their patients, was to characterize patients with migraine with and without MOH including clinical characteristics, disease burden, treatment patterns such as prescribed treatments and use of OTC, and treatment outcomes. Exploratory analyses were also conducted to assess the alignment of treatment satisfaction between physicians and patients and to explore the factors associated with treatment satisfaction.
Methods
Study Design
This study was an analysis of secondary data derived from the Adelphi Migraine Disease Specific Programme (DSP)™, a large, cross-sectional survey of physicians and their consulting patients presenting in a real-world clinical setting, conducted in Japan between August 2023 and February 2024. The DSP methodology has been previously described [23, 24], validated [25], and demonstrated to be representative and consistent over time [26]. The methodological approach is well established, with studies implemented globally across many different disease areas [24].
Eligibility Criteria
Physicians were recruited to participate in the DSP by local fieldwork agents following completion of a short screening questionnaire. Primary care practitioners (PCPs), neurologists, and neurosurgeons were eligible if they were responsible for treatment decisions and management of patients with migraine. PCPs were required to manage at least 10 patients with migraine per month, while neurologists and neurosurgeons were required to manage at least 20 patients with migraine per month. Physicians received compensation for their participation, based on fair market research rates.
Patients were eligible for inclusion in the survey if they met the following criteria: (1) aged ≥ 18 years, (2) had a physician-confirmed diagnosis of migraine, (3) were not involved in a clinical trial related to migraine, and (4) had consulted with the physician for the treatment of migraine. Patients were not compensated for participation in this study.
Physician-Reported Data
Physicians were instructed to complete patient record forms for the next 1–18 consecutive patients with migraine who presented for routine care related to migraine treatment to minimize selection bias. Each form was completed at the time of their most recent consultation, collecting cross-sectional data at the point of consultation, as well as retrospective information derived from patient historical clinical records.
The patient record form contained detailed questions on an individual patient’s demographics, clinical characteristics, presence of MOH, current treatment status (including physician-prescribed acute and preventative treatment history and additional use of OTC medications), satisfaction with physician-prescribed acute and preventative treatments, symptomatic burden, and comorbidities.
The patient record forms were completed by the participating physicians based on existing clinical records, supplemented by their own clinical judgment and diagnostic expertise. This represents the evidence they had when making any clinical treatment and other management decisions at the time of the consultation. Physician satisfaction with treatment was evaluated based on their personal judgment without any set criteria.
Patient-Reported Data
Each patient for whom the physician completed a record form was then invited to voluntarily complete a questionnaire. Questionnaires were filled out independently by the patients and returned to the physician in a sealed envelope. Patients reported on their current symptom burden, migraine pain severity, level of satisfaction with their acute and preventative treatments, use of OTC, and responses to the Migraine Treatment Optimization Questionnaire (mTOQ6) [27]. For data collection in Japan, the English tool was translated into Japanese by an accredited translation agency. A score of > 24 was used to determine adequate treatment response because of a score of 4 being determined as ‘adequate’ for each of the tool’s 6 subscales.
Migraine disability was assessed by the migraine disability assessment (MIDAS). The MIDAS is a patient-reported tool which measures the impact of migraine on a patient’s life. The MIDAS gives a score defining level of disability: 0–5 is little to no disability, 6–10 equals mild disability, 11–20 is moderate disability, and 21 + is severe disability [28–30].
Ethical Considerations
Data collection was undertaken in line with European Pharmaceutical Marketing Research Association guidelines and as such did not require ethics committee approval [31]. The survey materials were submitted to the PEARL Institutional Review Board (Ref #22-ADRW-143) and deemed to be exempt. In addition, each survey was performed in full accordance with relevant legislation at the time of data collection and in accordance with the Declaration of Helsinki of 1964 and its later amendments.
Using a checkbox, patients provided informed consent to take part in the survey. No identifiable protected health information was extracted during the survey. Data were collected in such a way that patients and physicians could not be identified directly, with data aggregated before being shared with the subscriber and/or for publication.
Data Analysis
Comparative analysis between patients with migraine, with and without MOH, was conducted on patient demographics, migraine diagnosis, migraine attack severity, physician-prescribed acute and preventive treatment, and treatment satisfaction. When analyzing physician survey data, neurologists and neurosurgeons were combined.
Means and standard deviations (SD), or medians and interquartile ranges (IQR), were reported for continuous variables (where appropriate) and frequencies and percentages for categorical variables. T-tests and analysis of variance (ANOVAs) were used to compare means for numeric variables. Chi-squared tests and Fisher’s exact tests were used to measure differences in response to categorical response questions. Mann-Whitney U tests and Kruskal-Wallis tests were used to compare ordinal response options.
Kappa Analysis
The alignment of satisfaction with both acute and preventive treatment between physicians and patients was assessed by calculating Cohen’s weighted kappa (κ) statistic. The kappa analyses for both acute treatment satisfaction and preventive treatment satisfaction were performed for all patients and two patient subgroups: those with MOH and those without MOH. Only patients for whom both patient- and physician-reported satisfaction data were available for each treatment type were included in this analysis. The κ values were interpretated as follows: poor (< 0.00), slight (0.00‒0.20), fair (0.21‒0.40), moderate (0.41‒0.60), substantial (0.61‒0.80), or almost perfect (0.81‒1.00) [32].
Multivariable Regression Analysis
For the exploratory analysis, multi-level mixed effects ordered logistic regression models were used to investigate potential factors related to physician- and patient-reported satisfaction with acute and preventive treatment. Outcome variables were acute and preventive treatment satisfaction, both grouped into three levels: 1 = extremely satisfied, 2 = satisfied, and 3 = slightly satisfied–extremely dissatisfied. Models were established separately for each outcome variable. Each patient in the model was represented by two observations, one for physician-reported satisfaction and the other for patient-reported satisfaction. Covariates included age, sex, presence of mental health conditions including anxiety, depression, or stress, and the use of OTC treatment. Odds ratios, p values, and 95% confidence intervals were reported for each main effect and interaction term. A standalone odds ratio and its 95% confidence interval were also calculated for physicians and patients separately. Odds ratios > 1 imply an association between a covariate and non-extreme satisfaction with treatment.
All analyses were conducted in Stata v18 [33]. Missing data were not imputed. A significance level of α = 0.05 was used; all tests were two sided.
Results
Study Sample
Overall, 122 physicians participated in the study. Sixty-six physicians were primary care practitioners and internists, of which 97.0% (n = 64/66) had a special interest in headaches. Fifty-six physicians were neurologists or neurosurgeons, of which 67.9% (n = 38/56) were headache specialists. In total, physicians completed patient record forms for 820 of their consulting patients with a physician-confirmed diagnosis of migraine. Of these patients, physicians reported 7.0% (n = 57/820) had a diagnosis of MOH. Of the 820 patients involved in the study, 41.5% of patients (n = 340/820) completed the voluntary patient-reported questionnaire.
Patient Demographics
Data on patient age and sex were available for all patients. Overall, 70.2% (n = 40/57) of patients with MOH and 73.7% (n = 562/763) of patients without MOH were female. The mean ± SD ages of patients with and without MOH were 44.1 ± 13.6 years and 43.3 ± 14.0 years, respectively. Overall, there was no significant difference in either age or sex between patients with and without MOH. Regarding employment status, 72.2% (n = 39/54) of patients with MOH and 61.4% (n = 446/727) of patients without MOH worked full time (Table 1).
Table 1.
Patient demographics and characteristics
| Overall | Patients with MOH | Patients without MOH | p Value | Test | |
|---|---|---|---|---|---|
| Physician-reported patient sex, n (%) | |||||
| n | 820 | 57 | 763 | 0.54 | (FE) |
| Female | 602 (73.4) | 40 (70.2) | 562 (73.7) | ||
| Male | 218 (26.6) | 17 (29.8) | 201 (26.3) | ||
| Physician-reported patient age | |||||
| n | 820 | 57 | 763 | 0.64 | (TT) |
| Mean (SD) | 43.3 (14.0) | 44.1 (13.6) | 43.3 (14.0) | ||
| Physician-reported patient employment status, n (%) | |||||
| n | 781 | 54 | 727 | 0.75 | (FE) |
| Working full time | 485 (62.1) | 39 (72.2) | 446 (61.4) | ||
| Working part time | 99 (12.7) | 7 (13.0) | 92 (12.7) | ||
| On long-term sick leave | 5 (0.7) | 0 (0.0) | 5 (0.7) | ||
| Homemaker | 96 (12.3) | 4 (7.4) | 92 (12.7) | ||
| Student | 37 (4.7) | 1 (1.9) | 36 (5.0) | ||
| Not working because of retirement | 17 (2.2) | 0 (0.0) | 17 (2.3) | ||
| Unemployed | 42 (5.4) | 3 (5.6) | 39 (5.4) | ||
| Physician-reported monthly headache days | |||||
| n | 820 | 57 | 763 | < 0.001 | (TT) |
| Mean (SD) | 6.7 (5.7) | 12.1 (9.3) | 6.3 (5.2) | ||
| Physician-reported monthly migraine days | |||||
| n | 820 | 57 | 763 | < 0.001 | (TT) |
| Mean (SD) | 5.4 (4.6) | 7.4 (6.7) | 5.2 (4.4) | ||
| Physician-reported migraine type, n (%) | |||||
| n | 820 | 57 | 763 | 0.0012 | (FE) |
| Chronic | 482 (58.8) | 45 (79.0) | 437 (57.3) | ||
| Episodic | 338 (41.2) | 12 (21.1) | 326 (42.7) | ||
| Physician-reported current migraine severity, n (%) | |||||
| n | 820 | 57 | 763 | < 0.001 | (MW) |
| Very mild | 180 (22.0) | 6 (10.5) | 174 (22.8) | ||
| Mild | 445 (54.3) | 28 (49.1) | 417 (54.7) | ||
| Moderate | 163 (19.9) | 17 (29.8) | 146 (19.1) | ||
| Severe | 32 (3.9) | 6 (10.5) | 26 (3.4) | ||
| Very severe | 0 (0.0) | 0 (0.0) | 0 (0.0) | ||
| Patient-reported current migraine severity, n (%) | |||||
| n | 337 | 11 | 326 | 0.18 | (MW) |
| Very mild | 51 (15.1) | 1 (9.1) | 50 (15.3) | ||
| Mild | 161 (47.8) | 4 (36.4) | 157 (48.2) | ||
| Moderate | 101 (30.0) | 4 (36.4) | 97 (29.8) | ||
| Severe | 22 (6.5) | 2 (18.2) | 20 (6.1) | ||
| Very severe | 2 (0.6) | 0 (0.0) | 2 (0.6) | ||
| Physician-reported patient comorbidities (Top 10), n (%) | |||||
| n | 820 | 57 | 763 | ||
| None | 634 (77.3) | 24 (42.1) | 610 (80.0) | < 0.001 | (FE) |
| Stress | 50 (6.1) | 10 (17.5) | 40 (5.2) | 0.0014 | (FE) |
| Anxiety | 45 (5.5) | 7 (12.3) | 38 (5.0) | 0.03 | (FE) |
| Depression | 36 (4.4) | 10 (17.5) | 26 (3.4) | < 0.001 | (FE) |
| Sleeping disorders | 26 (3.2) | 0 (0.0) | 26 (3.4) | 0.25 | (FE) |
| Neck Pain | 17 (2.1) | 3 (5.3) | 14 (1.8) | 0.11 | (FE) |
| Gastrointestinal problems/dyspepsia | 16 (2.0) | 0 (0.0) | 16 (2.1) | 0.62 | (FE) |
| Menstrual disorders | 11 (1.3) | 3 (5.3) | 8 (1.1) | 0.04 | (FE) |
| Vertigo | 8 (1.0) | 2 (3.5) | 6 (0.8) | 0.10 | (FE) |
| Tumor without metastases | 8 (1.0) | 3 (5.3) | 5 (0.7) | 0.01 | (FE) |
| Muscle weakness/ fatigue | 8 (1.0) | 1 (1.8) | 6 (0.8) | 0.44 | (FE) |
| Other | 7 (0.9) | 1 (1.8) | 6 (0.8) | 0.40 | (FE) |
| Patient-reported MIDAS overall score | |||||
| n | 314 | 10 | 304 | 0.40 | (TT) |
| Mean (SD) | 6.2 (12.6) | 9.5 (9.1) | 6.1 (12.7) | ||
| Physicians’ specialties, n (%) | |||||
| N | 820 | 57 | 763 | ||
| PCP/ GP/internist | 459 (56.0) | 20 (35.1) | 439 (57.5) | 0.0013 | (FE) |
| Neurologist (headache specialist) | 166 (20.2) | 19 (33.3) | 147 (19.3) | 0.02 | (FE) |
| Neurologist (non-headache specialist) | 84 (10.2) | 8 (14.0) | 76 (10.0) | 0.36 | (FE) |
| Neurosurgeon (headache specialist) | 81 (9.9) | 5 (8.8) | 76 (10.0) | 1.00 | (FE) |
| Neurosurgeon (non-headache specialist) | 30 (3.7) | 5 (8.8) | 25 (3.3) | 0.05 | (FE) |
Specialist physicians (neurologists/neurosurgeons) were more likely to manage patients with MOH than those without MOH (64.9% vs 42.5%, p = 0.003) (Table 1).
Burden of Migraine
Patients with MOH experienced significantly higher headache frequency than those without MOH: the mean number of monthly headache days (MHDs) experienced over the last 3 months was 12.1 ± 9.3 in the patients with MOH and 6.3 ± 5.2 in the patients without MOH (p < 0.001). The mean number of monthly migraine days (MMDs) experienced was 7.4 ± 6.7 in patients with MOH versus 5.2 ± 4.4 in those without MOH (p < 0.001).
Physicians reported that patients with MOH were significantly more likely to have chronic migraine diagnoses than patients without MOH (79.0% [n = 45/57] vs 57.3% [n = 437/763], respectively, p = 0.001) (Table 1).
Migraine severity over the past 3 months was assessed by both physicians and patients using a 5-point scale ranging from “very mild” to “very severe.” Physicians reported significantly greater degrees of severity for patients with MOH compared to patients without MOH (p < 0.001): physicians reported 40.4% (n = 23/57) of MOH patients and 22.5% (n = 172/763) of patients without MOH experienced moderate–very severe migraine; 54.6% (n = 6/11) of patients with MOH reported moderate–very severe migraine, whereas 36.5% (n = 119/326) of those without MOH reported moderate–very severe migraine (p = 0.18) (Table 1). On average, patients with MOH reported a mean ± SD MIDAS score of 9.5 ± 9.1 (n = 10) and patients without MOH reported a mean ± SD score of 6.1 ± 12.7 (n = 304). This difference did not reach statistical significance (Table 1).
Patients with MOH were significantly more likely to have comorbidities than patients without MOH (57.9% [n = 33/57] vs 20.1% [n = 153/763], p < 0.001). In particular, stress (17.5% [n = 10/57] vs 5.2% [n = 40/763], p = 0.001), anxiety (12.3% [n = 7/57] vs 5.0% [n = 38/763], p = 0.030), and depression (17.5% [n = 10/57] vs 3.4% [n = 26/763], p < 0.001) were all significantly more common in patients with MOH than in those without MOH (Table 1).
Treatment Patterns
For the current use of migraine medications, a higher percentage of patients with MOH received both acute and preventive medications that were prescribed by physicians. Of the 57 patients with MOH, 79.0% (n = 45/57) were prescribed both acute and preventive treatments, while 49.9% (n = 381/763) of patients without MOH received both treatment (Table 2).
Table 2.
Treatment patterns
| Overall | Patients with MOH | Patients without MOH | p Value | Tests | |
|---|---|---|---|---|---|
| Physician-reported current treatment status, n (%) | |||||
| n | 820 | 57 | 763 | < 0.001 | (FE) |
| Acute only treatment | 310 (37.8) | 7 (12.3) | 303 (39.7) | ||
| Preventive only treatment | 55 (6.7) | 4 (7.0) | 51 (6.7) | ||
| Acute and preventive treatment | 426 (52.0) | 45 (79.0) | 381 (49.9) | ||
| No current treatment | 29 (3.5) | 1 (1.8) | 28 (3.7) | ||
| Physician-reported current acute class, n (%) | |||||
| n | 820 | 57 | 763 | ||
| Triptans (including combinations) | 561 (68.4) | 38 (66.7) | 523 (68.6) | 0.77 | (FE) |
| Non-opioid analgesics (including combinations) | 127 (15.5) | 7 (12.3) | 120 (15.7) | 0.57 | (FE) |
| NSAIDs (including combinations) | 90 (11.0) | 11 (19.3) | 79 (10.4) | 0.05 | (FE) |
| Serotonin 5-HT1F agonist (Ditan) | 59 (7.2) | 8 (14.0) | 51 (6.7) | 0.06 | (FE) |
| Other acute drug therapies | 15 (1.83) | 0 (0.00) | 15 (1.97) | 0.62 | (FE) |
| No acute drug treatment | 84 (10.2) | 5 (8.8) | 79 (10.4) | 1.00 | (FE) |
| Physician-reported current preventive class, n (%) | |||||
| n | 820 | 57 | 763 | ||
| Anti-CGRP mAbs | 183 (22.3) | 24 (42.1) | 159 (20.8) | < 0.001 | (FE) |
| Anticonvulsants | 109 (13.3) | 19 (33.3) | 90 (11.8) | < 0.001 | (FE) |
| Beta-blockers | 104 (12.7) | 10 (17.5) | 94 (12.3) | 0.30 | (FE) |
| Calcium antagonists | 99 (12.1) | 5 (8.8) | 94 (12.3) | 0.53 | (FE) |
| Antidepressants/anxiolytics/benzodiazepines | 30 (3.7) | 6 (10.5) | 24 (3.2) | 0.01 | (FE) |
| Other preventive drugs | 23 (2.8) | 5 (8.77) | 18 (2.39) | 0.02 | (FE) |
| No preventive drug treatment | 339 (41.3) | 8 (14.0) | 331 (43.4) | < 0.001 | (FE) |
| Physician-reported current OTC, n (%) | |||||
| n | 669 | 41 | 628 | ||
| Patients not currently taking OTC products for their migraine | 647 (96.7) | 38 (92.7) | 609 (97.0) | 0.15 | (FE) |
| Ibuprofen | 13 (1.9) | 2 (4.9) | 11 (1.8) | 0.19 | (FE) |
| Loxoprofen | 5 (0.8) | 1 (2.4) | 4 (0.6) | 0.27 | (FE) |
| Ibuprofen and acetaminophen | 4 (0.6) | 0 (0.0) | 4 (0.6) | 1.00 | (FE) |
| Acetaminophen | 3 (0.5) | 0 (0.0) | 3 (0.5) | 1.00 | (FE) |
| Patient-reported current OTC status, n (%) | |||||
| N | 331 | 11 | 320 | 0.35 | (FE) |
| Yes, the patient is currently receiving OTC | 37 (11.2) | 2 (18.2) | 35 (10.9) | ||
| No, the patient is not currently receiving OTC | 294 (88.8) | 9 (81.8) | 285 (89.1) | ||
Acute Treatment Patterns
Acute medications were the mainstay of migraine treatment for patients included in this study; 91.2% (n = 52/57) of patients with MOH and 89.7% (n = 684/763) of patients without MOH received acute treatment. Of the patients prescribed acute treatment, 66.7% (n = 38/57) of patients with MOH and 68.6% (n = 523/763) of patients without MOH were prescribed one or more triptans (p = 0.77). The second most prescribed acute treatments were non-opioid analgesics (including combinations), followed by NSAIDs and ditans. There was little statistical difference in the use of acute medications between the two groups (Table 2).
According to the mTOQ, 30.0% of patients with MOH and 43.2% of patients without MOH scored an adequate response for acute treatment (p = 0.53) (Table 3).
Table 3.
Satisfaction with current acute treatment
| Overall | Patients with MOH | Patients without MOH | p Value | Test | |
|---|---|---|---|---|---|
| Physician-reported satisfaction with current acute treatment, n (%) | |||||
| n | 733 | 52 | 681 | 0.39 | (MW)a |
| Extremely satisfied | 202 (27.6) | 14 (26.9) | 188 (27.6) | ||
| Satisfied | 414 (56.5) | 26 (50.0) | 388 (57.0) | ||
| Slightly satisfied | 65 (8.9) | 7 (13.5) | 58 (8.5) | ||
| Neither satisfied nor dissatisfied | 33 (4.5) | 1 (1.9) | 32 (4.7) | ||
| Slightly dissatisfied | 10 (1.4) | 1 (1.9) | 9 (1.3) | ||
| Dissatisfied | 7 (1.0) | 3 (5.8) | 4 (0.6) | ||
| Extremely dissatisfied | 2 (0.3) | 0 (0.0) | 2 (0.3) | ||
| Patient-reported satisfaction with current acute treatment, n (%) | |||||
| n | 300 | 7 | 293 | 0.14 | (MW)a |
| Extremely satisfied | 46 (15.3) | 3 (42.9) | 43 (14.7) | ||
| Satisfied | 173 (57.7) | 3 (42.9) | 170 (58.0) | ||
| Slightly satisfied | 53 (17.7) | 0 (0.0) | 53 (18.1) | ||
| Neither satisfied nor dissatisfied | 25 (8.3) | 1 (14.3) | 24 (8.2) | ||
| Slightly dissatisfied | 1 (0.3) | 0 (0.0) | 1 (0.3) | ||
| Dissatisfied | 0 (0.0) | 0 (0.0) | 0 (0.0) | ||
| Extremely dissatisfied | 2 (0.7) | 0 (0.0) | 2 (0.7) | ||
| Patient-reported migraine treatment optimization (mTOQ) | |||||
| n | 325 | 10 | 315 | ||
| Mean (SD) score | 20.5 (4.4) | 19.7 (4.9) | 50.5 (4.4) | 0.56 | (TT) |
| Inadequate response, n (%) | 186 (57.2) | 7 (70.0) | 179 (56.8) | 0.53 | (FE) |
| Adequate response, n (%) | 139 (42.8) | 3 (30.0) | 136 (43.2) | ||
aOverall distributions of responses were compared between patients with and without MOH
Preventive Treatment Patterns
As described earlier, patients with MOH received preventive medications more commonly than patients without MOH (86.0% [n = 49/57] vs 56.6% [n = 432/763], respectively, p < 0.001). Anti-CGRP mAbs were significantly more likely to be prescribed for patients with MOH (42.1% [n = 24/57] vs 20.8% [n = 159/763], respectively, p < 0.001). Other preventive treatments including anticonvulsants, antidepressants, anxiolytics, and benzodiazepines were also prescribed more often to patients with MOH (Table 2).
Use of OTC Medication Patterns
Both physicians and patients reported the use of OTC medications. Although 11.2% (n = 37/331) of all patients reported currently using OTC medications in addition to physician-prescribed acute and preventive treatments, physicians reported that only 3.3% (n = 22/669) of all patients were currently using OTC medications. Physicians reported 7.3% (n = 3/41) of patients with MOH were currently using OTC medications, whereas 18.2% (n = 2/11) of patients with MOH self-reported currently using OTC. Among patients without MOH, physicians reported OTC use in 3.0% (n = 19/628) of patients without MOH, whereas 10.9% (n = 35/320) of patients without MOH self-reported using OTC medications. There was no statistically significant difference in the use of OTC medications between patients with MOH and without MOH in either physician- or patient-reported data (Table 2).
Treatment Satisfaction
Physicians and their patients independently reported their satisfaction with both current acute treatment and current preventative treatment on a 7-point scale, ranging from “extremely satisfied” to “extremely dissatisfied.”
Treatment Satisfaction with Acute Treatment
Physicians reported satisfaction with acute treatment (defined as slight satisfaction–extreme satisfaction) in 90.4% (n = 47/52) of patients with MOH and 93.1% (n = 634/681) of patients without MOH (p = 0.39). In patient-reported data, 85.7% (n = 6/7) of patients with MOH were satisfied with current acute treatment compared with 90.8% (n = 266/293) of patients without MOH (p = 0.14) (Table 3).
In the kappa analysis of treatment satisfaction for acute treatment (n = 300), a kappa value ± standard error (SE) of 0.33 ± 0.03 was observed, suggesting fair alignment between physician- and patient-reported satisfaction with acute treatment (Table 4). The analysis on patients with MOH (n = 7) and without MOH (n = 293) provided similar kappa values (0.32 ± 0.29 for patients with MOH; 0.33 ± 0.03 for patients without MOH), suggesting fair alignment in both subgroups. However, these results should be interpreted carefully because of the low sample size.
Table 4.
Physician and patient alignment regarding satisfaction with current acute treatment
| Physician- and patient-reported satisfaction with acute treatment (all patients), n (%) | ||||||||
|---|---|---|---|---|---|---|---|---|
| Physician reported | ||||||||
| n | Extremely satisfied | Satisfied | Slightly satisfied | Neither satisfied nor dissatisfied | Slightly dissatisfied | Dissatisfied | Extremely dissatisfied | |
| Patient reported | ||||||||
| n | 300 | 46 | 173 | 53 | 25 | 1 | 0 | 2 |
| Extremely satisfied | 78 | 33 (11.1%) | 33 (11.1%) | 6 (2.0%) | 5 (1.7%) | 0 (0.0%) | 0 (0.0%) | 1 (0.3%) |
| Satisfied | 184 | 12 (4.0%) | 127 (42.3%) | 33 (11.0%) | 12 (4.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Slightly satisfied | 27 | 1 (0.3%) | 11 (3.7%) | 10 (3.3%) | 5 (1.7%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Neither satisfied nor dissatisfied | 6 | 0 (0.0%) | 1 (0.3%) | 3 (1.0%) | 1 (0.3%) | 1 (0.3%) | 0 (0.0%) | 0 (0.0%) |
| Slightly dissatisfied | 3 | 0 (0.0%) | 1 (0.3%) | 1 (0.3%) | 1 (0.3%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Dissatisfied | 1 | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 1 (0.3%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Extremely dissatisfied | 1 | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 1 (0.3%) |
| Kappa | 0.33 | |||||||
| Standard error | 0.03 | |||||||
| p value | < 0.001 | |||||||
| Physician- and patient-reported satisfaction with acute treatment (patients with MOH), n (%) | ||||||||
|---|---|---|---|---|---|---|---|---|
| Physician reported | ||||||||
| n | Extremely satisfied | Satisfied | Slightly satisfied | Neither satisfied nor dissatisfied | Slightly dissatisfied | Dissatisfied | Extremely dissatisfied | |
| Patient reported | ||||||||
| n | 7 | 3 | 3 | 0 | 1 | 0 | 0 | 0 |
| Extremely satisfied | 3 | 2 (28.6%) | 1 (14.3%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Satisfied | 4 | 1 (14.3%) | 2 (28.6%) | 0 (0.0%) | 1 (14.3%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Slightly satisfied | 0 | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Neither satisfied nor dissatisfied | 0 | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Slightly dissatisfied | 0 | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Dissatisfied | 0 | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Extremely dissatisfied | 0 | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Kappa | 0.32 | |||||||
| Standard error | 0.29 | |||||||
| p Value | 0.14 | |||||||
| Physician- and patient-reported satisfaction with acute treatment (patients without MOH), n (%) | ||||||||
|---|---|---|---|---|---|---|---|---|
| Physician reported | ||||||||
| n | Extremely satisfied | Satisfied | Slightly satisfied | Neither satisfied nor dissatisfied | Slightly dissatisfied | Dissatisfied | Extremely dissatisfied | |
| Patient-reported | ||||||||
| n | 293 | 43 | 170 | 53 | 24 | 1 | 0 | 2 |
| Extremely satisfied | 75 | 31 (10.6%) | 32 (10.9%) | 6 (2.0%) | 5 (1.7%) | 0 (0.0%) | 0 (0.0%) | 1 (0.3%) |
| Satisfied | 180 | 11 (3.8%) | 125 (42.7%) | 33 (11.3%) | 11 (3.8%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Slightly satisfied | 27 | 1 (0.3%) | 11 (3.8%) | 10 (3.4%) | 5 (1.7%) | 0 (0%) | 0 (0.0%) | 0 (0.0%) |
| Neither satisfied nor dissatisfied | 6 | 0 (0.0%) | 1 (0.3%) | 3 (1%) | 1 (0.3%) | 1 (0.3%) | 0 (0.0%) | 0 (0.0%) |
| Slightly dissatisfied | 3 | 0 (0.0%) | 1 (0.3%) | 1 (0.3%) | 1 (0.3%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Dissatisfied | 1 | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 1 (0.3%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Extremely dissatisfied | 1 | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 1 (0.3%) |
| Kappa | 0.33 | |||||||
| Standard error | 0.03 | |||||||
| p Value | < 0.001 | |||||||
For the exploratory multivariable regression analysis, 272 patients were included in the model, of which 65 were male, 30 were using OTC, 272 had a MIDAS score, and 29 had any concomitant mental health conditions (stress, anxiety, or depression). The mean ± SD MIDAS score for patients included in this analysis was 6.7 ± 13.4. There was a significant difference in satisfaction between physicians and patients even after adjusting for the aforementioned confounding factors (age, sex, mental health conditions, and the use of OTC treatment) (p < 0.001).
When assessing the impact of the independent factors on physician satisfaction, the highest odds ratios for extreme satisfaction vs non-extreme satisfaction with acute treatment were associated with patients being male (OR 0.64, 95% CIs 0.20 and 2.04, p = 0.45) and OTC usage (OR 0.76, 95% CIs 0.21 and 2.80, p = 0.68). As to the impact of the independent factors regarding patient satisfaction, the highest odds ratio for extreme satisfaction vs non-extreme satisfaction with acute treatment was again associated with patients being male (OR 0.40, 95% CIs 0.13 and 1.25, p = 0.12). OTC usage was associated with non-extreme patient-reported satisfaction with acute treatment (OR 19.61, 95% CIs 4.85 and 79.31, p < 0.001). These results suggest that OTC treatment usage was significantly associated with patients not being extremely satisfied with their current acute treatment (p < 0.001). Notably, the proportion of patients in this analysis currently using OTC was 11.0% (n = 30/300), and wide confidence intervals were observed when assessing this effect (95% CIs = 4.85 and 79.31).
Treatment Satisfaction with Preventive Treatment
Physicians reported satisfaction with preventive treatment (defined as slight satisfaction–extreme satisfaction in 88.0% (n = 44/50) of patients with MOH and 91.7% (n = 399/435) of patients without MOH (p = 0.12). In patient-reported data, 87.5% (n = 7/8) of patients with MOH reported satisfaction with current preventive treatment, whereas 84.6% (n = 126/149) of patients without MOH reported satisfaction (p = 0.67) (Table 5).
Table 5.
Satisfaction with current preventive treatment
| Overall | Patients with MOH | Patients without MOH | p Value | Test | |
|---|---|---|---|---|---|
| Physician-reported satisfaction with current preventive treatment, n (%) | |||||
| n | 485 | 50 | 435 | 0.12 | (MW) |
| Extremely satisfied | 144 (29.7) | 14 (28.0) | 130 (29.9) | ||
| Satisfied | 247 (50.9) | 19 (38.0) | 228 (52.4) | ||
| Slightly satisfied | 52 (10.7) | 11 (22.0) | 41 (9.4) | ||
| Neither satisfied nor dissatisfied | 17 (3.5) | 3 (6.0) | 14 (3.2) | ||
| Slightly dissatisfied | 13 (2.7) | 1 (2.0) | 12 (2.8) | ||
| Dissatisfied | 10 (2.1) | 1 (2.0) | 9 (2.1) | ||
| Extremely dissatisfied | 2 (0.4) | 1 (2.0) | 1 (0.2) | ||
| Patient-reported satisfaction with current preventive treatment, n (%) | |||||
| n | 157 | 8 | 149 | 0.67 | (MW) |
| Extremely satisfied | 36 (22.9) | 3 (37.5) | 33 (22.2) | ||
| Satisfied | 70 (44.6) | 2 (25.0) | 68 (45.6) | ||
| Slightly satisfied | 27 (17.2) | 2 (25.0) | 25 (16.8) | ||
| Neither satisfied nor dissatisfied | 20 (12.7) | 1 (12.5) | 19 (12.8) | ||
| Slightly dissatisfied | 3 (1.9) | 0 (0.0) | 3 (2.0) | ||
| Dissatisfied | 1 (0.6) | 0 (0.0) | 1 (0.7) | ||
| Extremely dissatisfied | 0 (0.0) | 0 (0.0) | 0 (0.0) | ||
In the kappa analysis of all patients receiving preventive treatment (n = 157), a kappa value ± SE of 0.46 ± 0.05 was observed, suggesting moderate alignment between physician- and patient-reported satisfaction with preventive treatment. Patients with (n = 8) and without MOH (n = 149) showed similar kappa values (0.51 ± 0.22 for patients with MOH; 0.46 ± 0.05 for patients without MOH). (Table 6).
Table 6.
Physician and patient alignment regarding satisfaction with current preventive treatment
| Physician- and patient-reported satisfaction with preventive treatment (all patients), n (%) | ||||||||
|---|---|---|---|---|---|---|---|---|
| Physician reported | ||||||||
| n | Extremely satisfied | Satisfied | Slightly satisfied | Neither satisfied nor dissatisfied | Slightly dissatisfied | Dissatisfied | Extremely dissatisfied | |
| Patient-reported | ||||||||
| n | 157 | 36 | 70 | 27 | 20 | 3 | 1 | 0 |
| Extremely satisfied | 55 | 31 (19.7%) | 21 (13.4%) | 2 (1.3%) | 1 (0.6%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Satisfied | 72 | 4 (2.5%) | 42 (26.8%) | 19 (12.1%) | 6 (3.8%) | 1 (0.6%) | 0 (0.0%) | 0 (0.0%) |
| Slightly satisfied | 17 | 1 (0.6%) | 6 (3.8%) | 4 (2.5%) | 5 (3.2%) | 1 (0.6%) | 0 (0.0%) | 0 (0.0%) |
| Neither satisfied nor dissatisfied | 4 | 0 (0.0%) | 1 (0.6%) | 1 (0.6%) | 2 (1.3%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Slightly dissatisfied | 3 | 0 (0.0%) | 0 (0.0%) | 1 (0.6%) | 1 (0.6%) | 1 (0.6%) | 0 (0.0%) | 0 (0.0%) |
| Dissatisfied | 6 | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 5 (3.2%) | 0 (0.0%) | 1 (0.6%) | 0 (0.0%) |
| Extremely dissatisfied | 0 | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Kappa | 0.46 | |||||||
| Standard error | 0.05 | |||||||
| p Value | < 0.001 | |||||||
| Physician- and patient-reported satisfaction with preventive treatment (patients with MOH), n (%) | ||||||||
|---|---|---|---|---|---|---|---|---|
| Physician reported | ||||||||
| n | Extremely satisfied | Satisfied | Slightly satisfied | Neither satisfied nor dissatisfied | Slightly dissatisfied | Dissatisfied | Extremely dissatisfied | |
| Patient reported | ||||||||
| n | 8 | 3 | 2 | 2 | 1 | 0 | 0 | 0 |
| Extremely satisfied | 2 | 1 (12.5%) | 1 (12.5%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Satisfied | 2 | 2 (25.0%) | 0 (0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Slightly satisfied | 3 | 0 (0.0%) | 1 (12.5%) | 2 (25.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Neither satisfied nor dissatisfied | 0 | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Slightly dissatisfied | 1 | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 1 (12.5%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Dissatisfied | 0 | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Extremely dissatisfied | 0 | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Kappa | 0.51 | |||||||
| Standard error | 0.22 | |||||||
| p Value | 0.01 | |||||||
| Physician- and patient-reported satisfaction with preventive treatment (patients without MOH), n (%) | ||||||||
|---|---|---|---|---|---|---|---|---|
| Physician reported | ||||||||
| n | Extremely satisfied | Satisfied | Slightly satisfied | Neither satisfied nor dissatisfied | Slightly dissatisfied | Dissatisfied | Extremely dissatisfied | |
| Patient reported | ||||||||
| n | 149 | 33 | 68 | 25 | 19 | 3 | 1 | 0 |
| Extremely satisfied | 53 | 30 (20.1%) | 20 (13.4%) | 2 (1.3%) | 1 (0.7%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Satisfied | 70 | 2 (1.3%) | 42 (28.2%) | 19 (12.8%) | 6 (4%) | 1 (0.7%) | 0 (0.0%) | 0 (0.0%) |
| Slightly satisfied | 14 | 1 (0.7%) | 5 (3.4%) | 2 (1.3%) | 5 (3.4%) | 1 (0.7%) | 0 (0.0%) | 0 (0.0%) |
| Neither satisfied nor dissatisfied | 4 | 0 (0.0%) | 1 (0.7%) | 1 (0.7%) | 2 (1.3%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Slightly dissatisfied | 2 | 0 (0.0%) | 0 (0.0%) | 1 (0.7%) | 0 (0%) | 1 (0.7%) | 0 (0.0%) | 0 (0.0%) |
| Dissatisfied | 6 | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 5 (3.4%) | 0 (0.0%) | 1 (0.7%) | 0 (0.0%) |
| Extremely dissatisfied | 0 | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
| Kappa | 0.46 | |||||||
| Standard error | 0.05 | |||||||
| p Value | < 0.001 | |||||||
The same multivariable regression model as described in Sect. "Treatment satisfaction with acute treatment" was adopted to explore whether there was a significant discrepancy between physician- and patient-reported satisfaction with preventive treatment. In total, 142 patients were included in the model analysis, of which 38 were males, 13 were using OTC, 142 had a MIDAS score, and 16 had stress, anxiety, or depression. The mean ± SD MIDAS score for patients included in this analysis was 6.6 ± 14.1. There was a significant difference in satisfaction between physicians and patients after adjusting for the confounding factors (p = 0.005).
When assessing the impact of the independent factors on physician-reported satisfaction, the highest odds ratios for extreme satisfaction vs non-extreme satisfaction with preventive treatment were associated with patients being male (OR 0.52, 95% CIs 0.068 and 3.89, p = 0.52). The highest odds ratios for non-extreme satisfaction with preventive treatment were associated with the presence of mental health conditions (OR 7.42, 95% CIs 0.77 and 71.22, p = 0.08), followed by OTC usage (OR 2.53, 95% CIs 0.24 and 26.26, p = 0.44). In the analysis of patient-reported satisfaction, the highest odds ratio for extreme satisfaction vs non-extreme satisfaction with preventive treatment was associated with patients being male (OR 0.86, 95% CIs 0.096 and 7.69, p = 0.89). The highest odds ratios for non-extreme satisfaction with preventive treatment were associated with OTC usage (OR 43.90, 95% CIs 1.52 and 1267.34, p = 0.03). This suggests OTC treatment usage was significantly associated with not being extremely satisfied with their current preventive treatment (p = 0.03) for both physicians and patients. However, the proportion of patients in this analysis currently using OTC was 9.2% (n = 13/142), and wide confidence intervals were observed when assessing this effect (95% CIs = 1.52 and 1267.34).
Discussion
In this study, the prevalence of MOH among patients with migraine was 7.0%. In contrast, a previous study reported that the proportion of MOH in headaches or centers of tertiary care in Europe was 30%, and in the USA, it was even > 50% [34]. This discrepancy may be partly explained by the higher proportion of primary care physicians who enrolled patients, as they are more likely to encounter individuals with less severe headache symptoms. In such settings, identifying the MOH may be more challenging, and accurately tracking the number of days of OTC medication use may not always be feasible.
We observed a higher proportion of patients with MOH currently consulting with a specialist physician (neurologist/ neurosurgeon) and conversely a lower proportion consulting with primary care physicians/internists compared to patients without MOH. This result may indicate that the specialists have greater familiarity with MOH, leading to more frequent diagnoses of MOH among the patients they examine. A previous study in Japan reported that only half of patients with migraine consulted with a physician specialist at diagnosis [35]. Given the significance of specialist care in the effective management of migraine, it is crucial to educate patients about the necessity of seeking specialist support for their condition.
This study found that, despite a few differences in patient demographics, patients with MOH were more likely to experience chronic migraine. This finding affirms the connection between chronic migraine and MOH. In addition, physicians reported greater migraine frequency and disease severity in patients with MOH, with more patients having stress, anxiety, and depression. Furthermore, 30.0% of patients with MOH reported an adequate response to their acute treatment, in contrast to 43.2% among those without MOH. These findings highlight the additional symptomatic burden and diminished HRQoL associated with MOH in individuals with migraine.
Interestingly, overall acute treatment usage did not differ greatly between patients with and without MOH. An overwhelming majority of patients with MOH were prescribed acute treatment, half of which were triptans, either alone or in combination with other acute medications.
In contrast, patients with MOH were significantly more likely to be prescribed preventive treatment, specifically anti-CGRP mAbs. In addition, 14.0% (n = 8/57) of patients with MOH and 6.7% (n = 51/763) of patients without MOH were prescribed lasmiditan (p = 0.06). This suggests physicians that participated in this study may be recognizing the increased number of headache days experienced by the patient and are taking measures to counter migraine chronification. Studies in Japan have shown that using anti-CGRP mAbs to treat migraine with MOH is safe and effective, resulting in reduced MHD and MMD and improvements in HRQoL [36–39]. Our findings suggest that the participating physicians with higher expertise had greater knowledge of measures to manage MOH. However, sustained high usage of triptans suggests that either physicians may find it difficult to implement withdrawal of acute treatment or that knowledge regarding MOH management is still insufficient.
The exploratory kappa analysis of physician and patient alignment on treatment satisfaction suggested that physicians and patients are not completely aligned in their satisfaction with either acute or preventive treatment. Notably, despite moderate alignment for preventive treatment, it remained only fair for acute treatment. The exploratory multivariable model analysis supported this misalignment. It could be postulated that use of OTC medications by patients in addition to their physician-prescribed treatment regimens contributes to the disconnect between physician and patient treatment satisfaction, particularly with acute treatments. There are several possible reasons for this difference: physicians may not accurately grasp the OTC usage of patients, leading them to believe the acute treatments they prescribed were effective. Additionally, patients may be hesitant to tell physicians that their prescribed acute treatment drugs were ineffective because of the risk of losing access to these treatments. Another possible explanation is that physicians prescribing preventive drugs may have a deeper understanding of pharmacotherapy for migraine including the risks associated with MOH and OTC drugs, and their characteristics may differ from those of physicians prescribing acute treatment drugs.
The burden of migraine in Japan remains substantial, regardless of the presence of MOH. Although inadequate treatment can lead to the development of MOH, a significant proportion of patients do not actively seek treatment [40–42], despite many reporting moderate or severe levels of disease burden [41]. Instances such as this have also been reported in studies outside of Japan [43, 44]. This study revealed that in real-world settings, there is a disconnect between physician and patient treatment satisfaction, especially regarding satisfaction with physician-prescribed acute treatments. Therefore, there is a need to improve patient and physician communication and awareness of the symptomatic burden of migraine, including the appropriate monitoring of OTC medications, to improve patient outcomes.
This study had a number of strengths and limitations. While physicians were recruited to provide a geographically diverse and pragmatic sample, participation was influenced by willingness to complete the survey. This study's cross-sectional design limits causal conclusions but allows identification of significant associations. For example, due to the retrospective nature of data collection, our study is limited in its ability to determine the precise onset of MOH. Physicians provided data for consecutively consulting patients to avoid selection bias; however, those who visit their physician more frequently may be more severely affected than those with milder disease and thus more likely to be receiving treatment. In some instances, analysis groupings contained < 30 patients, so caution is advised when interpreting these results because of low base size. Data were collected at the point of consultation to mitigate against recall bias, with physicians also able to refer to retrospective data from patient medical records for completion of the patient record forms. Real-world studies play an important part in highlighting areas of concern that are not addressed in clinical trials, with the data in this study representative of current clinical practice at the time the survey was conducted.
Conclusion
Our study revealed a discrepancy between physicians and patients regarding treatment satisfaction, especially with acute medications. This gap in perception was associated with OTC treatment use, with a potential explanation being physicians lack of awareness of this usage of OTC treatment. This finding underscores the need for improved communication between physicians and patients, including careful assessment and monitoring of OTC use, to ensure aligned treatment goals and optimize outcomes of patients with MOH.
Acknowledgements
The authors thank the physicians and patients for their involvement in this study.
Medical Writing, Editorial, and Other Assistance
Medical writing and editorial support on behalf of Adelphi Real World (Bollington, UK) was provided by Gary Sidgwick (PhD CMPP) of Adelphi Real World, under the guidance of the authors and in accordance with Good Publication Practice 2022 (GPP 2022) guidelines (https://www.ismpp.org/gpp-2022).
Author Contributions
All authors were involved in (1) conception or design, or analysis and interpretation of data; (2) drafting and revising the article; (3) providing intellectual content of critical importance to the work described; (4) final approval of the version to be published, and therefore meet the criteria for authorship in accordance with the International Committee of Medical Journal Editors (ICMJE) guidelines. In addition, all named authors take responsibility for the integrity of the work as a whole and have given their approval for this version to be published. Conceptualization: Ryotaro Ishii, Takahiro Kitano, Masahiro Iijima, Mitsuhiro Nagano, Reiko Yoshikawa, Kanae Togo. Data Curation: James Jackson, Sophie Barlow, Emily Green, William Whitton, Lucy Hancock. Formal analysis and Visualization: Sophie Barlow, Emily Green, William Whitton, Lucy Hancock. Funding acquisition: Kanae Togo. Project administration: Takahiro Kitano, Kanae Togo, James Jackson, Emily Green, William Whitton, Lucy Hancock. Supervision: Ryotaro Ishii, Masahiro Iijima, Kanae Togo, JJ. Investigation, Methodology, Validation, Writing (Original Draft) and Writing (review and editing): all authors.
Funding
Data collection was undertaken by Adelphi Real World as part of an independent survey, entitled the Adelphi Real World Migraine DSP. The analysis described here used secondary data from the Adelphi Real World Migraine DSP. The DSP is a wholly owned Adelphi Real World product. Pfizer Japan Inc. was one of multiple subscribers to the DSP. Pfizer Inc. did not influence the original survey through either contribution to the design of questionnaires or data collection. Publication of survey results was not contingent on the subscriber's approval or censorship of the manuscript. Statistical analysis and medical writing were provided by Adelphi Real World, which received funding from Pfizer Inc. in connection with the development of this manuscript. The rapid service fee for publication of this manuscript was also funded by Pfizer Inc.
Data Availability
All data, i.e., methodology, materials, data, and data analysis, that support the findings of this survey are the intellectual property of Adelphi Real World. All requests for access should be addressed directly to Lucy Hancock at lucy.hancock@adelphigroup.com.
Declarations
Conflict of Interest
Ryotaro Ishii has served as a consultant for Amgen K.K., Eli Lilly Japan K.K., Daiichi Sankyo Co., Ltd., Pfizer Japan Inc., and Otsuka Pharmaceutical Co., Ltd. He has received speaker honoraria from Amgen K.K., Daiichi Sankyo Co., Ltd., and Otsuka Pharmaceutical Co., Ltd. Takahiro Kitano, Masahiro Iijima, Mitsuhiro Nagano, Reiko Yoshikawa, and Kanae Togo are employees of Pfizer Japan Inc. Masahiro Iijima and Kanae Togo are shareholders of Pfizer Inc. James Jackson, Sophie Barlow, Emily Green, William Whitton, and Lucy Hancock are employees of Adelphi Real World.
Ethics/Ethical Approval
Data collection was undertaken in line with European Pharmaceutical Marketing Research Association guidelines and as such did not require ethics committee approval. The survey materials were submitted to the PEARL Institutional Review Board (Ref #22-ADRW-143) and deemed to be exempt. In addition, each survey was performed in full accordance with relevant legislation at the time of data collection, including the Helsinki Declaration of 1964 and its later amendments. Using a checkbox, patients provided informed consent to take part in the survey and for the use of their data in scientific publications. No identifiable protected health information was extracted during the survey. Data were collected in such a way that patients and physicians could not be identified directly, with data aggregated before being shared with the subscriber and/ or for publication.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
All data, i.e., methodology, materials, data, and data analysis, that support the findings of this survey are the intellectual property of Adelphi Real World. All requests for access should be addressed directly to Lucy Hancock at lucy.hancock@adelphigroup.com.