OBJECTIVE: The objective of this study was to describe and discuss patterns of migraine medication use in the entire Norwegian population.
METHODS: In this nationwide, observational study, all individuals with a migraine-related prescription between 2010 and 2020 were identified using the Norwegian Prescription Database. The outcomes of interest were the incidence and 1-year prevalence of migraine medication users, as well as individuals with triptan overuse. Patterns of medication use were statistically compared between women and men adjusted for age, year of treatment start, comorbidities and county of residence calculating adjusted odds ratios (aOR) with 95% confidence intervals (CI).
RESULTS: We identified 327,904 migraine medication users. The incidence ranged from 0.39% to 0.46%, and the 1-year prevalence increased from 1.99% to 2.99%. Preventive use increased >50% during the study period. Preventives were significantly more often prescribed to women than to men (39.72% vs. 33.75%; aOR 1.41, 95% CI 1.38 to 1.44). Triptan overuse was significantly more common among women, but women with overuse were more often using preventives, as compared to men (56.64% vs 52.69%; aOR = 1.43, 95% CI 1.37 to 1.49).
CONCLUSIONS: The prevalence of medically treated migraine is low. Overuse of triptans is frequent, especially among women. Clinicians should be encouraged to try out different triptans, recognize triptan overuse, and prescribe preventives when indicated.

OBJECTIVE: To confirm a previously reported association of TRPV1 rs8065080 with the risk of transformation from episodic (EM) to chronic migraine (CM) and to extend knowledge about the role of other TRPV1 single nucleotide polymorphisms (SNPs), we first investigated the impact of three TRPV1 SNPs (rs8065080, rs222747 and rs222749) on the risk of migraine chronification in a case-control study. A systematic review and meta-analysis were then conducted to summarize the accumulated findings.
METHODS: Genotyping of the selected TRPV1 SNPs was performed using TaqMan real-time PCR in 167 EM and 182 CM participants. Crude and adjusted odds ratios with associated 95% confidence intervals were calculated in the log-additive, dominant, and recessive genetic models. A comprehensive literature search was performed in PubMed, Web of Knowledge, Cochrane Library, and OpenGrey until February 2024.
RESULTS: In our case-control study, no association was found between TRPV1 SNPs and the risk of migraine chronification, both in the unadjusted logistic regression models and after adjustment for confounding clinical variables. The results of the meta-analysis with a total of 241 participants with EM and 223 with CM confirmed no association between TRPV1 SNPs and the risk of migraine chronification in any of the genetic models tested.
CONCLUSIONS: The results of the present case-control study and meta-analysis exclude a major role of TRPV1 rs8065080, rs222747, and rs222749 as risk factors for migraine chronification. However, further research is needed to investigate the gene-gene and gene-environment interactions of TRPV1 SNPs on the risk of transformation from episodic to chronic migraine.

OBJECTIVE: The objectives of this real-life study were to analyze the reversion of chronic migraine (CM) to episodic migraine (EM) with fremanezumab, evaluate its benefit on the symptomatology, and determine the influence of possible clinical features on the reversion.
BACKGROUND: The clinical manifestations of CM have a high impact on the quality of life of patients, and monoclonal antibodies such as fremanezumab are used as prophylactic treatment.
METHODS: Diagnosed CM patients treated for at least 3 months with monthly fremanezumab were interviewed. The data to assess efficacy were before treatment and at the time of the interview: monthly headache days (MHDs), daily headache hours (DHHs), monthly symptomatic medication days (MSMDs), percentage of patients with symptomatic medication overuse (SMO), and pain intensity with the numerical rating scale (NRS) score. Possible predictors of reversion were analyzed: percentage of patients treated for at least 12 months, hypertension, diabetes mellitus, depression, anxiety, symptomatic control with non-steroidal anti-inflammatory drugs (NSAIDs), triptans or both, and amitriptyline prophylaxis.
RESULTS: A total of 54 patients were included, of whom 40 (74.1%) were converters to EM. There were significant improvements in converters compared to pre-treatment in MHDs (28.0 vs. 5.0 days), as well as on the variables DHHs, MSMDs, and SMO. The percentage of erenumab failures was significantly higher in non-converters than in converters, as was the percentage of patients with anxiety.
CONCLUSIONS: High reversion from CM to EM was achieved with fremanezumab and notable symptomatological improvement, establishing previous failure to erenumab and anxiety as possible detrimental factors for reversion.

OBJECTIVE: We assessed whether the effectiveness of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway changes according to the duration of chronic migraine (CM) over 12 months.
BACKGROUND: In most patients, CM is a progressive disease starting with episodic migraine. Longer CM duration might be associated with more difficult treatment, probably because the mechanisms underlying chronicization are strengthened. Therefore, early treatment of CM could lead to better outcomes compared with later treatment.
METHODS: This cohort study included individuals with CM treated with anti-CGRP mAbs in two tertiary headache centers from April 2019 to May 2023. The primary outcome included a change in monthly migraine days (MMDs) from baseline to the third trimester of treatment, 10-12 months. Secondary outcomes established whether response to anti-CGRP mAbs has a more rapid onset in individuals with shorter CM duration compared with longer duration; they included change in MMDs, monthly headache days (MHDs), and days and number of intakes of acute medication during each trimester compared to baseline. Additional outcomes included persisting MMDs, MHDs, and days and number of intakes of acute medication during each trimester of treatment. Patients were compared across tertiles of the overall CM duration.
RESULTS: The study included 335 individuals with CM, with a median (interquartile range [IQR]) age of 48 (39-57) years; 270 (80.6%) were women. Patients in the highest tertile of CM duration (aged 18-60 years) were older than patients in the lower duration tertiles (0-7 years and 8-18 years, respectively), with a median (IQR) age of 56 (48-64) years compared with 42 (31-50) years, and 48 (39-56)years, respectively (p = 0.025); however, this difference was likely due to a correlation between age and disease duration. The change in MMDs from baseline to the last trimester of treatment (10-12 months) was comparable across tertiles of CM duration (median [IQR] -12 [-18 to -5] days, -12 [-17 to -6] days, and -12 [-18 to -4] days; p = 0.946). No difference emerged in secondary outcomes, suggesting a similar time to onset of anti-CGRP mAbs effect across all tertiles of CM duration.
CONCLUSIONS: Our data showed that anti-CGRP mAbs are effective and have a rapid onset of action in CM regardless of disease duration.

UNASSIGNED: Migraine has a negative impact on patients\' quality of life, with the frequency of attacks being associated with greater disability and poorer health status. Frequent migraine-type headaches require prophylactic treatment, which has so far been of limited effectiveness until advent of calcitonin gene-related peptide (CGRP) monoclonal antibody.
UNASSIGNED: A prospective analysis was conducted of data from 41 migraine patients who experienced 4 or more monthly migraine days (MMD) longer than three months. At the beginning of the study, treatment with monoclonal antibodies against CGRP (fremanezumab 225 mg or erenumab 70 or 140 g per month) was prescribed according to the indications. The effect of the medications was evaluated after 3-month period.
UNASSIGNED: The mean age of patients was 37.17 (±11.78) years. It was found that 17 patients (41.5%) had episodic migraine (EM) and 24 (58.5%) had chronic migraine (CM). Fremanezumab was prescribed to 26 patients (63.4%) and erenumab to 15 patients (36.6%); among the latter, 13 patients used 70 mg/month and 2 patients used 140 mg/month. Three months after treatment, CM changed to EM for 19 patients (79.2%), 27 patients (65.9%) had ≥50% reduction in the number of MMD and total migraine disability assessment (MIDAS) score was reduced by >50% in 31 patients (75.6%). Also, all areas of quality of life of patients were improved after 3 months continued treatment compared to baseline.
UNASSIGNED: For more than half the patients using fremanezumab or erenumab after 3-month period, MMD decreased by ≥50% and total MIDAS score by >50 points. All areas of quality of life were improved after prophylactic treatment of migraine.
UNASSIGNED: Migrena neigiamai veikia pacientų gyvenimo kokybę ir galvos skausmų dažnis yra susijęs su didesnia negalia ir blogesne sveikata. Esant dažnam migreniam galvos skausmui yra reikalingas profilaktinis gydymas, kurio efektyvumas, iki atsirandant biologinei terapijai, buvo ribotas.
UNASSIGNED: Perspektyviniame tyrime dalyvavo 41 migrena sergantys pacientai, kuriems pasireiškė 4 ir daugiau migreninių dienų per mėnesį (MDM) ilgiau kaip 3 mėnesius. Pacientams paskirti su kalcitonino genu susijusį baltymą ir jo receptorius veikiantys (angl. calcitonin gene-related peptide, CGRP) monokloniniai antikūnai (fremanezumabas 225 mg ar erenumabas 70 mg ar 140 mg per mėnesį). Gydymo efektyvumas įvertintas po 3 mėnesių.
UNASSIGNED: Pacientų amžiaus vidurkis buvo 37,17 (±11,78) metų. Nustatyta, kad epizodinę migreną (EM) turėjo 17 (41,5 proc.) pacientų, o lėtinę migreną (LM) – 24 (58,5 proc.) pacientai. Fremanezumabas paskirtas 26 (63,4 proc.), o erenumabas – 15 (36,6 proc.) pacientams; atitinkamai, 13 pacientų naudojo erenumabo 70 mg per mėnesį, o 2 pacientai – 140 mg per mėnesį. Po trijų mėnesių vartojant monokloninius antikūnus, LM pasikeitė į EM 19 (79,2 proc.) pacientų, ≥50 proc. MDM sumažėjo 27 (65,9 proc.) pacientams ir 31 (75,6 proc.) pacientui bendras migrenos įtakos veiklai (angl. migraine disability assessment scale, MIDAS) balas sumažėjo >50 proc. Visose srityse gyvenimo kokybės įvertinimas pagerėjo 3 mėnesius skiriant monokloninius antikūnus.
UNASSIGNED: Daugiau kaip pusei pacientų sumažėjo ≥50 proc. MDM ir >50 proc. MIDAS balai, gyvenimo kokybės įvertinimas visose srityse pagerėjo po 3 mėnesių skiriant gydymą monokloniniais antikūnais.

UNASSIGNED: Real-world studies have shown the sustained therapeutic effect and favourable safety profile of OnabotulinumtoxinA (BoNTA) in the long term and up to 4 years of treatment in chronic migraine (CM). This study aims to assess the safety profile and efficacy of BoNTA in CM after 5 years of treatment in a real-life setting.
UNASSIGNED: We performed a retrospective chart review of patients with CM in relation to BoNTA treatment for more than 5 years in 19 Spanish headache clinics. We excluded patients who discontinued treatment due to lack of efficacy or poor tolerability.
UNASSIGNED: 489 patients were included [mean age 49, 82.8% women]. The mean age of onset of migraine was 21.8 years; patients had CM with a mean of 6.4 years (20.8% fulfilled the aura criteria). At baseline, patients reported a mean of 24.7 monthly headache days (MHDs) and 15.7 monthly migraine days (MMDs). In relation to effectiveness, the responder rate was 59.1% and the mean reduction in MMDs was 9.4 days (15.7 to 6.3 days; p < 0.001). The MHDs were also reduced by 14.9 days (24.7 to 9.8 days; p < 0.001). Regarding the side effects, 17.5% experienced neck pain, 17.3% headache, 8.5% eyelid ptosis, 7.5% temporal muscle atrophy and 3.2% trapezius muscle atrophy. Furthermore, after longer-term exposure exceeding 5 years, there were no serious adverse events (AE) or treatment discontinuation because of safety or tolerability issues.
UNASSIGNED: Treatment with BoNTA led to sustained reductions in migraine frequency, even after long-term exposure exceeding 5 years, with no evidence of new safety concerns.

OBJECTIVE: To evaluate the effectiveness of a multidisciplinary program, including Cognitive behavioral therapy (CBT), in the treatment of patients with chronic migraine (CM) and concomitant chronic insomnia (CI).
METHODS: The study included 96 patients with CM and CI, average age 35.7±8.6. All patients underwent clinical interviews and testing using clinical and psychological techniques. Patients were randomized into two groups: group 1 received study treatment (an multudisciplinary program including CBT for pain and insomnia, combined with standard treatment for migraine), group 2 received standard treatment for migraine (preventive and acute pharmacotherapy for migraine, recommendations about lifestyle and sleep hygiene). All patients were assessed for clinical and psychological parameters before treatment and at 3, 6, 12 and 18 months follow-up.
RESULTS: At 3 month follow-up a statistically significant improvement was observed in group 1: a decrease in the frequency of headaches and the use of painkillers, parameters on the Insomnia Severity Index (ITI), the State-Trait Anxiety Inventory (STAI), the Beck Depression Inventory, and the Migraine Disability Assessment (MIDAS) (p<0.05). At 6, 12 and 18 months follow-up the achieved improvements were maintained. At 3 month follow-up, group 2 showed a statistically significant improvement in only 4 parameters: a decrease in the frequency of headaches and painkiller use, and parameters for ITI and MIDAS. These parameters increased to values that were not statistically significantly different from the parameters before treatment in group 2 at 6 month follow-up. At 3 month follow-up in group 165% of patients achieved clinical effect (CE) according to CM (headache frequency decreased by 50% or more), in group 2 - 40%, which was not statistically significantly different (p>0.001); in group 1, 76% of patients achieved CE according to CI (ITI decreased by 8 points or more), which is statistically significantly more than in group 2 with 45% of patients with CE (p<0.001). At 18 month follow-up, in group 1, 81.5% of patients achieved CE according to CM, which is statistically significantly more than in group 2 with 33% of patients with CE (p<0.001); in group 1, 85% of patients achieved CE according to CI, which is statistically significantly more than in group 2, where 38% of patients had CE (p<0.001).
CONCLUSIONS: High effectiveness of CBT in patients with CM and combined CI was noted.
UNASSIGNED: Оценить эффективность междисциплинарной программы, включающей когнитивно-поведенческую терапию (КПТ), в лечении пациентов с хронической мигренью (ХМ) и сочетанной хронической инсомнией (ХИ).
UNASSIGNED: В исследование включены 96 пациентов с ХМ и ХИ, средний возраст 35,7±8,6 года. Со всеми пациентами проводились клиническая беседа и тестирование с помощью клинико-психологических методик. Пациенты были рандомизированы в две группы: 1-я группа получала стандартное лечение (фармакотерапию профилактическую и для купирования мигрени, рекомендации по образу жизни и гигиене сна) и КПТ, 2-я группа — только стандартное лечение. У всех пациентов оценивались клинико-психологические показатели до лечения и на 3, 6, 12 и 18-й месяцы после лечения.
UNASSIGNED: Через 3 мес терапии в 1-й группе наблюдалось статистически значимое улучшение: снижение частоты приступов головной боли и приема обезболивающих, показателей по Индексу тяжести инсомнии (ИТИ), шкале личностной и ситуативной тревоги Спилбергера—Ханина, шкале депрессии Бека, шкале оценки влияния мигрени на повседневную активность (ШОВМА) (p<0,05). Через 6, 12 и 18 мес терапии достигнутые улучшения сохранились. Через 3 мес терапии во 2-й группе наблюдалось статистически значимое (p<0,05) улучшение только по 4 параметрам: снижение частоты приступов головной боли и приема обезболивающих, показателей по ИТИ и ШОВМА. С 6 мес терапии во 2-й группе эти показатели статистически значимо не отличались от показателей до лечения. Через 3 мес терапии клинического эффекта (КЭ) по ХМ (снижение частоты головной боли на 50% и более) в 1-й группе достигли 65% пациентов, во 2-й группе — 40%; КЭ по ХИ (ИТИ уменьшился на 8 баллов и более) в 1-й группе — 76% пациентов, во 2-й группе — 45% (p<0,001). Через 18 мес терапии КЭ по ХМ в 1-й группе достигли 81,5% пациентов, во 2-й группе — 33% (p<0,001); КЭ по ХИ в 1-й группе — 85% пациентов, во 2-й группе — 38% (p<0,001).
UNASSIGNED: Отмечена высокая эффективность КПТ у пациентов с ХМ и сочетанной ХИ.

OBJECTIVE: To describe the association between day-to-day peak pain severity and clinical factors in individuals with chronic migraine (CM).
BACKGROUND: Little is known about how clinical factors relate to day-to-day pain severity in individuals with CM.
METHODS: Adults with CM were enrolled into this observational prospective cohort study that collected daily data about headache, associated symptoms, and lifestyle factors using a digital health platform (N1-Headache™) for 90 days. \"Migraine days\" were defined as days in which a headache occurred that had features described by the International Classification of Headache Disorders criteria. On these days, peak pain severity was recorded on a 4-point scale; on non-headache days peak pain severity was imputed as \"0/none\". The associations between peak pain severity and 12 clinical factors were modeled and adjusted for sex, age, daily headache, presence of menstrual bleeding, day of the week, and disability. All numerical and Likert scale variables were standardized prior to analysis.
RESULTS: Data were available for 392 participants (35,280 tracked days). The sample was predominantly female (90.6%), with a mean (standard deviation) age of 39.9 (12.8) years. In the final multivariable model with random intercept and slopes, higher than typical self-reported levels of standardized stress (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.04-1.11), standardized irritability (OR 1.05, 95% CI 1.02-1.08), standardized sadness (OR 1.05, 95% CI 1.02-1.07), fatigue (OR 1.25, 95% CI 1.15-1.36), eyestrain (OR 1.38, 95% CI 1.26-1.52), neck pain (OR 1.94, 95% CI 1.76-2.13), skin sensitivity (OR 1.61, 95% CI 1.44-1.80), and dehydration (OR 1.29, 95% CI 1.18-1.42) were associated with higher reported peak pain severity levels, while standardized sleep quality (OR 0.96, 95% CI 0.93-0.99) and standardized waking feeling refreshed (OR 0.84, 95% CI 0.81-0.88) were associated with lower reported peak pain severity levels. The inclusion of a random intercept and random slopes improved upon more parsimonious models and illustrated large differences in individuals\' reporting of peak severity according to the levels of the associated clinical factors.
CONCLUSIONS: Our data showed that the experience of CM, from a pain severity perspective, is complex, related to multiple clinical variables, and highly individualized. These results suggest that future work should aim to study a personalized approach to both medical and behavioral interventions for CM based on which clinical factors relate to the individual\'s experience of pain severity.

OBJECTIVE: To analyze the specificity of calcitonin gene-related peptide (CGRP) levels, we measured alpha-CGRP circulating levels in a large series of patients with a recent diagnosis of inflammatory bowel disease (IBD) who were interviewed regarding comorbid headache.
BACKGROUND: Several studies have found an association between migraine and IBD.
METHODS: In this cross-sectional study performed in an IBD clinic, morning serum alpha-CGRP levels were measured by enzyme-linked immunosorbent assay in 96 patients who were recently diagnosed with IBD and compared to those from 50 similar patients with chronic migraine (CM) and 50 healthy controls (HC).
RESULTS: Alpha-CGRP levels were higher in patients with IBD (median [interquartile range] 56.9 [35.6-73.9] pg/mL) and patients with CM (53.0 [36.7-73.9] pg/mL) compared to HC (37.2 [30.0-51.8] pg/mL; p = 0.003; p = 0.019, respectively). Regarding IBD diagnostic subtypes, alpha-CGRP levels for ulcerative colitis (67.2 ± 49.3 pg/mL; 57.0 [35.6-73.4] pg/mL) and Crohn\'s disease (54.9 ± 27.5 pg/mL; 57.7 [29.1-76.1] pg/mL) were significantly higher than those of HC (p = 0.013, p = 0.040, respectively). Alpha-CGRP levels were further different in patients with IBD with migraine (70.9 [51.8-88.7] pg/mL) compared to HC (p < 0.001), patients with IBD without headache (57.5 [33.3-73.8] pg/mL; p = 0.049), and patients with IBD with tension-type headache but without migraine (41.7 [28.5-66.9] pg/mL; p = 0.004), though alpha-CGRP levels in patients with IBD without migraine (53.7 [32.9-73.5] pg/mL) remained different over HC (p = 0.028).
CONCLUSIONS: Together with CM, circulating alpha-CGRP levels are different in patients with IBD, perhaps reflecting a chronic inflammatory state. IBD is an example of how alpha-CGRP levels are not a totally specific migraine biomarker. However, alpha-CGRP levels were further increased in patients with IBD who have a history of migraine, which reinforces its role as a biomarker in migraine patients, always bearing in mind their comorbidities.

OBJECTIVE: To compare the real-world effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) and onabotulinumtoxinA in chronic migraine (CM) patients.
METHODS: This multicenter study involved retrospective analysis of prospectively collected data of CM patients treated with CGRP mAbs or onabotulinumtoxinA, including difficult-to-treat (DTT) patients (i.e., ≥3 preventive failures). Treatment outcomes were determined at 6 months based on prospective headache diaries and Migraine Disability Assessment (MIDAS).
RESULTS: The study included 316 (55 M/261F, mean age 44.4 ± 13.5 years) and 333 (61 M/272F, mean age 47.9 ± 13.4 years) CM patients treated with CGRP mAbs or onabotulinbumtoxinA, respectively. At 6 months, CGRP mAb treatment was associated with a greater decrease in monthly migraine days (MMDs) (-13.0 vs. -8.7 days/month, p < 0.001) and a higher ≥50% responder rate (RR) (74.7% vs. 50.7%, p < 0.001) compared with onabotulinumtoxinA injections. The findings were consistent in DTT patients (-13.0 vs. -9.1 MMDs, p < 0.001; ≥50% RR: 73.9% vs. 50.3%, p < 0.001) or those with medication-overuse headache (MOH) (-13.3 vs. -9.0 MMDs, p < 0.001; ≥50% RR: 79.0% vs. 51.6%, p < 0.001). Besides, patients receiving CGRP mAbs had greater improvement (-42.2 vs. -11.8, p < 0.001) and a higher ≥50% RR (62.0% vs. 40.0%, p = 0.001) in MIDAS scores and a lower rate of adverse events (AEs) (6.0% vs. 21.0%, p < 0.001). However, none of the patients discontinued treatment due to AEs.
CONCLUSIONS: In this multicenter, real-world study, CGRP mAbs were more effective than onabotulinumtoxinA in CM patients, even in DTT or MOH patients. All of these injectables were well tolerated. Further prospective studies are needed to verify these findings.