Treatment Of Migraine Attacks Research Articles

Patterns, Barriers, and Preferences of Treating Migraine Within the School Setting: A Survey Study of Students

Background/Objectives: Migraine affects 10% of adolescents and children. Typical school protocols in the USA require pharmacological medications to be administered by school nurses, often resulting in treatment delays or omissions when migraine attacks occur during school hours. The Remote Electrical Neuromodulation (REN) wearable is an FDA-cleared smartphone-controlled device delivering acute and preventive treatment of migraine attacks in patients aged 8 and above, allowing safe, effective, discreet, and independent usage. Methods: This retrospective study (NCT06180577) evaluates treatment patterns, barriers, and preferences among school-age students. REN users < 18 years old were invited to complete an online survey. Participants signed an assent form, and their parents/legal guardians signed an informed consent form. Results: 332 patients aged 7–17 (15.5 ± 2.1) participated (80.4% female). After being prescribed the REN wearable, the percentage of students who treated their headaches at school increased from 78.3% to 89.8%. Most participants (65.4%) treated with either REN standalone (38.0%) or in combination with medications (27.4%). Common barriers to treatment included the need to leave class for the nurse’s office (64.2%), concerns about standing out (42.2%), and one barrier unique to REN–permission needed to use a smartphone in class (22.9%). The most common reasons given for preferring REN treatment at school are the ability to avoid going to the nurse’s office (42.5%) and to treat discreetly (39.2%). Conclusions: This study underscores the challenges of managing migraine at school while suggesting the importance of the REN wearable as a discreet and independently used first-line treatment for children and adolescents.

Long-Term (12-Month) Safety and Tolerability of STS101 (Dihydroergotamine Nasal Powder) in the Acute Treatment of Migraine: Data from the Phase 3 Open-Label ASCEND Study.

STS101 is an investigational drug-device combination comprising 5.2 mg dihydroergotamine (DHE) powder (6.0 mg DHE mesylate) in a single-use nasal delivery device for the acute treatment of migraine. The primary objective of the ASCEND trial was to assess long-term safety and tolerability of STS101 in the acute treatment of migraine attacks across 12-18 months, with secondary objectives describing efficacy. ASCEND was an open-label study of STS101 in adults aged 18-65 years with a ≥ 1 year history of migraine with or without aura, with onset before the age of 50 years and 4-12 migraine attacks/month and < 15 headache days/month in each of the 3 months prior to screening. Exclusion criteria included diagnosis of non-migraine headache, history of cerebrovascular disease, and ≥ 2 cardiovascular risk factors. After establishing eligibility, participants could self-administer STS101 5.2 mg as needed for up to 2 doses within 24 h to treat a single migraine attack and up to 12 doses/month. Safety and tolerability evaluations included physical and nasal examinations, vital signs, laboratory tests, and treatment-emergent adverse event (TEAE) assessments. Participants used an electronic diary to record exploratory efficacy parameters, including intensity of headache pain and associated migraine symptoms (photophobia, phonophobia, and nausea). Participant impression questions were asked at months 3, 6, and 12. Of the 6610 migraine attacks treated with a total of 8234 STS101 doses in 344 participants, 945/6610 (14.3%) were associated with a TEAE. Events were predominantly mild or moderate in nature and rarely led to premature study discontinuation (15/344 [4.4%] participants). Treatment was associated with rapid onset of freedom from pain (36.6%, 67.1%, and 85.5% of treated attacks 2, 4, and 24 h post-dose, respectively), freedom from most bothersome symptoms (54.3%, 79.6%, and 91.3%), and headache relief (66.5%, 89.1%, and 94.3%). Most participants rated treatment results as good or very good and ease of use as easy or very easy at all time points (months 3, 6, and 12) and indicated they were likely or very likely to use STS101 again. The repeated long-term, as-needed use of STS101 was well tolerated, demonstrating a favorable safety profile in the acute treatment of migraine attacks in appropriately indicated adults. Exploratory efficacy evaluations indicated beneficial effects, which warrant further evaluation. ClinicalTrials.gov identification NCT04406649.

First real-world study on the effectiveness and tolerability of rimegepant for acute migraine therapy in Chinese patients

BackgroundRimegepant, a small molecule calcitonin gene-related peptide (CGRP) receptor antagonist, is indicated for acute and preventive migraine treatment in the United States and other countries. However, there is a lack of prospective real-world evidence for the use of rimegepant in Chinese migraine patients.MethodsThis was a single-arm, prospective, real-world study. While taking rimegepant to treat migraine attacks as needed, eligible participants were asked to record their pain intensity, functional ability, and accompanying symptoms for a single attack at predose and 0.5, 1, 2, 24, and 48 h postdose via a digital platform. Adverse events (AEs) during the rimegepant treatment period were recorded and analysed. The percentages of participants who experienced moderate to severe pain at predose and 0.5, 1, 2, 24, and 48 h postdose were assessed. Additionally, the percentages of participants who reported better/good outcomes in terms of pain intensity, functional ability, and accompanying symptoms at 0.5, 1, 2, 24, and 48 h postdose were analysed. In addition, the total cohort (full population, FP) was stratified into a prior nonresponder (PNR) group to observe the effectiveness and safety of rimegepant for relatively refractory migraine and a rimegepant and eptinezumab (RE) group to observe the effectiveness and safety of the combination of these drugs.ResultsBy November 24th, 2023, 133 participants (FP, n = 133; PNR group, n = 40; RE group, n = 28) were enrolled, and 99 participants (FP, n = 99; PNR group, n = 30; RE group, n = 23) were included in the analysis. Rimegepant was effective in treating migraine in the FP and both subgroups, with a significant decreasing trend in the percentages of participants experiencing moderate to severe pain postdose (p < 0.05) and a marked increase in the percentages of participants who reported better/good outcomes in terms of pain intensity, functional ability, and accompanying symptoms at 0.5, 1, 2, 24, and 48 h postdose compared with predose. AEs were reported by 6% of participants in the FP, and all AEs were mild.ConclusionsIn the real world, rimegepant is effective in the acute treatment of migraine patients in China. The low incidence rate of AEs highlighted the favourable tolerability profile of rimegepant.Trial registrationClinicaltrials.gov NCT05709106. Retrospectively registered on 2023-02-01.Graphical

Effect of kyron T-134 and crospovidone as a fast disintegrating agent on formulation properties of fast dissolving tablet containing ketorolac and rizatriptan using direct compression method

Background and objective: Fast dissolving tablets (FDTs) are "they are uncoated tablets that are supposed to be placed in the mouth and dispersed quickly before being swallowed" within minutes. This study aimed to formulate and evaluate a combination of ketorolac and rizatriptan as orally fast-dissolving tablets using the most common and easiest method to treat migraine attacks with or without aura. To investigate the effects of various types of diluents and super disintegrants on wetting time, water absorption ratio, disintegration, and dissolution time of combined drugs (ketorolac and rizatriptan) as oral dissolving tablets prepared by direct compression technique. Methods: Pre-formulation experiments were carried out in order to rule out any physicochemical interactions between the two medications (ketorolac and rizatriptan) as well as between each drug and its excipients. Four different formulations of fast-dissolving tablets with different types and ratios of diluents and super disintegrants were created using the direct compression technique in order to improve the formulation. Organoleptic characteristics, weight variation, thickness, friability, hardness, disintegration duration, wetting duration, water absorption ratio, drug content, in-vitro dissolution, stability, and comparison tests have all been characterized. Results: According to FT-IR, the two drugs and excipients exhibit no physicochemical interactions. The ideal formula F4 contains crospovidone and Kyron T-134 at optimal concentrations of 2.5% and 2.5%, respectively, and provides the majority of pharmaceutical drugs to be released within the first five minutes, a strong stability profile, the shortest wetting time with the fastest disintegration time (10 sec), and a pleasant flavor (strawberry flavoring agent). Conclusion: Kyron T-134 with Crospovidone in a (1:1) ratio provided rapid disintegration. Ketorolac tromethamine and rizatriptan benzoate may be made into fast-dissolving oral tablets using Kyron T-134 and Crospovidone. Improving migraine compliance is a reasonable goal.

Efficacy and safety of Russian tableted rizatriptan 10 mg in the treatment of migraine attacks in clinical practice

Efficacy and safety of Russian tableted rizatriptan 10 mg in the treatment of migraine attacks in clinical practice

Use of rimegepant as an alternative to triptans in migraine treatment

Introduction and aim of study: Migraine is a chronic neurological disorder that is considered one of the leading causes of disability worldwide. Increasing evidence indicates that the calcitonin gene-related peptide (CGRP), a neuropeptide released during trigeminal nerve activation, plays a major role in pathophysiology and serves as an important therapeutic target. Rimegepant is an antagonist for the receptor of this peptide and an alternative to the commonly used triptans. Materials and Methods: Two databases, Pubmed and Medline, were searched using the terms "rimegepant" and "migraine." Results: By reducing the severity and frequency of migraine attacks, rimegepant significantly improves patients' daily functioning and quality of life. A single 75 mg dose of rimegepant provided better efficacy than placebo in the acute treatment of migraine. Two hours after dosing, significantly more patients in the rimegepant group than in the placebo group reported pain relief (59.3% vs. 43.3%). Rimegepant was also effective in the long term when taken every other day for preventive treatment of migraine and/or as needed for acute migraine treatment. When used, rimegepant was well tolerated in both acute and preventive migraine treatment. The most common adverse events included nasopharyngitis, nausea, urinary tract infection, and upper respiratory tract infection. Conclusions: Rimegepant is an effective drug for treating migraine attacks, offering quick and long-lasting pain relief with a favorable safety profile, especially for patients with contraindications to triptans. Therefore, rimegepant represents a valuable alternative for patients who do not respond adequately to other available migraine therapies.

Rizatriptan as an Over-the-Counter Triptan in the Treatment of Migraine Attacks.

Around 91% of migraine patients use over-the-counter medicines to treat attacks, often without further treatment or medical consultation. This therapeutic principle is established in most countries, regardless of how the healthcare system is otherwise structured or financed. Using Germany as an example, the basis for an expansion of attack therapy with rizatriptan as an over-the-counter triptan is described. To achieve the best possible tolerability and safety in the context of self-medication, the lowest possible dose should be selected to provide the most favourable tolerability and safety profile in the context of self-medication through low dosages. The lowest approved dose of rizatriptan is 5mg. This was investigated in three randomized controlled trials with 752 patients. The results show that rizatriptan at a dose of 5mg is more effective than the triptans naratriptan 2.5mg, almotriptan 12.5mg and sumatriptan 50mg, which were previously available for self-medication in Germany. There was no significant difference in the frequency of adverse events with rizatriptan 5mg compared to placebo. Rizatriptan 5mg does not have a higher side effect potential than sumatriptan 50mg, which is already exempt from the prescription requirement. The reasons given show that rizatriptan in a dose of 5mg for the treatment of acute migraine attacks fulfils the requirements for a transfer from prescription to pharmacy-only status at least as well as sumatriptan 50mg, naratriptan 2.5mg and almotriptan 12.5mg. From a clinical care perspective, it is desirable for affected patients to have other options available for self-medication. Non-responders to other substances also have a further treatment option with rizatriptan 5mg, with the same or even better risk-benefit profile, to treat migraine attacks safely, effectively and in a tolerable manner as part of self-medication.

Цервикалгия у пациентов с мигренью – коморбидная нозология или клинический аспект центральной сенситизации?

Relevance. The phenomenon of central sensitization occurs when physiological activity in nociceptive pathways increases and leads to abnormal sensitivity; it is defined as “increased sensitivity of nociceptive neurons of the central nervous system to their normal or subthreshold afferent input,” according to the definition provided by the International Association for the Study of Pain (IASP). The excitability of spinal cord neurons significantly modifies the gain of the somatosensory system. Chronic pain syndromes, anxiety-depressive disorder, sleep disorders are currently very common in the population, significantly reducing the quality of life of the population; the pathogenesis of these nosologies lies in central sensitization. Objective. To study the clinical manifestations of central sensitization in patients with episodic migraine associated with neck pain or cervicogenic headache. Materials and methods. The longitudinal prospective study included 180 patients, divided into 3 groups: 1) patients with a combination of migraine and cervicogenic headache – 60 people (study group); 2) patients with a combination of migraine and cervicalgia diagnoses – 60 people (control group); 3) patients diagnosed with migraine without complaints of pain and limitation of movements in the cervical spine – 60 people (additional group). Results. In patients with migraine and comorbid cervical headache, more pronounced central sensitization was revealed when compared with comorbid cervicalgia. Myofascial pain syndrome involving the trapezius and temporal muscles can resolve on its own with specific migraine therapy with monoclonal antibodies, however, to relieve tension and soreness in the masseter and inferior oblique muscles, the addition of therapeutic exercises and gentle manual techniques is more effective. Taking into account the identified direct relationships of moderate strength between the number of painful points of exit of the trigeminal nerve, the muscles of the pericranial region involved, as well as the effect of treatment of migraine attacks with monoclonal antibodies, it can be concluded that central sensitization is more pronounced when the masseter and inferior oblique muscles are involved. Conclusions. During examination of patients with migraine with comorbid active cervicalgic factor or even if it is absence, it is necessary to make a thorough examination of the facial and cranioverebral region muscles, even in the absence of patient complaints of pain in the face or neck, and also prescribe specific therapeutic exercises to increase the effectiveness of treatment. In all patients with migraine, regardless of chronicity, it is necessary to assess the intensity of central sensitization for timely and more complete provision of medical care.

Real-world effectiveness and satisfaction with intravenous eptinezumab treatment in patients with chronic migraine: REVIEW, an observational, multi-site, US-based study

BackgroundDespite recent advancements in migraine treatment, some patients continue to endure significant disease burden. Due to the controlled nature of randomized trials in migraine prevention, many real-world patients with comorbidities or prior exposure to certain therapies are excluded. Capturing evidence of the effectiveness of treatment in real-world clinical settings can further shape treatment paradigms. The objective of this study was to develop a comprehensive understanding of both patients’ and physicians’ real-world experiences with eptinezumab for chronic migraine (CM).MethodsREVIEW (Real-world EVidence and Insights into Experiences With eptinezumab) is an observational, multi-site (n = 4), US-based study designed to evaluate real-world experiences of patients treated with eptinezumab and their treating physicians. Patients were ≥ 18 years of age, with a diagnosis of CM, who had completed ≥ 2 consecutive eptinezumab infusion cycles (≥ 6 months of exposure). The study included a retrospective chart review, a patient survey, and a semi-structured physician interview that assessed patient and/or physician satisfaction with elements of daily living / well-being, migraine symptomology, and perspectives of the eptinezumab infusion experience.ResultsOf the 94 patients enrolled, 83% (78/94) were female, the mean age was 49.2 years, and the mean time since migraine diagnosis was 15.4 years. Before eptinezumab treatment, patients experienced a mean of 8 self-reported “good” days/month, which increased to 18 after treatment. Most patients took, on average, ≥ 10 days/month of prescription and/or over-the-counter medication (81% [75/93] and 66% [61/93], respectively) to treat migraine attacks before eptinezumab treatment, which dropped to 26% (24/93) and 23% (21/93) following eptinezumab treatment. Prior to receiving eptinezumab, 62% (58/93) of patients indicated being at least slightly concerned about infusions; after eptinezumab infusion, this dropped to 14% (13/93). These patient survey findings were consistent with physician responses.ConclusionThis real-world evidence study demonstrated high overall satisfaction with the effectiveness of eptinezumab treatment for CM among most patients and their physicians.

Dipyrone for the acute treatment of migraine attacks in children and adults

Dipyrone for the acute treatment of migraine attacks in children and adults

Breastfeeding-Related Adverse Drug Reactions of Triptans: A Descriptive Analysis Using Four Pharmacovigilance Databases.

Objective: Migraine attacks are common in women of reproductive age. Although attacks are often less severe and less frequent during pregnancy, they regularly reoccur shortly after delivery. When first-line analgesic treatment is insufficient, triptans may be used for acute treatment of migraine attacks. Milk levels of occasional triptan use have shown to be low, and no adverse effects in breastfed infants have been reported. However, the available knowledge on the safety of triptans during breastfeeding is still limited. Methods: Four (inter)national pharmacovigilance databases were searched for breastfeeding related adverse drug reactions of triptans. These included the Dutch Pregnancy Drug Register and three databases of spontaneous reports (Netherlands Pharmacovigilance Centre Lareb, the European Medicines Agency [EudraVigilance], and the World Health Organization [VigiBase]). Results: A total of 26 reports on 27 breastfeeding related adverse drug reactions were identified (one report involved two separate adverse drug reactions). These involve three main complaints: painful breasts and/or nipples, painful milk ejection reflex, and a decrease in milk production. Discussion and Conclusion: The hypothesized pharmacological mechanism relates to the serotonin-receptor agonistic properties of triptans. These may lead to vasoconstriction in the breasts and nipples, including the vasculature surrounding the milk ducts and alveoli, and may also influence the hormonal function and levels of prolactin. The reported adverse drug reactions do not negatively impact the overall compatibility of triptans with breastfeeding. However, breastfeeding women may experience them as unsettling. Awareness of these potential adverse drug reactions is essential and should be weighed against the potential adverse effects of (untreated) symptoms of migraine attacks.

Medication "underuse" headache.

Many risk factors have been associated with migraine progression, including insufficient and ineffective utilization of migraine medications; however, they have been inadequately explored. This has resulted in suboptimal usage of medications without effective altering of prescribing recommendations for patients, posing a risk for migraine chronification. Our aim is to conduct a comprehensive review of the available evidence regarding the underuse of migraine medications, both acute and preventive. The term "underuse" includes, but is not limited to: (1) ineffective use of appropriate and inappropriate medication; (2) underutilization; (3) inappropriate timing of usage; and (4) patient dissatisfaction with medication. The underuse of both acute and preventive medications has been shown to contribute to the progression of migraine. In terms of acute medication, chronification occurs as a result of insufficient drug use, including failure of the prescriber to select the appropriate type based on pain intensity and disability, patients taking medication too late (more than 60 minutes after the onset or after central sensitization has occurred as evidenced by allodynia), and discontinuation because of lack of effect or intolerable side effects. The underlying cause of inadequate effectiveness of acute medication lies in its inability to halt the propagation of peripheral activation to central sensitization in a timely manner. For oral and injectable preventive migraine medications, insufficient efficacy and intolerable side effects have led to poor adherence and discontinuation with subsequent progression of migraine. The underlying pathophysiology here is rooted in the repetitive stimulation of afferent sensory pain fibers, followed by ascending brainstem pain pathways plus dysfunction of the endogenous descending brainstem pain inhibitory pathway. Although anti-calcitonin gene-related peptide (CGRP) medications partially address pain caused by the above factors, including decreased efficacy and tolerability from conventional therapy, some patients do not respond well to this treatment. Research suggests that initiating preventive anti-CGRP treatment at an early stage (during low frequency episodic migraine attacks) is more beneficial than commencing it during high frequency episodic attacks or when chronic migraine has begun. The term "medication underuse" is underrecognized, but it holds significant importance. Optimal usage of acute care and preventive migraine medications could potentially prevent migraine chronification and improve the treatment of migraine attacks.

How early can we treat migraine attacks? A perspective based on prodrome

Treating migraine attacks early at the onset of a headache is a common proven strategy. But does this strategy work before headache onset? In the PRODROME trial, Dodick etal. showed that ubrogepant taken during the prodrome can prevent headache attacks and reduce functional disability.1.

Exploration of Lasmiditan 200 mg Versus 100 mg for the Treatment of Migraine: A Meta-analysis Based on Aggregate Data.

Lasmiditan holds important potential in treating migraine, but its ideal dose remains elusive. This meta-analysis is conducted based on aggregate data and aims to compare the efficacy of lasmiditan 200 mg versus 100 mg for acute treatment of migraine attack. PubMed, Embase, Web of Science, EBSCO, and Cochrane Library databases were systematically searched, and we included the randomized controlled trials comparing the efficacy of lasmiditan 200 mg versus 100 mg for migraine patients. This meta-analysis was conducted using the random-effect model or fixed-effect model based on the heterogeneity. The primary outcome was pain free at 2 hours. Secondary outcomes included pain relief at 2 hours, pain free at 24 hours, most bothersome symptom free at 2 hours, and adverse events. Seven randomized controlled trials and 6515 patients were included in this meta-analysis. Compared with lasmiditan 100 mg for migraine patients, lasmiditan 200 mg was able to significantly improve pain free at 2 hours (odd ratio [OR], 1.28; 95% confidence interval [CI], 1.14-1.44; P < 0.0001) and pain free at 24 hours (OR, 1.35; 95% CI, 1.14-1.60; P = 0.0005), but showed no effect on pain relief at 2 hours (OR, 1.00; 95% CI, 0.90-1.12; P = 0.98) or most bothersome symptom free at 2 hours (OR, 0.93; 95% CI, 0.83-1.03; P = 0.17). Lasmiditan 200 mg was associated with the increase in adverse events compared with lasmiditan 100 mg (OR, 1.28; 95% CI, 1.15-1.43; P < 0.0001). Lasmiditan 200 mg is more effective to improve pain free at 2 hours and 24 hours than lasmiditan 100 mg for the acute treatment of migraine patients.

New migraine drugs: A critical appraisal of the reason why the majority of migraine patients do not receive an adequate medication.

The last three decades have produced several novel and efficient medications to treat migraine attacks and reduce attack frequency. Additionally, promising approaches for the development of acute therapy and migraine prophylaxis continue to be pursued. At the same time as we witness the development of better and more efficient medications with continuously fewer side effects, we also realise that the high cost of such therapies means that only a minority of migraine patients who could benefit from these medications can afford them. Furthermore, information on cost-effectiveness is still lacking. Here, we compare availiable data, highlight open questions and suggest trials to close knowledge gaps. With good reason, our medicine is evidence-based. However, if this evidence is not collected, our decisions will continue to be based on marketing and assumptions. At the moment, we are not doing justice to our patients.

Pharmacology of erenumab in human isolated coronary and meningeal arteries: Additional effect of gepants on top of a maximum effect of erenumab.

Multiple drugs targeting the calcitonin gene-related peptide (CGRP) receptor have been developed for migraine treatment. Here, the effect of the monoclonal antibody erenumab on CGRP-induced vasorelaxation was investigated in human isolated blood vessels, as well as the effect of combining erenumab with the small molecule drugs, namely rimegepant, olcegepant, or sumatriptan. Concentration-response curves to CGRP, adrenomedullin or pramlintide were constructed in human coronary artery (HCA) and human middle meningeal artery (HMMA) segments, incubated with or without erenumab and/or olcegepant. pA2 or pKb values were calculated to determine the potency of erenumab in both tissues. To study whether acutely acting antimigraine drugs exerted additional CGRP-blocking effects on top of erenumab, HCA segments were incubated with a maximally effective concentration of erenumab (3μM), precontracted with KCl and exposed to CGRP, followed by rimegepant, olcegepant, or sumatriptan in increasing concentrations. Erenumab shifted the concentration-response curve to CGRP in both vascular tissues. However, in HCA, the Schild plot slope was significantly smaller than unity, whereas this was not the case in HMMA, indicating different CGRP receptor mechanisms in these tissues. In HCA, rimegepant, olcegepant and sumatriptan exerted additional effects on CGRP on top of a maximal effect of erenumab. Gepants have additional effects on top of erenumab for CGRP-induced relaxation and could be effective in treating migraine attacks in patients already using erenumab as prophylaxis.

New therapeutic era for migraine attacks with recently approved monoclonal antibodies, ditans and gepants

Treatment of migraine attacks is advised in all patients, using non-steroidal anti-inflammatory drugs when the pain is mild and triptans when the pain intensity is moderate-severe. However, the effectiveness of these drugs is moderate, a high percentage of patients have side effects, and triptans are contraindicated in people with a history of stroke, ischaemic heart disease or poorly controlled hypertension. Hence, there is an urgent need for new therapeutic alternatives. In recent years, new drugs for migraine attacks have become available, most notably ditans (lasmiditan) and gepants (ubrogepant and rimegepant). Furthermore, eptinezumab, which has been approved for the preventive treatment of migraine in adults, has also been used for migraine attacks. This manuscript reviews the efficacy and safety results of the new drugs for migraines that will soon be on the market.

A retrospective analysis of primary headache management from emergency departments to neurology clinics

Objective: To analyze the primary headache type, medical treatments initiated, and imaging characteristics of patients referred to neurology outpatient clinics from the emergency department. Methodology: Patients referred to neurology outpatient clinics from the emergency department between January 2014 and January 2024 were included in the study. Demographic data and case information were obtained from the hospital database. Results: The study included 6940 primary headache patients. Of the patients included in the study, 4164 (60%) were female and 2776 (40%) male. The mean age was 36.02±15.21 years. The most common headache in female patients was migraine, and in male patients, it was a tension-type headache. The proportions of patients who underwent one, two, three, or more cranial imaging procedures in the emergency department within 10 years were 20%, 35%, and 45%, respectively. Eletriptan was the most used drug in the treatment of migraine attacks in 37.8%, Amitriptyline was used in 32.8% of patients for migraine prophylaxis and duloxetine was used in 31.1% of patients for tension-type headaches. Conclusion: The management of primary headaches remains a challenge for primary care physicians. In a patient with severe pain, both medical history and neurologic examination are time-consuming. Considering the patient density and fast pace of work in the emergency department, misdiagnosis and analgesic treatments administered at every emergency department visit without considering the patient's past information delays the prophylactic treatment process in primary headaches and make treatment difficult.

Modern strategies for the treatment of migraine attacks and the possibility of a differentiated approach

Treatment strategies for migraine attacks include the use of nonspecific drugs (simple and combined analgesics, antiemetics) and specific drugs (triptans, ergotamine derivatives, gepants, ditans), as well as neuromodulation methods. Despite the expansion of the range of specific drugs, the effectiveness of relieving headache attacks during migraine remains unsatisfactory. The choice of drug for the treatment of migraine attacks is based on their stratification according to the degree of impairment of the functional activity of patients and involves the prescription of specific anti-migraine drugs for moderate and severe disability. The stratified approach has a number of advantages in terms of the main parameters of analgesic effectiveness, is associated with lower treatment costs and carries a lower risk of analgesic abuse. Migraine attacks are characterized by high polymorphism and the presence of many clinical manifestations, which largely determine the severity of the patient’s disability and sometimes require independent treatment. Specific drugs for the treatment of migraine attacks (triptans) can relieve not only headaches, but also symptoms of nausea, vomiting, photo- and phonophobia. The choice of drug is based on the individual characteristics of the patient, the profile of migraine attacks and involves taking into account the pharmacological properties of the drug. Features of migraine such as a high rate of increase in pain during an attack, the presence of rapidly developing nausea, and the need to provide long-term pain relief require the use of fast-acting forms of medications. The benefits of choosing these forms are supported by patient preference studies. Clinical trial data and research results from actual clinical practice allow us to formulate some approaches to differentiated drug selection.

Ubrogepant for the treatment of migraine attacks during the prodrome: a phase 3, multicentre, randomised, double-blind, placebo-controlled, crossover trial in the USA

Ubrogepant is a calcitonin gene-related peptide (CGRP) receptor antagonist that is approved for acute treatment of migraine. The prodrome is the earliest phase of a migraine attack and is characterised by non-aura symptoms that precede headache onset. The aim of this trial was to evaluate the efficacy, safety, and tolerability of ubrogepant 100 mg compared with placebo for the acute treatment of migraine when administered during the prodrome. This PRODROME trial was a phase 3, multicentre, randomised, double-blind, placebo-controlled, crossover trial of ubrogepant 100 mg conducted at 75 research centres and headache clinics in the USA. Eligible participants were adults aged 18-75 years who had at least a 1-year history of migraine with or without aura and a history of two to eight migraine attacks per month with moderate to severe headache in each of the 3 months before screening. Eligible participants were randomly assigned (1:1) to either receive placebo to treat the first qualifying prodrome event and ubrogepant 100 mg to treat the second qualifying prodrome event or to receive ubrogepant 100 mg to treat the first qualifying prodrome event and placebo to treat the second qualifying prodrome event. An automated interactive web-response system used permuted blocks of four to manage randomisation. All people giving interventions and assessing outcomes were masked to group assignment during the study. People doing data analysis, which occurred after study completion, were not masked to group assignment. During the double-blind treatment period, each participant was instructed to orally take two tablets of the study drug at the onset of each qualifying prodrome event. The primary endpoint was absence of moderate or severe intensity headache within 24 h after study-drug dose; efficacy analyses were conducted with the modified intention-to-treat (mITT) population, defined as all randomly assigned participants with at least one headache assessment within 24 h after taking the study drug during the treatment period. The safety population included all treated participants who took at least one administration of study drug. The trial is registered with ClinicalTrials.gov (NCT04492020). Between Aug 21, 2020, and April 19, 2022, 518 participants were randomly assigned to double-blind crossover treatment. The safety population included 480 participants and the mITT population included 477 participants; 421 (88%) of 480 participants were female and 59 (12%) were male. Absence of moderate or severe headache within 24 h after a dose occurred after 190 (46%) of 418 qualifying prodrome events that had been treated with ubrogepant and after 121 (29%) of 423 qualifying prodrome events that had been treated with placebo (odds ratio 2·09, 95% CI 1·63-2·69; p<0·0001). Adverse events that occurred within 48 h after study-drug administration were reported after 77 (17%) of 456 qualifying prodrome events that had been treated with ubrogepant and after 55 (12%) of 462 events that had been treated with placebo. Ubrogepant was effective and well tolerated for the treatment of migraine attacks when taken during the prodrome. AbbVie.