Migraine is a common form of primary headache that significantly impairs the quality of life of young, able-bodied patients. The prevalence of migraine in Europe and the United States averages 14%; migraine is much more common in women [1]. Migraine is characterized by intense, paroxysmal, often unilateral headache, lasting from 4 to 72 hours, which intensifies with physical activity. In 20% of cases, migraine attacks are accompanied by transient focal neurological manifestations, which allows us to distinguish 2 forms of migraine: migraine without aura and migraine with aura [2]. The origin of migraine is associated with the existence of genetically determined mechanisms for changing the state of excitability of the cortical and stem structures of the brain, which play a key role in the activation of the trigeminovascular system, which implements the actual headache attack. The mechanism of migraine aura is associated with the spread of a wave of excitation of cortical neurons (spreading cortical depression) from the visual cortex to the somatosensory and frontotemporal region. Spreading cortical depression determines the nature and sequence of aura symptoms: visual, sensory, speech [3].
Most migraine attacks occur suddenly. But often an attack can be provoked by a number of endogenous and exogenous factors (migraine triggers). Many authors believe that a combination of several triggers is necessary to trigger a migraine attack. Currently, about 60 different factors that provoke migraine attacks have been described (Table 1)
[4].
Table 1. Factors that provoke a migraine attack
Diagnosis of migraine is carried out clinically and is based on a detailed clinical interview and examination of the patient. Information about the age of onset of the disease, family history, characteristics of the attack, provoking and alleviating factors, and the absence of signs of a secondary nature of the headache is extremely important. When establishing a diagnosis, one should rely on the diagnostic criteria of the International Classification of Headache Disorders, version 3 beta (ICHD-3 beta) [2]. With a typical clinical picture of migraine, additional studies are not indicated and should be carried out only if the symptomatic nature of cephalgia is suspected.
The main goals of migraine treatment are to alleviate the course of migraine, prevent chronicity of the disease and improve the patient’s quality of life. Achieving these goals requires multiple approaches [5]: migraine management, preventative treatment, lifestyle recommendations, and behavioral therapy.
Preventive therapy for migraine is carried out to patients if there are appropriate indications (frequent attacks of headaches, a high degree of patient maladjustment, complete ineffectiveness of symptomatic remedies, etc.). In general, 10 to 30% of patients require preventive medications to reduce the frequency of attacks. Meanwhile, the strategy for stopping attacks should be applicable to every patient who seeks advice, since the severity of migraine cephalalgia, as a rule, requires drug relief, and the vast majority of patients use drugs for each migraine attack.
The goal of relieving a migraine attack is to reduce the intensity, duration of pain and accompanying symptoms (nausea, vomiting, phono- and photophobia, etc.) and normalize the patient’s general condition. Pharmacological agents used for the symptomatic treatment of migraine include the following several groups of drugs. Drugs with a nonspecific mechanism of action:
analgesics (paracetamol, codeine), non-steroidal anti-inflammatory drugs (NSAIDs), combination drugs.
Specific antimigraine drugs:
selective agonists of 5 HT1 B/1D receptors (triptans), non-selective agonists of 5 HT1 receptors (ergotamine, dihydroergotamine).
When choosing a specific drug to relieve an attack, the individual characteristics of the patient should be taken into account, such as the intensity of the headache, the rate of its increase, the presence of associated symptoms, the degree of maladaptation, previous experience and patient preferences. From this point of view, a stratified approach is used, which involves taking into account the most important characteristic of a migraine attack - the level of maladjustment of the patient. This approach is based on ranking migraine attacks according to severity and degree of impairment in patient adaptation, for which the MIDAS scale (The Migraine Disability Assessment Scale)
[6]. For patients with mild attacks and a good level of adaptation, simple analgesics and NSAIDs are prescribed, possibly in combination with drugs that improve their absorption. And patients with severe and moderate attacks require the use of triptans.
Another important principle for relieving a migraine attack is the early administration of an anti-migraine drug. Early use of a triptan provides a more complete analgesic effect and a lower likelihood of headache recurrence. In addition, as the attack progresses, most patients develop gastroparesis with impaired passage of oral medications into the intestine and their poor absorption [7].
The purpose of the study was to evaluate the effectiveness and safety of L.P. Migrepam in comparison with L.P. Sumatriptan in the relief of 3 migraine attacks with and without aura.
What are triptans?
According to modern research, one of the causes of migraines lies in congenital serotonin deficiency.
In the 90s of the last century, substances that were derivatives of serotonin were synthesized, and therefore have a high tropism for the 5HT1D and 5HT1B serotonin receptors. This class of drugs is called triptans.
One of the causes of migraines lies in serotonin deficiency
What does serotonin do in migraines?
Normally, the supply of serotonin is contained in platelets - blood cells responsible for blood clotting. If the lack of this neurotransmitter reaches a critical level, it is released into the blood from platelets, which, along with other factors, leads to a sharp narrowing of the blood vessels in the brain. With the subsequent depletion of serotonin reserves and the expansion of the branches of the carotid artery going to the membranes of the brain, a large volume of blood rushes into them. The result is neurogenic inflammation and an attack of acute pain. The nuclei and branches of the trigeminal nerve are included in the pain reaction process.
How do triptans help with migraines?
Triptans are effective for moderate to severe migraines. They prevent the pathological expansion of blood vessels in the head and block pain at the receptor level of the trigeminal nerve.
Taking triptans helps:
- quickly relieve the condition during an attack;
- reduce or completely remove pain;
- remove swelling and inflammation of the blood vessels of the head without affecting the general blood flow;
- eliminate other symptoms of migraine: nausea, phono- and photophobia;
- prevent relapse of the attack.
Triptans tablets
Sumatriptan (Sumamigren, Imigran, Amigrenin), eletriptan (Relpax), and zolmitriptan (Migrepam) are widely used in Russia.
Sumatriptan is considered the gold standard treatment for migraine. Studies have found that 70% of people experience headache relief after taking sumatriptan, and 60% return to their normal lives within two hours.
All migraine medications have contraindications and restrictions for use, as well as possible side effects: be sure to read the official instructions before taking them.
Sumatriptan - instructions for use
Some restrictions
In general, triptans should not be used for the following diseases:
- cardiac ischemia,
- cerebrovascular accidents,
- hypertension,
- arrhythmia,
- spontaneous angina.
If a person has a high sensitivity to the components that make up triptans, their use is also dangerous. These drugs should not be used during adolescence.
Triptans for migraines should be used with extreme caution during pregnancy, lactation, and with renal or liver failure.
The range of side effects of these effective drugs is quite wide, so the choice of drug should be discussed with your doctor:
- from the nervous system, dizziness, sensory disturbances, a feeling of stiffness in the limbs, a feeling of warmth, drowsiness, asthenia may occur,
- from the musculoskeletal system, myalgia (muscle pain) and muscle weakness may well be observed,
- The digestive system may also be affected: nausea, dry mouth, abdominal pain, hemorrhagic diarrhea, splenic or intestinal infarction, ischemic colitis,
- on the part of the cardiovascular system, angina pectoris, tachycardia, spasm of coronary vessels, myocardial infarction, increased blood pressure may develop,
- from the urinary system, frequent urination and polyuria (increased amount of urine) may occur,
- Allergic reactions are also possible.
How to take triptans?
Any drug from the triptan class should be taken once and preferably at the very beginning of an attack, before a severe headache develops. A single dose for an adult is a 50 or 100 mg tablet. The maximum effect of triptans occurs within 2-4 hours after taking the first dose and lasts for several hours.
It is permissible to take the next tablet if the attack subsides and then resumes (no less than 2 hours later).
You should not take several drugs from this group at the same time, or together with other serotonergic drugs.
It is permissible to use triptans alternately with anti-inflammatory analgesics to prevent the development of dependence on these drugs.
conclusions
Triptans for migraines are the drugs of choice when NSAIDs (nonsteroidal anti-inflammatory drugs) are ineffective. It is best to use other migraine medications in parallel with them - this is stated by those who have already taken anti-migraine medications for several years. Taking into account the high effectiveness of triptans, as well as the pronounced metabolic effect that they have on the human body (in scientific language this is called pharmacodynamics), the course of treatment with the drugs in question should not last more than ten days, regardless of the severity of the patient’s condition. It is better to take triptans for migraines after consulting a neurologist.
Release forms
With nausea, gastric atony and vomiting, which often accompany a migraine attack, the bioavailability of the drug in tablets is greatly reduced. Along with taking tablets, there are other ways of administering the drug: intranasal, subcutaneous, in the form of suppositories, etc.
Nasal spray
Imigran nasal spray became an innovative form of sumatriptan. The technique for using it is similar to a regular runny nose spray. The effect of this administration of sumatriptan occurs twice as quickly as from taking a tablet. Also an undeniable advantage is the ability to use the spray for nausea and vomiting.
Skin patch
There is another dosage form of sumatriptan, which, unfortunately, is not registered in Russia. It is a microprocessor-powered, battery-powered transdermal patch-style system that releases the drug under the patient's skin through microinjections. The patch with the system is glued to the skin of the shoulder directly during an attack. The effect occurs within 10-15 minutes.
Material and methods
An open, randomized, prospective, comparative study was conducted in 60 patients with episodic migraine with and without aura aged 18 to 65 years. The study included patients with migraine, the diagnosis of which was established in accordance with the ICHD-3 beta diagnostic criteria (2013). The frequency of headache attacks was no less than 2 and no more than 15 days in 1 month, which excluded the participation of patients with chronic migraine. The study did not include patients under 18 years of age or over 65 years of age, patients with drug-induced headache, taking migraine prophylaxis or other specific anti-migraine drugs. Patients with other neurological or psychiatric pathologies, as well as with a history of coronary heart disease or cerebrovascular disease were also not included.
Two groups were formed using simple randomization. Group 1 included 30 patients, whose average age was 31.0±6.7 years ( p
<0.01), predominantly women - 90% (
n
= 27).
6 (20%) patients had migraine with aura and 24 (80%) without aura, with a frequency of 2.2±1.0 attacks per month ( p
<0.01). Patients of group 1 took L.P. Migrepam in accordance with the instructions for medical use of the drug in a therapeutic dose of 2.5 mg.
Group 2 also included 30 patients, of which 24 (80%) were predominantly women. The mean age in the group was 31.5±7.4 years ( p
<0.01).
9 (30%) patients had episodic migraine with aura and 21 (70%) without aura with an average frequency of 2.2±1.3 attacks per month ( p
<0.01). In group 2, patients were prescribed L.P. as a drug to relieve headache attacks. Sumatriptan at a dose of 50 mg.
A comparison of the baseline characteristics of the study groups is presented in Table. 2.
Table 2. Comparative analysis of clinical and demographic indicators of the study groups Note. Data are presented in number (%) or mean (SD) format. VAS - visual analogue scale. * - p-value - statistical significance of differences compared to the average value in the study groups (p <0.05). Note. Data are presented in number (%) or mean (SD) format. VAS - visual analogue scale. * — p-value — statistical significance of differences in comparison with the average value in the study groups (p<0.05)
When examined in the study groups, the average age was comparable and fell in the third decade of life; in terms of gender distribution, females predominated in both groups. According to diagnostic criteria, migraine without aura predominated in both groups, with comparable frequency and intensity of headaches.
Participation in the study included three follow-up visits.
During the first (baseline) visit, inclusion criteria were determined, a clinical neurological examination was performed, vital signs (blood pressure, heart rate) were recorded, and concomitant medications or other therapy were assessed. The intensity of headache, photo- and phonophobia was determined using a 10-point VAS scale. The criteria for assessing headache included the following characteristics: frequency, severity of associated symptoms, number of attacks relieved by triptans. In addition, we studied indicators of the degree of influence of headache on the general condition and quality of life (HIT-6 index - Headache Impact Test), time of disability associated with headache (HALT index - The Headache-Attributed Lost Time), and the degree of maladaptation caused by migraine (MIDAS). Patient satisfaction with the therapy used for migraine attacks was assessed (MIGRAINE-ACT - The Migraine Assessment of Current Therapy). On the 2nd visit after 30 days, while taking L.P. Migrepam and L.P. Sumatriptan was subjected to a clinical neurological examination and assessment of headache characteristics (frequency, severity of attack and associated symptoms when relieved with the appropriate triptan). During the visit, questionnaires HIT-6, HALT, MIDAS, MIGRAINE-ACT were filled out. At the 3rd visit, after 60 days, the patients were finally examined and all the above-mentioned questionnaires were filled out. The effectiveness of therapy for L.P. Migrepam and L.P. Sumatriptan was assessed using specially designed symptom diaries completed by patients during three consecutive attacks.
Clinical characteristics of the impact of headache on patients in the study groups during the baseline visit are presented in Table. 2. The average value of the degree of influence of headache on the general condition and quality of life (HIT-6 index) was 59.9±5.9 points in group 1, 55.9±8.9 points in group 2, ( R
<0.05), which corresponds to a significant impact of migraine on daily activities.
The severity of pain and the degree of maladjustment on the MIDAS scale in group 1 exceeded the value in group 2 ( p
<0.01), however, both indicators indicated the presence of a pronounced limitation of daily activity in patients of both groups (≥21 points corresponds to grade IV severity ) [8].
The HALT index over the last 3 months before the start of treatment in the 1st group was 27.5±4.7 days, and in the 2nd group - 22.4±7.4 days ( p
<0.01), which indicates on the strong influence of headache on the functional state in the study groups and the need for drug correction of headaches. During the examination, satisfaction with the previously used therapy for migraine attacks according to the MIGRAINE-ACT questionnaire in group 1 was noted by 9 (30%) patients, which was comparable to the value in group 2 - 11 (38%).
Statistical analysis was carried out depending on the distribution of the sample population using parametric tests of Student, Pearson and Fisher's exact test using Excel 2021 and the statistical software package Statistica 12. To present the obtained data, methods of descriptive statistics were used (with the calculation of average values, standard deviation, standard errors of the mean). The results were regarded as significant at p
-value <0.05.