Melatonin has a role in the body and therapeutic possibilities. Experience of using the drug Melaxen in medical practice

Melatonin has a role in the body and therapeutic possibilities. Experience of using the drug Melaxen in medical practice

Melatonin: role in the body and therapeutic possibilities. Experience in the use of the drug Melaxen in Russian medical practice | Mendel V.E., Mendel OI | "Breast Cancer" №6 from 18.03.2010

Melatonin – neuropeptide, synthesized mainly by the small brain gland of the epiphysis, and has a unique effect on the human body and animals. With the help of melatonin, the epiphysis is involved in the organization of diurnal periodism and in the regulation of cyclic processes, acting as an intermediary between the pacemaker mechanism of suprachiasmatic nuclei (SCN) and peripheral organs. The epiphysis, along with the SCN of the hypothalamus, is part of the so-called biological clock of the body, which plays a key role in the mechanisms «internal time accounts» and aging [Arushanyan EB, 2005; Anisimov V.N., 2007]. The main­E functions of the pineal gland in the body are: regulation of circadian and seasonal rhythms; regulation of reproductive function; antioxidant protection and antitumor protection [Anisimov VN, 1998, 2003].

According to the chemical structure, melatonin (N – acetyl – 5– methoxytryptamine) is a derivative of the biogenic amine serotonin, which, in turn, is synthesized from the amino acid tryptophan from food. It is established that melatonin is formed in the cells of the epiphysis, and then secreted into the blood, mainly in the dark, at night, in the light, in the morning and afternoon hours, the production of the hormone is sharply suppressed. Information about the external illumination of the epiphysis is obtained by a complex neural pathway, in which the SCN of the hypothalamus plays a nodal, switching role. Information from the retina through the branch of the optic nerve enters the SCN, then these signals descend through the hypothalamus along the pathways along the brainstem to the cervical spinal cord, from where they reach the brain through the sympathetic nerves and finally reach the epiphysis. At night, in the dark, when most of the SCN neurons are inactive, these nerve endings release norepinephrine, which activates the synthesis of enzymes forming melatonin in the epiphysis cells (pinealocytes). The epiphysis of a healthy adult during the night releases about 30 μg of melatonin into the blood. Bright light instantly blocks its synthesis, while in constant darkness the daily rhythm of the emission, maintained by the periodic activity of the SCN, is preserved. Therefore, the maximum level of melatonin in the epiphysis and in human blood is observed at night, and the minimum – in the morning and afternoon. Although the main source of melatonin circulating in the blood is the epiphysis, paracrine synthesis of melatonin was found in almost all organs and tissues: the thymus, the gastrointestinal tract, gonads, connective tissue [Reiter R.J .; Raikhlin IM, Kvetnoy I.M .; Huether G.]. Such a high level of melatonin in the body emphasizes its need for human life.

In addition to the rhythm-organizing effect, melatonin has a pronounced antioxidant and immunomodulatory effects. Some authors believe that the epiphysis through melatonin, by controlling the endocrine, nervous and immune systems, integrates the systemic response to adverse factors, acting on the resistance of the organism. Melatonin binds oxygen free radicals while simultaneously triggering a natural antioxidant defense system through activation of SOD and catalase. As an antioxidant, melatonin acts everywhere, penetrating all biological barriers. In research­before­In vitro, it was found that melatonin has a significantly greater antioxidant activity in terms of interrupting lipid peroxidation and inactivating active –OH and ROO– free radicals than the known antioxidants­Danty [Reiter et al., 1995].

It has been established that melatonin plays an essential role in immunoregulation [Quet­Noi I.M.]. Studies have shown that it can have a dual effect on the function of the immune system: against the background of its preliminary inhibition, there is a clear stimulation, repeated administration of low doses of melatonin to animals weakens the impaired production of antibodies and increases antiviral resistance. Under conditions of the initial hyperactivity of the immune system, melatonin inhibits the formation of a number of cytokines in a dose-dependent manner in response to the introduction of the phytogem­glutenin reduces the function of activated macrophages and T-helper cells. Melatonin immunomodulation is based on direct effects through specific receptors on the function of the cells of the lymphoid organs and blood cell elements, as well as indirect effects through the mobilization of opioid mechanisms and modification of the production of corticosteroids by the adrenal cortex.

Melatonin has a positive effect on fat and carbohydrate metabolism, reduces the amount of cholesterol in the blood. It is able to normalize the process of lipid oxidation, thus reducing the risk of atherosclerosis, participates in the hormonal regulation of blood pressure (BP), reducing the release of ACTH, production of norepinephrine, vasopressin and renin [Slepushkin VD, 1990; Dolgov GV, 2004].

The amount of melatonin varies throughout a person’s life. Secretion of the hormone begins on the 3rd month of child's development, and its concentration reaches a maximum in the first years of life (no later than 5 years). Until puberty, melatonin synthesis remains at a constant and high level, then its amount decreases sharply and continues to decrease for another 5 years. After this change in melatonin does not occur until 40–45 years, after which its number begins to decline steadily, which coincides with the onset of menopause, and this process continues until the end of a person’s life.

Artificially produced melatonin has been extensively studied as a pharmacological agent. This is a low toxic compound with an LD50 for laboratory animals above 800 mg / kg. Parenterally administered melatonin easily penetrates the blood-brain barrier, quickly accumulates in the cerebrospinal fluid and brain tissue. The maximum level of melatonin was found in rats after 1 h in the mediobasal hypothalamus, striatum and neocortex. In humans, the introduction of melatonin for 1 month. up to 6 g daily did not cause side effects, except for spasms in individual subjects [Komarov et al., 2004]. When used orally, the peak concentration of melatonin is observed after an hour, and a sufficiently high level in the blood plasma is maintained for another 3-4 hours. Today, therapeutic doses of melatonin in the composition of drugs and dietary supplements are 3-6 mg. Most clinical trials in the world have been conducted using these dosages.

One of the main therapeutically significant areas associated with the use of melatonin in medicine is the use of its drugs for the normalization of sleep disorders and the prevention / treatment of desynchronosis, caused by a violation of the light regime. The conducted somnological studies suggest the existence of distinct hypnogenic properties in melatonin and recommend it as a hypnotic. The hypnotic properties of melatonin are closely related to its chronotropic activity, with the formation of a fundamental daily biorhythm. The anti-anxiety and anxiolytic activity of melatonin also contributes to normalization of sleep. Taking melatonin causes a feeling of calm and a decrease in anxiety. As established on the experimental model of a conflict situation [Arushanyan E.B. et al., 1993], melatonin weakens disturbing behavior in experimental animals, reduces fear of painful punishment. The resulting anti-anxiety action is comparable in its severity to the effect of the reference anxiolytic drug diazepam. The origin of this action depends on the enhancement of inhibitory processes in the limbic structures of the brain due to the mobilization of melatonin receptors. Another cause of anti-anxiety and at the same time anti-stress capabilities of the epiphyseal hormone are the conjugate relations of the epiphysis with the hypothalamic-pituitary-adrenocortical system. When the pineal gland is stressed by means of melatonin, it begins to demonstrate restraining control over the secretion of corticosteroids, which is absent in normal conditions. In recent years, melatonin has been shown to be able to optimize the cognitive activity of the brain and at the same time counteract the pathological processes that cause­tantalizing her disruption. In animal and human studies have been shown to me­tropic properties of melatonin, including the ability to alleviate memory disorders in the form of amnesia [Arushanyan EB, 2005]. The antiamnesic effect of melatonin is clearly manifested when it is necessary to protect neurons from ischemic damage. Briefly­Temporary global cerebral ischemia, which impaired learning and working memory in animals in the labyrinth, provoked less pronounced morphological and behavioral shifts with the introduction of melatonin. Improvement of brain activity with melatonin can be determined by several mechanisms: antioxidant activity, weakening of glutamate neurotoxicity, activation of neuronal growth factors and restriction of apoptosis of nerve cells. These properties make melatonin the drug of choice for treating sleep disorders in the elderly and in patients with vascular diseases of the brain.

With the rapid transmeridian movement of people in the latitudinal direction and the usual sleep-wakeful shift by several hours, desynchronosis occurs with a whole complex of transient mental and somatic disorders. Melatonin reduces these unpleasant consequences by rearranging all the biological rhythms of the body in accordance with local time. Taking melatonin daily, you can shift the daily cycle of activity – rest – such a need arises during shift or watch work.

The effect of melatonin (drug Melaxen) on sleep and cognitive function

in patients with insomnia

The efficacy and safety of exogenous melatonin (Melaxen) in patients with sleep disorders (insomnia) was studied on the basis of several leading Russian medical institutions. Among them, MMA them. THEM. Sechenov Department of Nervous Diseases FPPO, Center for Somnological Research [Wayne AM, Levin Ya.I., 1997], Department of Nervous Diseases [Yakhno N.N., 1997], RMAPO, Department of Gerontology and Geriatrics [Lazebnik LB ., 1998].

The drug was administered to patients with sleep disorders daily at a dose of 3-4.5 mg / day. (at night, 40 minutes before bedtime) for a period of time from 7 days to 4 weeks. The age of patients ranged from 40 to 75 years. Duration­Insomnia was from 6 to 360 months, the frequency of insomnia episodes was from 3 to 7 per week. All patients 5–7 days before the study began, stopped taking any other sleeping pills or sedatives. The studies studied: (1) clinical characteristics of patients, (2) subjective sleep characteristics (sleep time, sleep duration, number of night awakenings, sleep quality, number of dreams, quality of the morning awakening, total score) based on a special somnological questionnaire using a five-point system , (3) assessment of cognitive functions on the Sandoz geriatric scale, (4) SAN test (autonomy, activity, mood). In total, as a result of research, it was found that in patients with insomnia, taking Melaxen at a dosage of 3-4.5 mg once a night improves night's sleep – accelerates falling asleep, reduces the number of nighttime awakenings, and improves well-being after the morning awakening. At the same time, the appointment of Melaxen had a positive impact on the intellectual-mnestic functions and the emotional – personal sphere (Table 1). Improvement in emotional­but – the personal sphere and by the intellectual­but-mnestic functions in patients with insomnia during the treatment with Melaxen expressed in a decrease in emotional lability and anxiety, improvement in­building, improving clarity of consciousness, improving memory for current events, reducing feelings of fatigue, increasing social activity and contact.

Melatonin (Melaxen) in therapy

Melatonin has a role in the body and therapeutic possibilities. Experience of using the drug Melaxen in medical practice

sleep disorders in patients with acute

period of ischemic stroke

A study conducted at the Federal Center for Somnological Research [Levin Ya.I., 2006] demonstrated the efficacy and safety of Melaxen therapy for the normalization of sleep disorders in patients with acute cerebral circulation disorders. 15 patients in the acute period of stroke (12 of them with ischemic stroke) and insomnia with inversion of the sleep cycle (with wakefulness at night and drowsiness during the day) received Melaxen 3 mg each for 30 minutes. before sleeping for the night for 14 days. According to the survey, it was found that at the end of the course of treatment with melaxen, the quality of sleep improved, the total score of night sleep increased, and daytime sleepiness disappeared. According to polysomnography, the duration of sleep has increased, the time of falling asleep has decreased, the number of awakenings has decreased. The drug was well combined with other drugs that were prescribed to patients. Thus, the researchers concluded that Melaxen is the drug of choice for the treatment of sleep disorders in patients with impaired cerebral circulation.

Melatonin (Melaxen) in correction

sleep disorders and depressive disorders

in patients with arterial hypertension (AH)

Insomnia is recognized as one of the significant factors of ineffective therapy of arterial hypertension (AH). In a number of foreign studies, it was found that in patients with cardiovascular diseases there is a decrease in melatonin synthesis. The study of the relationship between hypertension, sleep disorders and changes in the psycho-emotional sphere was conducted at bases 50 and 81 of the Moscow City Clinical Hospital [Lyubshina OV et al., 2006]. The study included 176 inpatients over 18 years of age with documented hypertension. At the 1st stage of the study,­It was the dependence of the structure of sleep on the level of blood pressure of patients. At the 2nd stage, medical correction of sleep disorders was carried out in 88 patients with hypertension. The patients were randomly divided into 2 groups depending on the prescribed therapy: the 1st group (44 people) received Melaxen in a dose of 3 mg once a night, the 2nd group (44 people) received Citalopram 20 mg once a night. As a result of the study, it was found that (1) in 77.2% of hypertensive patients in proportion to the degree of increase in blood pressure, sleep disturbances are observed, including in the greater half – severe insomnia, manifested by a lengthening of latency to sleep, a decrease in sleep efficiency and an increase in CEA and apnea indexes ; (2) The frequency and nature of sleep disorders depend on the type of antihypertensive therapy. In patients receiving atenolol or nifedipine, insomnia occurs 1.5–2 times more often than with enalapril; (3) additional use of citalopram or melatonin, especially in hypertensive patients under 60 years of age and with a disease duration of less than 15 years, leads to an improvement in the subjective assessment of sleep quality by 72.8 and 79.5%, respectively, to a decrease in the number of patients with mild depression by 29 and 12% respectively. A polysomnographic study revealed that after the appointment of Melaxen there was a decrease in the time of falling asleep (p = 0.03), a tendency to increase the representation of the deep stages of sleep (p = 0.7). The fast sleep phase increased to normal (p = 0.02), the REA index decreased by almost 2 times compared to the baseline (p = 0.06); (4) in patients with hypertension with marked sleep disorders, the correction of insomnia with citalopram or melatonin leads to an increase in the effectiveness of antihypertensive therapy. After 4 weeks of treatment with Melaxen, the mean daily values ​​of CAD and DBP decreased significantly to 137.4 ± 7.8 (7.4%) and 79.3 ± 11.9 mm Hg. (6.8%), maximum – up to 168.6 ± 5.9 (5.7%) and 99.4 ± 8.6 mm Hg (8.2%), respectively. The SAD and DBP time index significantly decreased in this period of time to 42.6 ± 6.9% and 37.9 ± 5.7%, and the GAD and DBP area index decreased to 167.5 ± 13.2 (37.8% ) and 55.4 ± 8.6 (39.6%), respectively (5). It was established that, despite the fact that both Melaxen and Citalopram significantly reduced both the magnitude and speed of the morning BP rise, the data obtained indicate that citalopram has a lesser effect on the decrease in the BP rise rate in the morning than Melaxen (p<0,05). 

The effect of Melaxen on the chronostructure

physiological parameters in the elderly and the role of melatonin in the correction

desynchronosis of various etiologies

At the Department of Biology of the State Educational Institution of Higher Professional Education TGMA Roszdrav researchers [Gubin GD et al.] studies were conducted to study the effect of exogenous melatonin (Melaxen) on the chronostructure of physiological parameters in elderly and senile people and to study the role of melatonin in the correction of desynchronosis of various etiologies. Chronobiologists­A coherent analysis of the results allowed the researchers to draw the following conclusions: (1)­Biological use of 1.5 mg of exogenous melatonin in the form of the drug Melaxen in elderly and senile individuals has a direct physiological (hypotensive effect on GARDEN, DAD and BPA and hypothermic effect on body temperature), the severity of which depends on the time of day (chrono-dependent effect); (2) the hypotensive effect of melatonin is due to a chrono-dependent decrease in vascular OPS during night hours and is accompanied by a decrease in the value of pulse BP, while the systolic volume in the morning hours increases; (3) exogenous melatonin (Melaxen), when administered at 22:30, has a pronounced chronobiotic effect, synchronizing the circadian rhythms of physiological parameters in elderly and senile persons; (4) The chronobiotic efficiency of melatonin contributes to the preservation of the temporal ordering of physiological functions, preventing the growth of entropy in the architectonics of an aging organism.

Melatonin (Melaxen) in complex

therapy of hypertension in elderly patients

Currently, the violation of the temporal organization of hemodynamics, which is manifested by the phenomenon of internal and external desynchronosis of circadian and circus rhythms of hemodynamic parameters in patients with hypertension, is undisputed. Detection of circadian rhythm desynchronosis in hemodynamic parameters in patients with hypertension [Zaslavskaya RM et al.] is consistent with the results of studies of the daily dynamics of the secretion of certain hormones and the levels of electrolytes in the blood of patients with hypertension [Yakovlev, G.M. et al., 1991]. Due to the fact that one of the main functions of melatonin in the human body is the regulation of the circadian rhythms of physiological systems, it is legitimate to assume that the rhythms of the regulatory system in people with hypertension are associated with violations of the daily production of melatonin.

Melatonin has a role in the body and therapeutic possibilities. Experience of using the drug Melaxen in medical practice

Researchers [Zaslavskaya R.M. et al., 2004] studied the effect of melatonin (Melaxen) on hemodynamic parameters and chronostructure of hypertension AH stage 2 in 30 elderly patients (mean age 67.4 ± 1.8 years) with a disease duration of 8.7 ± 0.86 years. The examined individuals lacked the daily rhythm of a number of studied hemodynamic parameters (DBP, HR, PD), the shift in the average acrophasis of the CAD and BP was noteworthy. at night hours. These data indicate a violation of the temporary organization of blood circulation with symptoms of internal and external desynchronosis in the examined individuals. Melatonin at a dose of 3 mg was prescribed to these patients 1 time per day. at 22.00. Before and after the 10-day course of melatonin therapy, the daily profile of blood pressure, heart rate (HR), double work (DP), central hemodynamic parameters were studied. The level of blood pressure and heart rate is constantly monitored throughout the course of therapy. The study found that the average daily level of systolic blood pressure (MAP) under the influence of treatment decreased from 161.4 ± 7.9 to 135.02 ± 5.9 mm Hg, diastolic blood pressure (DBP) decreased from 90 1 ± 6.6 to 76.1 ± 5.5 mm Hg (R<0,05).

Thus, the inclusion of melatonin in the treatment of hypertension in elderly patients not only enhances the effectiveness of treatment with standard antihypertensive agents, but also contributes to the normalization of impaired circadian hemodynamics. In addition, this therapy can effectively eliminate sleep disorders, often present in patients with hypertension, especially in old age.

Biorhythm Correction by Melaxen

flight crew

An important factor affecting the health of flight crews and flight attendants is transmeridian flights, causing a mismatch of biological rhythms, both internal and external (coordination of biological rhythms of the body with the external environment). As you know, desynchronosis (both internal and external) in itself can be the cause of various pathological conditions, including hypertension. In a clinical study, the efficacy and safety of taking the drug Melaxen (as monotherapy and in combination with indopamide) was demonstrated in 36 civil aviation pilots aged from 37 to 50 years old suffering from Stage 1 hypertension performing transmeridian flights [N. Musina. et al.]. Treatment with Melaxen at a dose of 3 mg / day. within 2 weeks contributed to the restoration of biological rhythms and the elimination of the symptoms of desynchronosis in pilots, which, in particular, was expressed in the normalization of the structure of blood pressure, elimination of insomnia and irritability. Melatonin therapy was more effective at night (a decrease in the GARDEN by 7.6%, DBP by 6.19%, respectively). Psychological research at the end of the course of treatment showed that taking Melaxen did not adversely affect the cognitive functions of patients.

Melatonin (Melaxen) in complex

treatment of coronary heart disease (CHD)

Among the new approaches to the treatment of postinfarction cardiosclerosis (PICS) and heart failure (HF), one of the most rational is the corrective effect on the disturbed myocardial metabolism and the chronostructure of central hemodynamic parameters. It is known that not only intracardiac hemodynamics, but also activation of lipid peroxidation (LPO), as well as depletion and then suppression of antioxidant protection (AOD) and, as a result, imbalance in the system play a large role in impaired myocardial metabolism. oxidants / antioxidants with the development of oxidative stress. A number of authors in experimental studies on isolated rat hearts showed that melatonin leads to a decrease in the number of free radicals, protecting the myocardium during the post-ischemic reperfusion, reduces the size of myocardial infarction and reduces the duration of ventricular tachycardia, and also has an almost neutral effect on hemodynamic parameters and coronary blood flow . In addition, melatonin affects the POL and the activity of antioxidant (AO) enzymes, reducing the level of malondialdehyde and increasing the activity of Cu, Zn – superoxide dismutase and glutathione content. Girotti L. et al. (2000) studied the level of melatonin in the urine of IHD patients in comparison with healthy individuals. The results of the study showed that patients with IHD have low melatonin production compared with healthy individuals.

As part of studying the effect of melatonin drugs on the course of CHD and its researchers [Zaslavskaya R.M. et al., 2004] studied the group of elderly patients (42) with coronary artery disease, stable angina II – III FC (CC) who had myocardial infarction and suffering from heart failure (CH) II – III FC according to the NYHA classification. All patients in this group received standard therapy, including nitrates, b-blockers, ACE inhibitors, antiplatelet agents and diuretic drugs, in combination with melatonin. This group of patients was divided into 2 subgroups (21 patients each) depending on the dose of melatonin taken. Patients of the first subgroup (PP) took Melaxen in a dose of 3 mg, the second subgroup (VP) – 6 mg for 21 days. Before and after the course of treatment, all patients underwent a general clinical examination, echoCG, ECG-Holter monitoring, as well as determination of the degree of oxidative stress (OS) and antioxidant protection (AOD).

As a result of the study, it was found that Melaxen in daily doses of 3 mg and 6 mg against the background of standard treatment in elderly patients with coronary artery disease, stable angina II – III FC, who had myocardial infarction and suffering from heart failure II – III FC, has a pronounced antianginal and antiischemic effects, significantly improving clinical symptoms, reduces the number of episodes of depression and ST-segment elevation up to their complete disappearance. A higher dose of Melaxen – 6 mg – significantly improves the systolic function of the left ventricle, which does not occur when taking Melaxen at a dose of 3 mg. In addition, the effect of Melaxen in doses of 3 mg and 6 mg per POL is shown to be a significant decrease in the level of MDA. Thus, taking into account the wide spectrum of biological activity of melatonin, including its antioxidant, pro-antioxidant, anti-stress effects, as well as the normalizing effect on the chronostructure of hemodynamic parameters and vasodilating effect, the inclusion of melatonin into complex therapy of patients with coronary heart disease seems appropriate.

Melatonin in the treatment of pathological menopause

Desynchronization of the circadian periodicity of the pineal gland, which is expressed in the progressive reduction of melatonin night peaks, may be associated with the onset and development of menopause. An age-related decline in melatonin signals a breakdown in the pineal and pituitary control of the ovarian cycle and the progressive extinction of the woman’s fertility function [Oosthuizen G.M., 2001; Rohr, U.D., 2002]. From a biorhythmological position, menopausal syndrome is the clinical implementation of maladjustment of a woman’s body in conditions requiring increased activity of the body’s adaptive system. Russia­Skye researchers [Maltseva L.I. et al., 2007], in a clinical study, it was shown that the administration of melatonin drugs (Melaxen) to the treatment regimen (as monotherapy or in combination with HRT drugs depending on the severity of the disease) allows to achieve fast and stable results in women with climacteric syndrome. Thus, in women with a mild menopausal syndrome, who received Melaxen as monotherapy, re-evaluation of clinical, hormonal and biochemical parameters after 1 month. revealed a positive trend. The level of blood hormones approached the control indicators, FSH decreased 2.29 times, LH – 2.1 times. In the study of the lipid spectrum of blood before and after therapy with Melaxen, there was a tendency to a decrease in total cholesterol and atherogenic index, while the number of HDL cholesterol did not change. Repeated study of the blood lipid spectrum, conducted after 2 months. after the abolition of melatonin, revealed the normalization of triglyceride levels, and the amount of LDL did not increase. In women with severe menopausal syndrome and an incomplete effect of HT, combination therapy of HT and Melaxen was very effective. All hormonal, biochemical and mediator changes detected in women of this group prior to treatment, normalized after a month of therapy: FSH decreased 2.4 times, LH – 2 times, estradiol level increased 2 times and amounted to 72.59 ± 17.55 mg / ml, which is most consistent with normal values. In addition, they had a pronounced decrease in the number of catecholamines (adrenaline and noradrenaline) in daily urine and the maximum normalization of these parameters after 1 month. treatment. Probably, acting on the same causes of the development of the climacteric syndrome, but using different mechanisms, combination therapy leads to a more rapid normalization of hormonal and mediator shifts. Subjectively, women noted an improvement in mood, an increase in working capacity and a sense of psychological comfort. Kupperma Index­It decreased by 3 times and approached the control values ​​as much as possible (16.88 ± 2.63 points).

Conclusion

Studies of the drug Melaxen, conducted on the basis of a number of clinics, confirmed its effectiveness and high safety in treating sleep disorders in patients of different age groups and with various concomitant diseases. Moreover, it was established not only the normalizing effect of Melaxen therapy on sleep disorders, but also on intellectual and mnestic functions (improving clarity of consciousness, social activity and contact, improving memory for current events) and the psycho-emotional sphere (reducing emotional lability and anxiety, improving mood, reducing feelings of fatigue) of the studied patients.

A study of the effectiveness of drug therapy Melaxen in patients with sleep disorders and cardiovascular­Judging by pathology suggests that Melaxen is the drug of choice for the treatment of sleep disorders in this category of patients, as well as the feasibility of using diseases associated with circadian rhythms in the complex therapy. In these diseases, in addition to a positive effect on sleep parameters, melatonin is able to have a positive effect on the manifestations and course of the underlying disease.

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