Introduction
It is known that the term “asthenia” (from the Greek.
asthéneia - impotence, weakness) characterizes the patient's condition, which is manifested by increased fatigue, a rapid decrease in vital activity and is accompanied by significant mood swings, decreased self-control, sleep disturbances, loss of ability for prolonged mental and physical activity, poor tolerance of intense sounds and bright light, strong odors [12]. Asthenic syndrome is a complex of clinical manifestations covering various elements of physical and mental activity, characterized by quickly onset fatigue, a constant feeling of “being overwhelmed,” a decrease in cognitive functions (memory, concentration, learning ability, speed of decision-making), as well as mental disorders ( increased anxiety, irritability, changing mood, decreased various motivations, fear of the future, decreased interest in what is happening around). Many diseases can be accompanied by asthenic symptoms [2]. The prevalence of asthenia among the population, according to various sources, varies from 10 to 45% [3, 4].
Currently, two main concepts are used in the literature - asthenic syndrome, which is traditionally used in domestic literature and clinical practice, and chronic fatigue syndrome ( English:
Chronic Fatigue Syndrome (CFS), which is common in the English literature [5, 6].
The following clinical forms of the disease are also distinguished: functional asthenia (somatogenic) and organic asthenia (cerebrogenic). Within the framework of the latter, psychogenic reactive forms are considered separately - overload syndrome and neurasthenia.
This article deals with the treatment of functional asthenia. Therefore, let's look at it in more detail.
Functional asthenia makes up 55% of the structure of asthenia and is characterized by clinical reversibility of symptoms [7]. Functional asthenia includes reactive asthenia - an asthenic syndrome that occurs in healthy people when exposed to various unfavorable factors. For example, asthenia after infectious or somatic diseases, surgical interventions. Symptoms of asthenia develop in people who are in a state of significant physical and mental (intellectual) overload, as well as in people whose profession requires intense attention, is associated with emotional overload, shift work, long trips (with time zone changes) [7] .
Asthenia is based on a decrease in the body’s resources [8]. A long-term decrease in energy potential leads to the development of a neurotransmitter imbalance, which causes the formation of cognitive and emotional disorders that reduce the quality of life of patients. One of the most important mediators for cognitive processes is acetylcholine. It is believed that the psychophysiological role of acetylcholine is to ensure sustained attention, and acetylcholinergic deficiency leads to the development of cognitive deficits [10].
When treating asthenic disorders, it is first necessary to organize an adequate work and rest regime for the patient (ensuring a normalized working day and adequate working conditions, normal sleep, combating hypoxia and physical inactivity, giving up bad habits) [4, 7-9], but a certain place Pharmacotherapy also occupies a role. However, despite the wide range of modern pharmacological agents, the treatment of asthenic disorders is a rather complex medical problem. The fact is that treatment in these cases is mainly symptomatic. As a rule, such patients are prescribed several drugs at the same time in order to reduce cephalgia, dizziness, improve memory, mood, reduce anxiety and depressive symptoms, etc. Anxiolytics, antidepressants, antipsychotics, vegetotropic drugs, vitamins, herbal medicines, dietary supplements are also used [8] . Meanwhile, adequate therapy should be pathogenetically substantiated and aimed at the basis of asthenic syndrome - a decrease in energy potential. Timely neurometabolic energy correction can influence, as mentioned above, neurobiochemical imbalance.
Currently, new pharmacological drugs have appeared, the effects of which are associated with a complex neuroprotective effect. These drugs include citicoline - neipilept [10]. Choline, which is part of citicoline, serves as the basis for the formation of acetylcholine, the deficiency of which in the brain is of great importance. Under conditions of energy deficiency, the physiological mechanism for the synthesis of endogenous CDP-choline is weakened due to disruption of energy metabolism and a deficiency of high-energy compounds, therefore timely correction of the deficiency of this mediator is necessary. Citicoline, being a source of choline, is involved in the synthesis of the neurotransmitter acetylcholine, stimulates the activity of tyrosine hydroxylase and the secretion of dopamine [10]. The stress-protective effect of citicoline is manifested in the normalization of somatovegetative disorders, restoration of sleep-wake cycles, and improvement of mood. The antidepressant effect is associated with its ability to improve the activity of the noradrenergic, dopaminergic and serotonergic systems, as shown by a study assessing the temporal dynamics of the levels of monoamine metabolites included in these systems and manifestations [11].
The purpose of this study is to determine the possibility of using citicoline (Neipilept) to correct the clinical manifestations of asthenic syndrome.
Neypilept 100 mg/ml 30 ml No. 1 solution for oral administration
Instructions for medical use of the drug NEIPILEPT Trade name Neipilept International nonproprietary name Citicoline Dosage form Oral solution 100 mg/ml, 30 ml Composition per 1 ml active substance - citicoline sodium (in terms of citicoline) 100.0 mg excipients: sorbitol, glycerin , sodium citrate, potassium sorbate, methyl parahydroxybenzoate, strawberry flavor, propyl parahydroxybenzoate, sodium saccharinate, citric acid monohydrate, purified water. Description Transparent, colorless or slightly yellowish liquid with a characteristic strawberry odor. Pharmacotherapeutic group Nervous system. Psychoanaleptics. Psychostimulants used for attention deficit hyperactivity disorder (ADHD - Attention deficit hyperactivity disorder) and nootropic drugs. Other psychostimulants and nootropics. Citicoline Code ATX N06BX06 Pharmacological properties Pharmacokinetics Absorption: Citicoline is well absorbed when taken orally. Absorption after oral administration is almost complete, and bioavailability is almost the same as after intravenous administration. Metabolism: Citicoline is metabolized in the intestines and liver to form choline and cytidine. After administration, the concentration of choline in the blood plasma increases significantly. Distribution: Citicoline is widely distributed in brain structures, with rapid incorporation of choline fractions into structural phospholipids and cytidine fractions into cytidine nucleotides and nucleic acids. Having reached the brain, citicoline is integrated into cellular, cytoplasmic and mitochondrial membranes, taking part in the construction of the phospholipid fraction. Excretion: Only 15% of the administered dose of citicoline is excreted from the human body: less than 3% by the kidneys and about 12% by exhaled CO2. There are two phases in the excretion of the drug in the urine: the first phase, around 36 hours, in which the rate of excretion decreases rapidly, and the second phase, in which the rate of elimination decreases much more slowly. The same phasicity is observed during excretion with CO2; the rate of excretion of exhaled CO2 quickly decreases after approximately 15 hours, and then it decreases much more slowly. Pharmacodynamics Citicoline is a natural endogenous compound that is an intermediate metabolite in the synthesis of phosphatidylcholine, one of the main structural components of the cell membrane. Citicoline has a wide spectrum of action - it promotes the restoration of damaged cell membranes, inhibits the action of phospholipases, prevents the excessive formation of free radicals, and also prevents cell death by affecting the mechanisms of apoptosis. In the acute period of stroke, citicoline reduces the volume of brain tissue damage and improves cholinergic transmission. In case of traumatic brain injury, it reduces the duration of post-traumatic coma and the severity of neurological symptoms, in addition, it helps to reduce the duration of the recovery period. In chronic cerebral hypoxia, citicoline is effective in the treatment of cognitive disorders such as memory impairment, lack of initiative, and difficulties in performing daily activities and self-care. Increases the level of attention and consciousness, and also reduces the manifestation of amnesia. Citicoline is effective in the treatment of sensory and motor neurological disorders of degenerative and vascular etiology. Indications for use - stroke and its consequences - traumatic brain injury and its consequences - cognitive, sensory and motor neurological disorders caused by degenerative and vascular disorders of the brain. Method of administration and dosage Neypilept oral solution is administered orally. Before use, Neypilept can be diluted in a small amount of water (100-120 ml or 1/2 cup). Take with meals or between meals. Recommended dosage regimen Adults: 500–2000 mg (5–20 ml) per day. The dosage and duration of treatment depend on the severity of the symptoms of the disease. Elderly patients When prescribing citicoline to elderly patients, no dose adjustment is required. Side effects Side effects are grouped by frequency of occurrence: very common (> 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10000 up to <1/1000), very rare (<1/10000), frequency not established. Very rare (< 1/10000 (including individual cases): - allergic reactions (rash, itching, anaphylactic shock) - headache, dizziness, hallucinations, agitation, insomnia, feeling hot, tremor - shortness of breath - nausea, vomiting, diarrhea - swelling - decreased appetite - numbness in paralyzed limbs - changes in liver enzyme activity In some cases, citicoline may stimulate the parasympathetic system and also cause a short-term change in blood pressure If any of the side effects listed in the instructions for use get worse or you notice any other side effects not specified in the instructions, inform your doctor. Contraindications - hypersensitivity to any of the components of the drug - should not be prescribed to patients with severe vagotonia (high tone of the parasympathetic part of the autonomic nervous system) - patients with rare hereditary fructose intolerance, impaired absorption of glucose-galactose or sucrose - isomaltose due to the presence of sorbitol Drug interactions Citicoline enhances the effects of L-dihydroxyphenylalanine. Should not be used concomitantly with medicinal products containing meclofenoxate. Special instructions Due to the presence of methyl parahydroxybenzoate and propyl parahydroxybenzoate in the composition, allergic reactions (including delayed ones) may develop. It contains sorbitol, so patients with rare hereditary problems of fructose intolerance should not take the drug. In the cold, a small amount of crystals may form due to temporary partial crystallization of the preservative. With further storage under recommended conditions, the crystals dissolve within several months. The presence of crystals does not affect the quality of the drug. Use in pediatrics Experience in children is limited: therefore, the drug can be prescribed only in cases where the expected therapeutic benefit outweighs any possible risk. Use during pregnancy and breastfeeding There is no sufficient data on the use of citicoline in pregnant women. During pregnancy, citicoline is prescribed only in cases where the expected benefit to the mother outweighs the potential risk to the fetus. When using citicoline during lactation, women should consider stopping breastfeeding, since there is no data on the excretion of citicoline into breast milk. Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms When using the drug, care should be taken when driving and when engaging in other potentially dangerous activities that require increased concentration and speed of psychomotor reactions. Overdose Given the low toxicity of the drug, cases of overdose have not been described, even if therapeutic doses are exceeded. Release form 30 ml in brown glass bottles, sealed with a plastic screw cap with first opening control. 1 bottle together with a plastic dosing pipette and/or a plastic measuring cup and instructions for medical use in the state and Russian languages in a cardboard pack. Storage conditions At a temperature not higher than 25 oC. Do not freeze. Keep out of the reach of children. Shelf life 2 years. The period of use after opening the bottle is 6 days. Do not use after the expiration date. Dispensing conditions By prescription 141345, Russia, Moscow region, Sergiev Posad municipal district, rural settlement Bereznyakovskoye, pos. Belikovo, d. 10, d. 11, d. 12 Owner of the registration certificate of CJSC “Pharm”, Russia, Moscow region, Sergiev Posad municipal district, rural settlement Bereznyakovskoye, pos. Belikovo, 11. Name, address and contact details (telephone, fax, e-mail) of the organization on the territory of the Republic of Kazakhstan that accepts claims (suggestions) on the quality of medicines from consumers and is responsible for post-registration monitoring of the safety of the medicine: TOO "EL company ( EL company)" 050022, Republic of Kazakhstan, Almaty, st. Masanchi 98 A, office 41 Phone, fax: 292-26-37
Material and methods
We observed 55 patients aged 30-40 years with functional asthenia, who were divided into two groups.
The main group included 40 patients, 14 (35%) men and 26 (65%) women, with an average age of 34.4 years. The control group included 15 patients, average age - 34.2 years. The groups were comparable in age, education and general examination results.
The duration of the asthenic state in all cases was about 6 months. The onset of the disease was preceded by mental stress in 22% of men and 56% of women; in 46 and 38% of cases, respectively, there was physical overexertion, violations in the organization of working conditions (irregular working hours, long absence of vacations, large volume of work). The patients had no history of clinically significant diseases.
In all cases, a complete somatic and neurological examination was performed. The severity of asthenic manifestations was determined using the asthenia rating scale - MFI-20. In addition, the Hamilton Depression and Anxiety Scales (HAM-D and HAM-A) were used, and the Frontal Dysfunction Battery and MoCA scale were used for general assessment of cognitive functions.
As basic therapy, patients received vitamin preparations of comparable composition. In addition, for the treatment of patients in the main group, a citicoline drug, Neipilept, was used, which was prescribed as a solution for oral administration at a dose of 500 mg per day for 30 days.
Statistical processing of the obtained results was carried out using the statistical software package Statistica 6.0.
