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Lexapro is a highly selective antidepressant from the group of selective serotonin reuptake inhibitors (SSRIs). Used to treat depressive episodes and generalized anxiety disorder, as well as other anxiety disorders (social phobia, panic disorder, etc.).

Characteristics of the substance Escitalopram

Escitalopram oxalate is a powder of white or slightly yellow color. Easily soluble in methanol and dimethyl sulfoxide, difficult to dissolve in water and ethanol, slightly soluble in ethyl acetate, insoluble in heptane. The molecular weight is 414.40.

The mechanism of antidepressant action is presumably associated with increased serotonergic activity in the CNS as a result of inhibition of reverse neuronal serotonin uptake. In vitro and in vivo studies on animals have shown that escitalopram is highly selective to inhibit reverse neuronal serotonin uptake in the CNS with minimal effect on the reuptake of norepinephrine and dopamine. Escitalopram is at least 100 times more potent serotonin reuptake inhibitor than R-enantiomer. Tolerance in the simulation of the antidepressant effect does not develop with prolonged (up to 5 weeks) administration to rats.

Escitalopram does not interact or has a very weak ability to bind to serotonin (5-HT1–7) or other receptors, including alpha- and beta-adrenergic receptors, dopamine (D1–5), histamine (h1–3), muscarinic (M1–5) and benzodiazepine receptors (antagonism to muscarinic, histamine and adrenergic receptors, presumably, causes various anthohyl receptors, in particular, in ours, which also develop their anthiramins, histamine and adrenergic receptors, various anthistamine receptors, antagonistically induces various antichores, antagonisms to the anthistamine, histamine and adrenergic receptors. side effects of other psychotropic drugs). Escitalopram also does not bind or has a very low affinity for various ion channels, including the Na +, K +, Cl-, and Ca2 + channels.

The pharmacokinetics of escitalopram is linear and dose-dependent in the administration of single and multiple doses (in the range of 10-30 mg / day). Tablets and oral solution containing escitalopram oxalate are bioequivalent. The absorption of escitalopram is independent of food intake. When ingested a single dose of 20 mg Tmax is about 5 hours. The binding of escitalopram to human plasma proteins is approximately 56%. When taken 1 time per day, the equilibrium concentration in plasma is established within approximately 1 week of therapy. In equilibrium, the level of escitalopram in plasma in young healthy subjects is 2.2-2.5 times higher than the concentration after taking a single dose.

Metabolized mainly in the liver with the formation of S-demethylcytalopram (S-DTT) and S-didemetiltsitalopram (S-DDTsT). In vitro studies using human liver microsomes indicate the involvement of CYP3A4 and CYP2C19 isoenzymes in the process of N-demethylation of escitalopram. In human plasma, escitalopram prevails unchanged. In equilibrium, the concentration of S-DCT in plasma is approximately 1/3 of the concentration of escitalopram. The level of S-DDCT was not determined in most subjects.

In vitro studies have shown that the pharmacological activity of escitalopram (inhibition of serotonin reuptake) is higher than that of S-DTT by at least 7 times, S-DDDC - by 27 times, which indicates that the metabolites do not make a significant contribution to the anti-depressive effect of escitalopram . S-DTTs and S-DDTsT also do not interact or have a very weak affinity for serotonin (5-HT1-7) or other receptors, including alpha and beta adrenoreceptors, dopamine (D1–5), histamine (H1–3), muscarinic (M1–5) and benzodiazepine receptors are not associated with various ion channels, including the Na +, K +, Cl- and Ca2 + channels.

It was shown that after oral administration, escitalopram is detected in the urine in unchanged form (about 8%) and in the form of S-DTT - 10%. Oral clearance of escitalopram is 600 ml / min, of which approximately 7% is renal. Terminal T1 / 2 about 27–32 h.

The dependence of pharmacokinetics parameters on some factors

Age. The pharmacokinetic parameters of escitalopram when taking single and multiple doses in people over 65 years of age and young people are comparable. When taking the recommended dose (10 mg) in the elderly, the AUC and T1 / 2 increased by about 50%, Cmax was not changed.

Floor. When using multiple doses of escitalopram (10 mg / day for 3 weeks), 18 men (9 elderly and 9 young) and 18 women (9 elderly and 9 young) showed no differences in the values of AUC, C max and T1 / 2. There is no need to adjust the dose depending on gender.

Decreased liver function. For most patients with impaired liver function, a dose of 10 mg escitalopram is recommended.

Decreased renal function. There is no information on the pharmacokinetic parameters of escitalopram in patients with severe renal insufficiency (with Cl creatinine less than 20 ml / min).

Clinical trials

The effectiveness of escitalopram oxalate in the treatment of depression was established in 3 placebo-controlled studies of 8 weeks duration in adult outpatients (age 18–65 years) with major depressive disorder (in accordance with DSM-IV criteria). The main criterion of effectiveness in all 3 studies was the change in the total score on the Montgomery – Asberg scale (MADRS).

A fixed dose study comparing 10 and 20 mg / day of escitalopram oxalate, placebo and 40 mg / day of citalopram showed that the improvement was significantly more pronounced in the groups of patients taking 10 and 20 mg / day of escitalopram, compared with placebo (according to rated by MADRS). Efficacy rates in the groups of patients receiving 10 or 20 mg / day of escitalopram were similar.

In another study with a fixed dose of escitalopram oxalate 10 mg / day, the improvement was significantly higher in this group compared to placebo (according to the MADRS estimate).

In a study using different dose ranges of escitalopram, titrated between 10 and 20 mg / day, compared with placebo and different doses of citalopram, titrated between 20 and 40 mg / day, the improvement in the group treated with escitalopram oxalate was significantly higher. versus placebo (according to MADRS score).

The effectiveness of escitalopram for maintenance therapy in the treatment of depression was evaluated in a placebo-controlled study with a 36-week open phase. The study included 274 patients with major depressive disorder (according to DSM-IV criteria) who were responders after the initial 8-week treatment of an acute condition and then were randomly assigned to continue escitalopram at the same dose (10 or 20 mg / day). ) or placebo. The response to treatment in the open phase of the study was defined as a reduction in scores on the MADRS ≤12 scale. Relapse during a double-blind study was defined as an increase in the number of points on the MADRS scale ≥22 or cancellation of therapy due to an unsatisfactory clinical response. In patients who continued to receive escitalopram for 36 weeks, the time of remission was significantly longer compared with placebo.

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Adequate controlled studies of the efficacy of escitalopram in the treatment of hospitalized patients with depression have not been conducted.

Depression is a disease of our time

Studies in all countries of the world show: depression, like cardiovascular diseases, is becoming the most common ailment of our time. This is a common disorder that affects millions of people. According to different researchers, it affects up to 20% of the population of developed countries.

Depression is a serious disease that drastically reduces the ability to work and brings suffering to both the patient and his family. Unfortunately, people are very little aware of the typical manifestations and consequences of depression, so many patients are helped when the condition becomes protracted and severe, and sometimes it does not turn out at all. In almost all developed countries, the health services are concerned about the situation and are making efforts to promote information about depression and how to treat it.

Depression is a disease of the whole body. Typical signs of depression

The manifestations of depression are very diverse and vary depending on the form of the disease. We list the most typical signs of this disorder:

    Emotional manifestations

  • anguish, suffering, depressed, depressed mood, despair
  • anxiety, sense of internal tension, expectation of trouble
  • irritability
  • guilt, frequent self-incrimination
  • dissatisfaction with oneself, reduced self-confidence, reduced self-esteem
  • decrease or loss of the ability to experience the pleasure of previously pleasant activities
  • reduced interest in the environment
  • loss of ability to experience any feelings (in cases of deep depression)
  • depression is often combined with anxiety about the health and fate of loved ones, as well as the fear of appearing untenable in public places

    Physiological manifestations

  • sleep disorders (insomnia, drowsiness)
  • changes in appetite (loss or overeating)
  • violation of bowel function (constipation)
  • reduced sexual needs
  • decrease in energy, increased fatigue under normal physical and intellectual stress, weakness
  • pain and a variety of unpleasant sensations in the body (for example, in the heart, in the stomach, in the muscles)

    Behavioral manifestations

  • passivity, difficulty of engaging in purposeful activity
  • avoiding contact (tendency to solitude, loss of interest in other people)
  • rejection of entertainment
  • alcoholism and substance abuse, providing temporary relief

    Mental manifestations

  • difficulty concentrating, concentrating
  • difficulty making decisions
  • the predominance of dark, negative thoughts about yourself, about your life, about the world as a whole
  • dark, pessimistic vision of the future with a lack of perspective, thoughts about the meaninglessness of life
  • thoughts of suicide (in severe cases of depression)
  • having thoughts about your own uselessness, insignificance, helplessness
  • slow thinking

For the diagnosis of depression, it is necessary that some of these symptoms persist for at least two weeks.

Depression needs to be treated

Depression is often perceived by both the patient and others as a manifestation of bad character, laziness and selfishness, debauchery or natural pessimism. It should be remembered that depression is not just a bad mood (see manifestations above), but a disease that requires the intervention of specialists and is quite well treatable. The earlier the correct diagnosis is made and the correct treatment is started, the more chances for a quick recovery, that depression will not happen again and will not take a severe form, accompanied by a desire to commit suicide.

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What usually keeps people from asking for help about depression?

Often, people are afraid to contact a mental health specialist because of the perceived negative effects:

1) possible social restrictions (registration, a ban on driving motor vehicles and going abroad);

2) conviction if someone finds out that the patient is being treated by a psychiatrist;

3) fears of the negative impact of drug treatment of depression, which is based on widespread, but not correct, ideas about the dangers of psychotropic drugs.

Often people do not have the right information and misunderstand the nature of their condition. It seems to them that if their condition is connected with understandable life difficulties, then this is not a depression, but a normal human reaction that will go away on its own. It often happens that the physiological manifestations of depression contribute to the formation of a conviction about the presence of serious somatic diseases. This is the reason for going to the general practitioner.

80% of patients with depression initially seek the help of general practitioners, and about 5% of them are diagnosed correctly. Even less patients receive adequate therapy. Unfortunately, the usual admission in the clinic is not always possible to distinguish between the physiological manifestations of depression and the presence of a true somatic disease, which leads to the formulation of an incorrect diagnosis. Patients are prescribed symptomatic therapy (medications "for the heart," "for the stomach," for headaches), but there is no improvement. There are thoughts of a severe, unrecognized somatic disease, which, according to the mechanism of the vicious circle, leads to a worsening of depression. Patients spend a lot of time on clinical and laboratory examinations, and, as a rule, they go to a psychiatrist with severe, chronic manifestations of depression.

The main types of depression

Often depressions occur on the background of stress or long-term severe traumatic situations. Sometimes they occur for no apparent reason. Depression may be associated with somatic diseases (cardiovascular, gastrointestinal, endocrine, etc.). In such cases, it significantly aggravates the course and prognosis of the underlying somatic disease. However, with the early detection and treatment of depression, there is a rapid improvement in mental and physical well-being.

Depression can occur in the form of single episodes of a disease different in severity, or can be prolonged in the form of repeated exacerbations.

In some patients, depression is chronic in nature - lasts for many years, not reaching significant severity.

Sometimes depression is limited mainly to bodily symptoms without distinct emotional manifestations. At the same time, clinical and laboratory examinations may not reveal any organic changes. In such cases, consult a psychiatrist.

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