Selective serotonin reuptake inhibitors

Is it possible to teach our brain to artificially produce the “happiness hormone” - serotonin? This task is not easy, but feasible, because managing the delicate hormonal balance is within the power of any person. You just need to want it - and literally in 5 minutes you will be in a great mood and ready to “move mountains.” Hormones of pleasure and happiness will help you in this endeavor:

• serotonin - it is called the hormone of happiness, which gives a feeling of euphoria;
• dopamine – it is responsible for pleasure and reinforces positive experiences;
• Oxytocin - it gives rise to feelings such as love, tenderness and affection.

Most often, this “trinity” works in tandem, forming all our positive emotions. But now we will talk specifically about serotonin. Many people already know the name of this hormone of joy and happiness. But not everyone understands how it works. And even fewer people know how to regulate the level of this hormone in the body.

How to learn to manage serotonin?

This neurotransmitter, which regulates our mood, is not as simple as it might seem at first glance. Surely you think that serotonin is another hormone that is produced in the human brain. This is true, but only partly. Here are the hard facts: 95% of serotonin is produced in the intestines. And only 5% is in the brain.

So really, the path to our happiness lies through the stomach? And this is not entirely true. Serotonin is a complex chemical substance, a derivative of the amino acid tryptophan and, concurrently, the manager of our brain. This hormone is responsible for a wide range of processes both in the brain itself and throughout the human body:

1. Serotonin in the brain helps nerve cells communicate better.
2. The joy hormone affects sleep and appetite, muscle condition and body function, character and mood.
3. The most important neurotransmitter affects cognitive functions (attention, memory, communication, etc.).
4. Serotonin is responsible for normal blood clotting and stable functioning of the circulatory system.
5. The joy hormone helps us experience interest and attraction to the opposite sex.

Catecholamines

In the middle of the twentieth century, J. Shildkraut (1961) formulated the so-called catecholamine theory of the origin of depression. This theory suggested dysregulation of the brain system sensitive to norepinephrine as one of the important links in the pathogenesis of depression during depression (Praag H., 1994; Ashmarin I.P., et al., 1999).

It is now known that the content of norepinephrine in brain cells is controlled by special endings of the nerve cell - presynaptic adrenergic receptors. Stimulation of these receptors inhibits the release of norepinephrine, which in turn leads to its deficiency in the synapse and a decrease in neurotransmission. Blockade of these receptors by antidepressants, on the contrary, leads to an increase in the release of norepinephrine.

Fundamental studies of the reticular formation of the brain have shown that antidepressants, the action of which is aimed at changing the content of norepinephrine, have a general activating or psychostimulating effect. These drugs maintain the level of wakefulness, help improve the processes of perception, thinking, memory and increase concentration. However, despite the fact that taking antidepressants increases norepinephrine levels almost immediately, the clinical effect of the drug appears much later.

According to the catecholamine hypothesis of J. Schildkraut. (1978) the development of depression, especially endogenous, is caused by a decrease in the content of catecholamines, mainly norepinephrine, in certain brain structures. It was also assumed that the functional activity of noradrenergic systems during depression can be indirectly assessed by the content in the urine of such a metabolite of norepinephrine as MOPEG (3-methoxy-4-hydroxyphenylethylene glycol).

Based on a number of observations (Schildkraut J., 1978, Beckmann H., Goodwin F., 1980), it was suggested that the level of MOEFG can serve as a predictor of the effectiveness of therapy for various antidepressants. Depressed patients with lower MOPEG levels may benefit from imipramine and desipramine, but are resistant to amitriptyline.

It has been suggested that in this group of patients the primary predominant disorder is norepinephrine metabolism. On the contrary, depressed patients with high daily levels of MOFDH excretion respond better to amitriptyline therapy. At the same time, it was shown that in mentally healthy people the daily excretion of MOPEG fluctuates four times, and these fluctuations overlap the parameters of the shifts noted in patients suffering from depression (Hollister L. et al., 1978). In addition, it was found that during the period of clinical remission, the shifts in catecholamines found in patients with depression do not normalize, and even during severe depression, the content of catecholamines may be within normal limits. (Cazzulo S., Sacchetti E. et al., 1982).

Based on data obtained by J. Costa, E. Silva (1980), a theory arose suggesting the presence of two variants of the occurrence of depression, one associated with the depletion of norepinephrine and more sensitive to treatment with some antidepressants (desimipramine or imipramine) and the other associated with a deficiency of serotonin and responding to therapy with other drugs (amitriptyline). It was assumed that antidepressants exert their therapeutic effect by facilitating the transmission of both norepinephrine and serotonin (Haefely W., 1985).

Recent research in the field of brain physiology has shown that the norepinephrine-sensitive system in the brain has a pronounced influence on the serotonin-sensitive system. It turned out that nerve cells sensitive to norepinephrine control the rate of serotonin release by influencing the endings of neurons located on the bodies of serotonergic neurons. An increase in the excitability of serotonergic neurons, in turn, increases the release of serotonin in nerve endings (De Boer T., et al., 1994).

What happens if serotonin levels are disrupted?

Very often we hear about how low levels of the happiness hormone are bad. But the human body is harmed not only by a deficiency, but also by an excess of serotonin. In other words, any disruption in the production of this neurotransmitter provokes a whole list of negative consequences and conditions:

• bad mood and chronic depression;
• a sharp decrease in sexual desire;
• problems with digestion and sleep;
• cravings for sweets and weight gain;
• decreased activity.

The problems listed above are just the tip of the iceberg. The work of serotonin, based on two substances - the amino acid tryptophan and its derivative 5-hydroxytryptophan, is very complex. Sometimes the hormonal imbalance is so pronounced that specialists have no choice but to prescribe antidepressants - serotonin reuptake inhibitors.

The neurobiological basis of depression is not fully understood. At the same time, the monoamine hypothesis, which appeared in the 70s of the last century, remains relevant and very convincing, according to which mood disorders are associated with disruption of the synaptic transport of serotonin, norepinephrine and dopamine. The validity of this hypothesis is proven not only by modern research, but also by the clinical effects of antidepressants1​᠎.

Antidepressants used in modern psychiatric practice can be systematized (taking into account different classifications) approximately as follows​2​᠎.

— tricyclic antidepressants (TCAs):

imipramine, clomipramine, amitriptyline;

— tetracyclic antidepressants:

maprotiline;

— monoamine oxidase inhibitors (MAOIs)

​3​᠎
):
pirlindol, moclobemide;

- and reuptake inhibitors

,
SARI ):
trazodone, nefazodone;

— selective serotonin reuptake inhibitors (SSRIs):

fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, escitalopram;

— Selective serotonin and norepinephrine reuptake inhibitors (SNRIs):

venlafaxine, duloxetine, milnacipran;

— norepinephrine reuptake inhibitors:

atomoxetine​4​᠎, reboxetine, viloxazine;

— norepinephrine and dopamine reuptake inhibitors:

bupropion;

- noradrenergic and specific serotonin antidepressants

,
NaSSA ):
mirtazapine, mianserin;

— serotonin modulators and stimulants:

vilazodone, vortioxetine;

— melatonergic antidepressants:

agomelatine.

The disadvantage of the modern classification of antidepressants is its eclecticism: some groups of drugs are distinguished based on the predominant type of pharmacological action (for example, suppression of presynaptic uptake of serotonin), others based on structural features. The TCA group is heterogeneous in terms of the pharmacological properties of the drugs: for example, clomipramine and imipramine predominantly inhibit the reuptake of serotonin and to a much lesser extent interfere with the presynaptic uptake of norepinephrine, while amitriptyline has a balanced effect on both of these neurotransmitters. The imperfect and somewhat arbitrary nature of the above taxonomy is also manifested in the fact that, for example, mirtazapine in different classifications is classified as both a TCA (in terms of chemical structure) and NaSSA (based on the characteristics of pharmacological mechanisms). Although SSRIs are considered to be selective serotonergic antidepressants, all six drugs in this group also (to varying degrees) affect the synaptic transport of norepinephrine and dopamine.

The presented list begins with TCAs and MAOIs as first-generation antidepressants, although, in accordance with modern international and many national clinical guidelines, SSRIs are the first choice drugs in the treatment of depression and anxiety-related disorders, which is determined by the optimal balance of their effectiveness and tolerability.

Of course, for the successful treatment of depression, improving the interneuronal transmission of three key monoamines - serotonin, norepinephrine and dopamine - is important, but it is believed that increased serotonin neurotransmission plays a special role in the clinical effectiveness of modern antidepressants [1].

The following groups of drugs have serotonergic properties: TCAs, tetracyclic antidepressants, MAOIs, SARIs, SSRIs, SNRIs, NaSSA, as well as serotonin modulators and stimulants.

TCAs—especially clomipramine—show significant ability to facilitate synaptic transport of serotonin and demonstrate high efficacy in the treatment of depression, including its most severe, including psychotic, forms. Significant disadvantages of TCAs include frequent side effects (including cardiotoxicity and the ability to provoke the development of type 2 diabetes) and low overall tolerability.

SSRIs, as first-line drugs in the treatment of depression and anxiety-related disorders, are tolerated by patients much better than TCAs and other first-generation antidepressants, but are also not completely free from adverse effects; A typical reason for premature discontinuation of SSRIs is sexual dysfunction - most often decreased libido and deterioration of erection (in men).

SARIs, most notably trazodone5​᠎, occupy an intermediate position between TCAs and SSRIs.

Trazodone is the first serotonergic antidepressant, proposed for clinical use in the treatment of depression in 1981 and preceded the appearance seven years later of fluoxetine, followed by other SSRIs. On the Russian pharmaceutical market, trazodone is presented under the name trittico.

Trazodone affects various types of serotonin receptors. The predominant pharmacological effect of trazodone is considered to be an antagonistic effect on serotonin 5-HT2A and 5-HT2C receptors7​᠎; A certain importance in the antidepressant effect of the drug is also attached to the suppression of serotonin reuptake, which brings trazodone closer to SSRIs and SNRIs. The complex effects of trazodone on serotonin neurotransmission allow it to be considered as a multifunctional serotonergic antidepressant [2].

Trazodone is used in many countries as a treatment for major depressive disorder in adults. Clinical studies indicate significant effectiveness of trazodone in the treatment of depression, comparable to that of TCAs, SSRIs and SNRIs [3]. Pronounced thymoanaleptic properties and proven clinical effectiveness make it possible to prescribe trazodone for depression of varying severity; in addition, the drug is used to augment (strengthen) the action of other antidepressants, including SSRIs, such as fluoxetine [4].

If the combination of two antidepressants is common in clinical practice, then the advisability of simultaneous prescribing of three antidepressants seems controversial to many specialists and causes debate, mainly due to the increase in the total risk of side effects of therapy. Highlighting the controversial nature of the simultaneous use of three antidepressants, R. Lopes et al. [15] described a case of successful treatment of treatment-resistant depression by adding trazodone to the ineffective combination of paroxetine and mirtazapine.

Due to its multifunctional effects on serotonin receptors, trazodone is particularly effective in the treatment of depression accompanied by insomnia and anxiety [6]. According to E. Frecska [7], the introduction into widespread practice of treating depression of trazodone, which has a hypnotic and anxiolytic (anti-anxiety) effect, can reduce the need to prescribe benzodiazepines as an additional component of antidepressant therapy.

The wide range of pharmacological effects of trazodone has provided the basis for its use in clinical practice in a number of countries, along with the treatment of depression for additional indications and primarily for the treatment of insomnia. The drug is most often used in the treatment of sleep disorders in the USA8​᠎; trazodone is invariably included in the list of antidepressants that have a hypnotic effect, and is often the leader in this list [8, 9].

In addition to treating depression and insomnia, trazodone is used in the treatment of generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, bulimia nervosa, alcohol dependence and benzodiazepine dependence, as well as neuropathic pain and other chronic pain syndromes [7, 10]. .

According to some data, trazodone has a moderate beneficial effect on the negative symptoms of schizophrenia, and also in some cases helps reduce delusional disorders that are resistant to antipsychotics [7, 11]. In the practice of treating elderly patients, the ability of trazodone not only to mitigate the negative symptoms of schizophrenia, but also to reduce the manifestations of tardive dyskinesia has been noted [12].

Improved sleep under the influence of trazodone expands the indications for its use in combination therapy for depression: on the one hand, the drug is prescribed in addition to other antidepressants in order to augment their thymoanaleptic effect, and on the other, it is used as a corrective to eliminate anxiety and insomnia caused by other antidepressants , including fluoxetine, bupropion, and monoamine oxidase inhibitors [7].

It should be noted that the apparent hypnotic effect of trazodone has led to certain undesirable consequences: many doctors have ceased to perceive the drug as a significant treatment for major depressive disorder and prescribe it mainly for the treatment of insomnia, which does not allow the full therapeutic potential of trazodone and significantly narrows the range of patients who may benefit from this antidepressant; in other words, trazodone can and should be prescribed for the treatment of depression, regardless of whether it is accompanied by sleep disorders or not.

While demonstrating comparable effectiveness in treating depression as other antidepressants, trazodone is superior in tolerability not only to TCAs, but also to drugs of new generations; its use as an alternative to SSRIs allows one to avoid such undesirable effects associated with the use of the latter, such as anxiety, insomnia and sexual dysfunction [3].

The high adherence of patients to trazodone therapy is largely due to the lack of ability to worsen sexual functions. On the contrary, trazodone is capable of increasing libido (in both men and women) and even, in some cases, causing priapism; however, the frequency of this side effect does not exceed 0.01% [13–17]. Unlike a number of antidepressants, trazodone does not cause or worsen movement disorders, in particular restless legs syndrome and periodic limb movements [18]. A significant advantage of trazodone compared to some newer generation antidepressants, which promotes adherence to therapy (especially in women), is the absence of its effect on body weight [7].

Unlike TCAs, which can increase insulin resistance and provoke the development of type 2 diabetes and aggravate its course, trazodone does not have an adverse effect on carbohydrate metabolism [16].

The effect on anxiety and sleep disorders, combined with good tolerability, including in elderly patients, allows us to consider trazodone one of the drugs of choice for the treatment of depression in late life; in addition, depression comorbid with dementia or psychomotor agitation is an indication for trazodone; An improvement in the quality of life of patients suffering from cerebral atrophy under the influence of trazodone was also noted [6].

Proven clinical efficacy comparable to that of TCAs, SSRIs and SNRIs, combined with good tolerability, warrants re-opening .

rediscovering) of trazodone for the treatment of depression [3].

Summarizing data from various studies, A. Fagiolini et al. [3] concluded that trazodone is an effective and well-tolerated antidepressant that plays an important role in the modern treatment of major depressive disorder, either as monotherapy or as a component of combination treatment. They emphasize that trazodone controls a wide range of depressive symptoms and does not have a negative effect on sleep, but rather has the ability to significantly improve sleep function.

In conclusion, we can add that trazodone, the high clinical effectiveness of which was actively discussed in scientific publications of the 80s and 90s of the previous century, has now, for a number of reasons, turned out to be undeservedly forgotten, although the pharmacological spectrum of this drug provides every reason for its successful use in the treatment of depression (as well as a number of other mental disorders) as an alternative to both TCAs and newer generations of antidepressants.

Conflict of interest: the article was prepared with the support of Pharmaceutical.

Of course, the pathogenesis of depression is extremely complex, associated with many factors and is by no means reduced to a violation of the neurotransmission of monoamines.

Not all of the listed drugs are registered in the Russian Federation.

This list contains only selective and reversible MAO-A inhibitors.

Atomoxetine is the only drug listed here that is not used to treat depression, but as a means of correcting attention deficit hyperactivity disorder.

Another SARI representative, nefazodone, is absent from the Russian pharmaceutical market, which can hardly be considered a significant loss for domestic clinical practice: due to its pronounced hepatotoxic effect, nefazodone in the United States is labeled with the so-called “Black Box Warning” by the FDA.

As mentioned above, antidepressants of early generations already had pronounced serotonergic activity, for example, the powerful tricyclic antidepressant clomipramine, but trazodone is the first drug whose clinical effectiveness is determined by its multimodal effect on the neurotransmission of serotonin.

Some authors, including those cited in the text by A. Schatzberg and C. DeBattista [4], classify trazodone (together with nefazodone) as HT2 receptor antagonists, which, in our opinion, does not fully reflect the spectrum of its pharmacological activity.

The undoubted advantage of trazodone over benzodiazepines, which determines its widespread use in the United States as a treatment for insomnia, is the absence of a negative effect on cognitive functions, as well as the ability to cause addiction and dependence.

Insomnia and anxiety are often at the root of benzodiazepine abuse; Due to its hypnotic and anxiolytic effects, trazodone can successfully replace benzodiazepines and similar hypnotic-sedative drugs.

But is it worth using “heavy artillery” right away?

We know that antidepressants work quickly. But we also know that they have a lot of disadvantages, the most important of which are addiction and various side effects that can seriously undermine already weakened health. The image below shows how hard antidepressants work. It’s worth thinking about whether such radical measures are necessary???

Is there a safe alternative to pills? Eat. This is the right way of life and the ability to look at the world positively. The “recipe” for your happiness will not consist of a set of drugs, but of completely different components:

1. Nutrition. Healthy foods contain everything you need to produce the hormone serotonin in sufficient quantities. Give up fast carbohydrates and junk food in favor of healthy carbohydrates and foods containing tryptophan. Serotonin “grows” on variety: grains and cereals, vegetables and fruits, eggs and dairy products, lean meat and fatty fish, nuts, seeds and dried fruits.

   The image shows foods rich in tryptophan.

2. Movement. Scientists have repeatedly proven that any physical activity quickly (literally in 30-40 minutes) increases the level of serotonin in the blood. Dancing, walking, swimming, cycling, morning jogging - there are many activities, you don’t have to go to the gym. But there is one “but”: you need to be active constantly, and not from time to time.
3. Sleep and meditation. A happy person knows how to “switch off” in time and let go of negativity from his life. Sometimes this is difficult to do. And then meditation and healthy sleep come to the rescue, during which the level of the happiness hormone also increases. Train yourself to go to bed and get up at the same time - and you will not have problems with serotonin.
4. More sun. In our climate, sunny days are a rare occurrence. But even on a cloudy day, our skin still receives its portion of ultraviolet radiation. This means that the answer to the question “how to increase serotonin” is simple: walk more often. Walking will give the body maximum happiness hormone and beneficial vitamin D.
5. Omega-3. It is difficult for us to maintain an optimal level of essential polyunsaturated fatty acids, which are found in excess only in the meat of fatty fish from the northern seas. But now there is already a worthy alternative - dietary supplement complexes with Omega-3. Such supplements are a real “delicacy” for the brain and prevent a number of diseases.
6. Pleasure. Serotonin is responsible for pleasure and enjoyment. How can you get more of these emotions? There are a lot of ideas: for example, falling in love, finding a new exciting hobby, meeting friends more often, spending more time with loved ones. The more bright emotions and positivity there are in your life, the higher the level of the happiness hormone will be.
7. "Helpers." Unfortunately, even with proper nutrition, it is not possible to obtain from food 100% of the substances necessary to nourish the brain and body. And then “serotonin in tablets” comes to the rescue. These are special plant vitamin complexes that help the happiness hormone be produced correctly and in the required volume.

Serotonin 10mg/ml 1ml 5 pcs. injection

Composition and release form Serotonin 10 mg/ml 1 ml 5 pcs. injection

Solution for intravenous and intramuscular administration - 1 ml serotonin adipate - 10 mg excipients: unithiol; water for injection in a blister pack 5 ampoules of 1 ml each; in a cardboard pack 1 package.

Description of the dosage form

A colorless or slightly colored transparent solution with a faint odor of hydrogen sulfide.

Characteristic

Hemostatic agent.

Directions for use and doses

IV, IM. In case of severe bleeding, they begin with intravenous injection; when bleeding decreases, they switch to intramuscular injection. The initial dose is 5 mg; in the absence of side effects, the dose is increased to 10 mg, but not more than 15-20 mg/day. The course of treatment is 10 days (on average). Preparation of a solution for intravenous administration. 5-10 mg is diluted in 100-150 ml of 0.9% sodium chloride solution (or in 5-10 ml of 0.9% sodium chloride solution, which is then diluted in 100-150 ml of 5% dextrose solution, plasma, preserved blood) and administered dropwise (at a rate of no more than 30 drops/min). Preparation of a solution for intramuscular administration. 5-10 mg is diluted in 5 ml of 0.5% lidocaine solution; administered 2 times a day with an interval of at least 4 hours. For ischemia of the lower extremities in patients with diabetes mellitus, a 1% solution of 2 ml in 200 ml of Ringer's solution is administered dropwise for 1.5 hours. For complex therapy, patients in critical condition (shock) ) condition, intravenous administration is carried out at a rate of 5-10 mg/h. The selection of the dose and rate of administration of the drug is determined individually. In case of vascular insufficiency - under blood pressure control until it stabilizes. In FKN - until the appearance or strengthening of intestinal motility, restoration of the motor-evacuation function of the gastrointestinal tract.

Pharmacodynamics

The effect is mainly associated with the ability to increase platelet aggregation and reduce capillary permeability, as well as a reduction in bleeding time. Serotonin causes vasoconstriction in the kidneys and has an antidiuretic effect. It binds to serotonin receptors of the smooth muscles of internal organs and normalizes its contractile activity and automaticity (endogenous vasomotor, peristalsis). A manifestation of normalization of smooth muscle function with the administration of serotonin is stabilization of hemodynamics, restoration of motor-evacuation function of the gastrointestinal tract, and reduction of local hypoxia.

Pharmacokinetics

In the blood plasma it is deaminated and loses its activity. Does not have a cumulative effect.

Indications for use Serotonin 10 mg/ml 1 ml 5 pcs. injection

hemorrhagic syndrome (with Werlhof's disease, with malignant neoplasms, including during treatment with cytostatics; with acute, subacute and chronic radiation sickness); hypo- and aplastic anemia; thrombocytopenia, hemorrhagic vasculitis; hypoxemia, vascular insufficiency; diseases whose genesis is dysfunction of the smooth muscles of the microvasculature (including ischemic and diabetic angiopathy); functional intestinal obstruction (FIO); shock of various origins.

Contraindications

hypersensitivity to any component of the drug; kidney diseases, incl. glomerulonephritis (acute and chronic), oligo- and anuria; arterial hypertension; acute thrombosis; angioedema; bronchial asthma; diseases accompanied by hypercoagulation.

Application Serotonin 10 mg/ml 1 ml 5 pcs. solution for injection during pregnancy and lactation

During pregnancy, the effect of the drug has not been studied. Since the drug is quickly deaminated in the bloodstream, breastfeeding is not a contraindication for its use.

Side effects Serotonin 10 mg/ml 1 ml 5 pcs. injection

Pain along the vein (with rapid injection), with intramuscular injection - pain at the injection site; abdominal pain, cardialgia, increased blood pressure, heaviness in the head, difficulty breathing, nausea, diarrhea, decreased diuresis.

Drug interactions

Serotonin potentiates the effect of narcotic, hypnotic and analgesic drugs. Not administered together with calcium chloride preparations.

How do vitamins for a good mood work?

Unlike antidepressants, which inhibit serotonin reuptake, plant-based vitamins act differently—more gently. They bring all neurotransmitters into balance and help the happiness hormone be produced in the right quantity without causing serious harm to the human body:

• fight fatigue and irritability;
• increase memory, attention and concentration;
• eliminate insomnia and other sleep disorders;
• protect against depression and nervous disorders;
• restore interest in life and normalize appetite.

Constant stress at work and at home does not allow you to always be at the peak of activity. But now this problem can be easily solved: just one capsule of herbal vitamins a day - and it will be much easier for you to cope with the challenges that this world has prepared for you. Forgetfulness, absent-mindedness and apathy will be replaced by cheerfulness and a positive mood.

Managing happiness hormones is easy!

The secret to the effectiveness of herbal vitamins for mood is in the ideal composition. There is nothing superfluous in them besides the active components - extracts of medicinal herbs. For example, these could be:

• St. John's wort and clover grass;
• Rhodiola rosea and valerian;
• volodushka and muira puama bark.

Such vitamins, even with long-term use, often turn out to be more effective and safe in comparison with synthetic drugs and antidepressants, which cause addiction, withdrawal effects, drowsiness and other side effects.

Now you know how to properly increase the level of serotonin in the body so that a positive result is not long in coming. Allow the happiness hormone to be produced in full - and your life will become bright, and every day will bring maximum benefit and pleasure.

Citalopram

Citalopram has a significantly higher level of selectivity for serotonin transporters compared to norepinephrine and dopamine transporters.

The drug is prescribed in a dose of 20 mg. per day once a day in the morning. For most patients, this dose is the most effective; the maximum daily dose of the drug is 60 mg.

Citalopram practically does not enter into drug interactions, due to the fact that it has little effect on the activity of some liver enzymes (cytochrome P450 enzyme system). Therefore, it is often used in the treatment of depressive conditions that develop as a result of chronic somatic diseases. Interdrug interactions of the drug are minimal. Under the influence of cytochrome P450, citalopram is converted into two main metabolites: demethylcitalopram and didemethylcitalopram. These metabolites have pharmacological activity, but much less than that of citalopram itself. The half-life of citalopram is 30 hours. It is characterized by a linear dependence of plasma concentrations depending on the dose in the therapeutic interval. For the treatment of severe depression, the dose of the drug should be increased.

The use of citalopram is recommended in general medical practice, in elderly patients and persons who have suffered a cerebral stroke.

When prescribing citalopram, the percentage of men with sexual dysfunction, a side effect that is relatively common when prescribing drugs in this group, turned out to be extremely small. Headache and nausea were the most common side effects of citalopram treatment during the first two weeks of treatment.