Selective antidepressants. SSRI drugs - how they work, properties, list of drugs

Creation and beginning of practical application in the mid-1980s. a new class of psychotropic drugs - selective serotonin reuptake inhibitors(SSRI) - has become one of the most important achievements in the field of pharmacotherapy of mental disorders. Today they have become the drugs of first choice in many countries of the world in the treatment of the most widespread mental disorders - depression and pathological anxiety, replacing in this capacity in the first case tri- and heterocyclic antidepressants, and in the other - benzodiazepine tranquilizers.

This provision is enshrined in the guidelines for the treatment of mental disorders in all countries with developed psychiatric care, it is also contained in those in force since August 2005. " Protocols for the diagnosis and treatment of mental and behavioral disorders in the system of the Ministry of Health of the Republic of Belarus". The breadth of use of selective serotonin reuptake inhibitors is already evidenced by at least the fact that two of them (paxil and zoloft) are now included in top ten most widely sold in the world medicines generally.

In a number of countries, these drugs have gained great popularity not only among doctors, but also in society; their names are heard in films, newspapers, fiction; they have become a kind of symbol of our time (" prozac generation"). The high frequency of their use in the modern world becomes understandable if we take into account, on the one hand, their high efficacy and safety in comparison with older tricyclic antidepressants (TCAs), and on the other hand, remember those mental and behavioral functions that are "managed" neurotransmitter serotonin: maintaining the level of mood, a sense of pleasure in its various forms, appetite and satiety, sexual behavior and satisfaction, sensitivity to pain, regulation of sleep and wakefulness, the level of aggressiveness, etc.

Therefore, selective serotonin reuptake inhibitors are widely used in the treatment of not only depression and anxiety disorders, but also anorexia and bulimia nervosa, a number of sexual dysfunctions, aggressive and auto-aggressive behavior, chronic pain, pathological gambling and some other mental and behavioral disorders.

More than 20 years (since 1984) experience in the use of selective serotonin reuptake inhibitors has shown that, despite the similarity of the main mechanism of action, these drugs differ significantly from each other in their strength and selectivity, interactions with various brain receptors, effectiveness in various forms of disorders, pharmacokinetic parameters, side effects, drug interactions, etc. In other words, they are all good, but each in its own way.

The topic of this article is relevant, if only because today in the Republic of Belarus all six SSRI drugs used in the world are already registered and available: fluvoxetine, fluvoxamine, sertraline, paroxetine, escitalopram and citalopram(the last of them was registered quite recently - in April 2006), - in connection with which our psychiatrists have a real opportunity to choose and experience in their application has been accumulated. However, if some features of these drugs are already widely known and are usually taken into account in everyday practice, then others, such as the frequency and nature of drug interactions when using SSRIs with other drugs, are known and taken into account to a much lesser extent.

The purpose of this article is, based on literature data and our own experience, to discuss characteristics of these drugs, their strengths and weaknesses, indications, contraindications and application features.

1. The brightest and most famous distinctive features fluoxetine (prozac, in Belarus - drug fluoxicar) are a significant antidepressant "strength" and a distinct stimulating effect, and therefore in some patients it is able to cause increased anxiety at the start of treatment. The most indicated forms of pathology for its use are mild to moderate depressive episodes, obsessive-compulsive disorder, as well as premenstrual tension syndrome (premenstrual dysphoric disorder, premenstrual syndrome) and bulimia nervosa. Fluoxetine is used less frequently in the treatment of panic disorder and generalized anxiety disorder. In any case, it should not be used in patients who have previously responded to its use with increased anxiety and agitation.

Two more circumstances must be remembered: firstly, fluoxetine has the longest half-life of all selective serotonin reuptake inhibitors (approximately 72 hours), and secondly, to achieve its therapeutic concentration in the blood, a longer drug intake is required and the effect occurs. somewhat later than other selective serotonin reuptake inhibitors. Therefore it should not be used where the effect is important to get as soon as possible(eg, in severe depression with stupor and food refusal). It is also unprofitable to use it in cases where there is reason to believe that in the future there will be a need to change the antidepressant, since such a transition will require waiting for a “washout” period of up to 3, and according to some sources, even up to 5 weeks. (Note that for other selective serotonin reuptake inhibitors, a 2-3 day break is sufficient to switch from one drug to another, for example from fluvoxamine to sertraline or from sertraline to paroxetine.)

At the same time, a long half-life also has its advantages - fluoxetine is good in "forgetful" patients with low compliance, since skipping an appointment for 1-2 days does not change anything. Fluoxetine is the drug with the most stable regimen and has been found to be the least likely to be switched by physicians during treatment to another selective serotonin reuptake inhibitor.

Because fluoxetine is significantly inhibits hepatic enzymes of cytochrome P450, responsible for the metabolism of many drugs, it must be remembered that it has a significant number of drug interactions with both psychotropic drugs and drugs used in somatic medicine.

Fluoxetine increases the serum levels and effects of benzodiazepine tranquilizers - diazepam, chlordiazepoxide (elenium), alprazolam, temazepam, triazolam, etc., as well as beta-blockers, tri- and tetracyclic antidepressants, carbamazepine and valproate. The same applies to haloperidol and clozapine, therefore, when taken together in the first case, the risk of extrapyramidal side effects, and in the second - convulsive seizures. The use of fluoxetine in conjunction with other antipsychotics also requires great caution. The same applies to patients who regularly take medications for various somatic diseases.

Like all other selective serotonin reuptake inhibitors, it is understandably incompatible with any monoamine oxidase inhibitors (MAOIs) and tryptophan.

Finally, another feature of fluoxetine is its relative safety during breastfeeding; if there is a clear need for an antidepressant during pregnancy fluoxetine is considered the drug of first choice in such cases.

2. fluvoxamine(faverin, in Belarus - fevarin) - the first of the drugs of selective serotonin reuptake inhibitors that came into practice (in 1984). Antidepressant medium strength with a pronounced sedative and anti-anxiety effect. The most indicated forms of pathology for this remedy are depressive episodes of mild to moderate severity with the presence of anxiety and restlessness, as well as obsessive-compulsive disorder; to a lesser extent - panic disorder with agoraphobia. The half-life is approximately 15 hours, so it can be taken in one evening or in two divided doses; tablets should be swallowed whole.

Of the adverse features of this drug, it should be noted a slightly higher frequency and severity compared to other SSRIs. gastrointestinal side effects, as well as frequent drug interactions, as described above with fluoxetine - when taken together, fluvoxamine increases the serum levels and effects of benzodiazepines, carbamazepine, tricyclic antidepressants, beta-blockers, warfarin, theophylline. Serious complications are possible when the drug is combined with levomepromazine (tizercin), lithium, and alcohol.

Among the lesser-known positive aspects of the drug, we note that it is less likely than other selective serotonin reuptake inhibitors to cause side effects from the sexual sphere, which in outpatient treatment is often of paramount importance for maintaining compliance. (Note that when using all selective serotonin reuptake inhibitors in outpatient treatment, it is necessary to purposefully ask questions to identify such complaints, since patients themselves are often silent about this, but they may stop taking the drug because of this.)

3. Sertraline(in the Republic of Belarus available in the form of preparations Zoloft and stimuloton) is also well known to domestic specialists. The main indications for its use are depressive states, including severe and psychotic, as well as obsessive-compulsive disorder and premenstrual syndrome, to a lesser extent - panic disorder with agoraphobia. Possesses both sedative and stimulant, so some patients may exacerbate anxiety. The half-life is approximately 26 hours. The drug should be taken during or immediately after a meal.

One of the important positives is no effect on liver enzyme activity and as a result, almost complete absence drug interactions with both psychotropic and somatic drugs. Able to only slightly enhance the serum levels and effects of beta-blockers, desipramine and warfarin. Like fluoxetine, it is less dangerous than other SSRIs when breastfeeding, as well as when combined with alcohol.

4. Paroxetine (paxil, seroxat; the drug is registered and used in the Republic of Belarus rexetine). A "strong" broad-spectrum antidepressant, one of the most widely used selective serotonin reuptake inhibitor drugs in the world today. Possesses pronounced anti-anxiety and sedative effect and almost never exacerbates anxiety at the start of treatment. The main indications for its use are depression of any severity, including severe and psychotic, as well as panic disorder with agoraphobia, obsessive-compulsive disorder, social phobias and generalized anxiety disorder. The most indicated of all selective serotonin reuptake inhibitors in the treatment post-traumatic stress disorder. The half-life is about 24 hours, so it is taken once a day, usually in the morning with food. A specific difference in treatment with paroxetine is the need for a slow, 10 mg per week increase in dose.

The drug enters into a number of drug interactions. So, its level in blood serum and effects are enhanced while taking haloperidol, tricyclic antidepressants, thioridazine, and antacids. In turn, when taken together, it increases the concentration and effects of alprazolam, midazolam and triazolam, beta-blockers, haloperidol, tricyclic antidepressants, phenytoin, warfarin. The content of paroxetine in the blood and the effect is reduced when it is taken together with carbamazepine and phenytoin. The drug should not be administered together with MAOIs and thioridazine. It is also important to note that the drug does not impair motor skills and does not interact with alcohol.

With a sharp cessation of administration, the development of withdrawal symptoms (sleep disturbance, increased anxiety, dizziness, etc.) is possible, which is associated with the affinity of the drug to muscarinic receptors. Therefore, at the end of treatment, the dose should be reduced as gradually as it was increased at the beginning, or even more slowly; it is better not to use the drug in patients who are prone to skip doses or quit treatment on their own. It should be noted that paroxetine therapy, like other modern antidepressants, implies good compliance, and for this, constant psycho-educational work with the patient and his relatives.

5. Escitalopram(in the Republic of Belarus - a drug cipralex) has been used in our country since 2004. A moderately strong antidepressant with a pronounced anti-anxiety effect.

The main areas of application are mild to moderate depressive episodes (the possibility of use in severe depression is being studied), as well as panic and generalized anxiety disorders. The half-life is 30 hours, and therefore a single dose is sufficient.

It has little effect on the activity of liver enzymes, as a result of which it has a small number of drug interactions. When taken together, it increases the serum content and effects of tricyclic antidepressants, antipsychotics (in particular, levomepromazine), beta-blockers (propranolol, timolol, metoprolol, etc.) and antiarrhythmic drugs.

6. User experience citalopram(the drug has recently been registered in the Republic of Belarus starcitin) by domestic psychiatrists is still minimal.

Data on the main indications for the use of selective serotonin reuptake inhibitors in various forms of pathology are summarized in Table.

Table.
The main indications for the use of antidepressants - SSRIs in various forms of pathology

Concluding this review, we note once again the need to take into account possible drug interactions when using any of the SSRI drugs. It is important to keep in mind that the risk of developing side effects of these drugs (the so-called serotonin syndrome) increases significantly when lithium carbonate is added to SSRIs, as well as other serotonergic drugs, in particular tricyclic antidepressants (especially clomipramine), diazepam, alprazolam, tryptophan, fenfluramine. In turn, SSRIs, when taken simultaneously, increase the blood concentration and side effects of tricyclic antidepressants by 5-10 times, and also somewhat slow down the excretion of lithium, carbamazepine and valproate. Therefore, such combinations (selective serotonin reuptake inhibitors + tricyclic antidepressants), although in principle possible in the treatment of resistant depression, however only in hospital and only where the usual monotherapy with SSRIs or tricyclics, carried out according to all the rules, turned out to be ineffective. The combined use of SSRIs and MAOIs is unacceptable due to the high risk of side effects.

Finally, the combined use of selective serotonin reuptake inhibitors may exacerbate the extrapyramidal side effects of some antipsychotics and increase the effect of oral anticoagulants, which can lead to hemorrhages.

In conclusion, we present examples of use in practice the above features of the drugs - SSRIs. So, for example, if any of these drugs can be used for mild to moderate depression, then in the case of significant severity of this condition or the presence of psychotic symptoms, it is better to opt for paroxetine or sertraline. Where the fastest possible response to an antidepressant is required, fluoxetine should not be used. When treating social phobias, it is better to choose paroxetine. The presence of a serious somatic pathology in the patient, requiring constant use of other drugs, speaks in favor of sertraline or escitalopram. In a patient with increased anxiety, who is prone to increased anxiety for any reason, it is better to use paroxetine, but not fluoxetine. Similarly, fluoxetine should not be used in cases where there is reason to think of therapeutic resistance to antidepressants, which may subsequently require a change in drug. At the same time, fluoxetine may have an advantage in the outpatient treatment of a patient with low compliance. In the outpatient treatment of a patient who is fixated on the state of his sexual function, fluvoxamine, etc., may be useful.

Thus, the advent of antidepressants-SSRIs has significantly expanded and made safer the treatment of a number of common mental disorders in the modern world. Each of these drugs has a number of its specific features. For the fullest use of the opportunities that have opened up in this case, it is necessary that the drug chosen for treatment correspond as fully as possible to the characteristics of each individual case.

Serotonin is one of the mediators of the nervous system. It is also considered the hormone of happiness, as it has a very positive effect on a person's emotions. This biologically active substance is formed from the amino acid tryptophan, which comes from outside with food.

Synthesis of serotonin occurs in the pineal gland. As a mediator, serotonin takes part in the transmission of impulses between neurons, thus carrying information to different parts of the brain. Due to serotonin receptors, serotonin has the ability to regulate and control most of the processes occurring in organs and systems. This is possible because serotonin receptors are present not only in neurons, but also in the vascular walls, in the gastrointestinal tract, and in the muscles of the bronchial walls. The impulse is transmitted electrically, when ions pass between neurons.

First of all, for the work of neurons. In the CNS, it is responsible for:

• good mood;
• memory;
• cognitive functions;
• regulates appetite;
• food and sex;
• social behavior of the individual.

One of its great functions is that melatonin, the sleep hormone, is produced from serotonin. Thus, serotonin is directly involved in circadian rhythms - sleep and wakefulness.

Melatonin deficiency causes insomnia. Also, serotonin is involved in thermoregulation, the work of the thyroid gland, increasing the production of TSH in the pituitary gland. Serotonin also increases insulin production, which in turn increases tryptophan. Therefore, after eating a chocolate bar, your mood will improve: blood glucose rises - insulin rises - tryptophan rises - serotonin rises.

Serotonin increases the synthesis of prolactin and secretion of milk, is responsible for the correct course of pregnancy, childbirth and uterine contractions during them.

Participates in normal intestinal peristalsis, stimulates the frequency of breathing, increases blood clotting, reduces pain sensitivity, increases stress resistance. But an excess of serotonin exaggerates the positive, which is not very good.

What happens when there is a lack of serotonin

With its deficiency, a person develops anxiety, irritability. A person becomes sensitive to pain, his biorhythms go astray, the work of the central nervous system is disrupted. The main manifestation of this is the development of migraine pain and depression, obsessive-compulsive disorder syndromes, which can cause visual deceptions.

Antidepressants

To remove a person from a state of depression, one has to resort to the appointment of various psychotropic drugs; among them is a new generation of antidepressants - SSRIs. Deciphering means: selective serotonin reuptake inhibitors.

What can they give? How do they manifest themselves? They are able to improve mood, relieving a person of such negative moments as anxiety and apathy, melancholy and emotional stress.

They make a person stress-resistant, restore biorhythms, stabilize sleep and improve appetite.

Mechanism of action of SSRIs

To understand the mechanism of their action, it is worth remembering a little the physiology of the central nervous system. In places where impulses are transmitted between neurons, there is a synaptic cleft, where serotonin is released, which carries information.

What happens next: the mediator transmitted the signal, his role is over. Now it must be liquidated as unnecessary, according to the principle the Moor has done his job - the Moor can leave. The fact is that if the mediator is not removed and remains on the postsynaptic membrane, it will interfere with the flow of new information from new signals.

Removal of unnecessary neurotransmitter molecules occurs in several ways: diffusion, enzymatic cleavage and reuse by reuptake - serotonin reuptake. These reactions are very complex and there is no need to fill your head with them. You just need to know that SSRIs just block the inhibition of these molecules and prolong the effect of serotonin, accumulating and directing it into the bloodstream.

The selectivity of inhibitors is manifested in the fact that they selectively act on serotonin receptors only. Thus, serotonin can no longer return to its cell, its signal goes to other cells that are in a state of inhibition and depression.

They are activated and depression gradually softens and decreases. Serotonin itself in the synaptic cleft increases and goes into the bloodstream, acting on other receptors too.

The half-life of drugs takes about a day and it is excreted by the kidneys. The degree of effectiveness of this group of antidepressants varies.

List of SSRIs and their effects

The drugs are considered 3rd generation antidepressants. They have certain advantages and disadvantages. The pharmacological action is manifested in the correction of a depressive background, reduction of anxiety and melancholy, some phobias, appetite improves, a slight analgesic effect is manifested.

The advantage of inhibitors is that they are more easily tolerated by patients, do not give a cardiotoxic effect, do not exacerbate glaucoma, do not lead to severe sedation and hypotension, which is typical, for example, for TCAs (tricyclic antidepressants such as amitriptyline). SSRIs may be given on an outpatient basis. They can also be prescribed in the presence of contraindications to the use of TCAs.

The most popular in use are: Fluoxetine, Prozac, Paroxetine, Citalopram, Indalpin, Sertraline, Fluvoxamine, Femoxetine, etc. The result of treatment does not appear immediately, only after 4-5 weeks.

Stimulation of serotonin receptors by excitation during the entire period of taking SSRIs necessarily gives side effects, like a double-edged sword: due to the fact that receptors are very widely represented in various organs, long-term use of SSRIs causes dyspeptic manifestations: abdominal pain, nausea and vomiting, stool disorders, even gastrointestinal bleeding; sexual disorders such as anorgasmia, delayed ejaculation. There may be insomnia (every 4-5 patients), anxiety. Gastrointestinal disorders are noted at 1-2 weeks of admission, then they disappear. CNS disturbances are much more persistent.

Indications

In addition to depression, SSRIs are prescribed for social phobias, anxiety neurosis, panic attacks, obsessions, anorexia, stress after trauma, and chronic algia. In general practice, they are prescribed for uncontrolled appetite, obesity, PMS, borderline disorders, alcoholism.

Opinions about the effectiveness of SSRIs differ: psychiatrists in Russia believe that selective inhibitors help better with moderate forms of depression - mild and moderate; with severe effects less. But in the West, they prove in every possible way the effectiveness of these drugs in any form of depressive disorders.

What SSRIs do not work with

The simultaneous use of inhibitors and other drugs carries a great risk. SSRIs cannot be combined with MAOIs; this causes serotonin syndrome, one of the most serious complications in a patient. When combined with TCAs and SSRIs, the dosage of TCAs is reduced, otherwise their number may increase and a toxic effect may appear.

Lithium salts - increase the serotonergic effects of SSRIs, and the unpleasant effects of lithium itself are more pronounced. SSRIs, when used simultaneously with antipsychotics, increase extrapyramidal disorders, because they increase the content of antipsychotics in the blood serum.

The same applies to neuroleptics such as Rispolept (atypical). SSRIs cannot be combined with aspirin and NSAIDs, antiplatelet agents, the risk of gastrointestinal bleeding increases. In addition, NSAIDs significantly reduce the effect of SSRIs. The combination of the group with ethanol, sedatives, barbiturates - enhance the effect of the latter on the central nervous system.

Serotonin syndrome

This dangerous, potentially fatal condition is perhaps the most severe side effect of SSRIs. It develops when combined with serotonergic antidepressants - for example, MAOIs.

In the clinical picture, there are symptoms of 3 groups:

1. From the side of the central nervous system, ANS and neuromuscular apparatus.
2. From the side of the central nervous system, any manifestations of arousal: dysphoria, agitation, hypomania and anxiety, dyssomnia and hallucinations, confusion and delirium.
3. From the side of the ANS - symptoms of dyspepsia - rumbling in the abdomen, vomiting and nausea, loose stools, abdominal pain; fever, chills, hyperhidrosis, cephalgia, salivation and lacrimation, mydriasis, tachycardia, apnea, jumps in blood pressure.

Neuromuscular disorders: convulsions, increased reflexes - these 2 symptoms are the most common; violation of gait, coordination, paresthesia, muscle tension to rigidity, spasm of masticatory muscles, tremor of the whole body.

Against this background, there are violations of the cardiovascular system, severe myopathy with the destruction of muscle tissue (rhabdomyolysis), the appearance of myoglobin in the urine - appears during protein breakdown, acute renal failure, liver failure, an increase in the content of potassium in the blood, a dangerous form of violation of the ASC in the direction of oxidation (acidosis), aspiration pneumonia, NK, strokes, falling leukocytes and platelets, convulsions. To prevent such a complication, some precautions must be observed: at least 2 weeks must pass between taking drugs of different groups.

The same principle should be observed when prescribing drugs from the same group. An interval of 5 weeks should be after the abolition of Fluoxetine and the appointment of an irreversible MAOI, for the elderly - 8 weeks. Return transfer - 4 weeks.

At the first sign of complications, all medications taken are immediately canceled. Then self-elimination of manifestations during the day can occur. Symptomatic treatment of the condition is also carried out. In severe cases, serotonin antagonists are prescribed; infusion therapy; measures to reduce temperature, mechanical ventilation, lowering blood pressure, muscle relaxants.

Contraindications to the use of SSRIs

Individual intolerance, mania, taking MAOIs, gestation and breastfeeding, epilepsy. There are also no prescriptions for those with a history of antidepressant-induced mania. Contraindication is acute renal failure, liver failure; attacks of glaucoma; the presence of ulcerative lesions of the gastrointestinal tract; alcohol and other intoxications.

withdrawal syndrome

The withdrawal syndrome is characteristic not only for SSRIs, but also for all antidepressants. In this case, somatic and mental symptoms are noted. They occur with a sharp simultaneous withdrawal of the drug and are difficult to tolerate by patients.

They pass only in 5-6 weeks. Moreover, the shorter the half-life of the drug taken, the more severe the withdrawal syndrome. Especially this syndrome occurs when taking Paroxetine, then comes Fluvoxamine.

What symptoms can be? Weakness and cephalgia, dizziness, nausea and vomiting, diarrhea, muscle pain, paresthesia, tremor, insomnia, unsteady gait, unreasonable anxiety and irritability, agitation, mood swings, panic attacks and arrhythmias.

Anxiety and depression give the same withdrawal syndromes. In such cases, the drug is resumed and its gradual cancellation is made. To prevent this syndrome, drugs should be gradually discontinued, within a month, at least.

Criticism

Many foreign critics argue that there is no evidence that the root of depression is a lack of serotonin. The serotonin hypothesis is therefore incorrect. The same distrust is caused by the effects of SSRIs. But manufacturers and advertisers widely use this thesis. A number of well-known American and English psychiatrists question the serotonin theory too.

There is a lot of evidence for this opinion. Some clinical studies have shown a relationship between taking fluoxetine, sertraline and paroxetine and the appearance of hostility, a tendency to self-destruction, and aggression in patients. Many pharmaceutical companies that make SSRIs hide these facts and play them down.

This has been discovered by independent researchers and FDA (Fundamental Quality Administration) food products and medicines - Food and Drug Administration). They give such side effects a very vague name - emotional lability. It is noted that the number of suicides in America has increased since the late 1950s, when the first antidepressants began to appear on the market.

There were a lot of sensational cases about this in 2000. litigation for, for example, the side effects of Prozac has reached $50 million. WHO data also note that patients treated with paroxetine experience very severe withdrawal symptoms when compared with other antidepressants. GlaxoSmithKline, the company that makes paroxetine, has long and stubbornly denied that the drug is addictive.

The same applies to other manufacturers of SSRIs - Eli Lilly and Company and Pfizer. In 2002, the FDA issued a warning, and the International Federation of Pharmaceutical Manufacturers' Associations announced on TV in the United States about such fraud by pharmaceutical companies. Hundreds of lawsuits have been filed, although the companies assured that such manifestations are the result of depression itself or caused by an overdose of an antidepressant.

The BBC materials in 2002 also said that paroxetine causes aggression, a tendency to self-harm, suicide. Lawyers for the plaintiffs reviewed the companies' internal records and found that GlaxoSmithKline, as early as 1989, had evidence of an 8-fold increased risk of suicide when taking its products.

The fact is that the reuptake of serotonin is not as straightforward and good as it seems at first glance. Presynaptic neurons turn out to be unclaimed and they secrete less serotonin, while postsynaptic neurons are already insensitive to it.

After 4-5 weeks of taking selective inhibitors, the efforts of the brain to compensate and equalize the biochemical situation are not effective, and side effects appear. For example, excess serotonin leads to mania. To remove side effects, new drugs are prescribed all the time and long-term negative changes appear in the work of neurons.

When the drug is discontinued, serotonin rapidly decreases, and there is nothing to compensate for it. Presynaptic synapses no longer secrete it sufficiently, and postsynapses do not have the required number of receptors. Suicidal ideation and mania often occur in adolescents and children after the use of SSRIs. Suicidal behavior in adults is still under study. All this suggests that when prescribing SSRIs, the doctor should approach each patient individually and constantly monitor his condition. Today, SSRIs remain quite popular antidepressants and are widely prescribed in Russia.

For citation: Yavorskaya S.A. The use of selective serotonin reuptake inhibitors in neurological practice // BC. 2007. No. 5. S. 429

In modern medicine, the problem of depression is considered among the most important. The urgency of the problem is determined by the prevalence of depressive disorders in the general population, the tendency to their protracted and chronic course, and often by a high suicidal risk. The increase in the number of patients with depressive disorders has an increasing impact on the socio-psychological and economic aspects of the life and health of society. Depressive states are by now one of the most common mental disorders - its prevalence by the 90s of the twentieth century in the population of Europe and the United States was 5-10%. According to WHO forecasts, by 2020 depression will become one of the main causes of disability. Depressive disorders that develop in somatic and neurological diseases reduce the quality of life of patients, affect the course and prognosis of the disease. Often, depression comes under the guise of dementia and conversion disorders, which can make it difficult to recognize. Late diagnosis of depressive and depressive-anxiety disorder, delayed treatment contribute to the chronic course of the disease and aggravation of the severity of the condition and often lead to difficulties in further therapy. At the same time, the representation of depression in patients with somatic and neurological pathologies has not been sufficiently studied, and the literature provides quite heterogeneous information regarding its frequency and severity.

The development of depression can be situationally determined, but in neurological patients it is usually caused by organic brain damage or imbalance of neurotransmitter systems. Patients with chronic neurological diseases are more prone to depression than patients with somatic pathology. There are many neurological diseases that can cause depression. This disorder is one of the common symptoms in Parkinson's disease, Parkinson's syndrome, acute and chronic cerebrovascular diseases, degenerative dementia, pain syndromes, multiple sclerosis, brain tumors. Encephalopathy, which develops in the late stages of hepatic and renal failure, a number of endocrine, hematological and systemic disorders, with alcoholism, is also often accompanied by the development of depression, which is associated with hypoxic, dysmetabolic and toxic brain damage. Depressive disorders may be due to long-term medication. The list of these drugs is quite large, and many are very widely used. These are b-blockers, calcium channel blockers, corticosteroids, anabolic steroids, oral contraceptives, cardiac glycosides, barbiturates, clonazepam. Antipsychotic depression occurs against the background of long-term use of large doses of antipsychotics (buterophenones, fluphenazine, chlorpromazine, risperidone) and is accompanied by extrapyramidal disorders. Depressive disorders can occur under the guise of dementia and may accompany its development. At the same time, depression is often observed in vascular dementia and less often in Alzheimer's disease.
The modern pathomorphosis of depression has led to a change in its clinical picture, an increase in the frequency of atypical, latent, erased forms. Currently, the proportion of typical cases is only 10%, and the majority of depressions are atypical. In the practice of a neurologist, depression most often appears under the guise of autonomic dystonia syndrome, chronic pain syndromes, insomnia, and neuroendocrine disorders. The most striking manifestations of the syndrome of vegetative dystonia include vegetative crises (panic attacks). Another very common mask of depression is chronic pain syndromes, including in children. Depression accompanies and may intensify conversion disorders within psychogenic and psychoorganic diseases.
The mechanisms underlying depression are currently being actively studied. It is shown that not only the limbic system, but also cortical structures are involved in emotional reactions. Particular importance is attached to the frontal lobes of the brain. In a number of mental disorders that were traditionally considered “functional”, morphological changes in the nervous tissue were revealed, not only at the microstructural level (in the form of atrophy of synapses, shortening of dendrites and death of some neurons), but also at the macrostructural level (in the form of a decrease in the volume of the hippocampus and some other parts of the brain). Moreover, in recent years it has been shown that pathological processes in the brain can be partially reversible under the influence of therapy with drugs that have neurotrophic and neuroprotective properties. According to some reports, depression reveals signs of hyperreactivity of the hypothalamic-pituitary-adrenal system, there is also evidence of an increase in the number of neurons secreting corticotropin-releasing factor. In 33-66% of patients with depression, hyperplasia of the adrenal glands is noted, and the content of cortisol is increased and positively correlates with the severity of the condition. Chronic hypercortisolemia contributes to the formation of insulin resistance, arterial hypertension, hyperproduction of steroids, hyperglycemia, hypercholesterolemia, which increase the risk of cardiovascular complications. According to experimental data, in situations of chronic pain, emotional or social stress (which are models of depression), the volume of the hippocampus is statistically significantly reduced (up to 10%, as in patients with depression), the number of granule cells in the dentate gyrus decreases, and in the fields CA1 and CA3 of the hippocampus the size of the bodies of pyramidal cells decreases and atrophy of their dendrites develops (up to 50% of the length), which leads to a violation normal functioning limbic system and its connections with other parts of the brain. Thus, the consequences of chronic stress and affective disorders in humans, as well as behavioral disorders similar to depression in animals, are associated with damage and death of brain cells. These findings are consistent with the notion that stress-induced anxiety disorders may not only precede, but also cause, at least some forms of depressive disorders. The predominant localization of morphological changes, primarily in the limbic system, the basal ganglia, and the rostral cortex, can explain the disorders of both emotional, motor and cognitive functions that develop during depression. It is assumed that these morphological changes are a consequence of the cytotoxic action of a number of agents, primarily excitatory amino acids and possibly calcium. The development of excitotoxicity is largely facilitated by the increased content of corticosteroids (mainly cortisol) noted in depression, and a deficiency of g-aminobutyric acid. It is possible that a number of disorders are based on neurotransmitter dysfunctions, most likely associated with insufficiency of central serotonergic and noradrenergic structures. Some authors also mention the role of hypoglycemia and a possible decrease in cerebral blood flow in the pathogenesis of depression. Of particular importance in the pathogenesis of depression in the elderly is given to vascular lesions of subcortical-frontal connections with the occurrence, in addition to depression, of executive dysfunctions, psychomotor retardation, and apathy. Currently, several pathophysiological mechanisms of the influence of depression on the state of the cardiovascular system in the elderly are being considered. One of the main pathological processes in depressive disorders is the imbalance of the autonomic nervous system with the activation of the sympathetic division. Increased release of catecholamines leads to an increase in myocardial oxygen demand due to an increase in heart rate, blood pressure and force of contraction of the myocardium. It has been established that the appearance of depression in patients with diseases of the cardiovascular system is accompanied by a significant decrease in heart rate variability, reflecting the deterioration of regulatory mechanisms and a decrease in the adaptive capacity of the body in response to stress.
The achievement of neuroscience in recent years has been the proof that the destructive processes that occur in affective disorders are partially reversible under the influence of successful therapy with drugs that exhibit neurotrophic and neuroprotective properties. Restoration of brain tissue and its functions is associated with the reorganization and formation of new synapses, elongation and growth (sprouting) of dendrites and axons with neurogenesis. The effect of antidepressants is not limited to their regulatory effect on the content of monoaminergic neurotransmitters in the synaptic cleft and presynaptic structures, as well as on the number and sensitivity of postsynaptic receptors, but also extends to intracellular cascades of neurochemical processes. One of the compounds formed in this case is the cAMP-element-binding protein (CREB), which activates the “late” gene for brain derived neurotrophic factor (BDNF), which, in turn, enhances the expression of the gene for the main cytoprotective protein bcl-2, suppressing apoptosis, which contributes to the recovery and survival of neurons.
Symptoms of depression may be obvious. Along with depression (in typical cases in the form of vital melancholy), depression includes ideational and motor inhibition with a decrease in motivation for action or anxious excitement (up to agitation). Mental hyperalgesia (mental pain) characteristic of depressive patients is associated with guilt, low self-esteem, suicidal thoughts, and painful physical self-feeling - with "somatic" symptoms, such as sleep disorders with difficulty falling asleep and early awakenings; a sharp decrease in appetite and body weight; decrease in libido and menstrual irregularities up to amenorrhea, etc. Decreased mood usually persists throughout the entire depressive attack. A typical sign of depression is also a circadian rhythm with improvement or (rarely) worsening of well-being in the evening. Atypical manifestations of depression are the absence in some cases of complaints of low mood or the patient's fixation on excitability or anxiety, and not on low mood. Pain and psychosomatic disturbances can also be atypical manifestations of depression. The criteria for diagnosing masked depression are: frequent discrepancy between the patient's complaints and the nature of morphological changes; the possibility of the absence of objective signs of a somatic disease; periodicity (seasonality) of the manifestation of the symptoms of the disease; relapsing course with a possible change in the phases of exacerbations and relapses; connection of well-being with the biological rhythm of physiological functions (patients feel better in the evening); frequent re-applying medical care; insufficient effectiveness of symptomatic therapy or lack thereof; improvement in well-being while taking antidepressants.
The identification of depressive disorders is greatly facilitated by the use of psychometric scales and tests, the use of which can reduce the doctor's time spent on examination. The best known among the subjective psychometric scales for screening depression are the Hospital Anxiety and Depression Scale, the Tsung Scale, the Beck Depression Inventory [A. Beck, 1961].
The basis for diagnosing depression is an assessment of the anamnesis and clinical data. The results of paraclinical examination methods (including neuroimaging) are not of great importance, they only help to exclude neurological or somatic causes of the disease. The detection rate of depression by general practitioners does not exceed 50%. AT some degree This is due to the low specificity clinical manifestations of this disease. For example, weight loss and increased fatigue can be observed not only with depression, but also with oncological diseases, diabetes and thyroid disease.
In neurological practice, the diagnosis of depression is difficult not only because of the frequent combination of neurological symptoms and depression in the case of damage to the central nervous system, but also because of the influence of a neurological disease on the emotional behavior of the patient. Thus, the slowness and paucity of movements characteristic of parkinsonism, combined with a violation of the rhythm and intonations of speech, makes it difficult to correctly assess the emotional status. This task is even more complicated in patients with severe cognitive or speech disorders of various origins. Complaints about chronic pain- one of the most frequent "masks" of depression. The combination of depression and chronic pain syndromes is observed in 50-60% of patients.
Antidepressant therapy is the main treatment for depression. The question of starting drug therapy becomes relevant if the symptoms persist for 2-4 weeks or more. It should be noted that about 50% of cases of therapy failure are associated with its inadequate use. The most common mistakes, in addition to late initiation of treatment, as well as insufficient consideration of clinical indications and contraindications to the drug, are template (without taking into account individual characteristics) low-dose therapy or, conversely, frequent change, "juggle" drugs without observing the exposure of the desired duration, or premature cancellation of therapy, or ignoring the patient's medical appointments. As is known, in many cases the clinical effect develops gradually, and the suppression of actual psychopathological symptoms does not yet mean the achievement of a stable remission and the end of treatment. The effect of antidepressants usually does not appear immediately, but after a few weeks (usually from 3 to 6) after the start of treatment, which should be informed to the patient in a timely manner. After regression of symptoms of depression, therapy is continued for 4-5 months. Treatment failure associated with true drug resistance is very rare, therefore, only if the effect of the selected drug in an adequate dose does not appear after 6-8 weeks, they switch to an antidepressant of another group. It is important to emphasize that in most cases, the lack of effect from treatment is not due to true drug resistance, but to an insufficient dose or short duration of therapy, as well as non-compliance with medical prescriptions. The possibilities of psychotherapy, which, if necessary, can be supplemented with antidepressants, are currently being discussed, but the effectiveness of such a therapeutic approach requires further study.
In neurological practice, one often has to deal with the restrictive tactics of using antidepressants. Of those with an epidemiological diagnosis of depression in outpatient practice (who scored more than 18 points on the depression scale of the Center for Epidemiological Research), 72.2% of patients received treatment. However, drugs are usually used plant origin and tranquilizers. Only 8.7% of patients with depression took antidepressants. If the drugs of this group were nevertheless prescribed, then, as a rule, in fairly low daily doses. In the Russian multicenter study Compass, it was found that neurologists are only slightly more likely than other specialists (therapists, cardiologists) to prescribe any therapy for depressive conditions in general (74% versus 67.2 and 67.8%, respectively) and thymoleptics, in in particular (14.1% against 7.2 and 6.5% respectively). Thus, the role of drug treatment of depression needs further discussion.
Antidepressants are drugs that contribute to the reduction of ideational, motor and somato-vegetative disorders caused by depression. The basis of the clinical effect of modern antidepressants is the correction of the functions of the serotonergic and noradrenergic systems of the brain. Very convenient is the classification of antidepressants according to the mechanism of neurochemical action (Table 1). Among the clinical classifications of antidepressants, the convenient and simple classification of P. Kilgolts with the release of drugs with a predominantly sedative, stimulating or balanced effect has become the most widespread (Table 2). The scientific development of modern antidepressants, on the one hand, is in the direction of increasing the specificity of their biochemical action. In particular, selective agonists and antagonists of monoamine neuroreceptors are synthesized and tested. Substances have been found that selectively act on certain types of receptors (5HT1, 5HT2, and 5HT3 serotonin receptors). Examples are direct agonists of 5HT1a serotonin receptors (flesinoxan, ipsapirone, etc.). At the same time, there is a tendency to develop broad-spectrum drugs for various monoamine systems with minimal effect on receptors, which are associated with the development of side effects (milnacipran, venlafaxine, nefazodone, mirtazapine, duloxetine, etc.). And finally, the mechanism of action of some drugs with thymoanaleptic activity is not directly related to the monoamine system or is not clear enough (for example, tianeptine, alprazolam, S-adenosylmethionine, neuropeptides, etc.).
Among the most studied on the pharmaceutical market over the past two decades, the so-called third-generation antidepressants, which are representatives of a new class of pharmacological agents - selective serotonin reuptake inhibitors, have become widespread. These include, in particular, fluvoxamine.
Unlike tricyclic antidepressants, selective serotonin reuptake inhibitors are more addressed to a wide range of neurotic depressive states. They have a greater spectrum of psychotropic action with fewer side effects. Nuclear variants of the melancholic syndrome of endogenous depression with typical circadian symptoms, severe (psychotic) depression and depressive-delusional states respond worse to therapy with serotonin reuptake inhibitors. On the contrary, depressive states with obsessive-phobic, hypochondriacal and anxiety symptoms of a neurotic level are treated quite successfully. In addition to depression with atypical symptoms, serotonergic antidepressants have been shown to be highly effective in anxiety and obsessive-compulsive disorders in pure form or comorbid with depression, as well as in panic disorder, post-traumatic stress disorder, social phobia, somatoform disorders and other anxiety disorders.
Analysis of a number of randomized trials comparing the clinical effect of a group of selective neuronal reuptake inhibitors with tricyclic antidepressants such as imipramine found similar positive effects of non-selective and selective drugs. When summarizing all the clinical trials, it became clear that selective drugs do not have any clear advantages over the reference tricyclic antidepressants. The negative effects of drugs of these groups differ significantly. For example, sedation, anticholinergic effects, and cardiac arrhythmias are less likely to occur with selective serotonin reuptake inhibitors than with conventional antidepressants. On the other hand, the negative effects of selective neuronal reuptake inhibitors affect the gastrointestinal tract, causing nausea and diarrhea, and can also lead to insomnia, agitation, extrapyramidal disorders (drug parkinsonism) and withdrawal syndrome. When comparing the negative effects of selective neuronal reuptake inhibitors and conventional antidepressants, one cannot help but conclude that one group of negative effects changes to another and there is no difference in the number of people who can take these two groups of antidepressants. Fifty-eight clinical trials studied patients who stopped taking antidepressants and found no significant difference between selective neuronal reuptake inhibitors and conventional antidepressants.
Thus, numerous scientific studies of this group of drugs, including those conducted in comparison with reference tricyclic antidepressants traditionally used in psychiatry and neurology in the treatment of depression (amitriptyline, imipramine, clomipramine, etc.), have shown their high therapeutic efficacy, comparable to tricyclic antidepressants. compounds, with fewer side effects. However, despite belonging to the same group of chemical compounds, the spectrum of antidepressant activity of various selective neuronal reuptake inhibitors has its own characteristics, which determine the predominant indications for their individual use and deserve discussion.
Fluvoxamine is the ancestor of antidepressants of the group of selective serotonin reuptake inhibitors, the first and most widely studied drug in this group. Fluvoxamine is registered in more than 80 countries, has the largest database of clinical trials (among antidepressants), including the description of the results of treatment of 38 thousand patients. To date, more than 5,000 scientific works dedicated to the study of the drug. The drug has been successfully used since 1983 in the treatment of depressive disorders of varying severity, as well as the so-called borderline mental disorders (anxiety, panic, obsessive-compulsive, behavioral, etc., including in children from 8 years old). The mechanism of action of fluvoxamine is associated with selective inhibition of serotonin reuptake by brain neurons and is characterized by a minimal effect on noradrenergic transmission. Fluvoxamine has an unexpressed ability to bind to a-adrenergic, b-adrenergic, histaminergic, muscarinic cholinergic, dopaminergic or serotonergic receptors. Fluvoxamine has pronounced anxiolytic and sedative properties and is the drug of choice for the treatment of depression in combination with anxiety, panic and psychomotor agitation. The drug is also distinguished by moderate psychostimulating activity, resulting in the absence of suicidogenicity, hyperstimulation, increased irritability, and sleep disturbances. The powerful vegetative-stabilizing effect of fluvoxamine is especially important in the treatment of neurotic, somatized depression and dysthymia. The absence of behavioral toxicity does not impair attention, memory or cognitive function. Fluvoxamine is an effective antidepressant in the treatment of depression various types and varying degrees of expression. This is confirmed, in particular, by the data of a meta-analysis, according to which fluvoxamine is the drug of choice in the treatment of patients with severe depression in a hospital setting. In addition, fluvoxamine has been shown to be effective in preventing relapses of depression. After a course of drug treatment, relapses developed three times less often, and the period of remission to the first relapse was twice as long as with placebo. The pronounced antiquering effect of fluvoxamine eliminates or reduces the pathological craving for alcohol. In psychiatric practice, the drug has shown good efficacy in correcting negative (deficient) symptoms in patients with schizophrenia.
In the clinical department of endogenous mental disorders and affective conditions of the Scientific Center for Mental Health of the Russian Academy of Medical Sciences, fluoxetine, fluvoxamine, sertraline and paroxetine were clinically studied in different periods. A total of 129 patients with endogenous depression underwent course treatment with these drugs. Fluvoxamine made it possible to reduce the severity of depression in this group to a mild degree already by the 5th day of treatment, but its “significant” therapeutic effect was recorded after the 14th day (second week) of treatment, and by the end of the course of treatment, the total score for the symptoms of depression according to the Hamilton scale decreased by 64.6%. Fluvoxamine showed a good therapeutic effect equally in depressive states of mild and moderate severity, which, provided it is well studied, makes it the drug of choice for this group of conditions. The thymoleptic effect of fluvoxamine was manifested at the level of 76.1%, while the sedative-anxiolytic and stimulating components of the action of fluvoxamine were almost the same and less profound, they were manifested at the level of 67.8 and 64.5%, respectively. Izmailova I.G. et al. assessed the effect of fluvoxamine in a group of children with tension-type headache. The initial dose of fluvoxamine was 12.5 mg at night, with a further gradual increase in dose of 12.5 mg every two days to the optimal daily dose of 50-75 mg. The course of treatment was 1.5-2 months. The specified pharmacotherapy was combined with massage, psychotherapy, physiotherapy. The clinical effect in the form of a reduction in headache and an improvement in mood, patients began to note by the end of the first week of treatment, no side effects were observed. After 1.5 months of therapy in 25 children, the existing disorders were completely stopped; 5 children showed a decrease in the intensity and frequency of cephalalgia attacks. A dynamic study of the psychovegetative status showed a significant decrease in astheno-vegetative and anxiety-depressive disorders to close to normal levels, which confirms the anxiolytic, antidepressant, vegetotropic and mild anti-asthenic effect of the drug in the pediatric population. Follow-up (6 months) confirmed the preservation of the achieved results in 20 children.
Therapy with antidepressants of various structures has traditionally been used for a long time in chronic alcoholic disease. A number of domestic and European researchers strongly argue in favor of central serotonin deficiency as the main neurochemical mechanism for the development of depression in alcoholism. With the help of antidepressants, it is possible not only to influence depressive disorders, but also to stop the pathological craving for alcohol. And in this regard, selective serotonin reuptake inhibitors, which reduce the pathological craving for alcohol, are most preferable. According to numerous domestic data, it is fluvoxamine, an antidepressant “of a predominantly sedative effect with pronounced not only thymoanaleptic, but also vegetostabilizing and anxiolytic effects” that is most preferable in chronic alcoholism and drug addiction due to the high comorbidity of alcohol depression, anxiety, phobic, somnological, somatovegetative disorders, and also aggressiveness and suicidal behavior.
The good tolerability of fluvoxamine, in particular, the absence of a sedative side effect, allows its use in outpatient practice, without compromising the quality of life of the patient. It is important to emphasize that fluvoxamine is not only the most studied, but also the most economically available drug from the group of selective serotonin uptake inhibitors. The most important condition for the success of treatment is the rational combination of pharmacotherapy with socio-rehabilitation and psychotherapeutic measures, including psycho-educational work with the active involvement of the patient and his relatives in the treatment process.

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Update: October 2018

Depression can be described as general emotional exhaustion. As a rule, this is due to the inability to resolve an important, from the point of view of this person, task. When a person is suppressed by external circumstances and fails to adequately realize their desires and ambitions, the body may well respond with situational depression.

Another common type of depressive disorder is somatic depression. At the same time, mental discomfort results in diseases of internal organs (peptic ulcer, hormonal disorders, cardiovascular problems).

Depressions are also known against the background of fluctuations in the level of sex hormones (during menopause or after childbirth), as a result of prolonged stress, chronic or incurable illness, injury or disability.

In general, depression is irritability multiplied by weakness against the background of a low level of your own pleasure hormones (enkephalins and endorphins) in the brain, which leads to dissatisfaction with yourself and the surrounding reality in the absence of the strength to radically change anything.

Possible workarounds are support from the environment, a specialist (psychiatrist or psychologist) and / or medication. With a favorable set of circumstances, this will help to choose new priorities in life and get rid of the very reason that entailed a painful state of mind.

Medicines used to treat depression are called antidepressants. Their use has made a splash in psychiatry and has significantly improved the prognosis of patients with depression, as well as significantly reduced the number of suicides on the background of depressive disorders.

Antidepressants without a prescription

Today, only the lazy do not deal with depression. Psychologists with pedagogical education, coaches of all stripes, traditional healers and even hereditary sorceresses. All this heterogeneous company nevertheless reads something on the problem and understands that it is unlikely that it will be possible to cure a real clinically pronounced depression simply by talking and laying on hands.

Yes, and many who feel that they have begun to fall into a pit of a depressive state, but are afraid to contact a psychiatrist, do not mind taking drugs that could simply be bought without a prescription at a pharmacy. This is because the system of psychiatric care in our country is still more like a light mixture of the army and the bazaar, because either immediately “registered” or for money!

Let's immediately disappoint the audience with the message that antidepressants today are prescription drugs. If in some commercial pharmacy, in violation of the rules, they sell something without a prescription, then antidepressants do not become OTC from this. They have a lot of serious side effects, so the advisability of taking them, individual selection of dosages should be carried out only by the attending physician.

Unfortunately, simply taking some kind of antidepressant and hoping for a quick release from depression is a hopeless business. After all, there are different types of depression. On the same dosages of the same depression medication, one patient achieves a complete clinical recovery, while another is just beginning to develop suicidal thoughts.

What are the best antidepressants to take

Any sane person understands that it is better to be treated with those drugs that are prescribed by a specialist who understands this, is guided by the standards of treatment, information about the drug and his clinical experience in using the drug.

Turning your own precious body into a testing ground for antidepressants is, at the very least, imprudent. If such a fixed idea has already been visited, then it is better to find some Institute of Psychiatry, where programs for the clinical testing of medicines are regularly held (at least you will receive competent advice and free treatment).

In general, antidepressants are drugs that elevate mood, improve overall mental well-being and also cause emotional uplift without falling into euphoria or ecstasy.

Names of antidepressants

Antidepressants can be divided depending on the effect on the processes of inhibition. There are drugs with a calming, stimulating and balanced effect.

• Calming: Amitriptyline, Pipofezin (Azaphen), Mianserin (Lerivon), Doxepin.
• Stimulants: Metralindol (Inkazan), Imipramine (Melipramine), Nortriptyline, Bupropion (Wellbutrin), Moclobemide (Aurorix), Fluoxetine (Prozac, Prodel, Profluzak, Fluval).
• Balanced drugs: Clomipramine (Anafranil), Maprotiline (Ludiomil), Tianeptine (Coaxil), Pyrazidol.

All of them are divided into seven large groups, each of which has its own indications and preferences for certain manifestations of depression.

Tricyclic antidepressants

These are first generation drugs. They interfere with the reuptake in the nerve synapse of norepinephrine and serotonin. Due to this, these mediators accumulate in the nerve junction and accelerate the transmission of the nerve impulse. These funds include:

• Amitriptyline, Doxepin, Imipramine
• Desipramine, Trimipramine, Nortriptyline

Due to the fact that this group of drugs has quite a lot of side effects (dry mouth and mucous membranes, constipation, difficulty urinating, heart rhythm disturbances, hand tremors, visual impairment), they are used less and less.

Selective serotonin reuptake inhibitors

• Sertraline - Aleval, Asentra, Zoloft, Seralin, Stimuloton
• Paroxetine - Paxil, Reksetin, Adepress, Pleasil, Actaparoxetine
• Fluoxetine - Prozac, Fluval, Prodel
• Fluvoxamine - Fevarin
• Citalopram - Oprah, Cipralex, Selectra

Such antidepressants are preferred for neurotic depression, accompanied by fears, aggression,. Side effects of these medicines not extensive. The main one is nervous excitement. But large doses or an overdose can lead to the accumulation of serotonin and serotonin syndrome.

This syndrome is manifested by dizziness, trembling of the limbs, which can develop into convulsions, increased blood pressure, nausea, diarrhea, increased motor activity, and even mental disorders.

That is why popular and good antidepressants like fluoxetine (Prozac), which enterprising pharmacists sometimes sell without a prescription, if taken uncontrollably or in excess of doses, can bring a person from banal mood disorders to a convulsive seizure with loss of consciousness, a hypertensive crisis or cerebral hemorrhage, or even all the way to the “moving roof”.

Selective serotonin and norepinephrine reuptake inhibitors

They work similarly to the drugs of the previous group. Milnacipran and venlafaxine are indicated for depression with obsessive-compulsive disorder or phobias. Of the side effects, they are characterized by headache, drowsiness, anxiety.

Heterocyclic antidepressants

Heterocyclic antidepressants (with receptor action) are preferred in the elderly and in combinations of depression with sleep disorders. Cause drowsiness, may increase appetite and contribute to weight gain.

• Mianserin (Lerivon), Nefazodon
• Mirtazapine (Remeron), Trazodone (Trittico)

Monoamine oxidase inhibitors

Drugs of choice for depressive disorders with panic attacks, fear of open spaces, with psychosomatic manifestations (when depression provokes internal diseases). They are divided into:

• irreversible - Tranylcypromine, Phenelzine
• reversible - Befol, Pyrazidol (Normazidol), Moclobemide (Aurorix)

Serotonin reuptake activators - new generation antidepressants

Able to cope with the symptoms of depression in one week. They are effective in somatized depression with palpitations, headaches. They are also used for depression of an alcoholic nature or depression with psychosis against the background of cerebrovascular accidents. But these drugs can be addictive like opiates, these include: Tianeptine (Coaxil).

These powerful over-the-counter antidepressants were no longer sold after several years across the post-Soviet space many lovers of inexpensive highs misused them. The result of such experiments was not only multiple inflammation and thrombosis of the veins, but also a shortening of life up to 4 months from the start of systematic use.

Antidepressants of different groups

• Buspirone (Spitomin), Nefazadone
• Heptral (see)
• Bupropion (Wellbutrin)

List of new generation antidepressants

The most popular today are drugs from the group of selective serotonin and norepinephrine reuptake blockers.

• Sertraline(Serlift, Zoloft, Stimuloton) is the "gold standard" in the treatment of depression today. It is compared with other drugs in terms of effectiveness. It is preferred in the treatment of depression associated with overeating, obsessions and anxiety.
• Venlafaxine(Venlaxor, Velaksin, Efevelon) - prescribed for depression against the background of more severe mental disorders (for example, schizophrenia).
• Paroxetine(Paxil, Reksetin, Adepress, Cyrestill, Pleasil) - effective for mood disorders, melancholy and inhibited depression. Also removes anxiety, suicidal tendencies. Treats personality disorders.
• Opipramol- the best option for somatized and alcoholic depression, as it inhibits vomiting, prevents convulsions, stabilizes the autonomic nervous system.
• Light antidepressants are fluoxetine (Prozac), which are somewhat weaker but milder than other serotonin reuptake inhibitors.

Antidepressants and tranquilizers: difference between groups

In addition to antidepressants, tranquilizers are also used in the treatment of depression:

• This group of medicines eliminates the feeling of fear, emotional stress and anxiety.
• At the same time, drugs do not violate memory and thinking.
• Additionally, tranquilizers are able to prevent and remove convulsions, relax muscles, and normalize the functioning of the autonomic nervous system.
• In medium doses, tranquilizers reduce arterial pressure, normalize heart rate and blood circulation in the brain.

Thus, tranquilizers differ from antidepressants mainly by the opposite effect on the autonomic nervous system. Also, tranquilizers have the greatest effect on fear and anxiety, which can be removed even with a single dose, and antidepressants require a course of treatment. Tranquilizers are more likely to cause dependence and their withdrawal syndrome is more pronounced and severe.

The main side effect of the group is addiction. Also, drowsiness, muscle weakness, lengthening of reaction time, unsteady gait, speech disorders, urinary incontinence, weakening of sexual desire may also develop. In case of an overdose, paralysis of the respiratory center and respiratory arrest may develop.

With the abrupt cancellation of tranquilizers after their long-term use, a withdrawal syndrome may develop, manifested by sweating, trembling of the extremities, dizziness, sleep disturbances, intestinal dysfunctions, headache, drowsiness, increased sensitivity to sounds and smells, tinnitus, reality perception disorders, depression.

An Overview of Herbal Antidepressants (Over the Counter)

Often, antidepressants include herbal sedatives, which are not any antidepressants:

• Preparations of Valerian, Melissa, Peppermint, Motherwort
• Combined tablets - Novopassit, Persen, Tenoten - These are sedatives that will not help with depression.

The only thing medicinal plant with antidepressant properties - it is perforated and preparations based on it, which are prescribed for mild depressive states.

There is one thing: to eliminate the manifestations of depression, synthetic drugs that are ten times more effective than St. John's wort, you have to drink courses for several months. Therefore, St. John's wort will have to be brewed, insisted in kilograms, and consumed in liters, which, of course, is inconvenient, and inappropriate, although it can somewhat distract from sad thoughts about the frailty of everything during depression.

The pharmacological industry offers St. John's wort in tablet form without a prescription in as a lung an antidepressant (nootropic) for psychovegetative disorders, neurotic reactions, mild depressive states - these are Deprim, Neuroplant, Doppelherz nervotonik, Negrustin, Gelarium. Since the active substance in the preparations is the same, contraindications, side effects, interaction with other drugs of these drugs are similar.

Deprim Ingredients: dry standardized extract of St. John's wort. It has a pronounced sedative effect, since the active substances of St. John's wort - pseudohypericin, hypericin, hyperforin and flavonoids have a positive effect on the functional state of the central nervous system and the autonomic nervous system. Increases physical activity, improves mood, normalizes sleep. Indications: sensitivity to weather changes, mild depression, anxiety, Contraindications: severe depression, pills are contraindicated for children under 6 years old, capsules up to 12 years old, hypersensitivity - allergic reactions to St. Dosage: from 6 to 12 years only under the supervision of a physician, 1-2 tablets in the morning and evening, for adults, 1 capsule or tablet 1 r / day or 3 r / day, possibly 2 tablets 2 times a day. The effect occurs after 2 weeks of taking, you can not take a double dose in case of missing a dose. Side effects: constipation, nausea, vomiting, anxiety, fatigue, pruritus, skin redness, photosensitivity - simultaneous use of the drug and sunbathing can lead to (see). Tetracyclines, thiazide diuretics, sulfonamides, quinolones, piroxicam especially increase photosensitivity. Overdose: weakness, drowsiness, side effects increase. Special instructions: the drug should be carefully prescribed simultaneously with other antidepressants, oral contraceptives (see), it is not prescribed simultaneously with cardiac glycosides, cyclosporine, theophylline, indinavir, reserpine. Enhances the effect of analgesics, general anesthesia. Alcohol, sun exposure and other UV exposure should be avoided while taking. If after a month of taking there is no improvement, the reception is stopped and you should consult a doctor.

Neuroplant 20 tab. 200 rub. Ingredients: dry extract of St. John's wort, ascorbic acid. Indications and contraindications similar to the drug Deprim. In addition, Neuroplan is strictly contraindicated for children under 12 years of age, for women during pregnancy and lactation, with increased photosensitivity, it is prescribed with caution in diabetes mellitus. Dosage: It is better to take before meals, do not chew, but take 1 tablet whole with water. 2-3 r / day, also if there is no effect for several weeks of administration, the drug is canceled and the treatment is adjusted. Side effects: indigestion, skin allergic reactions, psycho-emotional stress, apathy,. Concomitant use with other drugs: reduces the concentration of hormonal contraceptives and increases the risk of . When taken simultaneously with antidepressants, the likelihood of side effects increases - causeless fear, anxiety, vomiting, nausea, as well as a decrease in the effect of amitriptyline, midazolam, nortriptyline. When taken with drugs that increase photosensitivity, the risk of photosensitivity increases. Neuroplant reduces the therapeutic effect of indinavir and other HIV protease inhibitors, drugs used to treat cancer that inhibit cell growth.

Doppelhertz nervotonic 250 ml. 320-350 rub. Ingredients: Elixir Doppelherz Nervotonik - liquid extract of St. John's wort, as well as cherry liqueur concentrate and liqueur wine. Indications and contraindications Deprim and Neuroplant are similar. Additionally: with caution, Doppelgerz Nervotonik is taken for diseases of the brain, for liver diseases, craniocerebral injuries, and for alcoholism. Side effects: rarely allergic reactions, in persons with fair skin with a tendency to photosensitivity - photosensitivity reactions. Application: 3 r / day, 20 ml. after eating for 1.5 -2 months, if there is no effect, you should consult a doctor. Special instructions: as with other drugs with St. John's wort extract, interactions with other drugs should be taken into account when taken simultaneously. The drug contains 18 vol.% ethanol, that is, when taking the recommended dose, 2.8 g of ethanol enters the body, therefore, driving Vehicle and one should refrain from working with other mechanisms that require the speed of psychomotor reactions (driving a car, working as a dispatcher, working with moving mechanisms, etc.)

Negrustin Capsules Negrustin - dry extract of St. John's wort Negrustin solution - liquid extract of St. John's wort Indications, contraindications and side effects similar to other preparations of St. John's wort. Dosage: children over 12 years old and adults 1 capsule 1-2 r / day or 3 r / day, 1 ml. solution, the course of therapy is 6-8 weeks, possibly repeated courses. Capsules can be taken with meals, washed down with liquid, the solution can also be taken diluted with meals, or not diluted. Special instructions: As with other drugs with the active ingredient of St. John's wort extract, care should be taken when combined with the drugs listed above. Negrustin's solution contains sorbitol and 121 mg of it is supplied at each dose. Also, the drug is prescribed with caution to persons with fructose intolerance. Negrustin, with the simultaneous use of alcohol or tranquilizers, affects the psychophysical abilities of a person (driving vehicles and working with other mechanisms).

Gelarium Dragee Gelarium Hypericum - dry extract of St. John's wort herb. Indications, contraindications, side effects, interaction with other drugs similar to all drugs with St. John's wort. Application: 1 tablet 3 r / day over 12 years and adults, a course of at least 4 weeks, during a meal, drinking water. Special instructions: the interval between taking the above drugs (when taken simultaneously) should be at least 2 weeks; in case of diabetes, it should be borne in mind that a single dose contains less than 0.03 XE.

In pharmacy chains, phytopreparations with St. John's wort are widely represented, the price is 20 filter bags or 50 gr. dry matter 40-50 rubles.

Antidepressants

Serotonin and norepinephrine reuptake inhibitors (tricyclic antidepressants and selective inhibitors):

Mechanism of action: increase noradrenergic and serotonergic activity as a result of suppression of the reuptake of both neurotransmitters; also have anticholinergic, antihistamine action and antagonism to alpha-adrenergic receptors.

Amitriptyline

Imipramine

Clomipramine

Opipramol

Doxepin

Dibenzepine

Nortriptyline

melitracene

Trimipramine

Amoxapine

Butriptyline

Lofepramine

Dosulepin

Maprotiline

Fluorocyzine

Desipramine

Viloxazine

Venlafaxine

Irreversible non-selective monoamine oxidase inhibitors:

Mechanism of action: increase noradrenergic and serotonergic activity, suppressing the destruction of serotonin and norepinephrine by inhibiting the enzyme - monoamine oxidase. Due to the non-specific action of drugs (inhibition of monoamine oxidase type A and type B), it is necessary to follow a tyramine-free diet, due to the possibility of developing "cheese reactions". It is also impossible to combine MAOIs with SSRIs due to the possibility of developing serotonin syndrome. SSRIs can be prescribed after a 2-week period has elapsed since the last intake of MAOIs.

Hydrosine derivatives:

Nialamide

Non-hydrozine:

Phenelzine

Tranylcypromine

Isocarboxazid

Reversible selective monoamine oxidase type A inhibitors:

Mechanism of action: they increase noradrenergic and serotonergic activity, suppressing the destruction of serotonin and norepinephrine by inhibiting monoamine oxidase type A, and the inhibition of the enzyme is reversible. In this regard, the need for a tyramine-free diet disappears. However, it is not recommended to prescribe type A MAOIs in combination with SSRIs.

Moclobemide

pyrazidol

Tetrindol

Selective serotonin reuptake inhibitors:

Mechanism of action: it is based on the suppression of serotonin rebtake systems, as a result of which it accumulates in the synaptic cleft.

Trazodone

fluoxetine

fluvoxamine

Sertraline

Paroxetine

Citalopram

Minaprin

Selective dopamine reuptake inhibitors:

Mechanism of action: it is based on the suppression of rebtake systems of dopamine, as a result of which it accumulates in the synaptic cleft.

Nomifenzine

Amineptine

Bupropion

Selective norepinephrine reuptake inhibitors:

Mechanism of action: it is based on the suppression of norepinephrine rebtake systems, as a result of which it accumulates in the synaptic cleft.

Tomoxetine

Pizoxetine

Alpha-2 receptor blockers:

Mechanism of action: Refers to alpha-2 receptor antagonists. Blocking these presynaptic receptors increases the release of norepinephrine and serotonin.

Mirtazapine

Mianserin

Other antidepressants:

Nefazodon. Mechanism of action: has a strong antagonism to serotonin receptors. Receptor antagonism is hypothesized to enhance serotonergic transmission through postsynaptic serotonin receptors, resulting in an antidepressant effect.

Tianeptine. Mechanism of action: stimulates the reuptake of serotonin at the presynaptic level. Tianeptine corrects the stress-induced increase in adrenaline release and increases extracellular dopamine content in the prefrontal cortex. In addition, stress-induced excitation of the HPA system is stopped.

Classification of antidepressants by pharmacological action:

Stimulant antidepressants:

Imipramine (melipramine, tofranil, priloygan)

Nortriptyline (Aventil, Psychostyle, Nortrilene)

Viloxazine

Desipramine (pertofran, petilil, norpramine)

Nialamide (Nuderal, Novazid)

Tranylcypromine (transamine, parnot)

Phenelzine (nardil)

Inkazan (Metralindol)

Moclobemide (Aurorix)

Fluoxetine (Prozac, Prodel)

Sertraline

Minaprin (cantor)

Amineptine (survector)

Bupropion

Tomoxetine

Sedative antidepressants:

Fluorocyzine

Amitriptyline (Laroxil, Elavil, Damilene, Triptizol)

Azaphen (pipofezin)

Amoxapine (moxadil, azendin, demolox)

Doxepin (sinequan, novoxapin, aponal)

Opipramol (Insidon, Pramalon)

Trimipramine (surmontil, gerfonal, sapilent)

Butriptyline (evaden)

Mianserin

Mirtazapine (remeron, mepirzapine)

fluvoxamine

Trazodone (deseryl, trittiko, pragmarel)

Nefazodon (serzon)

Balanced antidepressants:

Clomipramine (Anafranil, Hydifen)

Dosulepin (dothiepin, protiaden, idom)

Melitracen (Trausabun, Adaptol, Metraxil)

Lofepramine (Gamonyl, Thymelite)

Maprotiline (Ludiomil)

Venlafaxine

Sertraline

Paroxetine

Tianeptine (stablon, coaxil)

Pyrazidol (Pirlindol)

Antipsychotics

Mechanism of action: the antipsychotic effect of neuroleptics is due to the blocking of central dopamine receptors. Some neuroleptics also block adrenergic and serotonin receptors. In more detail, the mechanism of action will be analyzed using the example of chlorpromazine.

Phenothiazine derivatives (typical antipsychotics):

Aminazin

Propazine

Levomepromazine (tisercin)

Alimemazine

Meterazine

Etaperazine

Metophenazate

Triftazin

Fluorphenazine

Fluorphenazine Decanoate

Thioproperazine

Pipothiazine

Periciazine

Thioridazine

Thioxanthene derivatives (typical antipsychotics):

Chlorprothixene

Zuclopenthixol:

Clopixol Acufaz

Clopixol Depot

Clopixol

Flupentixol:

Fluanxol

Fluanxol Depot

Fluanxol Drops

Buterophenone derivatives (typical antipsychotics):

Haloperidol

Trifluperidol

Droperidol

Benperidol

Diphenylbutylpiperidine derivatives (typical antipsychotics):

Fluspirilen (Orap)

Penfluridol

Indole derivatives (typical antipsychotics):

Carbidine

Dibenzodiazepine derivatives (atypical antipsychotics):

Azaleptin (Clozapine)

Cholanzapine

Seroquel

Substituted benzamides (atypical antipsychotics):

Sulpiride

Sultopride

Prosulpin

Benzisoxazole derivatives (atypical antipsychotics):

Rispolept

Anxiolytics

Excite benzodiazepine receptors, which are GABA-benzodiazepine-chlorionoform, located on the postsynaptic membrane of the neurons of the limbic system, hippocampus, hypothalamus. As a result, a channel for chloride ions is formed in the CPM, its concentration increases, which leads to allosteric activation of GABA receptors, and as a result, the duration of action of the inhibitory mediator GABA is prolonged. These receptors are found in both the spinal cord and skeletal muscles. As a result of their activation, the effect of muscle relaxation is observed.

Benzodiazepine derivatives:

Chlosepides

Phenazepam

Lorazepam

Bromazepam

Gidazepam

Clobazam

Alprazolam

Tetrezepam

Carbamic esters of substituted propanediol:

Meprotan

Diphenylmethane derivatives:

Oxylidine

Trioxazine

Tofisopam

Sedatives

Rhizomes with valerian roots

Valocormid

Valosedan

Corvalol

Valocordin

motherwort herb

stressplant

Sodium bromide

Potassium bromide

Bromocamphor

Nootropic drugs

Piracetam

Aminalon

Sodium hydroxybutyrate

Pantogam

Picamilon

Pyriditol

Cinnarizine

Cognitive

Cerebrolysin

Normothymic drugs

lithium carbonate

Lithium hydroxybutyrate

Carbamazepine

Psychostimulants

Arylalkylamines:

Sidnocarb

Benzimidazole derivatives:

Fundamentals of adequate use of drugs in psychiatry

V. Kozlovsky

The adequacy of the drug therapy is of great importance, given the rich choice of drugs. There is no doubt that now in any medical specialty this issue is quite acute. Violation of the rational use of drugs is not always noticeable when it comes to the treatment of chronic diseases or when it is difficult to objectify the dynamics of the treatment process. These branches of medicine include psychiatry, in which the question of the correct prescription of individual drugs and even entire classes is most acute. This is due to the fact that the number of new drugs is constantly growing, the effect of their use develops rather slowly, and the spectrum of their psychotropic activity often does not fit into the usual patterns of action of classical drugs. As an illustration of alternative indications, we can recall the recommendations for prescribing antidepressants from the group of serotonin reuptake inhibitors in addition to depression in various anxiety disorders, the use of atypical neuroleptics in depressive states or anticonvulsants and calcium channel blockers in bipolar disorders, etc., there are many examples of this.

The purpose of this work was to consider the basic principles of rational therapy for mentally ill patients. First of all, a few words about the meaning of this question. As is known, the adequacy of prescribing drugs is associated with the doctor's actions in accordance with two areas that determine the effectiveness of therapy: pharmacokinetics and pharmacodynamics. Compliance general rules pharmacokinetics is aimed at achieving therapeutic concentrations of drugs at the target point, and pharmacodynamics - at the choice of the drug in accordance with the mechanism of its action and the specifics of the pathology.

Issues of psychopharmacology related to the observance of the general principles of pharmacokinetics are rarely considered in the scientific press. This is probably due to the fact that the chemical structure, which determines the chemical and physical properties of all psychotropic drugs, must always satisfy the main criterion of "psychotropy" - solubility in lipoids. The latter is directly related to the distribution of drugs in the body and their penetration into the CNS through the blood-brain barrier (BBB). It should be noted that the concept of the BBB implies the presence of not a static formation, but a functionally active system, the adequate operation of which depends on the state of the organism as a whole and at the same time is itself capable of controlling the normal course of physiological processes. For example, it is well known that the permeability of the BBB increases dramatically with convulsions, arterial hypertension, allergic and infectious injuries. In addition, it is well known that intravenous administration of hyperosmolar solutions (40% glucose solution, 30% sodium thiosulfate solution, 25% magnesium sulfate solution, etc.) can provoke a greater penetration of substances through the BBB. It is also known that in the brain there are areas of high BBB permeability for physiologically active substances and the presence of such points (pituitary and epiphyseal region, postrema region, preoptic cavity) is necessary for normal functioning, for example, neurohumoral and protective reactions (adequate functioning of biological feedback ). Therefore, to say that the substance is not capable of penetrating the BBB at all can only be very conditional, since small amounts of it are still able to enter the brain tissue and have a corresponding effect.

One of the important parameters characterizing the pharmacokinetics of drugs is the apparent volume of distribution. It shows the hypothetical volume of fluid in which the intravenously administered dose of the drug is distributed so that the resulting concentration at the end of its administration becomes equal to that determined in the blood plasma. Since most psychotropic drugs, in contrast to drugs of peripheral action, have a larger volume of distribution, they can to a certain extent almost evenly saturate all tissues of the body. For comparison: the volume of distribution of amitriptyline, nortriptyline, haloperidol is 20, 21, 23 l / kg, and for digitoxin, anaprilin, oxprenolol - 0.5, 4, 6 l / kg, respectively. However, it should be emphasized that the volume of distribution is not only determined by the solubility of drugs in lipoids, but also in water, and also depends on other properties of the drug molecule. In general, it is believed that the larger the volume of distribution, the better the penetration of the drug into various tissues of the body and the more difficult it is for the latter to get rid of it, even in the case of methods such as forced diuresis or renal dialysis. Nevertheless, it should be noted that endogenous substances and preparations similar to them, necessary for the normal functioning of the brain, are able to actively penetrate the BBB through specific transport systems that deliver them to the brain tissue (vitamins, hormones).

It is clear that the active therapeutic concentration of drugs in the blood plasma and brain, provided that there is good solubility in lipoids, primarily depends on the administered dose, and the constancy of the concentration will be determined by the rate of elimination of drugs from the body.

Mostly in psychiatry, the oral route of administration of drugs is used, in emergency cases intramuscular, and extremely rarely in urgent situations - intravenous. The peculiarities of drug entry into the blood plasma by these routes of administration are well known and, therefore, there is no need to dwell on them in detail. The elimination of the drug is associated with the work of the kidneys, liver and the activity of metabolic processes, all these characteristics depend on the chemical structure of the drugs and individual differences in the intensity of the work of the corresponding body systems.

It is believed that the determination of the concentration of the drug in the blood plasma is of great importance, since it can reflect the content of the active substance, including in the brain tissue, and the quality of the action depends on it - therapeutic or toxic. However, in relation to psychopharmacology, this provision may reflect the risk of “peripheral” side effects from the psychotropic drugs used, rather than characterize their psychotropic activity. This is confirmed by the fact that for such classes of psychotropic drugs as antidepressants and antipsychotics, no direct and absolute dependence was found: dose-severity of the psychotropic effect. This fact is associated with the peculiarities of the action of psychotropic drugs on the endogenous neurochemical systems through which their action is realized. The features of pharmacodynamics or the mechanism of action of psychotropic drugs are determined, on the one hand, by the functional state of the corresponding neurochemical systems (their ability to react / change under the influence of a psychotropic drug), and on the other hand, by the selectivity / specificity of their action on the target system. Due to the limited volume of this work, it is not possible to speak in more detail about the pharmacodynamics and pathophysiology of mental disorders.

With the dynamics of changes in the concentration of the drug in the body, the most well-known indicator characterizing this process is associated - the half-life of the drug from the blood plasma. It is generally believed that during the normal functioning of the organs responsible for the excretion of xenobiotics, the substance is completely removed from the body during its half-life, multiplied by 5. As a rule, for the vast majority of psychotropic drugs, this indicator turns out to be higher than for drugs of other groups used in related fields of medicine, in which drugs with less stringent requirements are used regarding their penetration through histohematological barriers. If we assume that for psychotropic drugs, the half-life almost always exceeds 12 hours, then the frequency of administration of these drugs should not be more than 2-3 times a day, and in most cases even a single prescription of drugs is sufficient. It is appropriate to say that in many guidelines on pharmacotherapy, the frequency of administration of drugs is often silent, and this reduces the value of the corresponding manuals for practicing physicians.

Returning to the indicator of the half-life or half-life of the drug, it should be noted that it must be distinguished from another indicator - the half-life of biological activity, which reflects the physiological or therapeutic effect of the substance. This indicator becomes important when the drug, metabolizing, forms active metabolites of the same spectrum of action as the main “mother” product. With the appearance of active and passive (inactive) metabolites, one of the stages of elimination (liberation of the body from the xenobiotic) is associated - biotransformation. Most often, drugs are metabolized in the liver, then in the blood, lungs, and muscles. This phase of metabolic transformations is also present when the drug is administered intramuscularly or subcutaneously, but is less significant when administered intravenously. As a rule, at this stage there is a biological oxidation of substances with the participation of a system of cytochrome P-450 isoenzymes. In addition, some drugs that enter the liver and are excreted unchanged with bile are able to be reabsorbed, entering the systemic circulation, the portal vein system, and again into the bile, repeating this cycle many times, they can be determined in the body for a long time at low concentrations. (chlorpromazine, chloral hydrate, methaqualone, diphenin, tricyclic antidepressants).

The concept of bioavailability is associated with biotransformation, which reflects the percentage of the active substance that enters the systemic circulation, remaining after the first passage through the liver. Already at this stage, substances may appear that are formed during the metabolism of the drug and have very active biological properties. They can cause not only therapeutic, but also toxic, oncogenic, teratogenic and other effects. The total amount of metabolites formed in the process of primary biotransformation reduces the amount of the active substance precisely by the part that they account for. Some drugs, having a relatively short half-life, can form long-lived active metabolites, the appearance of which in the blood plasma may suggest the development of cumulative effects. As an example, we can recall that the well-known drug from the group of selective serotonin reuptake inhibitors fluoxetine (T1 / 2 \u003d 50–70 h) - Prozac, Prodep, Portal, etc. - forms an active long-lived metabolite (T1 / 2 = 160–360 h), similar in spectrum of psychotropic activity to the drug itself. This, depending on the clinical situation, can be considered both as a positive moment and as a negative one. For example, with the successful use of a drug by a patient suffering from depression, the regimen of its use may be more free, skipping 1–2 or even 3–4 days in admission will not significantly affect the therapeutic effect of this drug. On the other hand, if the patient is resistant to this drug, the transition to another drug (MAO inhibitors, tricyclic antidepressants) or a combination of several should be carried out with extreme caution because of the risk of developing severe consequences in the form of a malignant serotonin syndrome.

At the stage of biotransformation, it is possible to change the pharmacokinetics of the main drug if it is administered in combination with other concomitant drugs. Particularly noteworthy are drug combinations containing inducers (ethanol, phenobarbital, diphenin, carbamazepine, hexamidine, diphenhydramine) and liver enzyme inhibitors (pyriditol, cimetidine).

Attempts to use the metabolic stage of drug transformations for the benefit of the patient were implemented when creating the so-called inactive prodrug, a drug from which a physiologically active substance is formed as a result of metabolism. Bupropion, a dopamine-positive antidepressant, is a prodrug among psychotropic drugs.

Unfortunately, reference books on psychopharmacology will never have a hypothetical indicator that can reflect the equipotentiality of the action of analogues. Any doctor is well aware of the differences in the biological effect of drugs from different manufacturers that have one active substance, such as diazepam (Valium, Relanium, Seduxen, Sibazon, Apaurin, Saromet, etc.). Despite the fact that all these drugs contain diazepam, the spectrum of their activity varies from a pronounced hypnotic to a mild sedative, and at the same time, both the severity and the speed of onset of the anxiolytic action characteristic of this drug change. Such differences in clinical performance are likely due to the fact that manufacturing companies use different excipients (“neutral” substances) necessary for the preparation of the dosage form. Most likely, the differences in the magnitude of some pharmacokinetic parameters that determine the level of concentration of the active substance in the blood plasma and target tissue are also due to the same reason.

In conclusion of this part of the work, it is also necessary to mention one more pharmacokinetic characteristic, which reflects the duration of the presence of the active substance in the body - binding to blood plasma proteins. As well as in the case of penetration through blood-tissue barriers, psychotropic drugs, as a rule, to a much greater extent than other drugs, are able to bind to blood plasma proteins (albumins, acid 1-glycoprotein). For example, protein binding for thioridazine is 99.5%, chlorprothixene is 97%, aminazine is 90%, haloperidol is 90%, amitriptyline is 95%, desipramine and doxepin are 80%, and for amidopyrine is 27%, digoxin is 30%, atropine - 50%, pindolol - 60%. Since the bound fraction of the drug is considered as a kind of depot from which the active substance gradually enters the blood plasma, then, as in the situations described above, the release of the body from the psychotropic drug is slower than elimination from another drug less associated with the protein fraction.

So, when considering the appearance of psychotropic effects, pharmacokinetic parameters were identified that can be used to control the therapeutic concentration of drugs in blood plasma. However, in contrast to therapeutic practice, in which the effect of the prescribed drug, as a rule, correlates with the content of the drug in the blood plasma, only a part of psychotropic drugs has a dependent psychotropic effect in accordance with changes in the dose and concentration of the drug. Such drugs include thymostabilizers (valproic acid derivatives, lithium preparations, carbamazepine), antiepileptic and anticonvulsant drugs, hypnotics, but, unfortunately, the main psychotropic classes - antidepressants and antipsychotics, do not have such an effect, both typical and atypical drugs of the new generations. If the absence of such a dependence was noted in special studies, then indirect, additional evidence of the correctness of this conclusion is that the therapeutic effect in the appointment of these drugs is formed from 2 to 6 weeks. When it comes to such a long period of therapeutic “inactivity” of drugs (this is a difficult period in the professional life of a psychiatrist), it can be assumed that some kind of restructuring of the neurochemical systems of the brain is required for the development of a psychotropic effect. They can be associated both with a change in the content of mediators and/or a change in the number of receptors in certain brain structures. In psychiatric practice, not only the period of “therapeutic inactivity” acquires importance, but also the absence of undesirable effects from the prescribed drug during this period. If within 2–3 weeks from the start of drug therapy the patient does not feel any effects from taking it, then it is possible that even an objective improvement in the condition may be underestimated in a subjective assessment (it seems to the patient that the medicine does not work on him, because he does not feel it). If the drug at the very beginning of therapy, without having a therapeutic effect, still causes the appearance of undesirable effects, then with the development of even minimal positive changes, the condition can be assessed not only by the patient, but also by the doctor with a clear overestimation of effectiveness. The role of psychological factors in drug therapy is described in detail in the monographs of I.P. Lapin.

It is probably legitimate to assume that the effect of psychotropic drugs on the mental state of healthy and mentally ill people differs. Moreover, it is likely that the differences between healthy and sick people are associated with the peculiarities of neurochemistry, against which the effect of the drug develops. Since antipsychotics and antidepressants have the corresponding (antipsychotic and antidepressant) effect only in patients and the reduction of pathological symptoms is clearly associated with their action, it is likely that their activity is aimed at changing the stable brain metabolism formed by the pathological system.

Researchers N.P. Bekhtereva et al. spoke about the development of a stable pathological condition in brain diseases. and G.N. Kryzhanovsky, noting stable changes both in the functioning of neurochemical systems and in the work of neurophysiological mechanisms that determine the corresponding changes in mental functions. Since most mental illnesses are chronic, often progressive either in the severity and severity of mental symptoms or in the nature of changes in the relapse-remission cycle, neurochemical changes do not stand still, but undergo some changes associated with the involvement of more and more new neurochemical systems. In connection with such dynamics, the activity of some drugs can also change in comparison with others, and previously inactive drugs at some stage of the disease may turn out to be effective.