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Depression is a mood disorder, that is, a complex of mental disorders associated primarily with the emotional sphere. This disorder is characterized by various emotional disorders in which people experience anguish, anxiety, guilt, anhedonia, that is, the loss of the ability to experience pleasure, or apathy – a state where a person does not experience either negative or positive emotions. In addition, depression is characterized by certain disorders in the field of thinking. For example, people with depression may find it difficult to concentrate, to carry out targeted mental activity, which is associated with concentration. In a depressed state, people have difficulty making decisions. They have dark thoughts about themselves, about the world around them, about people.

Depression has such physiological manifestations as sleep disturbances, intestinal functions, sexual needs. In patients with depression, the general energy tone is disturbed, they feel tired. With somatisation depression, the person experiences discomfort in the body. If you look at such a person, then in his behavior one can observe passivity, avoid contact with people, refusal from entertainment. Depression is often accompanied by increasing abuse of alcohol or other psychoactive substances that are used to improve mood.

Depression studies

Manifestations of melancholia have been described in Antiquity. Hippocrates introduced the terms “mania” and “depression.” At the end of the 19th century, the German psychiatrist Emil Kraepelin, the founder of the school of Crepelin, first described manic-depressive psychosis. Later they began to distinguish unipolar and bipolar forms of depressive disorder. In modern concepts, manic-depressive psychosis is called bipolar disorder. In addition, we can talk about the so-called neurotic depression, which can be exposed to people who do not suffer from mental illness, but have psychological difficulties that predispose to depression. Manic-depressive psychosis was described long ago, and now this concept is considered obsolete. In the modern world, the diagnosis of a depressive episode is more common, which can have varying degrees of severity.

Causes of Depression

Current views on depression are described in terms of biopsychosocial models. The causes of depression are never unambiguous. The biological factors of depression are confirmed by genetic studies, but the contribution of genetic factors is generally low. Neurochemical studies show that people prone to depression have impaired metabolism of neurotransmitters that contribute to the interaction between nerve cells and the passage of electrical impulses.

The psychological causes of depression can be summarized in two main directions. First of all, these are violations of self-esteem and self-esteem — introjective variants of depression, in which a person has a certain idea of ​​his own “I” as unworthy of love and respect. In connection with this, various variants of compensatory behavior are formed. For example, this may be expressed in such a personality trait as perfectionism. In this situation, a person can accept himself only when he is perfect, other people evaluate him ideally, and the products of his activity have no flaws. If the life and activity of a person is aimed at confirming a good attitude towards oneself, exhaustion depression occurs. That is, if all activity is aimed at achieving results, a person loses psychic energy, which is formed through experiencing positive emotions: joy, pleasure, interest. Such mechanisms of depression are more common in men.

Another direction in understanding the psychological causes of depression is problems in intimate relationships. When a person needs another person to feel alive and able to adapt to reality, he is inclined to merge with another person and to minimize the distance. In such cases, the person experiences himself through another person. This tendency to depend on relationships is fraught with depression. In such a relationship, the partner often feels strangled. He does not leave space, leaning too close to him. Such relationships often fall apart, and the person who needs this merger feels it as a loss of himself. People describe this experience as follows: “It’s as if I don’t exist if the other one leaves me.” Such dependence often leads to depression, because man does not have the power of the ego, which allows him to live autonomously.

In addition, depression has social mechanisms. There is a certain cultural influence that affects the severity of depression in a particular culture. In northern cultures, the incidence of depression is higher than in southern and eastern ones. Here comes to the fore the cult of success, rationality, well-being, which is implanted through the media and parenting. In the process of growing up, people introject, that is, take in, into their worldview, the idea that they need to have a certain list of achievements in order to be good. The mechanisms of social comparison are activated, and when a person compares himself with other people, and the comparison is not in his favor, it is fraught with depression. In addition, people pay a lot of attention to the achievements in relation to their own physicality: what should be the body, to be socially acceptable, and what should be done with this body to be accepted in society.

Manifestations of depression

Tosca can be felt physically, in the form of squeezing in some parts of the body. Most often, people talk about squeezing in the chest. There is the concept of vital angst when a person feels that something is bad, but does not understand what is concrete. He does not survive the loss, does not suffer from separation from a loved one, but experiences a state of life longing. Patients with this symptom often say that they are simply ill, complain of depressed mood.

Anxiety is a feeling of internal tension, an expectation of something negative. Anxiety often accompanies depression, but can manifest itself. For depression, anxiety can occur in addition to depression and depressed mood.

Guilt feelings and a general tendency to self-accusation are characteristic of people with low self-esteem. There is a connection between low self-esteem and depression. Guilt feelings, as a rule, are associated with personalization, that is, thinking error, in which a person often takes bad events on his own account, and considers good events as the result of external causes.

Anhedonia is a condition in which a person cannot experience the pleasure of something that has pleased him before. For example, a patient with depression says that he would have given half his life for a fishing trip, but now he does not even want to think about it. This is a consequence of anhedonia, a distance from everything that used to be touched.

People most often experience apathy through their own passivity. Apathy is the most severe manifestation of depression, because this condition is difficult to treat with psychological methods. When a person is apathetic, he does not touch anything emotionally, either in a bad or in a good way. In a state of apathy, a person wants to lie in bed, he has no emotions, nothing encourages him, no motive. In this case, the person has due. For example, he says to himself that he must get up, make breakfast, feed the children, but this is experienced as pressure, an obligation, and not as a goal or desire. Most often, people understand that they have apathy when they want nothing but to stay in bed.

Sleep and appetite. Emotions are psychological phenomena that have a large physiological, somatic component. They have a cognitive component at the level of experience: before we feel something, we interpret what is happening. When the emotional state is unfavorable, the functions of the autonomic nervous system are disturbed, which controls the internal organs. A person experiences a variety of physiological symptoms: appetite disturbances in one direction or another, sleep disturbances. Internal stresses make sleep superficial or impede entering sleep.

Behavior. At the level of behavior, depression manifests itself in passivity, avoidance of contacts, refusal from entertainment, gradual alcoholization or substance abuse.

In addition, emotions affect thinking. On the other hand, thinking affects emotions. In some people, depression develops due to biochemical mechanisms that do not depend on his personality. For example, a person from childhood knows that his mood is worse in the morning, and that after lunch, his mood improves. When a person feels a severe emotional state, he has an unconscious need to substantiate this state cognitively. A person has a need to think about the bad. Thinking can also affect emotions. The mechanisms of cognitive therapy of depression are based on the fact that with the help of a psychotherapist a person works on these thinking errors that are inherent in depressive thinking. He becomes aware of these errors at the cognitive level.

Forms of depression

One form of depression is bipolar disorder. It manifests itself as a mood disorder that proceeds with a phase flow. Phases are periods of time that last for weeks or months. Moreover, in bipolar disorder, the phase of depression replaces the phase of mania. Mania is characterized by a positive mood. In this state, a person is full of plans, sleeps little, does not analyze obstacles, commits rash acts.

In bipolar disorder, significant coefficients of the genetic contribution are observed. In neurotic depression, the genetic contribution is lower, and psychosocial factors play a more significant role. With such a disorder, there is no phase of mania, disturbed thinking and reality testing, delusions or hallucinations. Treatment of neurotic depression is more dependent on psychotherapeutic procedures.

Another form of depression is unipolar depression, that is, a depressive episode. It can have three degrees of severity: mild, moderate, and severe. This condition lasts at least two weeks. If the depressive episode is repeated, then the diagnosis changes from a depressive episode to a recurrent depressive disorder, that is, to a periodically pop-up depression. A person can suffer depression once in a lifetime, and can suffer from it twice a year.

In addition, there are such forms of mood disorders as cyclothymia and dysthymia. These are personality characteristics rather than illness. Dysthymia is a property of a person to remain in a gloomy mood, to have a pessimistic picture of the world, but at the same time to function all his life, never addressing psychiatrists. The intensity of depressive symptoms in dysthymic low, but lasts for years.

Cyclothymia is dysthymia with the presence of phases in which the dysthymic phase gives way to a good mood phase and so on. The difference from bipolar disorder is that it is a characteristic associated with a person’s worldview and personality. You can talk about cyclothymic or dysthymic personality. Such depression takes a lifetime if the person does not specifically work on it. And this does not radically restrict his ability to live. But when there is a real clinical depression, a person is limited in life activity. Often he cannot work due to the fact that he cannot concentrate, get out of bed, he has no mental tone, but there is a strong longing.

Treatment of depression

There are several psychotherapeutic areas for the treatment of depression. In particular, psychoanalysts work with depression. They are more focused on the analysis of early losses and injuries. One of the most effective is cognitive-behavioral therapy for depression, the author of which is Aaron Beck. Beck’s concept is called depression cognitive therapy. The basic theoretical premise is that a person has negative basic beliefs, ideas about himself, the world, and his future, which keep him inside the depressive pit.

A person follows a compensatory strategy of behavior in that he should like everyone and should not be mistaken. These behavioral strategies lead to exhaustion or frustration. In cognitive therapy, there are a number of techniques that are designed to correct these basic beliefs. First, more superficial beliefs are corrected. A person learns to recognize these thinking errors. When he tests this in his life, basic beliefs also begin to be corrected, too. He begins to accept himself as he is, ceases to depend on the opinions and assessments of others, allows himself to make mistakes and to treat them adequately. Beliefs are corrected, and the life situation begins to be interpreted through the prism of other beliefs and a worldview that is more adaptive.

In addition, depression is treated with medication. It is known that half of the inhabitants of the United States take antidepressants. In Russia, this practice is also common, but far fewer people turn to psychiatrists. The history of Soviet psychiatry in the Soviet period is rather repressive. There are prejudices in people’s minds.

Depression should be treated comprehensively. If a person treats depression with antidepressants, the mechanisms of psychological coping with emotions do not mature. As a result, sooner or later he attacks the same rake.

Frequency of depression

According to statistics, depression occurs more often in women than in men. This is due to the fact that women as a whole have a more delicate nervous organization and there are cyclical hormonal changes. The most vulnerable age range is after 45 years. In old age, depression is associated with anxiety. There are predictions that in the 21st century depression will take the second place after cardiovascular diseases for reasons of disability. In general, in Western countries, this is indeed a social disaster.

The effect of depression on physical health

There are two mechanisms of the effect of depression on physical health. First, there is somatization, in which it is not about physical health, but about the symptoms that a person experiences as a violation of physical health. Often, when a person is depressed, there are so-called psychalgia, that is, pain in different parts of the body. In this case, medical research does not lead to any results. But a person suffers systematically from the body: he may have a bad headache or, for example, a knee; besides, there are stomach or heart pains.

Another mechanism is the effect of depression on health, on changes in body tissues that are associated with depression. By itself, depression does not cause damage to internal organs. But a person who is depressed often leads an unhealthy lifestyle. Having a dark look at the state of things in life, he may not go to the doctors or, conversely, turn too often. The physiological, biochemical components of depression are not fully understood. As for psychology, there are also many white spots, in particular in the description of family and cultural mechanisms of depression. Scientists are trying to understand why, for example, in the southern countries patients with depression are less than in the north, but at the same time in India more than all over the world.

Clinical data

Mauri et al. The review reviewed randomized clinical trials (RCTs) and open trials over the past 13 years that examined the efficacy of quetiapine in depression as monotherapy or in combination with other drugs.In a study by Sajatovic et al. (2002) compared the efficacy and safety of quetiapine and risperidone for the treatment of psychosis in patients on an outpatient basis. The study was a multicenter, open, randomized duration of 4 months. The patients were divided into two groups, in which 554 patients took quetiapine and 175 patients received risperidone. Both drugs had a flexible dosage regimen; the average doses at the 16th week of the study were 318? Mg of quetiapine and 4.4? Mg of risperidone.

Improvement on the Hamilton scale for assessing depression (HAM-D) was observed in both groups, however, patients treated with quetiapine had better results (p = 0.0015), which suggests that the drug is effective for treating the symptoms of depression in patients with psychosis. Calabrese et al. (2005) studied the efficacy of quetiapine for the treatment of depression in BAR. The study involved 542 patients with BAR I (n = 360) and II (n = 182) types who were randomized to quetiapine (300-600? Mg / day) and placebo groups.

Quetiapine at a higher dosage showed a statistically significant improvement in the total score on the Montgomery-Asberg scale (MADRAS), compared with placebo, starting from the first week of treatment. At the end of the study, the percentage of patients who responded to treatment in the quetiapine groups (300 and 600? Mg / day) was 58.2% and 57.6%, respectively, compared to 36.1% in the placebo group. 52.9% of patients from the quetiapine group received remission (MADRAS? 12), compared with 28.4% in the placebo group.

Thus, the efficacy and safety of quetiapine monotherapy in bipolar depression has been demonstrated.In 2006? Hirschfeld et al. conducted a study that examined the effects of quetiapine monotherapy on anxiety symptoms in bipolar depression. The study involved 539 individuals with BAR I (n = 358) and BAR II (n = 181) types. The patients were divided into the quetiapine group (300-600? Mg / day) and placebo.

Persons taking both dosages of the drug showed a significant improvement in the total number of points on the Hamilton Anxiety Anxiety Score (HAM-A) compared with placebo (p <0.001). In patients with type I BAR, the drug reduced anxiety and tension on the HAM-A scale, its mental and somatic subscales, as well as indicators of the internal tension of the MADRS scale, points of mental (but not somatic) anxiety on the HAM-D scale (p <0.001). In patients with type II BAR, the use of quetiapine provoked an increase in anxiety scores on the HAM-A scale, internal tension on the MADRS scale and mental anxiety on the HAM-D scale (p <0.01).

At the end of the study, the authors concluded that monotherapy with quetiapine for the treatment of symptoms of anxiety with type I BAR is quite effective, as well as the need to further study the effect of the drug on patients with type II BAR.The purpose of the study Milev et al. (2006) was to study the long-term efficacy and safety of quetiapine, which was used as an additional therapy in patients with bipolar depression at a dosage of at least 400? Mg / day. According to the data obtained at the end of the study, patients showed a decrease in indicators on the HAM-D scale from 27.2 to 12.1 and on the general clinical impression scale (CGI) from 4.7 to 2.

Thus, the authors concluded that the drug is well tolerated and gives an additional advantage when it is added to the treatment regimen for patients with bipolar depression. In a RCT conducted by Endicott et al. (2007) with the participation of 542 patients with type I and II BAR, the effect of Quetiapine monotherapy at a dosage of 300-600? Mg / day on the quality of life of patients was evaluated. It was found that taking both dosages significantly improved the quality of life of patients compared with placebo, starting from the 4th week until the end of the study (8th week). Also, the drug improved the quality of sleep compared with placebo.

According to the authors, since an improvement in the quality of life can increase patient adherence to treatment, this indicator should be taken into account when conducting further clinical studies in patients with bipolar depression. Baune et al. (2007) studied the effectiveness of combination therapy with antidepressants (venfalaxine, escitalopram) and quetiapine with a flexible dosing regimen for MDD, with an emphasis on such indicators as physical activity, daytime sleepiness and sleep quality.

The authors concluded that quetiapine has an independent positive effect on the symptoms of depression, motor activity, and sleep, and its combination with antidepressants can optimize the treatment of symptoms of depression. Vieta et al. (2007) investigated the efficacy and safety of quetiapine monotherapy in patients with BAR type I and II with rapid phase change.

Quetiapine at a dosage of 300-600? Mg / day significantly improved performance on the MADRS scales (p <0.001), HAM-D, HAM-A, as well as the Pittsburgh sleep quality questionnaire (PSQI) and the questionnaire on life quality satisfaction. Thus, Quetiapine monotherapy has proven to be effective and safe for short-term use in patients suffering from rapid phase change BAR.

The efficacy and safety of quetiapine monotherapy for symptoms of depression in patients with type II BAR have been studied by Suppes et al. (2010). They conducted a retrospective analysis of data obtained from two 8-week RCTs. The primary evaluation criterion was the change in the total score on the MADRS scale from baseline. Taking quetiapine at a dosage of 300? Mg / day (n = 107) and 600? Mg / day (n = 106) showed a significant improvement compared with placebo (n = 108) starting from the first week until the end of the study.

There was also a positive trend in performance on the HAM-D, HAM-A and CGI scales. In general, the results of this retrospective analysis suggest that quetiapine monotherapy is more effective than placebo for the treatment of acute depressive episodes in patients with type II BAR.

A similar study was conducted by Weisler et al. (2008), which assessed the effectiveness of quetiapine monotherapy for depressive episodes in patients with type I BAR. This publication was a retrospective analysis of the BipOLar DEpRession (BOLDER) study. In the combined cohort of patients with episodes of depression with type I BAR, treatment with quetiapine significantly improved the MADRS score compared with placebo from the first week to the end of the study (week 8).In 2010? in another 8-week RCT, Suppes et al. (2010) evaluated the effectiveness of the XR form of quetiapine in bipolar depression.

Patients were randomized to receive 300? Mg of quetiapine XR (n = 133) or placebo (n = 137). The average change in the total score on the MADRS scale at week 8 of the study was -17.4 in the quetiapine XR group; -11.9 in the placebo group (p <0.001). The percentage of responders to treatment (? 50?% Reduction in the total score on the MADRS scale) and reached remission (total score on the MADRS scale? 12) was significantly higher in the quetiapine group than in the placebo group. Since quetiapine XR reduced the level of manifestation of key symptoms of depression, the authors concluded that quetiapine is effective in this form of release for the treatment of acute depressive episodes with BAR.In a study by Young et al. (2013) compared the efficacy and safety of quetiapine and lithium monotherapy for a major depressive episode with BAR compared with placebo.

The average change in the total score on the MADRS scale at the 8th week of the study was -15.4 in the quetiapine group at a dose of 300? Mg / day and -6.1 at a dose of 600? Mg / day, -13.6 – lithium and -11.8 – placebo. Quetiapine at a dosage of 600? Mg / day was statistically significantly more effective than lithium and reduced the total score on the MADRS scale. Also in patients in the quetiapine group, an improvement was noted in comparison with placebo on the HAM-D, CGI and HAM-A scales.

The authors concluded that quetiapine at 300 and 600? Mg / day is more effective than placebo for the treatment of acute depressive episodes with BAR. Lithium showed no statistically significant differences in key indicators compared with placebo.Mc Elroy et al. (2010) studied the efficacy and safety of quetiapine and paroxetine monotherapy in a major depressive episode in patients with BAR.

The average change in the total score on the MADRS scale on the 8th week of the study was -16.19 points when taking quetiapine at a dose of 300? Mg / day and -16.31 at a dose of 600? Mg / day, -13.76 – paroxetine and -12,60 – for placebo. Quetiapine in both dosages showed a more pronounced improvement on the MADRS and HAM-D scales than paroxetine.

The incidence of mania / hypomania during treatment was lower in the quetiapine group than in the paroxetine and placebo groups.The purpose of the study is Ketter et al. (2010) evaluated the effectiveness of quetiapine administered to patients in medical institutions for the treatment of symptoms of BAR. The average duration of Quetiapine treatment was 385 days, and the average daily dose was 196? Mg / day (half of the patients took 75? Mg / day). In 38.5% of patients, the duration of quetiapine intake was on average 328 days without additional psychotropic therapy. In 22.9% therapy lasted an average of 613 days, and at the same time, after 113 days, there was a need for an additional drug, often to relieve the symptoms of depression.

Apart from sedation, quetiapine was well tolerated by patients. The authors concluded that the data obtained – a moderate (38.5?% After 385 days) percentage of quetiapine withdrawal at the outpatient stage and the absence of the need for an additional drug – may indicate its effectiveness in patients in medical institutions.Weisle et al. (2008) analyzed the efficacy and safety of maintenance treatment with quetiapine compared with switching to lithium or placebo in patients with type I BAR. Patients with an established diagnosis of Type I BAR and a recent episode of mania, depressive or mixed episodes received 300-800? Mg / day of quetiapine for 4-24 weeks. After stabilization, patients were randomly assigned to quetiapine, placebo or lithium groups (0.6-1.2 meq / l).

Of the 2438 patients who completed the open phase, 1226 (50.3%) were included in the second double-blind phase of the study. The time before the onset of relapse of any of the affective episodes was significantly longer in the quetiapine and lithium groups than in the placebo group (p <0.0001). In patients whose condition stabilized when taking quetiapine, supportive therapy was statistically significantly more effective in preventing episodes of mania, depression, and other affective episodes compared with placebo.

Supportive lithium therapy has also been effective in preventing episodes of mania and depression.Kim et al. (2014) in an 8-week study compared the efficacy of quetiapine XR monotherapy and lithium in patients with symptoms of depression and sleep disorders in 42 patients with bipolar depression. In both groups, there was an improvement on the HAM-D scale, however, the percentage of remissions in the Quetiapine XR group was significantly higher than in the lithium group. There was also a significant improvement in PSQI at the 1st, 2nd, 4th, 6th, and 8th weeks of the study, as well as the effectiveness of sleep at the 6th and 8th weeks.

In addition, the number of awakening episodes after falling asleep at week 8 has decreased. Based on the findings, the authors concluded that quetiapine XR monotherapy for depression symptoms with BAR is more effective than lithium monotherapy, and that quetiapine XR treatment improves the subjective and objective sleep quality indicators in patients with bipolar depression.

Safety and Portability

As noted by Mauri et al., Quetiapine was generally well tolerated by patients.

In the majority of studies, participants did not experience significant weight gain, however, they were sometimes encountered in clinical practice. No extrapyramidal or anticholinergic side effects have been reported.Mc Elroy et al. (2010) in a double-blind, placebo-controlled study compared the efficacy and safety of quetiapine and paroxetine monotherapy in a major depressive episode in patients with BAR.

The most frequent side effects in the quetiapine groups (300 and 600? Mg) were dry mouth, drowsiness, sedation and dizziness, and in the paroxetine group: dryness ort, sedation, headache, insomnia and vomiting.In the quetiapine groups, the incidence of mania / hypomania during treatment was lower than in paroxetine and placebo groups. More significant weight gain occurred in both groups of quetiapine (9 and 11?%, Respectively) than in the paroxetine (3?%) Or placebo (4?%) Groups.

With regard to laboratory parameters, quetiapine did not cause any significant changes during the 8 weeks of the study, however, compared with baseline, there was a more pronounced fluctuation in triglyceride and insulin levels in the quetiapine and placebo groups than in the paroxetine group.

Findings

Quetiapine is a multifunctional drug due to its ability to modify noradrenergic, serotonergic, and dopaminergic neurotransmission. These effects are mediated by both the main active ingredient and the active metabolite, norkvetiapin.

According to the authors, monotherapy with quetiapine acute bipolar depression has advantages over antidepressants in terms of preventing phase transitions. Evidence of the efficacy of quetiapine monotherapy provides grounds for treating it as a first-line drug for the treatment of the acute phase and maintenance therapy for bipolar depression.

Quetiapine was first approved by the United States Food and Drug Administration (FDA) in 1997? for the treatment of acute episodes of schizophrenia in adults. Over time, the wide possibilities of the pharmacological properties of the drug, due to which in 2003? It was approved for the treatment of manic episodes in bipolar affective disorder (BAR), in 2006? for the treatment of depressive episodes with BAR, and in 2008? has been recommended as maintenance therapy for BAR (Hawkins et al., 2013; Sanford, 2011). Since 2009?

Quetiapine has been used as an adjunct in the treatment of major depressive disorder (MDD) in combination with antidepressants without FDA approval (Mauri et al., 2007). Currently, this drug is not registered indications (off-label) is used for mental disorders such as generalized anxiety disorders, as monotherapy for monopolar depression, with delirium, psychotic symptoms associated with dementia and obsessive-compulsive disorder. Thus, the range of Quetiapine use has gone far beyond that approved by the FDA.

The use of quetiapine in affective disorders has been reviewed in a large number of double-blind, randomized clinical trials (RCTs). Currently, quetiapine is one of the most commonly used drugs for bipolar and monopolar disorders (Lopez-Munoz et al., 2013).

The authors of the article conducted a thorough search in the PUBMED database of all RCTs published before December 2015? In which quetiapine IR or XR was used in patients with depressive episodes in bipolar and monopolar disorders. Among all the studies, RCTs were selected that meet the criteria for the analysis.

Pharmacokinetic Profile of Quetiapine

Quetiapine belongs to the group of preparations of dibenzothiazepine derivatives. Available in two forms: with immediate (IR) and prolonged (XR) release. With a single dose in therapeutic doses, the drug demonstrates linear kinetics with a half-life of about 7 hours. Both forms have the same bioavailability. At the same time, the peak plasma concentration in Quetiapine IR is 2 hours, and Quetiapine XR – 5 hours. Quetiapine XR is also characterized by a longer maintenance of high plasma concentrations. Therefore, to maintain therapeutic concentrations, it is possible to take the drug once a day, while Quetiapine IR should be taken 2 times a day (Mauri et al., 2007; Bui, 2013).

Quetiapine is metabolized in the liver to form various derivatives, and only 1?% Is excreted unchanged in the urine. N-dezalkilkvetiapin (norkvetiapin) is the most important metabolite of the drug. Norkvetiapin is formed by CYP3A4 isoenzymes of the cytochrome P450 system (Lopez-Munoz et al., 2013). Due to the lack of genetic polymorphism of CYP3A4, any differences in quetiapine metabolism associated with racial or genetic traits are unlikely. Nevertheless, some inducers (carbamazepine, phenytoin), which increase the amount of norkvetiapine, or inhibitors (ketoconazole, itraconazole, erythromycin, and fluvoxamine), which decrease its production, affect the activity of this isoenzyme (Winter et al., 2008; Prieto et al., 2010). In elderly patients and patients taking concomitant medications, pharmacokinetic variability was more pronounced in quetiapine than in norkvetiapin, hence the concentrations of norkvetiapin were more stable (Bakken et al., 2011).

The less significant metabolic pathway of quetiapine occurs through CYP2D6 to form 7-hydroxy-quetiapine, which is not supposed to have pharmacological activity (Fisher et al., 2012), and 7-hydroxy-dealkyl-quetiapine, which has pharmacological activity (Bakken et al., 2012). According to Mauri et al. (2007), the plasma concentrations of quetiapine are not high enough to determine its effect on the receptors or its clinical effects. According to scientists, the active metabolites of the drug are also responsible for its pharmacodynamic characteristics.

Pharmacodynamic profile of quetiapine

The main mechanism underlying the antipsychotic activity of quetiapine is the blockade of the dopamine D2 receptors of the mesolimbic nerve pathways. Both quetiapine and norkvetiapin have a moderate affinity for D1 and D2 receptors, and the former quickly dissociates with D2 receptors. This explains the need to receive sufficiently high doses of quetiapine for the development of antipsychotic effect (Altamura et al., 2012). However, quetiapine does not affect the regulation of the activity of these receptors, which explains the low level of development of tardive dyskinesia during prolonged therapy with this drug. In the nigrostrial and tuberoinfundibular dopaminergic nerve pathways, serotonin acts as an inhibitor due to its effect on 5HT2A receptors.

Quetiapine and norkvetiapin have a strong antagonistic effect on these receptors, which contributes to the release of dopamine and provides a low level of extrapyramidal side effects and hyperprolactinemia (Kapur et al., 2000). A large number of depressive symptoms, such as agedonia, psychomotor retardation, social exclusion and loss of motivation are the result of reduced dopamine neurotransmission in the prefrontal cortex. According to some scientists, norkvetiapin due to antagonism with 5HT2A – and 5HT2C-receptors promotes the release of dopamine in the prefrontal cortex and reduces the symptoms of depression in patients with affective disorders (Mundo et al., 2006).

Dopamine reuptake is carried out by a norepinephrine carrier protein. Quetiapine and norkvetiapin potentiate serotonergic transmission of nerve impulses, acting as partial 5HT1A receptor agonists, which are associated with antidepressant and anxiolytic effects. In particular, norkvetiapin has a high affinity for 5HT1A receptors, similar to buspirone and gepironom. Thus, it increases serotonergic neurotransmission in neurons of the brain stem seam, and also modulates the 5HT activity of the cortex and limbic system (Bjorkholm et al., 2013). Activating these receptors in the hippocampus, norkvetiapin affects the increase in trophic factors and activates the regeneration of nerve cells (Silverstone et al., 2012).

In addition, it has a high affinity for 5HT7 receptors, the association of which with symptoms of depression and circadian rhythm disorders has been proven experimentally. Antagonism of norkvetiapine in relation to these receptors contributes to the manifestation of the antidepressant effects of quetiapine (Sumegi et al., 2008). When comparing quetiapine and norkvetiapine with antidepressants in vitro, norkvetiapin showed the same activity against the norepinephrine transporter, as well as some antidepressants, while quetiapine was inactive.

In view of the foregoing, it can be concluded that quetiapine’s effectiveness for reducing depression symptoms is due, in part, to the pharmacological properties of its active metabolite, norkvetiapin, which selectively inhibits the reuptake of noradrenaline, acts as a partial agonist of 5-HT1A receptors, as well as antagonist of presinaptic? 2, 5-HT2C and 5-HT7 receptors (Bortnick et al., 2011).

Monopolar and bipolar depression

The clinical activity of quetiapine has a number of differences from other atypical antipsychotics, which is why this drug is quite effective in treating bipolar depression, MDD, and generalized anxiety disorder (GAD) (Suppes et al., 2008). For a long time, atypical antipsychotics have been banned for use in the treatment of BAR, as they were thought to provoke the symptoms of depression. However, recent studies have found that drugs such as quetiapine, aripiprazole, and lurazidone can be used in the treatment of both phases of BAR (Riedel et al., 2011). The affinity of these drugs for various 5HT receptors has a significant effect on their normo-chemical properties. By binding to these receptors, they, as well as lithium, alter the signal transduction along the intracellular pathways and the activity of nerve growth factor (Rush, 2010; Connolly et al., 2011).

Observing patients with ARD, clinicians determined that they most often had symptoms of depression rather than mania (Bakken et al., 2011). In this case, depression may be in the form of a major depressive episode requiring hospitalization, or chronic with subthreshold symptoms, as well as other symptoms, such as anxiety, somatic complaints, substance abuse, etc. Therefore, it is very important to choose the optimal treatment for the depressive phase of BAR. Data from several studies have shown that quetiapine monotherapy can be effective in this case. The recommended dosage regimen for quetiapine for depressive episodes: 1st day — 50 mg, 2nd — 100 mg, 3rd day — 200 mg, 4th and the next 300 mg. With BDR, quetiapine is recommended as an additional therapy according to the following scheme: 1st day – 50? Mg, 2nd – 100? Mg, 3rd and 4th – 150? Mg, the recommended daily dose is 150-300? Mg.

The problem of mental disorders in the elderly and senile age is one of the most important sections of modern gerontology and psychiatry, which formed a separate research direction – gerontopsychiatry. However, in this area, the focus is on senile dementia and other forms of involutional psychosis, affective disorders, and much less on the clinical and therapy features of schizophrenia.

Epidemiology and clinical features

Today in US, schizophrenia is 1.7% of the incidence of elderly and old people . About 10 ­ 15% of patients with schizophrenia pathology manifest uet after the age of 60 years. It is important to emphasize that in old age both a certain syndromological dynamics in patients with the onset of the disease at a younger age are revealed , as well as features of the clinical picture of schizophrenia in later age, namely: complication of productive symptoms due to the expansion and deepening of hallucinatory ­ delusions, paranoia Destroy PTS straight and absence of growth deficitsymptoms and even shenii Decrease the manifestations of autism. Attention is drawn to the frequency of the relationship of schizophrenia with senile dementia. It is the development of concomitant senile dementia that contributes to the further development of the mentioned clinical manifestations in the elderly.

Dementia modifies the course of the schizophrenic process in two opposite directions – smoothing out specific personality changes, simultaneously aggravating and weighing down productive psychopathology disorders . In cases of schizophrenia combination with senile dementia age recesses Destroy productive endogenous PTS etc. Practical coincides with the manifestation of dementia. In addition, schizophrenia in old age is characterized by increased and prolonged exacerbations, a decrease in the quality of remissions, a transition to a chronic course, greater acuity and worse compensation for paranoid and paranoid manifestations .

From the point of view of pharmacotherapy, schizophrenia in old age is also characterized by a number of features. The most important of these is the increase in resistance to preparations of conventional neuroleptics and the incidence of their side effects. Especially often in gerontopsychiatry, extrapyramidal disorders and cardiotoxic reactions are observed with the use of phenothiazine and butyrophenone derivatives, which is associated with the age-related weakening of dopaminergic processes, primarily in the nigrostriatal system, impaired conduction and metabolism in the myocardium, as well as slowing down the biotranslation patterns and aspirant patterns. in an aging body.

As a result, the development of neuroleptics, which are not inferior in effectiveness to conventional means, but surpass them in breadth of therapeutic action and safety criteria, has become one of the most important tasks of the development of psychopharmacology. The emerging drugs of the new generation have received the general name of atypical antipsychotics, which currently include clozapine, olanzapine, risperidone, quetiapine, ziprasidone, amisulpride, aripiprazole, and some others.

The specific antipsychotic activity of atypical antipsychotics is generally comparable to that of traditional antipsychotics and is associated with the general mechanism of action of drugs in this group – the blockade of dopamine D2 receptors. ­ type At the same time, the selective tropicity of theaction of atypical antipsychotics on the mesolimbic and mesocortical dopaminergic systems of the brain, as well as a much less pronounced effect on the nigrostriatal system, which is directly related to a significantly more favorable safety profile.

As a result, atypical antipsychotics optimally meet the following criteria for the effectiveness of antipsychotic therapy in geriatric practice, which implies:

• antipsychotic action, comparable in its severity with the classical representatives;
• effects on negative symptoms;
• effects on cognitive symptoms;
• effects on affective symptoms;
• effectiveness in many cases of resistance to conventional neuroleptics.

Finally, it is the assessment of the safety of pharmacotherapy with these drugs, based on the knowledge of the characteristics of the development of certain side effects, that becomes the decisive factor in choosing an instrument of treatment with neuroleptics in a particular patient in old age. As a result, the question arises about the criteria for choosing one or another atypical in gerontopsychiatry.

Each of the atypical antipsychotics is characterized by a peculiarity of the mechanisms of action, clinical effects, and finally, significant differences in the safety profile and, accordingly, differences in the therapeutic spectrum, which determines the feasibility of administering a particular drug in certain clinical forms and syndromes.

One of the most peculiar atypical antipsychotics is quetiapine . It is quetiapine that is considered today by many authors as one of the optimal antipsychotics for treating older patients of their age groups , which is largely due to its original, very own ­ figurative mechanism of action.

Mechanisms of action of quetiapine

Quetiapine blocks D2 receptors ­ type only in mesolimbic and mesocortical dopaminergic systems in the central nervous system, having a very low resistance to D2 ­ nigrostriatal and hypothalamic receptors ­ pituitary ary systems. According to modern ideas, D2 blockade ­ mesolimbic andmesocortical receptors are directly associated with manifestations of the antipsychotic effect, and interaction with D2 ­ receptors in the substantia nigra and striatum are associated with the development of extrapyramidal complications – syndrome of drug parkinsonism and late dyskinesias .Thus, it becomes clear one of the most important clinical benefits of quetiapine – the presence of a pronounced antipsychotic effect in combination with a minimal risk of neurological motor disorders.

Quetiapine is also quite intensively bound to serotonin 5 ­ NT2A ­by receptors. It is known that serotonin receptors of this type are widely represented in the frontal cortex and various parts of the brain, and that the serotonergic system after 5 ­NT2A ­receptors have a modulating effect ondopaminergic structures. According to modern concepts, the serotonergic system plays a key role in the pathogenesis of schizophrenia, in particular, its disorders are directly related to the development of negative symptoms, affective disorders, and secondary cognitive deficits.

Finally, the weakening of serotonergic processes and the imbalance between individual subtypes 5 ­ NT2 ­ receptors – one of the leading mechanisms of brain aging and development in zrastzavisimoy CNS pathology. Therefore, the serotonergic mechanisms of quetiapine action are of particular interest from the point of view of its use in gerontopsychiatry.

It is also important to emphasize the absence of any ­either quetiapine interactions with postsynaptic M ­cholinoreceptors, which is one of the most important clinical benefits of this drug – the almost complete lack of risk of extrapyramidal adverse reactions (acute dystonia, akathisia, catalepsy, tardive dyskinesia, drug parkinsonism) – the leading side effect of conventional antipsychotics.

In general, it seems today that the basis of the pharmacological effects of this drug is not so much blockade of certain receptors per se (in its neurochemical sense), but rather a modulating action aimed at normalizing the imbalance of activity of both individual neurotransmitter systems and within the same system (dopamine ­ and serotonergic ), mediated by different receptor subtypes. At the same time, it is this imbalance that serves as the foundation for aging of the brain and disorders of the integrative function of the central nervous system. Quetiapine, like no other atypic, has a normalizing effect on the imbalance mentioned, that is, to a certain extent one can speak of the presence of geroprotective (in their psychiatric understanding) properties of this drug.

In clinical practice, equal efficacy of quetiapine and conventional neuroleptics ( haloperidol , chlorpromazine , fluphenazine , etc.) was demonstrated in reducing positive clinical symptoms based on analysis of various clinical scales (short psychiatric rating scale, scale of overall clinical impression, assessment scale of negative symptoms, etc. ) both during the acute as well as stabilizing and n rotivoretsidivnoy therapy. At the same time, the most important aspect of quetiapine action , in contrast to classic drugs, is the beneficial effect on negative symptoms.

In gerontopsychiatry, an effective effect on hallucinatory ­ delusional symptomatology expressed Decrease the shenie paranoid symptoms.

The beneficial effects of quetiapine on cognitive functions, such as attention, performing functions, and verbal memory, deserve special attention . The severity of cognitive deficit in schizophrenia in old age is considered as the most important indicator in assessing the social and therapeuticprognosis of the disease.

Finally, quetiapine demonstrated the possibility of correcting affective symptoms (depression) in schizophrenic patients by positively affecting the entire cluster of affective disorders, according to a short psychiatric rating scale. Given the importance of the problem of depression in geriatrics, as well as the poor efficacy in stopping these symptoms of traditional antipsychotics and antidepressants, this property of quetiapine deserves special attention.

Quetiapine Safety Profile

Quetiapine optimally meets the criteria for selecting an atypical neuroleptic for geriatric practice in terms of effectiveness, breadth and variety of clinical ­ pharmacological action. However, the main advantage of Quetiapine, which ensured its wide popularity in the world psychiatric practice and, in particular, in gerontopsychiatry, is safety. It is by this criterion that it significantly exceeds not only conventional, but also the majority of atypical neuroleptics .

As already mentioned, due to the lack of affinity for M ­ brain cholinergic receptors, as well as a slight affinity for D ­ to the receptors in the nigrostriatal system, quetiapine is practically devoid of extrapyramidal side effects – the most important negative effect of the use of antipsychotics.

In this respect, the safety of quetiapine significantly higher than traditional drugs, and that kzhe risperidone and olanzapine, is important to emphasize that this characteristic of quetiapine is celebrated all over the therapeutic dose range (100 – 800 mg/day), that is, with increasing doses, as well as with long courses of use, the risk of developing extrapyramidal complications (including tardive dyskinesia) remains minimal.

As you know, serious problems associated with the use of both classical and atypical neuroleptics are the development of hyperprolactinemia (due to the effect on D ­receptors in the hypothalamo ­ pituitary system) and related sexual dysfunction (including gynecomastia, galactorrhea), as well as the formation of osteoporosis, disorders of water ­ salt metabolism, etc. Many atypical neuroleptics (risperidone, olanzapine, amisulpride) to some extent cause hyperprolactinemia, which in some cases can become a serious clinical problem and lead to the replacement of the drug.Quetiapine is almost completely devoid of the ability to cause these disorders, which significantly increases the safety of its use.

Finally, quetiapine has minimal risk (unlike traditional drugs and olanzapine) for developing metabolic disorders, such as weight gain and diabetes.

The most common side effects of quetiapine are sedation, somnolence, orthostatic hypotension, dizziness, dyspepsia, that is quite soft manifestations are typically dealt with decreasing dose. The likelihood of complications such as malignant neuroleptic syndrome and leukopenia is very low and does not differ in this respect from that of other atypical antipsychotics. Quetiapine, unlike clozapine, does not cause agranulocytosis.

In general, quetiapine can be characterized as one of the atypical antipsychotics most favorable in terms of safety. In combination with the characteristics of the clinical spectrum of action and pharmacokinetics, this allows recommending it as the drug of choice in elderly and senile patients, with a combination of psychotic disorders with dementia and Parkinson’s disease .

Quetiapine preparations Seroquel deserves special attention in the pharmaceutical market in the form of tablets of 25, 100 and 200 mg, which allows you to fully meet the needs for individualization of the dose regimen in different categories of patients depending on the clinical form of the pathology, severity of the condition, age, presence of concomitant diseases, features of combined pharmacotherapy, etc.

Seroquel It is produced in full compliance with all GMP requirements and European quality criteria and, at the same time, it is the most economically available drug Quetiapine , which significantly expands its prospects in domestic clinical practice and is a significant advantage over foreign counterparts.

In general, quetiapine is a promising atypical neuroleptic that deserves widespread introduction into domestic clinical practice. Further accumulation of experience in its use will allow optimizing the pharmacotherapy of schizophrenia in old age in accordance with modern international standards.

For many psychiatrists, it is typical to refuse to isolate and describe these psychoses as a separate group or form. Depending on which of the two endogenous diseases according to Kraepelin’s classification (schizophrenia or manic-depressive psychosis), the authors understand more widely, the psychoses in question are either classified as classic forms of schizophrenia or included in manic-depressive psychosis. This kind of reduction of these psychoses to better known ones is reflected in many textbooks, monographs, articles on acute schizophrenia, on the acute stage of schizophrenia, on the forms of the course of schizophrenia, on atypical forms of manic-depressive psychosis, etc.

Other authors have attempted a new clinical assessment, including psychopathological and nosological. So, T. Ya. Khvilivitsky (1957) subjected to clinical and laboratory study of 100 patients with atypical manic-depressive psychosis. As a type of atypical forms of circular psychosis, the author studied: a group of patients in whom the disease proceeded in the form of brief twilight and oneiroid disorders of consciousness on a depressive or manic background; diseases with oneiric states occurring in phases; cases of manic-depressive psychosis with catatonic symptoms; diseases with a picture of somatophrenia Bechterew; cases of mixed states. The author came to the conclusion that these atypical forms of manic-depressive psychosis are characterized by: the persistence of atypical manifestations over a long time, the possibility of asthenic-abulic personality changes, the presence of microorganic symptoms and other biological deviations. The author noted the paramount importance of exogenous hazards in the origin of these psychoses. He proposes to distinguish these forms from manic-depressive psychosis.

This desire is even more pronounced in the work of L. M. Lesokhina (1957), who believes that periodic psychosis is not reducible to manic-depressive psychosis or schizophrenia. As the general features and symptoms inherent in various types of attacks, the author describes: disorders of consciousness, vivid dreaming experiences, symptoms of depersonalization, various extremely painful sensations, quickly emerging peculiar and pronounced speech incoherence, sharp affective outbreaks (usually occurring outside the attack, etc.). The author describes 5 forms of attacks:

1) paroxysmal pseudo-mania states;

2) paroxysmal stuporous states

3) paroxysmal twilight states,

4) paroxysmal delusions;

5) seizures with a mixed clinical picture, in which episodes of agitation of stupor and delusional states are combined.

NN Bodnyanskaya (1958), entitled “Periodic psychosis in children and adolescents”, describes two types of such psychosis: periodic psychosis with an episodic course and periodic psychosis with a phase course. The first version includes three options:

1. a) with a predominance of acute disorders of consciousness (pathological drowsiness, oneiric states with fantastic content, twilight states); b) a variant with a predominance of motor disorders (stupor and psychomotor agitation), c) a variant with affective disorders (disinhibition with euphoria and depression).

In the clinical picture of the second type, a combination of disorders of consciousness (oneiric, twilight), affectivity (organic disinhibition with apathy), disorders of effector functions (agitation with elements of violence and catatonic symptoms) is noted. The author believes that infectious diseases with damage to the central nervous system (meningitis, paraencephalitis or secondary encephalitis, and cranial injuries that last suffered) are of primary importance in the occurrence of these psychosis. Psychosis occurs in a period of remote consequences. Age (puberty), infections, and psychogenic are important for the onset of an attack. A large group of Soviet psychiatrists conduct a consistent, long-term study of acute atypical psychoses. These studies, initiated by A. V. Snezhnevsky with employees at the Department of Psychiatry, have expanded considerably since 1962 and are currently being continued by both the staff of the Institute of Psychiatry of the Academy of Medical Sciences of the US and the Department of Psychiatry.

Despite the fact that acute psychosis under the name “periodic schizophrenia” was considered within the framework of schizophrenia, their study was actually conducted and is being conducted as a study of a kind of material that is clinically rather clearly defined.

At the first stage of research, attention, naturally, was directed to the clinical-psychopathological description and selection of the most frequently encountered types (forms) of periodic schizophrenia.

So, Druzhinina (1956), on the basis of a study of 80 patients, described a form of catatonic schizophrenia, which is characterized by the presence of oneiroid disorders – and paroxysmal course.

A detailed description of oneiric catatonia was made by V.N. Favorina (1956). The author highlighted the main clinical and structural features of the attacks. In addition to describing the external (catatonic) and internal (oneiric) aspect of the developed seizure, V.N. Favorina noted that there are certain regularities in the development and in the extinction of seizures. According to the peculiarities of the clinical picture of the attacks, the author divided the patients into a group with an expansive

a form of oneiric experiences and a group with a predominance of depression and stupor.

Further, the clinical picture of acute paraphrenia was described in detail (N. G. Shumsky, 1958; V. N. Favorina, 1959). The closeness of the clinical picture of attacks to the oneiric stupefaction and the possibility of mutual transitions have been proven. V.N. Favorina observed the course of the disease in the form of acute paraphrenic attacks of the same type as well as in the form of heterogeneous attacks (catatonic, acute paranoid, atypical manic, etc.). As with other attacks of recurrent schizophrenia, a favorable prognosis of attacks (at least at the onset of the illness) and a tendency to relapse were noted.

In the work of B. V. Sokolova (1957), depressive-paranoid schizophrenia was studied. Were described 3 of its varieties:

1) anxiety-depressive variant, which is characterized by prolonged anxious and melancholy states with agitated arousal, fear, confusion, bright Kotar syndrome and the course of psychosis in the form of the same type of attacks;

2) a variant with a predominance of delusional syndrome; when it is dominated by delusions of relationship and persecution, pronounced verbal hallucinosis and Kandinsky’s syndrome — Clerambo or illusory nonsense;

3) option with severe depressive stupor or catatonic disorders.

1. Ya. Ilon (1957) made a clinical description of circular schizophrenia. The author singled out three options: for the first of them (catatonic), the combination of affective manifestations with severe catatonic disorders was characteristic. The main feature of the second (delusional) variant of circular schizophrenia is, according to the author, a combination of affective disorders with delusions and hallucinations. In the third variant of circular schizophrenia, the author observed, as a distinctive feature, the onset of the disease with disorders characteristic of the first manifestations of a simple form of schizophrenia (a decrease in working capacity, a change in character, a disorder of thought). According to the forecast, this option is the least favorable. L. Ya. Ilon came to the conclusion that the three selected variants of circular schizophrenia can be compared with the three forms of Crepelin’s early dementia: catatonic, delusional and idle.

Thus, the first studies of periodic schizophrenia were characterized by a desire to establish the clinical and psychopathological features of various types of seizures when classifying them as early dementia. In particular, this is evident from the authors’ assertion about the onset of a typical schizophrenic personality change.

AV Snezhnevsky (1960), summarizing the research of his staff at the first stage of studying schizophrenia, came to the following conclusions: periodic schizophrenia can be included as separate clinical options for oneiric catatonia, circular, depressive-paranoid, depressive-stuporous schizophrenia, periodic paraphrenia and febrile catatonia. All these options are combined with the presence of common clinical ingredients: the oneiric-catatonic, affective, fantastically dreamy, and phenomena of mental automatism. The clinical variant of the attack is determined by the relative predominance of one of the many ingredients in the clinical picture.

The predominance of one or the other of the latter often varies from attack to attack in the same patient. So, often the first attack of psychosis in patients with circular schizophrenia proceeded in the form of oneiric catatonia. Acute paraphrenia sometimes occurred as another attack of oneiric catatonia or, more commonly, circular schizophrenia. It was established as a common feature of various options for the frequent occurrence of the next attack under the influence of psychogeny, infection and other harmful factors. Thus, an important clinical fact of the presence of internal kinship (according to the main structure) and the possibility of alternating seizures that are very different in the syndromic structure (affective, catatonic, delusional) were established.

In subsequent years, continued clinical study of recurrent schizophrenia, further differentiation of seizures and their psychopathological characteristics.

Based on a detailed analysis of a large number of patients with hypochondriacal schizophrenia, G. A. Rotshtein (1961) concluded that within the framework of depressive-paranoid (periodic) schizophrenia, episodes of depressive-hypochondriacal structure can be observed. We are talking about acute attacks, which are characterized by a clinical picture of either reduced Comar syndrome (in the form of “outlined hypochondria”), or normal, or paraphrenic-like Coarre syndrome.

A significant result of the study of the psychopathology of attacks of periodic schizophrenia was the description of the successive stages of the development of the oneiric stupefaction. It was proved that the oneiroid states occupy a large place in the clinic of attacks of periodic schizophrenia, and not only periodic catatonia, but also circular and depressive-paranoid (S. P. Stoyanov, 1961).

1. S. Tiganov (1960) described 4 types of attacks of febrile catatonia: attacks with typical catatonic excitement, attacks with amental-like excitement, type of attacks with hyperkinetic arousal, and the form of attacks with a picture of a sub-attacker. Based on the study of the clinical and psychopathological features of attacks of febrile catatonia, the nature of recurrent attacks, A. S. Tiganov concluded that febrile schizophrenia is a special type of periodic schizophrenia.

Italian psychiatrists are experiencing great uncertainty regarding acute atypical psychosis. Although they recognize the classification of Kraepelin’s psychosis, with regard to acute psychoses with confusion, Italian psychiatrists are closer to the French. As a result, some of the acute atypical psychosis is included in the framework of mental confusion (episodic twilight states of Kleist, Meduna one-point fermentation, periodic amentia, delirium acutum). With respect to other atypical schizoform psychosis, the authors’ efforts are directed at resolving the issue of their belonging to schizophrenia or manic-depressive psychosis.

Nobile and Sciorta (1953) divided “autonomous” and “mixed” psychoses into three groups:

1) cases in which there is a schizophrenic picture with elements of manic-depressive psychosis. Options: episodes of manic arousal and depression with schizophrenic elements; cyclical forms of schizophrenia; delusional forms with a rich affect (for example, fantastic parafrenia);

2) atypical pictures that can not be attributed either to schizophrenia or to manic-depressive. psychosis (states of inhibition, some manic and depressive states, polymorphic delusional episodes);

3) atypical pictures of manic-depressive psychosis (pictures mostly manic-depressive with schizophrenic elements).

Giannini (1959) divides the “mixed” psychosis into 4 groups: circular attacks with an outcome to dementia; alternation of episodes of clearly schizophrenic and more typical circular; combination of schizophrenic and circular symptoms in one attack; circular schizophrenia without outcome in dementia.

Gregoretti and Gasparone (1961) believe that acute delusional psychosis can be divided into a form with a delusion of interpretation and into a psycho-sensory-interpretative form. Deep anxiety and a narrowing of the field of consciousness are characteristic of all forms. Nosologically, these psychoses are unclear.

Fiume and d’Avossa (1959) described a similar psychosis called “oneiric syndromes”. In their opinion, these psychoses are characterized by the fact that hereditary readiness and psychogenic provocation play a decisive role in their occurrence. Psychopathologically, there is hyper-acidity of consciousness and its affective narrowing, arousal, quickly turning into a stupor, “pendulum transfer from the real world to the world of hallucinations”, fluctuation of affect, loss of temporal-spatial connections of experienced events. This “presence and non-presence in the world” gives rise to disorientation and secondarily delusional mood. The prognosis of the disease is very favorable. The authors attribute these “syndromes” to atypical schizophrenia. In another work – Giannini and Del Carlo Giannini (1959), on the contrary, believe that they should be attributed to atypical manic-depressive psychosis.

A great interest in these psychosis has been shown for many years. Scandinavian psychiatrists. The works of Langfeld (1939, 1961) and his collaborators on the division of “schizophrenia” into procedural and combined groups of “schizoform” psychoses are known. For these works, the desire is primarily with the help of the follow-up check to separate schizophrenia from schizoform psychosis.

Welner and Stromgren (1958) call these psychosis benign schizophrenia and attach great importance to the effects of nonspecific factors, and especially psychogenias. In addition to reactive (paranoid, depressive, confused) psychoses, it is assumed that “schizoform psychosis” sometimes includes true schizophrenia, atypical manic-depressive psychosis, and some organic psychoses (Stromgren, 1965).

In the works of Astrup, Possum and Stolmboe (1963), Astrup and Noreik (1966), “functional psychosis” was subjected to clinical and catamnestic, clinical and genetic studies, the study of prognostic factors, etc. Acute atypical psychosis is located between schizophrenia and manic-depressive psychosis. They are grouped around two diagnostic concepts – “schizoform” and “reactive” psychoses of depressive, paranoid, hysterical and confused types.

For the designation of individual types of attacks, either the terms of the Kleist – Leonhard school (various cycloid psychosis, unsystematic schizophrenia, etc.), or more general concepts: depression, agitation (mania), confusion, paranoid, hebephrenic, catatonic, were used.

The concepts of “schizoform” and “reactive psychosis” used by Scandinavian psychiatrists, as shown by their own tests, do not have a clear content. In a large number of cases [in 37% ‘of Astrup, Dalgard, Itolmboe (1967)] reactive psychosis, a follow-up revealed schizophrenia. The study of the frequency of diagnostic errors revealed some of their decline (Holm-boe, Noreik, Astrup, 1968).

The famous Dutch psychiatrist Rumke (1958) paid attention to the clinical division of pseudochemophrenia. Separating pseudo-schizophrenia from true schizophrenia, the author divides them into atypical circular psychosis, degenerative psychosis, paranoid psychosis, “acute outbreaks in schizoids, and occasional delusions of degenerants” (he refers to pseudoshizophrenia as organic psychoses).

In US psychiatry, the clinical side of these psychoses has been little studied. Some studies recognize the separation of schizophrenia into classical early dementia and reactive schizophrenia (Bellak, 1958). In the manual on psychiatry edited by Arieti (1959), these psychosis are mentioned when describing catatonic and schizoaffective forms of “schizophrenic reaction”, manic-depressive psychosis (acute parafrenia, delirium acutum), paranoid reactions (acute delusional psychosis). Polatin (1964) among atypical forms of schizophrenia describes: 1) acute states of confusion, characterized by sudden onset disorder of orientation and confusion. When they are observed “dreaming experiences and the similarity of the clinical picture with delirium.”

The author considers the clinical type of such psychosis to be transient, so-called “three-day schizophrenic reactions”, observed in the military during the war, some postpartum psychosis. In these attacks, psychomotor disorders (stupor or agitation), hallucinations and illusions also occur. These psychosis can be provoked; 2) “micro-catatonia”, which is “a periodic or cyclic form of schizophrenia with unreal experiences, special behavior and a sudden exit with almost no personality change”; 3) schizoaffective psychosis. Depressive psychosis in a broad sense. At the beginning of attacks to 30 years can not make a prediction.

A group of authors (Wada, Tanaka, Ogasavara and Sacu-rada, 1963), who agree with the concept, divides atypical psychosis into 3 groups: the first group is characterized by a pronounced disorder of consciousness, acute hallucinatory-delusional disorders, a one-way nervosa, delirium or stupor. The attack lasts 1-2 months, the prognosis is good. The second group is characterized by manic-depressive colouration, emotional instability, psychomotor symptoms, delusions and hallucinations. For phase, the duration of attacks 2-3 months., The prognosis is favorable. Patients of the third group have a pronounced “schizophrenic nuance”, catatonic symptoms, and a large variability of affect. The attacks last 4-5 months, the course of the type “continua”, the prognosis is relatively favorable.

Hatotani et al. (1962) believe that atypical psychosis is borderline between epilepsy, manic-depressive psychosis, and the schizophrenia group. According to the clinical picture, they distinguish between acute hallucinatory-delusional, oneiric, and confused-delirious states. The clinical picture is dominated by affective disorders, disorders of consciousness and psychomotor disorders.

Thus, in Japanese psychiatry, we find the same diversity of opinions on the clinical evaluation of these psychoses. In terms of the syndromological designation of seizures, the opinion of Kleist and Leonhard is quite common. In terms of the psychopathological structure, many Japanese psychiatrists accept the concept.

In modern Soviet psychiatry, the clinical assessment of acute atypical psychosis also gives rise to controversy. These disagreements concern not only the issues of nosological assessment, classification, typology, but also the definition of the psychopathological structure of the attacks, their designations, and systematics.

Epidemiology. Cocaine is a derivative of the coca plant (Egthroxylon coca, birthplace – Central America), the leaves of which the Indians have long used to chew in order to obtain a stimulating effect and reduce hunger. Cocaine was part of the original formula of coca-cola drink and, until now, has medical use as a local anesthetic. In connection with the cheaper manufacturing process, cocaine use has been steadily increasing since the late 1970s. Psychological mechanisms predisposing to cocaine use, are the desire to improve their self-affirmation, social status and escape from depression.

Clinic. The main pharmacodynamic effect of cocaine is blockade of dopamine, serotonin and epinephrine receptors. The nature of its specific activation of mesocortical dopaminergic structures is unclear. Cocaine powder is more often inhaled through the nose, or when smoking (“crack”) its alkaloid form is inhaled. Subcutaneous and intravenous administration is also used. The drug gives an intense feeling of euphoria, lasting 15-30 minutes. after intravenous or intranasal administration.

In addition to the main ones (see below), signs of acute intoxication can be impulsive sexual and psychomotor agitation, often reminiscent of a hypomanic condition, decreased concentration, insomnia. Signs of intoxication are spontaneously stopped within 48 hours, however, the state of dysphoria and increased fatigue accompanying the reversal is easily removed by cocaine, alcohol or sedatives, which stimulates repeated abuse. A characteristic behavioral trait is the desire, being in a social environment, often retire to take the drug.

Many of the users of cocaine, while controlling its use, have long avoided physical dependence, but the opinion that cocaine does not cause it, which was widespread in the 1970s, turned out to be erroneous. The period of dependence formation is 4 years in adults and 1.5 years in adolescents. Psychological dependence develops very quickly and may appear after a single dose. Under experimental conditions, monkeys, which are given the opportunity to introduce themselves to cocaine, do this all the time, until death occurs against the background of suppression of the activity of the centers of the medulla oblongata. People often have a “drunken” stereotype of use – from several hours to several days with weight loss, dehydration, high risk of psychosis and death. Death, however, is more likely when cocaine is used to potentiate the effects of opiates.

Cocaine psychosis is clinically similar to amphetamine. Perhaps dangerous to others aggressive behavior. Tactile hallucinations are often accompanied by a feeling of insects crawling under the skin. This phenomenon is referred to as “crawling”, “cocaine insect” or Magnan symptom, which was first described in 1889. It is usually associated with the parenteral administration of cocaine.

With prolonged intranasal admission develops chronic rhinitis, ulceration of the nasal mucosa, up to necrosis of the nasal septum due to vascular spasm. Reducing serotonin levels contributes to the appearance of depression and suicidal tendencies on the background of withdrawal syndrome. The peak of the withdrawal syndrome occurs at 2-4 days after discontinuation, although some symptoms (depression, irritability) can persist for up to several weeks.

Cocaine has a generalized sympathomimetic effect on the vascular system, which can lead to cardiac arrhythmias and a high rise in blood pressure with hemorrhage in the brain as a possible complication. Other complications can be myocardial infarction and status epilepticus.

The diagnosis of acute intoxication is made on the basis of common for Fix. On the criteria, as well as: 1) the presence of at least one of the following mental symptoms: a) euphoria with a sense of energy surge, b) a feeling of increased vigor, c) a tendency to reassess one’s own personality, grandiosity of plans, d) conflict, aggressive behavior, e a) affective instability, e) repeatability, stereotyped behavior, g) auditory, visual or tactile illusions, h) hallucinations with intact orientation, and) paranoid ideas, j) reduced mental productivity and productivity; 2) the presence of at least two of the following somatic symptoms: a) tachycardia (sometimes bradycardia), b) cardiac arrhythmia, c) hypertension (sometimes hypotension), d) alternation of profuse sweat with a feeling of cold, e) nausea, vomiting, e) loss weight, g) pupil dilation, h) psychomotor anxiety (sometimes adynamia), and) muscle weakness, j) chest pain, l) convulsive seizures.

The diagnosis of withdrawal syndrome is made on the basis of common criteria for Flx.3, the presence of affective disorders (for example, depression or anhedonia), as well as at least two of the following symptoms: a) feeling of increased fatigue, b) psychomotor retardation or anxiety, c) craving for cocaine, d) increased appetite, e) insomnia or increased sleepiness, f) freakish or unpleasant dreams.

Treatment. In case of acute cocaine intoxication, oxygenation of the lungs (if necessary under pressure) in the Trendelenburg pose is prescribed. In the presence of seizures, intravenous diazepam (5-10 mg). The latter is also indicated in the presence of anxiety with hypertension and tachycardia. It is also possible to introduce an antagonist of the sympathomimetic effect of cocaine – propranolol (every minute / 1 mg to 8 minutes), although it is not a defense against lethal doses or a treatment for severe overdose.

Emerging psychotic symptoms is an indication for the appointment of neuroleptics. A stationary stay when taken out of a state of intoxication has, inter alia, The goal is to prevent access to the drug and control suicidal tendencies. Sleep therapy (lorazepam) aims to better subjectively tolerate withdrawal symptoms. In some cases, tricyclic antidepressants, MAO inhibitors, and lithium (with an affect cycle) are effective for maintaining abstinence.

Psychotherapy and rehabilitation is carried out as in alcoholism. Significantly contributing to the substitution of the illusory psychological effect of cocaine more realistic self-affirmation of the patient in social life. Interpersonal therapy focuses on the analysis of communicative behavior, specific situations that are the starting points for anesthesia. In a state of cocaine abstinence, substitution alcoholism is fraught with a relapse of cocaine.

Mental and behavioral disorders resulting from the use of other stimulants, including caffeine

Clinic. The most well-known nervous system stimulants are amphetamine dextroamphetamine (dexedrine), methamphetamine (methedrine), methylphenidate (Ritalin). The pharmacodynamic effect is ensured by interfering with the metabolism of serotonin, norepinephrine and (more so than cocaine) dopamine. Stimulants are usually taken by mouth, although intravenous administration is also used. Small doses cause a rapid improvement in health, an increase in mental productivity, a decrease in feelings of fatigue and hunger, and a reduction in the pain threshold. This justifies the medical use of drugs for concentration disorders in children and adults, obesity and potentiation of the action of antidepressants.

High-risk groups of abuse: patients undergoing obesity treatment, professional athletes, drivers on long-haul flights. With an increase in tolerance, the daily dose can reach 1 g; conditionally lethal dose is 120 mg. The symptoms of acute intoxication and withdrawal are generally identical to those of cocaine use (see F14). In addition to the main somatic symptoms, in a state of intoxication can be observed: the game of vasomotors, cyanosis, minor hemorrhages, subfebrile, bruxism (gnashing of teeth), difficulty breathing, tremor, ataxia; in severe cases, coma. Here are often observed t. amphetamine stereotypes are essentially purposeless repetitive actions, such as the constant cleaning of shoes or the assembly and disassembly of electrical appliances. Mental manifestations may include anxiety, dysphoria, irritability, internal stress, logorei, insomnia, disturbances of the body, anxiety, confusion.

A characteristic sign of caffeine withdrawal may be a persistent or throbbing headache that develops 15–18 hours after the last dose. Death from overdose occurs on the background of hyperthermia, seizures, and cardiovascular insufficiency. The most dangerous and characteristic symptom of withdrawal is depression with suicidal tendencies. In contrast to schizophrenia, psychotic intoxication episodes characterize hyperactivity, hypersexuality, the prevalence of visual hallucinations over the auditory, less pronounced disorders of thinking.

Treatment. With overdose therapy, the oxidation of urine (ammonium chloride) contributes to the acceleration of the drug from the body. When treating withdrawal syndrome, hospitalization may be necessary to control suicidal and socially dangerous behavior. The high degree of dependence on the drug makes psychotherapy especially difficult here.

Clinic. Hallucinogens (psychedelics, psychotomimetics) are not a very successful designation for a team of over 100 natural and synthetic drugs. The most well-known of the natural ones are psilocybin, derived from mushrooms, and mescaline, produced from a certain type of cactus; Lysergic acid diethylamide (LSD), dipropyltryptamine (DPT) and 3,4-methylenedioxymethamphetamine (MDMA, also known as Extasy) are synthetic. Hallucinogens interfere with the metabolism of catecholamines, dopamine, acetylcholine, serotonin and GABA, causing the disinhibition of the activity of the occipital regions of the brain and limbic structures. For some drugs, there may be zones of specifically sensitive receptors in the brain.

Psilocybin has long been used in religious rituals of American Indians. The use of hallucinogens is largely susceptible to sociocultural influences. Their greatest popularity in the United States and Europe falls on the 60-70-ies, when they were considered one of the symbols of the youth subculture.

The quality and duration of subjective sensations when taking depends on the type of drug. Thus, affective changes are more characteristic of the action of MDMA; the widest range of perceptual disorders is characteristic of LSD. The effect occurs within an hour after oral administration and lasts 8-12 hours; with other drugs, the effect lasts from several hours to several days.

Psychological manifestations are largely determined by the personal characteristics of the user, his expectations and micro-social factors, but LSD almost always gives deep violations of perception, affect and thinking. In some cases, the effect of the drug is subjectively perceived as a manifestation of mental illness, accompanied by panic reactions. The intensity of perception of smells and tastes increases, the colors are perceived as richer, the texture and outlines of objects are more distinct, the emotional perception of music deepens. Marked so-called. synesthesia: colors may be perceived as sounding, sounds may be perceived as visible. Observed disorders of the body scheme, violations of the perception of space and time. Own Self is perceived dissolved in the surrounding world, separated from the body, floating in mystical ecstasy. Visual hallucinations predominate, often in the form of geometric shapes and figures. The intensity and changeability of emotions increases, various variants of affect can be felt simultaneously. Non-verbal perception becomes more significant, suggestibility increases sharply. A general increase in the severity of perception can cause a subjective feeling of internal organs, the emergence of long-forgotten memories. Usually there is a deepening of introspection, philosophical ideas, religious feelings, after which there remains a false idea of ​​increasing the creative potential of one’s own personality, of its cardinal changes.

The most typical complication is the so-called. “Bad trip” (bad trip), similar to a panic reaction with intoxication with cannabinoids, usually accompanied by psychotic symptoms lasting up to several weeks or longer. It occurs in approximately 25% of users. It is also possible flashback (return to the past), lasting from a few seconds to several hours, occurring outside the drug intake and provoked by a stressful state, the use of cannabinoids. Sometimes they can be called arbitrarily. In some cases, hallucinogens provoke endogenous psychosis. Anxiety-depressive syndromes with suicidal behavior are also a complication. The most susceptible are persons with anxious, unstable, schizoid personality traits and in a prepsychotic state.

Prolonged addiction rarely occurs due to the lack of reliable euphoria and the unpredictability of each episode of intoxication. There is no physical dependence, withdrawal syndrome. Tolerance develops quickly, disappearing just as quickly, within 2-3 days.

The diagnosis of acute intoxication is made on the basis of common criteria for F1x.0, as well as: 1) the presence in the clinical picture of at least one of the following signs: a) fear, anxiety, b) visual, auditory or tactile illusions and hallucinations with an increase in the perception acuteness and concentration, c) depersonalization, derealization, d) paranoid ideas, relationship ideas, e) affective instability, e) increased activity, g) impulsive behavior, h) concentration disturbances, and) a decrease in mental productivity; 2) at least two of the following symptoms: a) increased frequency, as well as increased heartbeat, b) alternation of profuse sweat and cold feeling, c) tremor, d) blurred vision, e) pupillary dilation, e) coordination disorder.

Treatment. In acute intoxication, emotional support and encouragement are usually sufficient, although in case of severe anxiety, the appointment of anxiolytics may be necessary, and sometimes – butyrophenones (phenothiazines should be avoided, since they can potentiate the anticholinergic effect).

F17 Mental and behavioral disorders due to tobacco use

Clinic. The average cigarette contains 0.5 mg of the active substance of tobacco – nicotine. A conditionally lethal dose is 60 mg. Physiological effects include narrowing of peripheral vessels, increased peristalsis, increased release of catecholamine, norepinephrine and epinephrine, a general decrease in metabolism, and tremor. In smokers, women have a low birth weight.

Social factors influence consumption: in adolescents, this may be a manifestation of reactions of protest, emancipation, the desire to appear as adults, conformity to the subculture of their peers. In adults, reinforcement is provided by pleasant associations with situations of feasts, sex; trade advertising plays a significant role.

Smokers are distinguished by a certain set of personality traits: greater impulsive behavior, a lower level of education, a higher frequency of divorces, greater extroversion, anxiety, ill will, and a tendency to alcohol abuse. Nicotine stimulates the hypothalamic pleasure center, which may explain the appearance of addiction. The euphoric effect is somewhat similar to the action of cocaine and opiates. The calming effect is proportional to the duration of the pause between smoking.

In addition to the main signs, the state of acute intoxication may include increased salivation, abdominal pain, diarrhea, headaches, dizziness. Smoking can complicate psychiatric medication, increasing liver metabolism and reducing the level of antipsychotics and antidepressants in the blood. Dependency, primarily psychological, develops quickly, about 85% of people continue to smoke after the first cigarette. To nicotine produced tolerance.

The withdrawal syndrome develops within 1.5-2 hours after the last use, reaches a peak during the first days and lasts for several weeks or longer. The core symptom of withdrawal — craving for smoking — can persist for many years of abstinence in the absence of other signs of withdrawal. Drowsiness during the day is combined with the difficulty of falling asleep. There is a slowing of the heartbeat, a decrease in blood pressure and motor activity. The temporal stereotype and mechanisms of recurrence are similar to those in the use of alcohol and opiates. Relapse is observed in 80% of smokers in the first 2 years of abstinence. Recurrence is promoted by a high level of social stress, social maladjustment, low self-esteem.

The diagnosis of acute intoxication is made on the basis of the criteria common to Flx.0, as well as: 1) the presence of at least one of the following symptoms: a) insomnia, b) fancy dreams, c) affective instability, d) derealization, e) reduced mental productivity; 2) at least one of the following symptoms: a) nausea, vomiting, b) profuse sweating, c) tachycardia, d) cardiac arrhythmia.

The diagnosis of withdrawal syndrome is made on the basis of common criteria for Flx.3, as well as the presence of at least two of the following symptoms: a) craving for tobacco use, b) malaise, weakness, c) anxiety, d) dysphoria, e) irritability or anxiety, e) insomnia, g) increased appetite, h) cough, and) ulceration of the oral mucosa, k) decreased concentration.

Treatment. Many therapeutic approaches are used, none of which have demonstrated advantages over the other. The most commonly used are various forms of suggestion (the so-called “coding”, acupuncture), aversive behavioral therapy, replacement therapy (chewing gum with nicotine to alleviate the withdrawal syndrome, or lobeline, giving a nicotine-related effect). In the period of cancellation, anxiolytic therapy is advisable. Success is promoted by the presence of support from relatives and a group of abstinent smokers, fear of the somatic consequences of smoking (lung cancer, CHD).

Smokers seeking help are the most therapeutically resistant, treatment programs yield not more than 20% of successful cases; at the same time, 95% of abstinents did not receive medical care, leaving it unclear how or why they stopped smoking. Prognostically unfavorable factors are unsatisfactory social adaptation, female gender, a high level of use before therapy.

F18 Mental and behavioral disorders due to the use of volatile solvents

Clinic. For narcotic purposes, the following volatile solvents are used: gasoline, lacquer solvents, various types of glue, cleaning liquids, aerosols (especially paints), amyl and butyl nitrates. Nitric oxide, ester, is specifically used by health professionals who have access to these substances and are a contingent that is fundamentally different from the main users. The overwhelming majority of users are children and adolescents from 6 to 16 years of age from low-income strata of society.

Inhalation is carried out directly from the packaging or with a cloth moistened with a substance or a plastic bag that is pulled over the head. Intoxication occurs in 5 minutes and lasts 15-30 minutes. During intoxication, the euphorizing effect is replaced by inhibition.

In addition to the main, signs of acute intoxication can be an overestimation of one’s own personality, a feeling of invulnerability, superior strength, a feeling of soaring, dizziness, disturbances in spatial perception, and certain psychotic symptoms. Possible amnesia period of intoxication. Rod aggressive behavior leads to frequent offenses; decrease in mental productivity is accompanied by difficulties in learning.

Among the somatic effects may be nausea, loss of appetite, decrease in tendon reflexes. Death may occur as a result of central respiratory arrest, cardiac arrhythmias and accidents. Somatic effects affect the bone marrow, kidneys, liver, peripheral neuritis. There is an increase in tolerance, although there is no convincing evidence of the presence of withdrawal syndrome. The use of volatile substances, being, as a rule, a transient disorder, often ends with a transition to other forms of drug addiction or alcoholism.

Diagnosis. Traces of volatile solvents (as well as hallucinogens) are not detected in the urine by laboratory methods. Tangible signs of use can be hyperemia of the skin in the nasal area, conjunctivitis, inflammation of the mucous membranes of the upper respiratory tract, peculiar smell from the mouth, traces of the substance on the face, hands and clothes. The diagnosis of acute intoxication is made on the basis of the criteria common to F1x.0 and: 1) the presence of at least one of the following mental symptoms: a) apathy, indifference, b) conflict, aggressive behavior, c) affective instability, d) reduced focus of thinking, d ) impaired concentration and memory, e) psychomotor inhibition, g) decreased mental productivity; 2) as well as at least one of the following neurological signs: a) unsteadiness of gait, b) Romberg’s negative test, c) blurred speech, d) nystagmus, d) impairment of consciousness (eg, stupor, coma), e) muscular weakness, g) blurred vision, diplopia.

Epidemiology. All hypnotics and sedatives potentiate the action of each other and alcohol. Abuse has different stereotypes. One of them is for persons of predominantly middle-aged persons to receive constant access to drugs through doctors as part of anxiety and insomnia therapy. They can prescribe medications from several doctors at the same time, drug dependence often remains unnoticed by others until the appearance of physical signs of abuse. Drugs can be used occasionally by adolescents to obtain a sedative or euphoric effect. They are used by experienced drug addicts for intravenous administration due to their greater cheapness compared to heroin or to potentiate the effect of weak opiates. Alcoholics use them to increase intoxication or alleviate the syndrome. Abusive stimulants use them to relieve excessive arousal. Diazepam is used by cocaine addicts to alleviate the withdrawal syndrome.

Clinic. Intoxication is subjectively perceived as a feeling of pleasant, warm drowsiness, its small degrees resemble alcohol intoxication. In addition to the main ones (see below), symptoms include a decrease in the focus of thinking and memory, a slowdown in speech and understanding, episodes of sexual disinhibition, and an accentuation of the main personality traits. General inhibition disappears in a few hours, but violations of fine motor skills, thinking and affect can last 10-20 hours. Against the background of dysphoria, transient paranoid perceptions and suicidal tendencies can occur.

Physical signs, besides the main ones (see below), may include diplopia, strabismus, decrease in blood pressure and height of tendon reflexes. Death can occur as a result of suicide, an accident, or an unintentional overdose (the lethal dose for an experienced drug addict can be, under certain conditions, not higher than for a novice). These drugs are most often used in the implementation of suicidal tendencies. Death comes on the background of deep coma, respiratory arrest and cardiac activity.

With regular admission, increased tolerance is produced. The dose of an experienced drug addict is 1.5-2 g per day. Physical dependence develops as a result of taking low doses (10-40 mg per day) for several years or high doses in just a few weeks or months. Receiving doses higher than therapeutic for several weeks or more becomes a prerequisite for the onset of withdrawal syndrome, characterized, in addition to the main symptoms (see below), anxiety, sweating, loss of appetite, fever, up to delirium (clinically indistinguishable from alcohol), amnestic syndrome and coma. The syndrome reaches its highest intensity on day 2–3 of abstinence. Convulsive manifestations always precede delirious. Symptoms last 2–3 days, rarely up to 2 weeks.

Unlike barbiturates, benzodiazepines have a higher safety threshold. They suppress the respiratory center to a lesser extent, the lethal dose correlates with the narcotic effective as 200: 1. High doses (more than 2 g) taken with a suicidal purpose cause drowsiness, ataxia, and sometimes confusion, leaving no residual marks. In individuals with low frustration tolerance, benzodiazepines can have a disinhibitive effect with aggressive behavior. Due to the lower level of euphoria attained, the risk of addiction is relatively lower, which does not exclude the possibility of increasing tolerance and the appearance of withdrawal syndrome.

The daily dose of an experienced drug addict can be 1–1.5 g of diazepam. Withdrawal syndrome develops on the background of a daily dose of about 40 mg, but can also be observed at therapeutic doses (10-20 mg) if the drug has been taken for more than a month. Longer-acting drugs (diazepam) give a more delayed withdrawal (5-7 days). Convulsive manifestations may be the first sign of not expected benzodiazepine withdrawal syndrome. Symptoms of withdrawal include anxiety, numbness of the limbs, dysphoria, increased sensitivity to light and sound, nausea, sweating, muscle twitching. Withdrawal syndrome is not necessarily accompanied by a desire to resume taking the drug. Due to the slow release of benzodiazepines from the body, signs of withdrawal can last up to several weeks.

The diagnosis of acute intoxication is made on the basis of common for measure:

1) the presence of at least one of the following mental symptoms:

a) euphoria and disinhibition,

b) apathy, sedation,

c) conflict, aggressive behavior,

d) affective instability,

e) decrease in concentration,

f) anterograde amnesia,

g) psychomotor disturbances, and a decrease in mental productivity;

2) at least one of the following somatoneurological signs:

a) uncertainty of gait,

b) Romberg negative test,

c) blurred speech,

d) nystagmus, and impairment of consciousness (stupor, coma),

e) skin erythema, pustules.

The diagnosis of withdrawal syndrome is made on the basis of common criteria for as well as the presence of at least three of the following symptoms:

1) tremor of the fingers of the outstretched hands, the tip of the tongue or eyelids,

2) nausea, vomiting,

3) tachycardia,

4) orthostatic hypotension,

5) psychomotor anxiety,

6) headaches,

7) insomnia,

8) weakness, malaise,

9) transient visual, tactile or auditory hallucinations or illusions,

10) paranoid perceptions,

11) large convulsive seizure.

The diagnosis is further confirmed by specific laboratory methods.

Treatment. It is more expedient to start the removal from the cancellation state in stationary conditions. In a state of coma or with marked signs of intoxication, the appointment of barbiturates is not recommended. When removing the moderate withdrawal syndrome method of sampling is selected dose of the drug, allowing to achieve a mild sedation. After keeping it for 1-2 days, the dose gradually decreases (not less than 10% per day, the last 10% is brought to zero within 3-4 days). When signs of withdrawal are resumed, dose reduction should be even more gradual. Short-term barbiturates should be replaced with drugs with a longer-term effect (phenobarbital). Replacing barbiturates with benzodiazepines is not advisable due to the risk of replacing one dependency with another.

With a psychological deficit of problem-solving behavior, a drug certainly helps to cope with internal stress, anxiety, a sense of its own low value. Therefore, at the exit to the full abstinence of the patient must be accompanied by appropriate psychosocial activities, otherwise he will be doomed to again turn to the use of the drug. Prevention of abuse requires the orientation of the doctor on the appointment of drugs in a short time in the presence of a specific therapeutic target. The doctor should be wary of such indirect signs of abuse as visits to other doctors, requests for higher doses, for issuing new prescriptions to replace lost ones.

Epidemiology, etiology.

Opium – the basic substance contained in the juice of opium poppy (Papaver somniferum). About 20 alkaloids are obtained from opium, the most famous of which is morphine. It is possible to get t, n. semisynthetic alkaloids based on naturally found in opium (heroin, codeine, hydromorphine), as well as fully synthetic (meperidine, methadone, propoxyphene). The most widely used opiate is heroin, the main supplier of which to the world market are the regions of the Middle and Far East. It is mainly used among the urban population, more often by men than by women (3: 1), at the age of 18-25 years. More than 50% of them come from incomplete or divorced families in which parents often abused psychoactive drugs. About 90% of them have any mental disorder, most often – depression, then – alcoholism, various forms of psychopathy.

In the overwhelming number of cases, the identity of patients is characterized by self-doubt, low self-esteem, asocial inclinations, dominant dysphoric affect, low frustration tolerance. Morbidity is also determined by the subcultural influence of certain groups of the population and by facilitated access to drugs, as a result of which the incidence is higher among doctors than in the population.

Clinic. Parenteral administration of the drug causes analgesia, indifference to pain, drowsiness, misting of consciousness, a feeling of warmth, heaviness in the limbs and dry mouth. As a rule, there is euphoria (“onset”) that occurs shortly after intravenous administration and lasts 10–30 minutes, then sedation (“dragging”) dominates. The first dose may be accompanied by a dysphoric affect tinge, nausea and vomiting.

The analgesic effect reaches a maximum after 20 minutes after intravenous administration, approximately one hour after subcutaneous administration and lasts 4-6 hours, depending on the type of drug, dose and length of anesthesia. Hyperemia and itching of the skin of the face, especially the nose, may occur. There is a narrowing of the pupil, a spasm of smooth muscles (including the ureter and biliary tract), constipation. Idiosyncrasy to the drug occurs in the form of allergic reactions, anaphylactic shock, pulmonary edema.

Overdose is accompanied by slowing of breathing, bradycardia, a decrease in response to external stimuli, a decrease in temperature and blood pressure. Opioids suppress the function of the respiratory center in the brainstem (this effect is potentiated by phenothiazines and MAO inhibitors, and tolerance to it is not developed). Death in overdose is usually associated with respiratory arrest. The classic triad of opiate overdose: coma, “pin head” type pupils and respiratory depression. Conditionally lethal dose with initial tolerance – 60 mg of morphine; a gradual increase in tolerance makes it possible to receive several thousand mg.

The withdrawal syndrome (“breaking”) of morphine and heroin begins 6-8 hours after the last dose, with a background of at least 1-2 weeks of constant intoxication. The highest intensity of the syndrome is observed on days 2–3, decreasing over the next 7–10 days, although some manifestations (insomnia, bradycardia) may persist for up to several months. The more active the opiate is, the faster, shorter and more intense the withdrawal syndrome is. The clinical picture in mild cases is a lot like the state of the flu. In addition to the main symptoms (see below), dysphoria, hot flashes, weight loss, temperature dysregulation can occur. Death against the background of cancellation is rare, mainly due to concomitant pathology of cardiac activity.

The desire to resume taking opiates rarely accompanies withdrawal syndrome when prescribing them as analgesics, for example, during surgical intervention. Side effects of opiate abuse: endocarditis, septicemia, pulmonary embolism, infection with hepatitis viruses and HIV.

Diagnosis. To make a diagnosis of acute intoxication, in addition to manifestations common to F1x.0, the condition must meet the following criteria: 1) at least one of the following symptoms: a) apathy, sedation, b) psychomotor inhibition or disinhibition, c) decreased concentration and memory , restriction of higher mental functions, reduced mental productivity; 2) the presence of at least one of the following signs: a) drowsiness, b) blurred speech, c) constriction of the pupil (or expansion due to anoxia in severe overdose), d) impairment of consciousness (stupor, coma).

For the diagnosis of withdrawal syndrome, in addition to manifestations common to F1x.3, the condition should be characterized by at least three of the following symptoms: a) desire to resume taking the drug, b) a runny nose or sneezing, c) sweating, d) nausea, vomiting, g ) tachycardia or hypertension, e) psychomotor restlessness, g) headaches, h) insomnia, and) general malaise, weakness, j) transient visual, tactile or auditory hallucinations or illusions, l) a large convulsive fit.

Treatment. With an overdose, an opiate antagonist is injected (naloxone, nalorphine – 0.4 mg IV, again 4-5 times during the first 30-45 minutes). Owing to the short duration of the operation of nalok-son, the appearance of a pre-comatose state is possible in the first 4-5 hours, which requires careful monitoring of the condition.

When suppressing withdrawal, synthetic opiate methadone is used to replace heroin (20–80 mg orally). It should be canceled after the withdrawal of withdrawal syndrome, since it itself has a narcotic effect. To relieve methadone withdrawal (much weaker than with heroin), clonidine is used, 0.1-0.3 mg 3-4 times a day for the period of detoxification. The advantages of methadone are oral intake, the possibility of its legal production and productive activities during the reception; disadvantage – the preservation of drug addiction. Its use is particularly indicated in the treatment of female drug addicts in the state of pregnancy to prevent withdrawal syndrome in the newborn.

Similar to methadone opiate L-alpha-acetylmethadol provides for the suppression of withdrawal within 72-96 hours, making it possible for more rare reception. The use of opiate antagonists (naloxone, naltrexone) interrupts the euphoric effect of the drug, but by itself does not provide the patient with motivation to stop the abuse.

Due to the fact that pharmacological intervention does not provide a definitive solution to all psychosocial problems of the patient, the treatment complex should always include rehabilitation measures. For this purpose, individual and group psychotherapy, self-help groups (the program “Anonymous Addict”) are used,

Psychotherapy increases the overall effectiveness of treatment programs, especially if there is a concomitant psychiatric pathology. The optimal framework for rehabilitation is a therapeutic community that tears the patient out of their usual habitat, where most of the staff consists of former drug addicts who have the skills to carefully control the patient’s motivation to withdraw, without which patients are not allowed to be treated. Patients are in groups of the therapeutic community for 12–18 months until they can return to their place of residence. The goal is not only to achieve abstinence, but also the acquisition of useful social skills, the correction of antisocial attitudes. 90% of applicants leave therapy during the first year; for those remaining, a rather high effect is achieved.

Mental and behavioral disorders due to cannabinoids

Indian cannabis plant-based drugs (Cannabis sativa) have different narcotic activity depending on the content of the most psychoactive of 60 cannabioids delta-9-tetrahydrocannabiol (THC), the percentage of which determines the quality of the narcotic products circulating in the market.

Marijuana (“plan”, “weed”) is a diverse mix of leaves, seeds, stems, and hemp flower heads. According to the degree of activity, the narcotic products made from it are divided into 3 categories, denoted by Indian names. The least active bhang product is made from the heads of uncultivated plants. A greater amount of hemp resin is found in ganja, obtained from flowering heads and leaves of carefully selected cultivated plants. The most active is charas, which is the actual resin obtained from the tops of mature hemp; he is designated as hashish.

Cannabinoids can be consumed with food and drink, but are usually inhaled during smoking. Marijuana is called the gateway to the world of drugs. The first experiments with it in adolescents are often not accompanied by dangerous consequences characteristic of other psychoactive substances, which reduces the fear of transition to them. With relevant experience, the combined use of alcohol gives here a significant additive narcotic effect. Usage usually begins in high school. Risk factors are pedagogical neglect, contacts with asocial subcultures, depressive symptoms, low skills of problem-solving behavior.

Clinic. Intoxication develops immediately after smoking, reaches a maximum in 10-30 minutes. and lasts 2-4 hours, although psychomotor disorders may persist for several hours. The effect of oral administration lasts from 5 to 12 hours. Introspection, suggestibility, sensitivity to external stimuli, sharpness of apperception, intensity of perception of color, taste and music increase. There is a feeling of greater saturation of time with events, self-confidence, at the same time a feeling of relaxation and soaring, an increase in sexual urges. A smoker can often perceive himself as if from the outside, laughing at the symptoms he has. Perhaps the emergence of anxiety, aggressive impulses occur rarely. The ability to maintain contact with reality may allow an experienced smoker to hide the state of intoxication from others.

In high doses, marijuana, like hallucinogens, can cause disorders of the body pattern, perception of space and time. In addition to the main somatic symptoms (see below), dilated pupils and cough may be noted. With long-term intake of high doses, some signs of increased tolerance and mild withdrawal reactions (sleep disturbance, anxiety, irritability, vomiting, tremor, sweating, muscle pain) are detected, which, however, do not present major problems for experienced smokers.

Observations on chronic smokers of the Caribbean islands and eastern cultures (Jamaica, Egypt, India, Jamaica) allow us to distinguish as the main so-called. amotivational syndrome (passivity, reduction of impulses, purposeful activity and higher mental functions, apathy, weight gain, sloppiness). The significantly lower severity of the syndrome in North American smokers suggests its etiology, participation of socio-cultural and personal factors.

Oral administration can be a triggering factor for the appearance of delirium, transient delusional syndromes. Delayed episodes of intoxication that occur outside of smoking usually follow the preceding use of hallucinogens. Long-term use may be accompanied by obstruction of the pulmonary tract, emphysema, an increased risk of lung cancer. It also marks the so-called. amotivational syndrome characterized by passivity, lack of interests and motivations, “fallout” in the process of conversation, and difficulty concentrating. Sometimes this term is also used to refer to deficiency symptoms in schizophrenia.

The diagnosis of acute intoxication is made on the basis of the condition, in addition to the general for Flx.0, the following criteria: 1) the presence of at least one of the following symptoms: a) euphoria and disinhibition, b) anxiety, anxiety, c) suspicion or paranoid views, d) a sense of slowing down the course of time, e) a decrease in the focus of thinking, e) a decrease in concentration, g) a decrease in the speed of reactions, h) auditory, visual or tactile illusions, and) hallucinations with intact orientation, j) depersonalization or deres lizatsiya, l) reduced mental productivity; 2) the presence of at least one of the following symptoms: a) increased appetite, thirst, b) dry mouth, c) conjunctivitis symptoms, d) tachycardia.

Treatment. There is no specific therapy for the abuse of can-nabioids. When using the drug as a means of relieving anxiety, depression, attention should be paid to the accompanying mental pathology. The correction of social life, family relations is decisive. The abstinence control includes the periodic determination of the relevant metabolites in the urine.