Antidepressants: what are they? Classification, properties and action. How effective are tricyclic antidepressants? Classification of antidepressants according to the principle of action on the body

Tricyclic antidepressants (TCAs) - classic psychotropic drugs for the treatment of various depressive disorders, chronic pain.
Tricyclic antidepressants are first-generation drugs and are therefore often called “old antidepressants.” They are prescribed for severe inpatient depression, which is why they are sometimes called “major depression”.

The closer the depression is to the classic version, the greater the effect of the TCA. A positive result in such cases is achieved in 60–80% of patients.

Tricyclic antidepressants: what are they?

The term "tricyclic antidepressants" refers to the drugs' general chemical structure: three rings joined together in a molecule.

The mechanism of action of tricyclics is not completely clear. Majority medicines have a direct effect on several neurons. Studies have found that they affect the reuptake of serotonin and norepinephrine in the brain, in varying degrees block transporters that capture other neurons.
The term is outdated, since not all drugs in this group have a tricyclic structure. However, it is the chemical structure of TCAs that determines a number of pharmacological effects that are not related to the desired therapeutic effect.

TCA group drugs block muscaronic acetylcholine, dopamine, serotonin, histamine receptors, alpha-adrenergic receptors, sigma receptors in the brain and peripheral tissues. Medicines also inhibit the reuptake of catecholamines in nerve endings. Therefore, tricyclic antidepressants develop a number of side effects:

• dry mouth;
• blurred vision;
• urinary retention;
• tachycardia;
• weight gain;
• drowsiness;
• decline blood pressure;
• dizziness;
• memory impairment, decreased concentration, difficulty in intellectual activity;
• sexual dysfunction in men;
• decreased secretion of bronchial glands;
• inhibition of hematopoiesis;
• convulsions;
• danger of overdose;
• , cardiac conduction disturbance, cardiac arrest.

The main reason for the high mortality rate of TCA overdose is blocking cardiac conduction - a cardiotoxic effect. This creates a serious risk for a depressed person who has suicidal intentions.

TCAs are the first non-selective antidepressants. They were intended for effective therapy patients in a hospital setting. Numerous side effects make it difficult to treat patients on an outpatient basis.

List of drugs for humans

Within the class of tricyclic antidepressants, there are two subclasses that differ in their chemical structure:

1. tertiary amines;
2. secondary amines.

Tertiary amines are distinguished by strong sedative and anti-anxiety activity, have a strong antidepressant effect, but also exhibit more pronounced side effects.
List of drugs - representatives of tertiary amines:

• imipramine (Melipramine, Imizin, Tofranil);
• amitriptyline (Amitriptyline, Triptisol, Saroten retard);
• clomipramine (Anafranil, Clofranil, Gidifen);
• trimipramine (Gerfonal);
• doxepin (Sinequan);
• dotiepin (Dosulepin).

These drugs have the most balanced effect on the reuptake of serotonin and norepinephrine.
Secondary amines have more pronounced stimulating activity. They have less sedative effect and are better tolerated. But the anti-anxiety and antidepressant activity of these TCAs is also less.

List of drugs - representatives of secondary amines:

• desipramine,
• nortriptyline,
• Protriptyline.

These drugs more actively suppress (inhibit) the reuptake of norepinephrine, while having virtually no effect on the reuptake of serotonin.

When choosing an antidepressant, in addition to its main action, its additional psychotropic effect, which can be sedative or stimulating, is taken into account. Moreover, it can be observed already in the first days of administration, although the main effect develops much later.
Additional effects of tricyclic antidepressants are listed in Table 1.
Table 1

Medicines that have a pronounced stimulant effect can cause sleep disturbances, increased anxiety and restlessness, and sometimes provoke increased delusions and hallucinations.

Sedative antidepressants are prescribed for anxiety states. They can be used as sleeping pills. But when outpatient treatment they cause drowsiness and lethargy. These medications are indicated to be taken in the afternoon.

Amitriptyline and imipramine are the most powerful drugs. The antidepressant effect of these drugs develops slowly: an increase in mood and the disappearance of ideas of self-blame occur approximately 10 to 14 days from the start of treatment.

Amitriptyline is prescribed as the drug of choice for preventive therapy migraine, tension headache, in the treatment of chronic back pain.
In the first days after taking the drugs, they are more pronounced additional effects. Amitriptyline is characterized by a pronounced sedative, anti-anxiety, hypnotic effect, while imipramine has an activating, disinhibiting effect.

Side effects associated with cardiac arrhythmias limit the use of TCA drugs in people over 40 years of age, especially when coronary disease heart, angle-closure glaucoma, adenoma prostate gland. The exceptions are Azafen and Gerfonal, the use of which is considered quite safe at any age.

The top ten most “prescribed” antidepressants include three drugs from the TCA group:

• imipramine,
• amitriptyline,
• clomipramine.

Tricyclic antidepressants have been the first-line treatment for anxiety disorders in the past. Now they are used less frequently. But this is not due to the fact that TCAs are less effective, but because the new drugs are safer. Tricyclic antidepressants are still considered highly effective treatments for severe forms depression.

What are antidepressants? This term speaks for itself. It refers to a group of medications aimed at combating depression. But their scope is much wider than their name suggests. In addition to depression, they are able to combat feelings of fear, anxiety and melancholy, normalize appetite and sleep, relieve emotional state. Some of them are used to combat nocturnal enuresis and smoking. In addition, antidepressants are used as pain relievers for chronic pain. Exists large number drugs related to antidepressants, the list of which is constantly growing.

How do antidepressants work?

These drugs act on the neurotransmitter systems of the brain through various mechanisms. Neurotransmitters are special substances that are necessary to transmit various “information” between nerve cells. Not only depends on the ratio and content of neurotransmitters emotional background and a person’s mood, but also all nervous activity.

Antidepressants help normalize the ratios and amounts of neurotransmitters, thus eliminating clinical manifestations depressive state. Therefore, they do not have a replacing effect, but a regulating one, therefore, contrary to existing opinion not addictive.

There is no other antidepressant that could have an effect from the very first pill. It takes quite a long time for results to be seen, which often leads to premature discontinuation of the drug.

Choosing an antidepressant

This drug is not so harmless, since has a large number of contraindications and side effects. In addition, symptoms of depression may indicate the development of more serious illness, for example, brain tumors, and as a result uncontrolled intake Antidepressants will only make the situation worse. Therefore, only a doctor should prescribe these drugs after establishing the correct diagnosis.

Features of application

These medications usually require a gradual increase in dose until the dose is effective. After this, antidepressants must be taken for some more time, and then they also begin to be gradually withdrawn. Thanks to this treatment regimen, it is possible to avoid the occurrence of side effects, as well as relapse of the disease in case of abrupt withdrawal.

There are no antidepressants that have an immediate effect. You cannot get rid of depression in 1–2 days. Therefore, drugs are prescribed for a long time, and the results from taking them usually appear in the second week of use, and in some cases much later. If after a month from the start of treatment there are no positive changes in well-being, then the medicine is replaced with another.

Almost all antidepressants are prohibited during pregnancy and breastfeeding. They are incompatible with drinking alcohol. In addition, their peculiarity is that the activating or sedative effect appears earlier than the antidepressant effect itself. Sometimes this quality is taken as a basis when choosing a drug.

Almost all antidepressants cause such unpleasant side effects as sexual dysfunction. It manifests itself as decreased sexual desire, erectile dysfunction, and anorgasmia. Not everyone experiences this complication when treated with antidepressants, but in any case, such a disorder is completely transient.

Thus, antidepressants should be selected individually by the attending physician, who takes into account various factors when choosing a particular drug. Next, you should familiarize yourself with the most used drug - tricyclic antidepressant.

Prescription of tricyclic antidepressants

This medicine is used to treat the following diseases:

• panic attacks;
• pain symptoms different etiologies;
• migraine;
• regular headaches;
• obsessive-compulsive disorder.

In addition, they are effective in treating sleep disorders. The great popularity of this drug is due to its effective effect on the chemical processes of the brain. It is prescribed strictly individually. The peculiarity of the use of tricyclic antidepressants is that they are initially prescribed in small doses, gradually increasing to the required concentration.

It should be remembered that depression must be cured. An untreated pathology can reappear after some time, because improvement does not mean healing. If a person relapses after treatment, the next course of therapy should be longer than the previous one.

Tricyclic antidepressants may not be suitable for everyone. The reason for this lies in the duration of their action. Some patients, especially those who are suicidal, do not experience relief from taking these medications. Besides this, overdose can be fatal. They are also contraindicated in some chronic diseases.

Tricyclic antidepressants include:

• Lofepramine;
• Doxelin;
• Mianserin;
• Imipramine;
• Trazodone.

Although there are no ideal medications, it is tricyclic antidepressants that most often achieve lasting results.

Efficacy of tricyclic antidepressants

Statistics show that in 7 out of 10 cases, when using this drug, there is a significant improvement in the condition even after taking it for a short time. They affect patients differently, which is caused by individual feature body. But in psychiatry there is such a rule: the more severe the depression, the higher the effectiveness of such drugs, provided that they are taken for a long time.

It often happens that a patient, taking tricyclic antidepressants for a week or two and not seeing results, stops using them. Doctors recommend doing this no earlier than 4 to 6 weeks after the start of treatment. If a depressive state is accompanied by headaches and sleep disturbances, the patient will feel a positive result immediately. Normalization of sleep and reduction of pain occurs a week after the start of treatment.

The course of treatment and purpose of this drug must be strictly individual. Each case of depression is individual and requires subtle diagnosis, in-depth analysis and consideration of the characteristics of the body, including age, gender, and general condition of the patient.

Risks of using tricyclic antidepressants

As medical statistics show, most patients treated with tricyclic drugs do not experience side effects or may experience minor deviations that go away very quickly. However, it is worth noting the following side effects of tricyclic antidepressants:

• constipation;
• excessive sweating;
• dry mouth;
• slight visual impairment.

Patients usually continue to take this medication after these symptoms occur. Some may experience lethargy and drowsiness. Such side effects disappear on their own after 1 to 2 weeks of treatment with tricyclic drugs. When using this medicine, sexual desire disorder, ejaculation disorders, and inability to experience orgasm often occur.

Addiction to antidepressants

There is a fairly widespread belief that tricyclic antidepressants can be addictive. This is wrong. Such drugs are not classified as tranquilizers, and therefore do not contribute to addiction. The course of treatment is stopped gradually, reducing the dosage over 3 to 4 weeks.

It is unacceptable to abruptly stop taking tricyclic drugs.. This can cause withdrawal syndrome, which is characterized by irritability, dizziness, diarrhea, sleep disturbances, cramping abdominal pain, etc. Withdrawal syndrome is observed very rarely and goes away on its own within 2 to 3 weeks.

Thus, antidepressants are drugs that help fight depression. But besides this, they cope with emotional stress, eliminate fear and anxiety, and normalize sleep. They should not be taken without a doctor's prescription, as this may cause serious complications.

Tricyclic antidepressants (TCAs) have been used for about 40 years and until recently were the gold standard against which all new antidepressants were compared. However, TCAs have different effects on a wide variety of neurotransmitters and therefore have many side effects. These are sedation, weight gain, dry mouth, confusion of thoughts, cardiac arrhythmias, decreased blood pressure, and urinary retention. Side effects TCAs make them difficult for doctors to use general practice. These effects may also lead to inappropriate treatment of depressed patients. TCAs are inexpensive and are used by patients of low socioeconomic status. However, a number of recent studies suggest that the overall cost of treatment may be lower with more expensive drugs with fewer side effects. The TCA group includes the following drugs: amitriptyline, clomipramine, desipramine, doxepin, imipramine, maprotiline, nortriptyline, protriptyline, trimipramine. Venlafaxine is a new generation of drugs - “dual reuptake inhibitors” of both serotonin and norepinephrine.

The classic TCA is amitriptyline (Amitriptyline). Syn.: Amizol, Damilena maleinate, Triptisol, Elivel. The spectrum of psychotropic activity of amitriptyline combines thymoanaleptic and sedative effects. The drug is used to treat anxious depression. The drug is not used to treat depression accompanied by severe lethargy. Contraindications: treatment with MAO inhibitors and a period of 2 weeks. after their cancellation; recent myocardial infarction; glaucoma; atony bladder; prostate hypertrophy; paralytic ileus; pyloric stenosis; chronic heart failure; heavy arterial hypertension; gastric ulcer and 12 p.c.; pregnancy and breastfeeding; childhood up to 7 years. Side effects: drowsiness, disorientation, increased psychotic symptoms, extrapyramidal disorders (rare), dry mouth, constipation, jaundice, urinary retention, accommodation disorders, tachycardia, orthostatic arterial hypotension, impaired cardiac conduction, extrasystole, decreased potency, changes in libido, gynecomastia, galactorrhea, allergic reactions. Precautions: the drug should not be prescribed with MAOIs; after using the latter, amitriptyline is prescribed only after 1–2 weeks. For elderly patients, the drug is prescribed in smaller doses. Use with caution for ischemic heart disease, arrhythmias, heart failure. Treatment is carried out under ECG control. Doses and application. Orally: single dose 12.5–75 mg; the average daily dose is 150–250 mg. At severe depression applied intramuscularly or intravenously at 20–40 mg 3–4 times a day. In general medical practice, amitriptyline is currently rarely used at a dose of 25–100 mg/day. Available in tablets of 0.025 g, 0.01 g and capsules of 50 mg.

Imipramine Syn. melipramine, tofranil - inhibits the reuptake of neurotransmitters (norepinephrine, dopamine, serotonin). The main feature of the psychotropic effect of imipramine is the combination of a thymoanaleptic effect with a stimulating one. The drug evens out pathologically low mood, reduces feelings of melancholy, hopelessness, and depression. The stimulating properties of imipramine are expressed in a decrease in inhibition, the appearance of vigor and activity. The drug is also effective for chronic pain syndrome and bedwetting (starting from the 5th year of life). Side effects during therapy with imipramine may include: dry mouth, impaired accommodation, constipation, sweating, dizziness, headache, tremor, tachycardia, urinary retention, galactorrhea, gynecomastia, decreased libido, erectile dysfunction, allergic reactions, photosensitivity. Thirst and itching are less common. Contraindications for use are common to all TCAs. Contraindicated in schizophrenia, epilepsy, prostate adenoma, glaucoma. Not compatible with alcohol, MAOIs. Reduces the effectiveness of phenytoin and beta-blockers. Anticholinergics, phenothiazines and benzodiazepines increase sedative and central anticholinergic activity. Doses and application. When taken orally, the initial dose is 25–50 mg/day, the average daily dose is 150–250 mg/day. In general medical practice, you should start taking it at a dose of 10 mg/day. Dose for bedwetting in children 3–6 years old: 5 mg; 7–12 years 25 mg at night. IM 75 mg in 3 divided doses; Once the effect is achieved, switch to taking the drug orally. In elderly patients, the optimal dose is 30–50 mg. In this case, it is necessary to monitor blood pressure, ECG, liver function, kidney function and blood picture. Available in 25 mg tablets and 2.0 ml ampoules of a 1.25% solution.

Clomipramine Syn.: Anafranil, Clofranil, Clominal. Has an effect on depressive syndrome in general, including psychomotor retardation, depressed mood and anxiety. Clomipramine also has a specific effect in obsessive-compulsive and chronic pain syndromes. Indicated for dysthymic conditions within the framework of psychopathic disorders in children and adolescents, with obsessive states, with bedwetting. Contraindications: hypersensitivity, recent myocardial infarction, treatment with MAOIs, pregnancy, breastfeeding. Side effects: dry mouth, profuse sweating, small tremor, dizziness, accommodation paresis, urinary retention, orthostatic arterial hypotension, lethargy, allergic skin reactions; rarely - liver dysfunction, hyperpyrexia, convulsions, agranulocytosis. Incompatible with MAOIs. Used orally at 25 mg/day in 2 divided doses. Doses and use. Within 1 week. the dose is gradually increased to 50 mg 2-3 times a day, and after reaching clinical effect switch to a maintenance dose of 25 mg 2-3 times a day. IM 25–50 mg/day, the dose is gradually increased by 25 mg daily to 100–150 mg/day. 50–75 mg IV drip (dissolved in 5% glucose solution or 0.9% sodium chloride solution) for 1.5–3 hours 1 time per day. For chronic pain 10–150 mg/day; in elderly patients, the initial dose is 10 mg/day with a gradual increase to 30–50 mg/day over 10 days. In general medical practice, especially for elderly patients, the drug is prescribed in an initial daily dose of 10 mg. Gradually, over 10 days, the dose is increased to the optimal level of 30–50 mg/day (in severe cases, the daily dose can reach a maximum of 250 mg/day). The advantage of clomipramine is a faster therapeutic effect on depression: when the drug is prescribed, this effect appears on the 2-4th day, and when using imipramine, usually on the 6-8th day of treatment.

When prescribing clomipramine, extreme caution should be exercised in patients with epilepsy and other diseases predisposing to the development of seizures, during alcohol withdrawal, in the presence of cardiovascular failure, intracardiac conduction disorders or arrhythmias. Patients with a history of increased intraocular pressure, acute-angle glaucoma or urinary retention; patients with hyperthyroidism or receiving medications thyroid gland; patients with severe liver disease or tumors of the adrenal medulla; Patients with chronic constipation should be treated with clomipramine under strict medical supervision. Available in tablets of 10, 25 mg, retard tablets of 75 mg; in a solution of 25 mg in 1 ampoule of 2.0 ml.

Desipramine (Dezipramini) (syn. Petilil ) – a tricyclic antidepressant indicated for depression with leading symptoms of lethargy and inhibition. Desipramine has an activating effect, so in addition to the side effects common to TCAs, in case of an overdose, sleep disturbances, increased fear, inner restlessness and agitation may occur. With concomitant schizophrenic symptoms, activation of psychotic symptoms and aggressiveness is possible. Elderly patients may have dysarthria, ataxia, delirium, states of confusion, insufficient ability to concentrate, hallucinations, phase inversion - the transition from depression to mania. Imipramine is better tolerated. In general medical practice, it should be prescribed with caution in small dosages - 25–50 mg/day. Available in 25 mg tablets.

Trimipramine by structure and main pharmacological properties is close to melipramine, but unlike it has a pronounced sedative and anxiolytic effect. Due to the weakly expressed central anticholinergic effect, the drug is well tolerated. Attention should be paid to the increased frequency of depression, in which low mood is combined with general lethargy and internal anxiety. The external picture of such depression resembles apathetic, but with more detailed study internal anxiety and concern are revealed. Doses and application. In general medical practice, trimipramine should be prescribed no more than 100 mg of the drug. It is necessary to complete therapy by slowly reducing the dose. After abrupt interruption of treatment, withdrawal symptoms may occur. Available in tablets containing 25 mg of trimipramine hydrochloride.

Doxepin (syn. Sinequan) – inhibits the reverse neuronal uptake of biogenic amines (norepinephrine, serotonin), also has an anxiolytic, sedative effect. Indicated for neuroses, sleep disorders of neurotic origin, and mild delusional syndromes arising from alcoholism. Contraindications: hypersensitivity, glaucoma, prostate adenoma, myocardial infarction, severe dysfunction of the kidneys, liver and hematopoietic system, children (up to 12 years), pregnancy and breastfeeding. Side effects: headache, dizziness, drowsiness or insomnia, confusion, disorientation, restlessness, excessive sedation, nausea, vomiting, constipation, dry mucous membranes oral cavity and nose, tachycardia or bradycardia, muscle tremors, excessive sweating, skin rash, itching. Drug interactions: enhances the effect of atropine, levodopa, increases the toxicity of barbiturates, morphine and pethidine. When combined with antipsychotics, the dose should be reduced by 50%; combination with lithium drugs can cause severe pernicious neurotic syndrome. Ethanol increases sedative activity. Precautions: do not use with MAO inhibitors (should be discontinued for 2-3 weeks), sultopride, chlorpromazine, quinidine; prescribe with caution simultaneously with digitalis glycosides and baclofen. During treatment, you should not drive vehicles or work with moving machinery. Use with caution in elderly, debilitated patients, in patients with severe cardiovascular diseases. vascular system. Doses and application. Prescribed orally 10–25 mg/day in 3 divided doses. For moderate to severe neurotic states up to 150 mg/day. The maximum daily dose is 300 mg. Children over 12 years old – 0.5 mg/kg body weight per day. Available in capsules of 10 or 25 mg No. 30.

Pipofezine. Syn. Azafen. A mild tricyclic antidepressant with moderate antidepressant activity; well tolerated by patients; in patients with schizophrenia does not cause exacerbation of symptoms; does not increase anxiety and fear; does not disturb sleep; does not have cardiotoxic properties. Due to the lack of anticholinergic effects, it can be prescribed to patients with glaucoma. Contraindications: hypersensitivity; liver, kidney and heart failure; myocardial infarction; IHD; state after acute disorder cerebral circulation; severe infectious diseases; diabetes mellitus Side effects: headache, dizziness, nausea, vomiting, allergic reactions. Precautions. The drug should not be prescribed together with an MAOI. After using the latter, pipofezin is prescribed after 1–2 weeks. During pregnancy and breastfeeding prescribed according to strict indications. Doses and application. Single dose 25–50 mg; the average daily dose is 100–200 mg. Azafen. Tablets 25 mg No. 250.

Maprotiline ( syn. Ludiomil®) is a tetracyclic antidepressant. The mechanism of action is associated with a pronounced and selective inhibition of norepinephrine reuptake in presynaptic neurons of the cerebral cortex. Ludiomil has a certain affinity for central alpha-1 adrenergic receptors, moderate inhibitory activity towards histamine H1 receptors, and has a moderate anticholinergic effect. It is believed that during long-term treatment maprotiline changes functional state endocrine system and neurotransmitters. Indicated for conditions of dysphoria or irritability, apathy (especially in old age), and psychosomatic disorders. Indications for prescribing ludiomil in general medical practice are: depressive states of various origins, including organic, symptomatic, climacteric and involutional. Contraindications: hypersensitivity, epilepsy, acute stage myocardial infarction, myocardial conduction disorders, arrhythmias, angle-closure glaucoma, prostate adenoma, acute alcohol intoxication, poisoning sleeping pills, central analgesics, psychotropic drugs, pronounced violations kidney and/or liver function, breastfeeding. Side effects: orthostatic arterial hypotension, tachycardia, arrhythmias, libido and potency disorders; gynecomastia, leukopenia, agranulocytosis, eosinophilia, local or generalized edema. Precautions for urinary problems, persistent constipation, increased intraocular pressure, diseases of the cardiovascular system. When prescribing the drug, monitoring of mental and neurological status, regular examination of the composition of peripheral blood, and determination of kidney and liver function are necessary. Patients with an increased risk of side effects from the cardiovascular system are advised to regularly monitor blood pressure and ECG. After using an MAOI, maprotiline is prescribed after 2 weeks; the same interval is observed when replacing maprotiline with MAOIs. Patients taking maprotiline should refrain from engaging in potentially hazardous activities that require increased attention and rapid mental and motor reactions. Drug interactions: reduces the antihypertensive effect of guanethidine, betanidine, reserpine, methyldopa, clonidine. Enhances the effect of sympathomimetic drugs (norepinephrine, adrenaline, isoprenaline, ephedrine and phenylephedrine, etc.) on the cardiovascular system. Increases the activity of ethanol. Doses and application. Used orally at 25–75 mg in 1–3 doses. On an outpatient basis, the drug is prescribed orally at 25 mg 1–3 times a day, or 75 mg in 1 dose. The maximum dose for outpatient treatment is 150 mg/day, for inpatient treatment – ​​225 mg/day. When decreasing depressive symptoms a single dose can be gradually reduced to 25–50 mg. IV daily dose of 25–100 mg dropwise over 1.5–2 hours (diluted in 250 ml of 0.9% sodium chloride solution or 5% glucose solution). When the antidepressant effect is achieved (after 1–2 weeks), switch to taking the drug orally. For elderly and somatically weakened patients, ludiomil is prescribed at an initial dose of 10 mg 3 times a day or 25 mg 1 time a day. Ludiomil should be prescribed with caution to patients with urinary disorders, persistent constipation, and increased intraocular pressure; patients with diseases of the cardiovascular system, patients with hyperthyroidism or receiving thyroid medications. During treatment, regular monitoring of blood pressure, ECG, and peripheral blood patterns is necessary. When ludiomil is co-administered with drugs that lower the threshold for seizure activity, the risk of developing seizures increases. It also reduces or eliminates the antihypertensive effect of drugs such as guanethidine and betanisine, reserpine, alpha-methyldopa, clonidine. Ludiomil is available in tablets of 10, 25, 50, 75 mg and in ampoules of 5.0 containing 25 mg of maprotiline.

Mianserin Syn. lerivon, miansan. The drug has a pronounced ability to block alpha-2 adrenergic receptors and long-term use secondary increase the release of norepinephrine (NA). The psychotropic activity profile of the drug consists of thymoanaleptic and sedative effects. According to the strength of its action, it is classified as a “minor” antidepressant, which determines its use primarily in general medical practice. Under its influence, symptoms such as anxiety, feelings of internal tension, and sleep disturbances are reduced. In its ability to relieve sleep disorders and anxiety, mianserin can compete with tranquilizers, but unlike the latter, it does not cause addiction or dependence. Therapeutic effect mianserina has 4 components that develop gradually. On the first day of therapy, a sedative effect and a positive effect on sleep appear. During the first week, an anti-anxiety effect develops. Then, in the first two weeks of therapy, antidepressant and antiaggressive (antisuicidal) effects appear. Doses and application. In general medical practice, it is recommended to use individually selected dosages, starting from 30 mg. In rare cases, during treatment with mianserin, impaired hemipoiesis, convulsions, hypomania, hypotension, arthralgia, edema, gynecomastia, liver dysfunction, and exanthema are observed. If mianserin is prescribed to a patient diabetes mellitus, diseases of the cardiovascular system, with insufficiency of renal or hepatic functions, then the doses of drugs included in concomitant therapy should be monitored. Patients with angle-closure glaucoma or prostate adenoma taking mianserin should be under constant monitoring. The drug is taken once a day in the evening or at night. The average daily dose is 30–90 mg; elderly patients 30 mg/day. Lerivon (mianserin) is available in 30 mg tablets.

Mirtazapine (Mirthazapine) ( With in. Remeron) – close in chemical structure to mianserin (6-azamianserin) drug. It weakly blocks the reuptake of NA, is an antagonist of presynaptic and postsynaptic alpha-2 adrenergic receptors and postsynaptic C2 and C3 serotonin receptors and, therefore, selectively potentiates the effect of serotonin on C1 serotonin receptors. That is, the drug has a mixed NA and serotonin-positive effect and is practically devoid of adrenolytic and cholinolytic properties, but has a moderate antihistamine effect.

The spectrum of psychotropic activity of mirtazapine is determined by a moderate thymoanaleptic effect and a sedative component, therefore it is indicated for anxious depression of various origins. Due to its moderate sedative effect, the drug does not actualize suicidal thoughts during therapy. Doses and application. Mirtazapine is prescribed in a dose of 15–30 mg once a day. The effect develops gradually over 2–3 weeks of therapy. But treatment with the drug should be continued for another 4–6 months. Side effects include daytime drowsiness, dry mucous membranes, increased appetite and weight gain, tremor, and suppression of bone marrow hematopoiesis. Since the P-450 isoenzyme is not involved in the metabolism of the drug, numerous drug interactions manages to be avoided. It is not recommended to use the drug in combination with MAOIs or during pregnancy. Remeron is available in tablets of 30 and 45 mg.

Tianeptine ( With in. Coaxil ) has a pronounced antidepressant and anxiolytic effect, occupying an intermediate position between sedative and stimulating antidepressants. Tianeptine belongs to the group of antidepressants with a poorly known mechanism of action (Mosolov, 1995). It is assumed that, unlike other antiserotonergic drugs, it facilitates the reuptake of serotonin by the presynaptic membrane and has virtually no effect on the noradrenergic and dopaminergic systems. Coaxil is the only antidepressant that increases serotonin reuptake. Thanks to the study of Coaxil, three hypotheses have been put forward for a new conceptual approach to the pathophysiology and treatment of affective disorders:

There are perhaps two types of depression; Available evidence suggests that some forms of depression are associated with excess serotonin, while others are associated with its deficiency.

Depression may develop as a result of excess serotonergic transmission rather than 5-HT deficiency. This excess can be secondarily corrected by antidepressants, even those that initially inhibit serotonin reuptake.

Depression may be characterized by instability of the serotonergic system rather than by an excess or deficiency of serotonergic neurotransmission.

It is important to note the properties of coaxyl that allow you to expand the range of its applications. Coaxil is able to increase the level of excitation of CA1 pyramidal cells of the hippocampus and suppress stress-related hyperactivity of the hypothalamic-pituitary-adrenal system, protecting the hippocampus from the direct and cumulative effects of stress.

According to the spectrum of psychotropic activity, Coaxil has a specific anxiolytic property without sedation and effectively affects all manifestations of depression, including asthenia, anxiety and a wide range of somatic symptoms, without compromising other areas of life. It is indicated for mixed anxiety and depression in premenopausal women, is effective for alcoholic depression and anxiety, and reduces alcohol motivation. Unlike most antidepressants, Coaxil does not affect attention, memory and cognitive function. The effectiveness and tolerability of Coaxil allows it to be recommended in general medical practice, especially in patients late age with accompanying somatic diseases. The drug can be prescribed long-term and to patients who have suffered cerebrovascular accidents. Side effects when prescribing Coaxil occur rarely and are fleeting. These are gastralgia, abdominal pain, dry mouth, anorexia, tachycardia, extrasystole, headaches, feeling of heat, muscle pain. However, these side effects are rare and are easier to tolerate compared to other antidepressants. In general medical practice, it is recommended to take the drug 1 tablet 3 times a day before meals. Coaxil is available in a dosage of 12.5 mg of tianeptine per tablet.

Precautions: discontinuation of the drug is carried out gradually, reducing the daily dose over 7–14 days. Tianeptine is incompatible with MAO inhibitors. Simultaneous use may lead to the development of collapse, convulsive syndrome, sudden rise in blood pressure, hyperthermia, death. Tianeptine is prescribed only 1-2 weeks after the use of MAOIs. Doses and use. Recommended dose 12.5 mg 2-3 times a day before meals. Available in tablets of 12.5 mg No. 30.

Properties of drugs and precautions when prescribing antidepressants of the imipramine group (bi-, tri- and tetracyclic drugs)

Treatment effectiveness: dose – 150 mg/day: the dose is achieved within 2–3 days. In cases of “severe” depression (60–75%). The half-life is more than 24 hours, therefore only one dose per day is possible.

Contraindications: glaucoma, prostatic hypertrophy, heart failure - when combined with non-selective MAO inhibitors.

Preliminary examination: ECG, condition of the prostate gland, ophthalmologist's report. If necessary: ​​thyroid condition, EEG.

Possible complications: tachycardia, orthostatic hypotension, tremor, dysarthria, dry mouth, constipation, night sweats. Urinary retention. Rare complications: confusion in elderly patients, epileptic seizures, inversion of affect - development of a manic state.

Monitoring parameters for TCA treatment:

Pulse, blood pressure, physiological functions, neurological status.

State of sleep.

Controlling the level of anxiety.

Reduced lethargy (risk of committing suicide on day 10).

Improved mood (days 15–20): therapeutic goal.

Disappearance of deep melancholy, melancholic thoughts, improved concentration.

Duration of treatment with antidepressants:

From 6 to 8 weeks – primary treatment,

From 4 to 6 months – prevention of exacerbation,

18 months and more - prevention of relapse by slowly reducing the dose by 25 mg every 2 weeks.

Reading time: 9 minutes. Published 08/16/2019

Tricyclic antidepressants (TCAs) were developed in the 1950s as a chemical treatment for depression. These drugs are known for their specific chemical structure, consisting of three rings of atoms, which is why they are called tricyclics. Tricyclics were developed after researchers began studying derivatives of the first typical antipsychotic drug, Thorazine (Aminazine). Experiments led to the development of the first tricyclic antidepressant - Imipramine.

Imipramine was not originally intended to treat depressive symptoms, but did cause mania. This led researchers to believe that it may have some antidepressant effects. In testing, Imipramine was found to produce a strong antidepressant response among people with depression. This led to the production of a new class of antidepressant drugs—tricyclic antidepressants (TCAs).

TCAs became widely used to treat depression and were considered very effective. At the time TCAs were approved, they were considered a first-line treatment option. These days they are still used to treat depression, but are considered second-line drugs. After and.

They are still considered highly effective by many, but doctors and patients prefer the new drugs because they have fewer side effects and are considered safer. TCAs are usually prescribed as a treatment alternative before use.

Tricyclic antidepressants list

Below are several lists of TCAs, grouped by how they function. Although some TCAs have similar effects on and , others to a greater extent influence one of them. In addition, there are others that do not affect any of the neurotransmitters. They are listed as "atypical" TCAs.

Balanced TCAs: Serotonin and Norepinephrine

Below is a list of tricyclic antidepressants that affect serotonin and norepinephrine to the same extent.

Amitriptyline (Amizol, Elivel). It is the most commonly used TCA. Created by Merck in 1961. In addition to affecting , it also affects Alpha-1 receptors and acetylcholine receptors.

Amitriptyloxide (Amioxide, Ambivalon, Equilibrine). Amitriptyl oxide appeared in Europe in the 1970s. It acts similarly to Amitriptyline because it is a metabolite. However, it works faster and with fewer side effects.

Butriptyline (Evadin). Butriptyline appeared in Europe in 1974. It is very similar to Amitriptyline, but has significantly fewer side effects and contraindications. It acts as a potent antihistamine and anticholinergic and is also a moderate agonist of the Alpha-1 receptor and 5-HT2 receptor. It affects serotonin to a very small extent.

Dosulepin (Protiaden). Used mainly in Australia, New Zealand and South Africa. In addition to affecting serotonin and norepinephrine, it also has anticholinergic and antihistamine properties and blocks the Alpha-1 receptor.

Doxepin (Sinequan, Spectra). Used all over the world for treatment major depression, anxiety disorders and insomnia. It is also considered a drug that can be used to treat hives and severe itching.

Melitracene (Adaptol). Used throughout Europe and Japan to treat depressive and anxiety disorders. The method of action is similar to the drugs Imipramine and Amitriptyline. Works faster and has fewer side effects.

Nitroxazepine (Syntamil). Marketed in India for the treatment of depression in 1982. Like many other TCAs, it can also be used to treat bedwetting in children. Similar to the drug Imipramine, but has fewer side effects (in particular, anticholinergic).

Noxiptyline (Agedal, Elronon). Combines Noxiptyline and Dibenzoxin. It was originally released in the 1970s in Europe and was considered one of the most effective TCAs.

Propizepine (Vagran). Released in France in the 1970s. Not many documents have been published on the pharmacology of this drug.

Tricyclic antidepressants that act on serotonin

Below is a list of TCAs that increase serotonin significantly compared to norepinephrine.

Clomipramine (Anafranil, Clofranil). Developed in the 1960s and is a derivative of the first TCA, Imipramine. It inhibits the reuptake of serotonin 200 times more than norepinephrine. In addition to this, it also acts as an antagonist at the histamine H1 receptor, alpha-1 adrenergic receptor and various acetylcholine receptors.

Dimethacrine (Istonil). Used to treat major depression throughout Europe. It was previously used in Japan. It is less effective compared to Imipramine. Rarely used due to effects on the liver.

Imipramine (Deprinol, Tofranil, Imizin). It is the first TCA discovered and has been used since the 1950s. Used to treat depression, but in some cases prescribed for bedwetting due to its ability to reduce delta brain waves during sleep. Although this drug has very potent serotonin reuptake inhibitory properties, it has effects on a number of other neurotransmitters including: norepinephrine, (to a very small extent at the D1 and D2 receptors), acetylcholine (anticholinergic), epinephrine (antagonist), and histamine (antagonist) .

Imipramine oxide (Elepsin). Created in the 1960s and used in Europe. In addition to affecting serotonin, it also acts on adrenaline, histamine and acetylcholine receptors as an antagonist. It acts similarly to Imipramine due to the fact that it is a metabolite and has a similar structure. However, Imipramine Oxide works faster and with fewer side effects.

Pipofezin (Azafen). Approved for the treatment of depression in the 1960s and used in Russia. This drug also has antihistamine properties due to the fact that many experience sedation as a side effect. In addition, it has anticholinergic and adrenergic effects.

Tricyclic antidepressants that act on norepinephrine

These are TCAs that affect norepinephrine more than serotonin. Many are more stimulating, which can also increase anxiety. They are suitable for people with lower levels of emotional arousal.

Demexiptyline (Deparon, Tinoran). Used in France. It works similarly to the more widely documented drug Desipramine.

Desipramine (Norpramin, Petilil). Used to treat major depression, but has been found useful in the treatment of neuropathic pain and some symptoms of ADHD. Desipramine is associated with an increased risk of breast cancer in women and is considered genotoxic. It contains the active metabolite of the drug Imipramine.

Dibenzepine (Noveril). Available in European countries only. Acts primarily as a norepinephrine reuptake inhibitor, but also has significant antihistamine properties. It is considered to be similar to Imipramine, but with fewer side effects and a similar degree of effectiveness.

Lofepramine (Gamanil). Introduced in 1983. It is a relatively weak acetylcholine receptor antagonist. It is considered to be less sedating and safer than other TCAs.

Metapramine (Prodasten). Appeared in France in the mid-1980s. Has little effect as an NMDA receptor antagonist. This drug also acts as an analgesic, so some doctors may prescribe it for pain relief. It does not have anticholinergic properties like other TCAs.

Nortriptyline (Pamelor). This is a second generation TCA used for depression and sometimes for childhood bedwetting. Due to its stimulant properties it is sometimes used for treatment chronic fatigue, neuropathic pain and ADHD.

Protriptyline (Vivaktil). Used to treat depression as well as ADHD. This drug is known for its stimulant effects and generally promotes alertness, so it is used in some cases for narcolepsy.

Atypical tricyclic antidepressants

Atypical TCAs work differently than most and have unique properties. Unlike other TCAs, which focus primarily on norepinephrine, serotonin, or a combination of both, these drugs may act on 5-HT2 receptors, dopamine, Sigma-1 receptors, or glutamate receptors.

Amineptine (Survector). Developed in the 1960s and approved in 1978 in France. Due to its euphoric stimulant effects, people began to use it recreationally and abuse it. In 1999, after reports of liver damage, the drug was withdrawn from sale.

Iprindol (Prondol, Galatur, Tertran). Used in Europe since 1967. Acts primarily as a 5-HT2 receptor antagonist with minimal effects on serotonin and norepinephrine.

Opipramol (Pramolone, Insidon). Used in various European countries to treat anxiety disorders as well as depression due to its strong anxiolytic and tranquilizing effects. Opipramol acts primarily as an agonist at the Sigma-1 receptor and to a lesser extent as an agonist at the Sigma-2 receptor. Compared to SSRIs and SNRIs, this drug has fewer side effects.

Quinupramine (Quinupril, Adeprim). Used in Europe. Acts primarily as an acetylcholine receptor antagonist and also as a histamine antagonist at the H1 receptor. Affects the 5-HT2 receptor as a moderate antagonist.

Tianeptine (Coaxil, Stablon). Developed in the 1960s and used to treat depression, but is sometimes prescribed to treat irritable bowel syndrome. Tianeptine affects both the activity of glutamate receptors AMPA and NMDA, and. The researchers also noted that it functions as an agonist at the mu and delta opioid receptor.

Trimipramine (Gerfonal, Surmontil). Used to treat depression as a 5-HT2 receptor antagonist and an H1 receptor antagonist. It is known for its very calming effects and in some cases this drug is good for treating insomnia and anxiety. It is considered unique in that it is the only medicine that does not affect sleep stages.

Conclusion

There is current debate as to whether tricyclic antidepressants deserve classification as second-line treatments for depression. SSRIs, SNRIs, and the newer atypical antidepressants are considered to be the safest, have the fewest side effects, and are more effective than TCAs. However, many people do not respond to these classes of drugs, and for them the tricyclic class may be an ideal option.

There is some evidence that tricyclics may be better for treating people who have significant melancholic features associated with depression. The tricyclic antidepressant class is often tested only when a patient has not experienced any improvement in depressive symptoms from newer classes of medications. Assuming a person can tolerate the initial side effects, TCAs can be very effective as antidepressants.

It should be noted that these drugs are sometimes also used for conditions other than depression, such as: ADHD, chronic pain, insomnia and nocturnal enuresis.

This group of antidepressants includes the very first drugs with an antidepressant effect, which were synthesized in the 50s of the last century. They received the name “tricyclic” because of their structure, which is based on a triple carbon ring. These include imipramine, amitriptyline and nortriptyline. Tricyclic antidepressants increase the concentration of neurotransmitters such as serotonin and norepinephrine in our brain by reducing their uptake into neurons. The effect of drugs in this group is different: for example, amitriptyline has a sedative effect, and imipramine, on the contrary, has a stimulating effect.

TCAs act faster than other groups, and in some cases, positive mood changes can be observed within a few days of starting use, although each individual and sometimes stable results are observed only after several months of use. Since these drugs also block other mediators, they cause a number of unwanted side effects. The most common of them are lethargy, drowsiness, dry mouth (in 85%), constipation (in 30%). Also observed increased sweating(25%), dizziness (20%), increased heart rate, decreased potency, weakness, nausea, difficulty urinating. Feelings of restlessness and anxiety may occur. Taking TCAs may cause problems for those with cardiovascular disease or those who are carrying contact lenses(usually there is a feeling of “sand in the eyes”).

These drugs are low cost. An overdose of TCAs can be fatal. This drug is often used for suicidal purposes.

Monoamine oxidase inhibitors (MAOIs).

MAOIs interfere with the action of the enzyme monoamoxidase found in nerve endings. This enzyme breaks down neurotransmitters such as serotonin and norepinephrine, which affect our mood. MAOIs are usually prescribed to those who do not improve after being prescribed tricyclic antidepressants. They are also often prescribed for atypical depression, a disorder in which some symptoms are opposite to typical depression (the person sleeps and eats a lot, feels worse in the evenings rather than in the mornings). In addition, because MAOIs have a stimulant rather than a sedative effect, they are preferable to TCAs for the treatment of dysthymia - minor depression. The positive effect occurs after a few weeks. The most common side effects are dizziness, blood pressure fluctuations, weight gain, sleep disturbance, decreased potency, increased heart rate, and swelling of the fingers.

The difference between MAOIs and other drugs is that you should not eat certain foods while taking them. This is a rather unusual list: aged cheeses, sour cream, cream, kefir, yeast, coffee, smoked meats, marinades, fish and soy products, red wine, beer, legumes, sauerkraut and pickled cabbage, ripe figs, chocolate, liver. There are also a number of medications that do not combine with MAOIs. In this regard, this class of antidepressants should be prescribed with extreme caution. Also, therapy with other antidepressants should begin no earlier than two weeks after discontinuation of MAO.

Nialamid (nuredal). Irreversible MAO inhibitor. Currently rarely used. “Small” antidepressant with a pronounced stimulating effect. Used for mild depression with lethargy, fatigue, anhedonia, lethargy. Due to the presence of an analgesic effect, it is also used to treat pain syndromes for neuralgia.

Pirlindol (pyrazidol). Moclobemide (Aurorix).

Antidepressants - SSRIs.

This is the name given to a class of antidepressants that have become popular due to fewer side effects compared to drugs from the other two previous groups. But SSRIs have a disadvantage - their high price.

The action of these drugs is based on increasing the supply of the brain with the neurotransmitter serotonin, which regulates our mood. SIZOS got their name due to their mechanism of action - they block the reuptake of serotonin at the synapse, as a result of which the concentration of this transmitter increases. Inhibitors act on serotonin without affecting other mediators, and therefore cause almost no side effects. This group includes fluoxetine, paroxetine, fluvoxamine and sertraline (Zoloft). On the contrary, people lose a little weight when taking SSRIs. Therefore, it is prescribed for overeating and obsessive states. They are not recommended for bipolar depression, as they can cause manic states, or for people with liver disease, since the biochemical transformations of SSRIs occur in the liver.

Side effects: anxiety, insomnia, headaches, nausea, diarrhea.

There are other antidepressants. These are bupropion (Wellbutrin), trazodone and venlafaxine, Remeron.

Anxiolytics (tranquilizers) and sleeping pills.

Anxiolytics are a broad group of drugs, mainly pharmacological effect which is the ability to eliminate anxiety.

Other effects:

Ø Sedative

Ø Sleeping pill

Ø Muscle relaxant

Ø Antiphobic

Ø Vegetative stabilizing

Ø Anticonvulsant.

In this connection, they are used for sleep disorders, addiction to psychoactive substances, epilepsy and other convulsive conditions, a number of neurological diseases, as well as many somatic and psychosomatic disorders, especially with coronary heart disease, hypertension, peptic ulcer, bronchial asthma and many others. In addition, they are used by surgeons as premedication agents.

Based on their chemical structure, anxiolytics are divided into two: large groups:

v Benzodiazepines , which include the majority of tranquilizers used in medical practice today;

v Non-benzodiazepine derivatives - bushpirone, oxidine, phenibut, etc.

According to their strength, that is, the degree of severity of sedative and anti-anxiety effects, these drugs are conventionally divided into:

§ Si linen, which include, in particular, clonazepam, alprozolam, phenazepam, triazolam, estazolam.

§ Medium strength - for example, diazepam, tranxene, lorazepam, chlordiazepoxide.

§ Weak – for example, oxazepam, medazepam, oxylidine and others.

Finally, another very important characteristic of this group of drugs is the average half-life, and therefore they are divided into:

· Short-lived drugs or drugs with a short half-life (conventional limit of 24 hours or less), for example, alprazolam, triazolam, estazolam, lorazepam, grandaxin, medazepam, phenazepam, oxazepam.

· Long-lived, or drugs with long period half-life - for example, clonazepam, clorazepate, diazepam, nitrazepam, etc.

Rules for prescribing tranquilizers:

1. Treatment begins with the lowest possible doses with a gradual increase, and the doses should be equally gradually reduced at the end of therapy; the patient should be warned in advance about side effects, especially in the first days of treatment ( muscle relaxation, lethargy, slowness of reaction, difficulty concentrating).

2. To avoid the danger of developing dependence, a prescription should be written for a small amount of the drug and the doctor should examine the patient at least once every 2 weeks.

3. If a long course is required (2-3 months or more), for example, with GAD, the drugs and their doses must be changed; monotonous administration of the drug in a consistently high dose for more than 3-4 weeks is unacceptable; drugs with a long half-life are preferable.

4. Constant monitoring is important so as not to miss the first signs of drug abuse and dependence.

5. Always remember that tranquilizers are by no means a panacea, but only one of the methods of treating anxiety disorders and should be used only where non-drug methods of treatment have not produced results.

Antidepressants

The main indication for the prescription of antidepressants is a persistent decrease in mood (depression) of various etiologies. This group includes agents that differ significantly both in chemical structure and mechanisms of action (Table 15.3). In psychopharmacological studies, the effect of antidepressants is associated with potentiation of monoamine mediator systems (mainly norepinephrine and serotonin). However, it is possible that the effect

Table 15.3. Main classes of antidepressants

is explained by a deeper adaptive restructuring of receptor systems, since the effect of any antidepressant develops relatively slowly (no earlier than 10-15 days from the start of treatment). Some psychostimulants (phenamine, sydnophen) and L-tryptophan (a precursor of serotonin) also have a short-term antidepressant effect.

Tricyclic antidepressants (TCAs) are currently the most commonly used drugs for the treatment of depression. Their chemical structure is close to phenothiazines. The most powerful drugs are amitriptyline and imipramine (melipramine). The antidepressant effect of these drugs develops relatively slowly, an increase in mood and the disappearance of ideas of self-blame are observed approximately 10-14 days from the start of treatment. In the first days after administration, additional effects are more pronounced. In particular, amitriptyline is characterized by a pronounced sedative, anti-anxiety, and hypnotic, and melipramine has an activating, disinhibiting effect (Table 15.4). At the same time, an M-anticholinergic effect develops, manifested by dry mouth, sometimes impaired accommodation, constipation, and urinary retention. An increase in body weight, a decrease or increase in blood pressure are often observed. Dangerous complications when using TCAs are cardiac arrhythmias and sudden cardiac arrest. These side effects limit their use to persons over 40 years of age (especially with coronary heart disease, angle-closure glaucoma, prostate adenoma). The exceptions are Azafen and Gerfonal, the use of which is considered quite safe at any age. Great similarity of the clinical effect with the effect of TCAs is found in ludiomil (maprotiline) and the sedative antidepressant mianserin (lerivon). In cases of resistance to TCAs, they may be more effective.

Table 15.4. The severity of sedative and psychostimulating effects in drugs with antidepressant action

Sedatives

Balanced

Stimulating

Fluoroacyzine

Ludiomil

Irreversible inhibitors

Gerfonal

Doxepin

Amitriptyline

Sydnofen

Mianserin

Pyrazidol

Aurorix

Amoxapine

Clomipramine

Wellbutrin

Venlafaxine

Fluoxetine

Trazodone

Desipramine

Nortriptyline

Opipramol

Melipramine Cefedrin Befol Incazan Heptral

Non-selective irreversible MAO inhibitors were discovered in connection with the synthesis of anti-tuberculosis drugs from the ftivazid group. In Russia, only nialamide (nu-redal) is used. The drug has a strong activating effect. The antidepressant effect is comparable in strength to tricyclic antidepressants, but develops somewhat faster. The use of the drug is limited due to significant toxicity caused by inhibition of detoxifying liver enzymes, as well as incompatibility with most psychotropic drugs (tricyclic antidepressants, reserpine, adrenaline, psychostimulants, some antipsychotics) and food products containing tyramine (cheese, legumes, smoked meats, chocolate, etc.). Incompatibility persists for up to 2 weeks after discontinuation of nialamide and is manifested by attacks of hypertension, accompanied by fear and sometimes cardiac arrhythmia.

Quadruple antidepressants (pirazidol) and other selective MAO inhibitors (befol) are safe antidepressants with a minimum number of side effects and a successful (psychoharmonizing) combination of anti-anxiety and activating effects. Compatible with any psychotropic drugs, used in patients of any age. However, their antidepressant activity is significantly lower than that of tricyclic antidepressants.

Selective serotonin reuptake inhibitors (fluoxetine, sertraline, paxil) are relatively new drugs. Their effectiveness is comparable to that of tricyclic antidepressants: the disappearance of signs of depression begins 2-3 weeks after the start of treatment. Side effects are limited to dry mouth, sometimes nausea, and dizziness. Used in patients of any age. Special effects include appetite suppression (used in the treatment of obesity). Important advantages of this group of drugs are ease of use (in most cases, for maximum effect, a single dose of 1 or 2 tablets per day is enough) and surprisingly low toxicity (there are cases of taking a 100-fold dose of the drug without risk to life). Incompatible with irreversible MAO inhibitors.

In recent years, antidepressants have been increasingly used to treat obsessive fears and panic attacks. Selective serotonin uptake inhibitors and clomipramine (Anafranil) are especially effective against anxiety attacks.

The use of drugs with a pronounced stimulating effect to treat depression can lead to increased anxiety and an increased risk of suicide. The use of antidepressants in patients with hallucinatory-delusional symptoms is associated with the risk of exacerbation of psychosis and therefore should be carried out carefully, in combination with the use of antipsychotics.

Tranquilizers (anxiolytics)

The tranquilizing (anxiolytic) effect is understood as the ability of this group of drugs to effectively relieve anxiety, internal tension, and restlessness. Although this effect may make it easier to fall asleep, it should not be considered as a synonym for a hypnotic effect, since calming patients is not always accompanied by drowsiness - sometimes, on the contrary, activity increases.

The point of application of tranquilizers is currently considered to be the chloride-ion receptor complex, consisting of the GABA receptor, the benzodiazepine receptor and the chloride channel. Although the main representatives of tranquilizers are benzodiazepines, any drugs that act on the chloride ion complex (GABAergic, barbiturates and others) can be considered as tranquilizers. The highly selective tropism of tranquilizers to benzodiazepine receptors determines, on the one hand, a small number of side effects, and on the other hand, a rather narrow spectrum of psychotropic activity. Tranquilizers as the main means can be used only for the mildest neurotic disorders. They are widely used healthy people when situationally determined anxiety and tension arise. For cupping acute psychosis(for example, in schizophrenia) tranquilizers are ineffective - it is preferable to prescribe antipsychotics.

Although in practice it is necessary to take into account some features of the spectrum of action of each drug (Table 15.5), the effects of various tranquilizers are characterized by significant similarity, and in most cases, replacing one drug with another in an adequate dose does not lead to a significant change in the condition.

When prescribing an anxiolytic drug, it is often necessary to take into account its pharmacokinetic characteristics (absorption rate, half-life, lipophilicity). The effect of most drugs develops quickly (with intravenous administration immediately, if taken orally after 30-40 minutes), the effect of the drug can be accelerated by dissolving it in warm water or by taking a tablet under the tongue. Keto-substituted drugs have the longest lasting effect.

benzodiazepines (Table 15.6) - radedorm, elenium, sibazon, flurazepam. After their use, patients may experience drowsiness, lethargy, dizziness, ataxia, and memory impairment for a long time. In elderly patients, there is usually a slowdown in the elimination of benzodiazepines from the body, and accumulation phenomena may occur. In this case, hydroxy-substituted benzodiazepines (oxazepam, lorazepam) are more easily tolerated. Triazole derivatives (alprazolam, triazolam) and the new sleeping pill Imovan have an even more rapid and short-term effect. The use of strong tranquilizers in the daytime is associated with a deterioration in performance, therefore a group of “daytime” drugs is distinguished

Table 15.5. Main classes of tranquilizers

Table 15.6. Chemical structure of benzodiazepines

derivatives

3-Hydroxy-

derivatives

Triazole and

imidazole

derivatives

Chlordiazepoxide

Oxazepam

Alprazolam

Diazepam

Lorazepam

Triazolam

Flurazepam

Temazepam

Estazolam

Nitrazepam

Brotizolam

Rohypnol

Midazolam

Phenazepam

Clorazepate

tranquilizers, the sedative effect of which is much less pronounced (nozepam, clorazepate, mebicar) or even combined with a slight activating effect (mezapam, trioxazine, grandaxin). If anxiety is severe, you should choose the most powerful drugs (alprazolam, phenazepam, lorazepam, diazepam).

Tranquilizers are low-toxic, combine well with most medications, and have few side effects. The muscle relaxant effect is especially pronounced in the elderly, and therefore the dosage should be lower the older the patient is. For myasthenia gravis, benzodiazepines are not prescribed. On the other hand, the muscle relaxant effect can be used for painful muscle spasms (osteochondrosis, headaches). The use of any tranquilizer worsens the severity of the reaction and is unacceptable when driving. With long-term (more than 2 months) use of tranquilizers, addiction may develop (especially when using diazepam, phenazepam, nitrazepam).

Many benzodiazepines have an anticonvulsant effect (nitrazepam, phenazepam, diazepam), but the pronounced sedative effect of these drugs prevents their widespread use for the treatment of epilepsy. For effective and safe prevention epileptic seizures More often, long-acting drugs without a pronounced sedative effect are used (clonazepam, clorazepate, clobazam).

A tranquilizing effect is found in many drugs used in somatic medicine and acting on other mediator systems - antihypertensive drugs (oxylidine), antihistamines (atarax, diphenhydramine, donormil), some M-anticholinergic drugs (amizil). Bushpirone is the first representative of a new class of tranquilizers, the action of which is probably associated with serotonergic receptors. Its effect develops gradually (1-3 weeks after administration), there is no muscle relaxant or euphoric effect, it does not cause addiction.

Psychostimulants

This group includes agents of various chemical structures that cause activation and increased performance, often due to the release of mediators present in the depot. The first drug introduced into practice was phenamine (amphetamine), however, due to its pronounced tendency to cause addiction, phenamine was included in the list of drugs in Russia (see section 18.2.4). Currently, sydnocarb is most often used; other drugs in this group are sydnophen and caffeine. In psychiatry, psychostimulants are used extremely limitedly. Indications are mild depressive states and apathetic-abulic states in schizophrenia. The antidepressant effect of psychostimulants is short-term. After each use of the drug it is required good rest to restore strength - otherwise tolerance increases with the subsequent formation of dependence. Psychostimulants (phenamine, fepranon) reduce appetite. Side effects include insomnia, increased anxiety and restlessness, and exacerbation of psychosis in patients with delusions and hallucinations.

29. Normotimics and antimanic drugs.

The most important property of this group of drugs is the ability to smooth out, eliminate and prevent pathological mood swings (normothymic effect), as well as to stop hypomania and mania, and therefore these drugs are used for the prevention of phases of bipolar disorder and schizoaffective disorder, as well as therapy manic states. For the preventive effect of these drugs to appear, they must be taken for a long time - 1-1.5 years or more.

This group includes lithium carbonate and other salts, as well as carbamazepine, valproic acid preparations, lamotrigine, etc.

Lithium carbonate. It has a pronounced antimanic effect, as well as a clear preventive effect in phasic affective and schizoaffective psychoses. The half-life is on average 22-32 hours.

Treatment method and dose: 300-600 mg per day in 2-3 doses. Then the lithium content in the blood plasma is determined and, depending on the result, a further dose is selected. When relieving manic states, the concentration of lithium in plasma should be 0.6-1.2 mmol/l - higher concentrations are toxic and dangerous, and at a dose below 0.4 therapeutic effect doesn't come. The doses required for this are 600-900-1200 mg per day. Determination at the beginning of therapy with increasing doses is repeated 1-2 times a week, when the desired concentration is achieved - weekly, subsequently - once a month. Kidney function should be checked periodically (twice a year general analysis urine and urea content in the blood).

Side effects: mild tremor, polyuria, polydipsia, slight increase in body weight, lethargy, especially at the beginning of therapy. The appearance of vomiting, drowsiness, muscle weakness, large-scale tremor indicates intoxication and requires cessation of therapy.

Carbamazepine (finlepsin, tegretol). A well-known antiepileptic drug. In addition to anticonvulsant activity, it also has antimanic and preventive effects, and therefore is used to relieve mania and for maintenance treatment of affective and schizoaffective disorders. The antimanic effect develops within 7-10 days from the start of treatment. It has a preventive effect in approximately 70-80% of cases. Does not have an antidepressant effect.

Doses: when relieving mania, the initial dose is 400 mg, the average is 600-800 mg orally per day in 2-3 doses after meals; for preventive therapy, treatment begins with 200 mg per day, then the dose is increased by 100 mg every 4-5 days until daily dose from 400 to 1000 mg per day in 3 doses, depending on tolerance. Most often, the dose for maintenance treatment is 400-600 mg per day. The criterion that the correct dose has been achieved is that the patient experiences very slight drowsiness, muscle relaxation on short periods after taking the drug, if this is more pronounced, the dose of the drug should be reduced.

Side effects: drowsiness, lethargy, difficulty concentrating, muscle weakness, nausea, dizziness, uncertainty when walking, occasionally hepatitis and changes in blood patterns.

Depakine (Depakine-Chrono, Convulsofin, Kovulex). Valproic acid or its salts - sodium valproate, calcium valproate, etc. When taken orally in small intestine Valproic acid is formed from valproates, which is active substance. The antimanic effect develops within 5-7 days from the start of administration. It has no direct antidepressant effect.

Doses: prescribed after meals, starting with 150-300 mg per day in 2 or 3 divided doses with a gradual increase in dose by 150-300 mg every 2-3 days. Usual doses for prevention are from 600 to 1200 mg per day, doses for the treatment of mania are slightly higher (800-1800 mg per day).

Side effects: nausea, vomiting, occasionally hair loss, thrombocytopenia. Drowsiness and muscle weakness usually do not cause.

Lamotrigine (Lamictal). The mechanism of action is associated with blocking sodium and calcium channels of neurons and inhibiting excess glutamate. Used in preventive treatment BAD, especially when depressive phases predominate.

Side effects: drowsiness, headache, tremor, skin rash.

Doses: from 100 to 300-400 mg per day in 1 or 2 doses, depending on the preventive effect.

Until recently, this group included only lithium salts (carbonate or hydroxybutyrate). Initially proposed for the treatment of mania, lithium salts are increasingly used to prevent both manic and depressive phases in MDP and schizophrenia. The disadvantage of these drugs is their small therapeutic range. In case of overdose, polyuria, hand tremors, dyspepsia, bad taste in the mouth, drowsiness, headaches, thyroid dysfunction. Therefore, the dose of lithium should be monitored weekly by determining its content in the blood plasma. Usually, 0.6-0.9 mmol/l is sufficient to prevent affective phases. For the treatment of acute mania, the concentration can be increased to 1.2 mmol/l, however, in recent years, antipsychotics (gapoperidol) have been increasingly used to treat mania. When taking lithium, you should strictly monitor salt and fluid intake, as well as diuresis, to avoid unwanted fluctuations in drug concentrations.

An action similar to that of lithium was discovered several years ago in some anticonvulsants- carbamazepine (Tegretol, Finlepsin) and valproic acid salts (Depakine, Konvulex). These drugs have a greater therapeutic range and have a sedative effect, but their effectiveness compared to lithium is debated.

Nootropics.

Nootropics (synonym: neurometabolic stimulants, cerebroprotectors) are a group of drugs that improve brain metabolism, higher brain functions (memory, learning, thinking) and increase resilience nervous system to the influence of aggressive factors external environment(shock, intoxication, trauma, infection).

Under the influence of therapy with these drugs, memory improves, performance increases, learning processes accelerate, the level of wakefulness increases, mental and physical asthenia decreases, and extrapyramidal and neurological symptoms are weakened.

They are used in the treatment of many organic and symptomatic mental disorders of the brain of traumatic, vascular, infectious and toxic nature.

Contraindications and complications of treatment There are practically no drugs for this group. There may be irritability, sleep disturbances, dyspeptic disorders (nausea, epigastric pain, diarrhea in people who have been using piracetam for a long time.