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 affect both and , others have a greater effect on 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 its effects on , 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 worldwide to treat 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 relative 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 is sometimes 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 to treat 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 new 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.

Antidepressants are a large group of drugs for mood correction.

History

The invention of mood pills dates back to the 50s, when the first two and a half ADs were synthesized:

• Isoniazid with Iproniazid, which were originally invented as a means to treat tuberculosis, but were found to cause inexplicable euphoria in patients and attracted the interest of psychiatrists;
• Imipramine is a tricyclic obtained by adding a pair of atoms to the nuclear neuroleptic Aminazine.

Before them, doctors tried to improve the mood of the sufferers with everything they could get their hands on: they used opiates, barbiturates, amphetamines, valerian, bromides, ginseng and rauwolfia. The effects were not bad, although far from antidepressant.

What is this

At the moment, there are three main groups of drugs, which differ greatly not only in their spectrum of action, but also in their side effects.

This is not a symptomatic treatment, they say the person became sad, they gave it and he became cheerful, no, this is pathogenetic.

TCA

Tricyclic antidepressants are the most reliable and studied group of antidepressants, which have a good list of side effects (drowsiness, dry mouth/eyes, constipation) and a low price - Amitriptyline 0.025, 17 rubles for 50 tablets. Their action is based on reducing the uptake of several mediators (serotonin, norepinephrine and dopamine), which together gives not only an antidepressant, but also a sedative effect.

The most epic of them are Imipramine, Amitriptyline and Nortriptyline. Since 2005, production of the first Soviet antidepressant Azafen began again, which is of some interest due to the absence of anticholinergic and cardiotoxic effects.

SSRIs

Selective serotonin reuptake inhibitors, as the name suggests, act primarily on serotonin, increasing its concentration and leading to the desired effect. Now this group is the most frequently used, and Flucosetine (Prozac) has been breaking all sales records for several years now, although many SSRIs have a very high price. This is facilitated by the small number of side effects when using small doses, so they are recommended for use even in general medical practice. Also, their use helps with other conditions, such as obsessive disorders and overeating.

There are just a lot of drugs for every taste: Fluoxetine, Sertraline, Fluvoxamine, Paroxetine, Dapoxetine, Citalopram, Escitalopram, Venlafaxine, Duloxetine; For more details, see the main article.

MAOI

Inhibitors monoamine oxidases- heavy artillery, used when no other drug has worked. Their use is limited due to extensive side effects and incompatibility with a huge list of drugs and foods that increase their toxicity. Although, due to their stimulating effect, they are highly indicated for patients with atypical and “minor” depression.

The most currently used MAOI drug is Moclobemide; in this group there is a real Russian drug - Pyrazidol, which does not have an anticholinergic effect, due to which it can be used as a replacement for tricyclic drugs in patients with glaucoma and BPH.

Other

In addition to these groups, there are drugs with a bi- and four-cyclic structure, called atypical antidepressants, some of which have a radically different mechanism of action - Mianserin does not affect either MAO or the uptake of neurotransmitters.

One of the most interesting: Bupropion.

How does this work

The basis of depression is considered to be a decrease in serotonin and norepinephrine transmission between neurons in the brain, therefore the main effects of the described group are based on an increase in the concentration of serotonin and norepinephrine. You can’t take the missing substances and put them into the brain - the administration of our body is not so stupid as to allow anything to act on them (as glutamate paranoids would like): antidepressants lead to an increase in these substances indirectly? - by blocking the enzymes that utilize them. Elimination slows down -> concentration increases, it’s simple. It is extreme idiocy to compare antidepressants with drugs; unfortunately, they do not work at all and, in principle, cannot - they do not act on a healthy person at all.

The effect of antidepressants is manifested in a positive effect on the affective sphere, which leads to an improvement in mood and a concomitant normalization of the general mental state with some additional effects that differ for each specific drug: Imipramine and Fluoxetine (and some MAOIs - Nialamid, Eprobemide) have a stimulating effect, Amitriptyline ( and other tricyclics) and Maprolitin act well as anti-anxiety drugs.

Doctor, what will happen to me?

An important aspect of the action of antidepressants is that their effect appears no earlier than 5-10 days of use, increasing gradually with the accumulation of target substances in the brain; and a stable response to therapy develops after at least 2-4 months of continuous use.

They are used not only by psychiatrists, but also by neurologists for the treatment of neurovegetative conditions and chronic pain, often without real depression in the patient, so do not be surprised by such prescriptions.

More

• Depressants are substances that depress the central nervous system. In large dosages, they remove internal inhibitions, weaken concentration and the ability to make balanced judgments. The coolest: alcohol, tranquilizers (Valium and Librium) and opiates (morphine and heroin).

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Notes

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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 (85%), constipation (30%). Increased sweating (25%), dizziness (20%), increased heart rate, decreased potency, weakness, nausea, and difficulty urinating are also observed. Feelings of restlessness and anxiety may occur. When taking TCAs, problems may occur for those who suffer from cardiovascular diseases, as well as for those who wear contact lenses (usually a sensation 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 due to neuralgia.

Pirlindol (pyrazidol). Moclobemide (Aurorix).

Antidepressants - SSRIs.

This is the name of 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 large group of drugs whose main pharmacological effect is the ability to eliminate anxiety.

Other effects:

Ø Sedative

Ø Sleeping pill

Ø Muscle relaxant

Ø Antiphobic

Ø Vegetostabilizing

Ø Anticonvulsant.

Therefore, it is 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 coronary heart disease, hypertension, peptic ulcer disease, 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 a long 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 use (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 of 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 foods containing tyramine (cheese, legumes, smoked meats, chocolate and 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 the effect 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 remedy can be used only for the mildest neurotic disorders. They are widely used by healthy people when situationally caused anxiety and tension occur. To relieve acute psychosis (for example, in schizophrenia), tranquilizers are ineffective - the use of antipsychotics is preferable.

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 (if administered intravenously immediately, if taken orally after 30-40 minutes), the effect of the drug can be accelerated by dissolving it in warm water or 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 of epileptic seizures, long-acting drugs that do not have a pronounced sedative effect (clonazepam, clorazepate, clobazam) are more often used.

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, proper rest is required to recuperate - 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. Normotimiki 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 for the treatment of 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 there is no therapeutic effect. 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. It is necessary to periodically check kidney function (twice a year, a general urine test and blood urea levels).

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. It has no 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, the dose begins with 200 mg per day, then the dose is increased by 100 mg every 4-5 days to a daily dose of 400 to 1000 mg per day in 3 doses, depending on tolerability. 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 and muscle relaxation for short periods after taking the drug; if this is more pronounced, then 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, valproic acid is formed from valproate in the small intestine, which is the 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 the preventive treatment of bipolar disorder, 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, unpleasant taste in the mouth, drowsiness, headaches, and dysfunction of the thyroid gland quickly develop. 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 your salt and fluid intake, as well as your urine output, to avoid unwanted fluctuations in drug concentrations.

An effect similar to that of lithium was discovered several years ago in some anticonvulsants - carbamazepine (Tegretol, Finlepsin) and valproic acid salts (Depakine, Convulex). 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 cerebral metabolism, higher brain functions (memory, learning, thinking) and increase the resistance of the nervous system to aggressive environmental factors (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.

Side effects of antidepressants

V. P. Vereitinova, Ph.D. honey. Sciences, O. A. Tarasenko National Pharmaceutical University of Ukraine

Psychopharmacology and psychopharmacotherapy of depressive conditions are dynamically developing areas, and antidepressants are the drugs that occupy the second place in prescription among all psychotropic drugs (after benzodiazepines). Such a high rating of these psychotropic drugs is due to the fact that about 5% of the world's population suffers from depression (according to WHO). An important factor stimulating the development of this area of ​​pharmacology is also the fact that 30-40% of depressions are resistant to pharmacotherapy.

Currently, there are about 50 active ingredients related to antidepressants, which are represented by several hundred drugs produced by various pharmaceutical companies. Of these, 41 trade names are registered in Ukraine.

It should be noted that antidepressants are widely used not only in psychiatric but also in general medical practice. Thus, according to foreign authors, the frequency of depressive disorders among hospitalized therapeutic patients is 15-36%, while at the same time, about 30% of outpatient patients with unknown somatic diagnoses suffer from somatized depression. Depression (regardless of its origin), which develops against the background of a severe somatic illness, significantly complicates its course and the patient’s rehabilitation. Somatized depression, masquerading as somatovegetative disorders, often leads to errors in diagnosis and, accordingly, incorrect treatment of the patient.

Taking into account the fairly widespread use of antidepressants and the ever-increasing need for the use of these drugs, it is necessary to have a clear understanding of their side effects, which will allow differentiated prescribing of these drugs for the treatment of depressive conditions of varying nature and severity.

Tricyclic antidepressants

This is a group of powerful classical antidepressants that have been used to treat depression since the early 50s and are one of the main groups of thymoanaleptics.

Tricyclic antidepressants (TCAs) increase the concentration of monoamines (serotonin, norepinephrine, and, to a lesser extent, dopamine) in the brain, due to a decrease in their absorption by presynaptic endings, promoting the accumulation of these mediators in the synaptic cleft and increasing the efficiency of synaptic transmission. In addition to influencing these mediator systems, TCAs also have anticholinergic, adrenolytic and antihistamine activity.

Due to this non-selective interference of TCAs in neurotransmitter metabolism, they have many side effects (Table 1). This is due, first of all, to their central and peripheral anticholinergic effects.

Table 1. Side effects of tricyclic antidepressants

Drugs	Orthostatic hypotension	Anticholinergic effect	Cardiac conduction disorder
Amitriptyline (amizole)	++	++++	+
Doxepin (sinequan)	++	+++	±
Imipramine (melipramine)	++	+++	+
Clomipramine (anafranil)	++	++	+
Trimipramine (Gerfonal)	++	+++	+
Desipramine (petylyl)	++	++	+
Maprotiline (ludiomil)	++	++	+
Amoxapine	++	±	+

The effect is moderately expressed, ++ - the effect is moderately expressed, +++ - the effect is strongly expressed, ± - the effect can be manifested.

The peripheral anticholinergic effect is dose-dependent and is manifested by dry mouth, impaired swallowing, mydriasis, increased intraocular pressure, impaired accommodation, tachycardia, constipation (up to paralytic ileus) and urinary retention. In this regard, TCAs are contraindicated in glaucoma and prostatic hyperplasia. Peripheral anticholinergic effects disappear after reducing the dose and are stopped by proserin. These drugs should not be combined with anticholinergic drugs. Amitriptyline, doxepin, imipramine, trimipramine, and clomipramine have the greatest anticholinergic activity.

Prescribing TCAs to elderly patients, as well as patients with vascular pathology and organic lesions of the central nervous system can lead to the development of delirious symptoms (confusion, anxiety, disorientation, visual hallucinations). The development of this side effect is associated with the central anticholinergic effect of tricyclic antidepressants. The risk of developing delirium increases when prescribed simultaneously with other TCAs, antiparkisonics drugs, antipsychotics, and anticholinergics. The central anticholinergic effects of TCAs are stopped by the administration of anticholinesterase agents (physostigmine, galantamine). To prevent the development of psychopharmacological delirium, patients at risk should not be prescribed drugs with a pronounced anticholinergic effect.

Among other autonomic disorders, when using TCAs, orthostatic hypotension may occur (especially in people with cardiovascular pathology), which is manifested by weakness, dizziness, and fainting. These phenomena are associated with the α-adrenergic blocking activity of TCAs. If severe hypotension develops, it is necessary to replace the prescribed drug with another one that has less α-adrenergic blocking activity. Caffeine or cordiamine are used to increase blood pressure.

Tricyclic antidepressants have the ability to actively interfere with the neurological status of patients. The most common neurological disorders are tremor, myoclonic muscle twitching, paresthesia, and extrapyramidal disorders. In patients with a predisposition to convulsive reactions (epilepsy, traumatic brain injury, alcoholism), seizures may develop. Amoxapine and maprotiline lower the threshold of convulsive excitability to the greatest extent.

It is also necessary to note the ambiguity of the effect of TCAs on the central nervous system: from severe sedation (fluoroacizine, amitriptyline, trimipramine, amoxapine, doxepin, azaphene) to a stimulating effect (imipramine, nortriptyline, desipramine); moreover, among representatives of this group there are drugs (maprotiline, clomipramine) with the so-called “balanced” (bipolar) action. Depending on the nature of the effect of TCAs on the central nervous system, corresponding mental changes occur. Thus, sedative drugs contribute to the development of psychomotor retardation (lethargy, drowsiness) and decreased concentration. Drugs with a stimulant component of action can lead to exacerbation of anxiety, resumption of delusions, hallucinations in mental patients, and in patients with bipolar affective disorders - to the development of manic states. Stimulant drugs may increase suicidal tendencies in patients. To prevent the described disorders, an antidepressant should be selected correctly, taking into account the predominance of a sedative or stimulating component in its pharmacodynamics. To prevent affect inversion in patients with bipolar depressive syndrome, it is necessary to combine TCAs with mood stabilizers (carbamazepine). Hypersedation decreases when mid-therapeutic doses of nootropil are prescribed. However, it would be incorrect to regard the sedative effect of TCAs as solely a side effect, since this effect is useful in cases where depression is accompanied by anxiety, fear, restlessness and other neurotic manifestations.

The active interference of tricyclic antidepressants in cholinergic, adrenergic and histamine transmission contributes to the disruption of cognitive functions of the brain (memory, learning process, level of wakefulness).

High doses and long-term use of drugs in this group lead to cardiotoxicity. Cardiotoxicity of tricyclic antidepressants is manifested by conduction disturbances in the atrioventricular node and ventricles of the heart (quinine-like effect), arrhythmias, and decreased myocardial contractility. Doxepin and amoxapine have the least cardiotoxicity. Treatment of patients with cardiovascular pathology with tricyclic antidepressants should be carried out under ECG monitoring and high doses should not be used.

When using TCAs, other side effects are also possible, such as allergic skin reactions (most often caused by maprotiline), leukopenia, eosinophilia, thrombocytopenia, weight gain (associated with blockade of histamine receptors), impaired secretion of antidiuretic hormone, sexual dysfunction, teratogenic effect . It is impossible not to note the possibility of developing severe consequences, including death, with an overdose of tricyclic antidepressants.

Numerous undesirable effects that occur with the use of TCAs and interactions with many drugs significantly limit their use in general medical practice and, especially, in outpatient practice.

Monoamine oxidase inhibitors

MAO inhibitors (MAOIs) are divided into 2 groups: earlier non-selective irreversible MAO inhibitors (phenelzine, nialamide) and later selective reversible MAOA inhibitors (pyra- zidol, moclobemide, befol, tetrindole).

The main mechanism of action of these antidepressants is inhibition of monoamine oxidase, an enzyme that causes deamination of serotonin, norepinephrine, and partially dopamine (MAO-A), as well as deamination of β-phenylethylamine, dopamine, tyramine (MAOB), which enters the body with food. Violation of tyramine deamination by nonselective irreversible MAO inhibitors leads to the so-called “cheese” (or tyramine) syndrome, manifested by the development of a hypertensive crisis when consuming foods rich in tyramine (cheese, cream, smoked meats, legumes, beer, coffee, red wines, yeast, chocolate, beef and chicken liver, etc.). When using non-selective irreversible MAOIs, these products must be excluded from the diet. Drugs in this group have a hepatotoxic effect; due to a pronounced psychostimulating effect, they cause euphoria, insomnia, tremor, hypomanic agitation, and also, due to the accumulation of dopamine, delirium, hallucinations and other mental disorders.

The listed side effects, unsafe interactions with certain medications, and severe poisoning that occurs during their overdose, sharply limit the use of non-selective irreversible MAOIs in the treatment of depression and require great caution and strict adherence to the rules for taking these medications. Currently, these drugs are used only in cases where depression is resistant to the action of other antidepressants.

Selective reversible MAOIs are characterized by high antidepressant activity, good tolerability, and less toxicity; they have found widespread use in medical practice, replacing MAOIs with non-selective irreversible action. Among the side effects of these drugs, it is necessary to note mild dry mouth, urinary retention, tachycardia, and dyspeptic symptoms; in rare cases, dizziness, headache, anxiety, restlessness, and hand tremors may occur; Allergic skin reactions also occur; with bipolar depression, a change from the depressive phase to the manic phase is possible. The good tolerability of selective reversible MAOIs allows them to be used on an outpatient basis without following a special diet.

MAO inhibitors should not be combined with serotonin reuptake inhibitors, opioid analgesics, or dextromethorphan, which is included in many antitussive drugs.

MAOIs are most effective for depression accompanied by feelings of fear, phobias, hypochondria, and panic conditions.

Selective serotonin reuptake inhibitors (SSRIs)

SSRIs are a group of drugs that are heterogeneous in chemical structure. These are single-, double- and multi-cyclic drugs that have a common mechanism of action: they selectively block the reuptake of only serotonin, without affecting the uptake of norepinephrine and dopamine, and do not act on the cholinergic and histaminergic systems. The SSRI group includes drugs such as fluvoxamine, fluoxetine, sertraline, paroxetine, citalopram. The scope of application of this group is moderate depressive states, dysthymia, obsessive-compulsive disorder. SSRI drugs are less toxic and better tolerated than TCAs, but do not exceed them in clinical effectiveness. The advantage of SSRIs compared to TCAs is that they are quite safe for patients with somatic and neurological pathologies, the elderly and can be used on an outpatient basis. It is possible to use drugs of this group in patients with concomitant diseases such as prostate adenoma, closed-angle glaucoma, and cardiovascular diseases.

Antidepressants in this group have minimal side effects, which are mainly associated with serotonergic hyperactivity (Table 2). Serotonin receptors are widely represented in the central and peripheral nervous system, as well as in peripheral tissues (smooth muscles of the bronchi, gastrointestinal tract, vascular walls, etc.). The most common side effects are gastrointestinal disorders (can be eliminated by domperidone): nausea, less commonly vomiting, diarrhea (excessive stimulation of 5-HT3 receptors). Excitation of serotonin receptors in the central nervous system and peripheral nervous system can lead to tremor, hyperreflexia, impaired motor coordination, dysarthria, and headache. Side effects of SSRIs include such manifestations of stimulant action (especially with fluoxetine), such as agitation, akathisia, anxiety (removed by benzodiazepines), insomnia (excessive stimulation of 5-HT2 receptors), but increased drowsiness may also occur (fluvoxamine). SSRIs can provoke a change in phases from depressive to manic in patients with bipolar disease, but this occurs less frequently than with the use of TCAs. Many patients taking SSRIs experience fatigue during the day. This side effect is most common with paroxetine.

Table 2. Side effects of serotonergic antidepressants

Side effects	Fluvoxamine (fevarin)	Fluoxetine (Prozac)	Paroxetine (Paxil)	Citalopram (cipramil)	Sertraline (Zoloft)
Nausea	+++	+++	+++	+++	+++
Diarrhea	+	++	+	+	+++
Decreased appetite	+/0	+++	+/0	+/0	+
Constipation	+	(+)	++	++	(+)
Insomnia	++	+++	++	+++	++/+
Drowsiness	+++	++	+++	++/+	++/+
Irritability	++	++	(+)	(+)	+
Anxiety	+	++	(+)	(+)	(+)
Mania	(+)	++	+	(+)	(+)
Sexual dysfunction	(+)	+++	+++	++	+++/+
Headache	++	++	+	+++	+++/+
Tremor	++	++	+++	+++	++/(+)
Hyperhidrosis	+	++	+++	+++	++
Dry mouth	++	++	++/(+)	+++	++
Skin rash	(+)	++	(+)	(+)	(+)
Allergic reactions	(+)/0	(+)	(+)	(+)	(+)/0
Extrapyramidal disorders	(+)	(+)	+	(+)	+
Hyponatremia	(+)	+	+	(+)	+
Edema	(+)	(+)	+	(+)	(+)
Convulsive syndrome	(+)	(+)	(+)	(+)	(+)/0

Common (15% or more) PE;
++ - rare (2-7%) PE;
+ - very rare (less than 2%) PE;
(+) - possible, but extremely rare PE;
0 - PE not detected.

In 50% of cases, while taking SSRIs (especially paroxetine, sertraline), patients experience sexual disorders, expressed in weakened erections, delayed ejaculation, partial or complete anorgasmia, often leading to the patient’s refusal to take the drug. To reduce sexual dysfunction, it is enough to reduce the dose of antidepressant.

A dangerous side effect of SSRIs that occurs during treatment is “serotonin syndrome.” The likelihood of this syndrome occurring increases when SSRIs are used in combination with clomipramine, reversible and irreversible MAO inhibitors, tryptophan, dextramethorphan, as well as when two serotonergic antidepressants are prescribed simultaneously. Clinically, “serotonin syndrome” is manifested by the development of gastrointestinal disorders (nausea, vomiting, abdominal pain, diarrhea, flatulence), the appearance of psychomotor agitation, tachycardia, hyperthermia, muscle rigidity, convulsions, myoclonus, sweating, disturbances of consciousness from delirium to stupor and coma with subsequent death. If the described syndrome occurs, it is necessary to immediately discontinue the drug and prescribe the patient antiserotonin drugs (cyproheptadine), β-blockers (propranolol), and benzodiazepines.

All SSRIs are inhibitors of cytochrome P2 D6, which is involved in the metabolism of many drugs, including antipsychotics and TCAs. In this regard, the use of SSRIs with psychotropic drugs, TCAs and drugs used to treat somatic pathologies requires caution due to slower inactivation and the risk of overdose.

Other adverse reactions (seizures, parkinsonism, leukopenia, thrombocytopenia, bradycardia, increased activity of hepatic transaminases) are sporadic.

SSRIs should not be used for anxiety, restlessness, insomnia, or suicidal tendencies. Contraindications to the use of SSRIs are also psychotic forms of depression, pregnancy, breastfeeding, epilepsy, renal dysfunction, poisoning with psychotropic drugs, and alcohol.

It should be noted that drugs from the group of selective serotonin reuptake inhibitors are widely used, but not the only modern antidepressants. Currently, selective/specific drugs and drugs of the so-called “bipolar action” have been created. The creation of these antidepressants was dictated by the search for even more effective, safe and better tolerated thymoanaleptics.

It is well known that 60-80% of patients with affective disorders occur in general medical practice. According to M. Yu. Drobizhev, from 20 to 40% of patients in the cardiology, therapeutic and rheumatology departments of one of the large multidisciplinary hospitals in Moscow need the prescription of thymoanaleptics. When prescribing antidepressant therapy to non-psychiatric patients, it is extremely necessary to take into account the characteristics of the psychotropic and somatotropic effects of the drug. As noted above, the severity of the latter is associated with the safety and tolerability of antidepressants. It follows from this that non-selectively acting antidepressants, which have a large number of side effects, are inappropriate for use in general medical practice.

According to the risk of side effects in somatic patients, thymoanaleptics are divided into drugs with low, medium and high risk (Table 3). Antidepressants are similarly differentiated according to their use in severe liver and kidney diseases (Table 4).

Table 3. Distribution of antidepressants according to the degree of risk of developing cardiotoxic and hepatotoxic effects

Risk of Cardiotoxicity			Risk of hepatotoxicity
Short	Average	High	Short	Average	High
Pyrazidol	TAD		Protriptyline	Amitriptyline	MAO inhibitors
SSRIs	MAOI		Paroxetine	Imipramine
Trazodone	Moclobemide		Citalopram	Nortriptyline
Mianserin	Nefazodone		Mianserin	Fluoxetine
Mirtazapine	Maprotiline		Tianeptine	Trazodone
Tianeptine				Mirtazapine
Venlafaxine

Table 4. Possibility of using antidepressants for severe liver and kidney diseases

Severe renal failure			Liver diseases
in usual doses	in reduced doses	contraindicated	in usual doses	in reduced doses	contraindicated
Amitriptyline	Paroxetine	Fluoxetine	Paroxetine	Fluoxetine	Sertraline
Imipramine	Citalopram		Mianserin	Citalopram	Venlafaxine
Doxepin	Trazodone		Tianeptine	Moclobemide
Sertraline				Nefazodone
Mianserin				Mirtazapine
Moclobemide				Amitriptyline

The targeted search for highly effective, safe and well-tolerated thymoanaleptics continues. Perhaps in the near future we will witness the appearance in medical practice of drugs that successfully combine all three of these criteria.

Literature

1. Andryushchenko A.V. Choice of therapy for depression // Modern psychiatry. 1998. T. 1. No. 2. P. 10-14.
2. Drobizhev M. Yu. The use of modern antidepressants in patients with therapeutic pathology // Consilium medicum.2002. T. 4. No. 5. P. 20-26.
3. Malin I., Medvedev V.M. Side effects of antidepressants // Psychiatry and psychopharmacotherapy. 2002. T. 4. No. 5. P. 10-19.
4. Muzychenko A.P., Morozov P.V., Kargaltsev D.A. et al. Ixel in clinical practice // Psychiatry and psychopharmacotherapy. 2000. T. 3. No. 3. P. 6-11.
5. Tabeeva G. R., Vein A. M. Pharmacotherapy of depression // Psychiatry and psychopharmacotherapy. 2000. No. 1. P. 12-19.

Tricyclic antidepressants (TCAs) are classic psychotropic drugs for the treatment of various depressive disorders and 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. Most drugs have a direct effect on several neurons. Studies have found that they affect the reuptake of serotonin and norepinephrine in the brain and, to varying degrees, block the 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 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;
• decreased 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 treatment of 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 stimulating effect can cause sleep disturbances, increased anxiety and restlessness, and sometimes provoke increased delusions and hallucinations.

Sedative antidepressants are prescribed for anxiety. They can be used as sleeping pills. But during 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 after the start of treatment.

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

Side effects associated with cardiac arrhythmia limit the use of TCA drugs in persons over 40 years of age, especially with coronary heart disease, angle-closure glaucoma, and prostate adenoma. 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 continue to be considered highly effective treatments for severe forms of depression.