What does it mean to inhibit neurotransmitter reuptake? Antidepressants without a prescription: what they are, how they differ from tranquilizers

Used as antidepressants until the mid-1950s. They disappeared from use due to a large number of side effects. However, some alkaloids were used longer - for example, preparations of St. John's wort extract were used for a long time as an auxiliary therapy.

The first synthetic antidepressants were introduced into medical practice in the mid-1950s. Until the 1990s, psychiatrists had only two groups of drugs available to them: MAO inhibitors and tricyclic antidepressants. In the 1990s, selective drugs were synthesized that had fewer side effects and a stronger antidepressant effect.

Further development

New drugs, called antidepressants in 1952, became prescription drugs by the mid-1950s. At that time, it was believed that only 50-100 people out of a million people suffered from depression, so pharmaceutical companies showed little interest in antidepressants. Sales of these drugs in the 1960s were not comparable in volume to those of antipsychotic and benzodiazepine drugs.

Later, imipramine came into widespread use, and its analogues were synthesized. In the 1960s, selective monoamine oxidase inhibitors, as well as selective serotonin reuptake inhibitors, appeared. Subsequently, the main direction in the creation of new antidepressants was to reduce side effects, as well as strengthen the main ones. This is achieved by increasing the selectivity of the action of drugs on the “necessary” receptors.

Action diagram

The main effect of antidepressants is that they block the breakdown of monoamines (serotonin, norepinephrine, dopamine, phenylethylamine, etc.) under the action of monoamine oxidases (MAO) or block the reverse neuronal uptake of monoamines. According to modern concepts, one of the leading mechanisms for the development of depression is a lack of monoamines in the synaptic cleft - especially serotonin and dopamine. With the help of antidepressants, the concentration of these mediators in the synaptic cleft increases, which is why their effects are enhanced.

It should be noted that there is a so-called “antidepressive threshold”, which is individual for each patient. Below this threshold, there is no antidepressant effect and only nonspecific effects appear: in particular, side effects, sedative and stimulant properties. Current evidence indicates that drugs that reduce monoamine reuptake must have a 5- to 10-fold reduction in monoamine reuptake to produce antidepressant effects. For the antidepressant effect of drugs that reduce MAO activity to manifest, it must be reduced by approximately 2 times.

However, modern research shows that antidepressants also act through other mechanisms. For example, it is suggested that antidepressants reduce stress hyperreactivity of the hypothalamic-pituitary-adrenal axis. Some antidepressants can also act as NMDA receptor antagonists, reducing the toxic effects of glutamate that are undesirable in depression. Modern studies have shown that some antidepressants reduce the concentration of substance P in the central nervous system. However, today the most important mechanism for the development of depression, which is affected by all antidepressants, is considered to be insufficient activity of monoamines.

Classification

The most convenient for practical use is the following classification of antidepressants:

1. Drugs that block neuronal monoamine uptake
   • Non-selective action, blocking neuronal uptake of serotonin and norepinephrine (imisin, amitriptyline)
   • Selective action
     • Blocking neuronal serotonin uptake (fluoxetine)
     • Blocking neuronal uptake of norepinephrine (maprotiline)
2. Monoamine oxidase inhibitors (MAO)
   • Non-selective action, inhibit MAO-A and MAO-B (nialamide, transamine)
   • Selective action, inhibit MAO-A (moclobemide).
3. • Noradrenergic and specific serotonergic antidepressants
   • Specific serotonergic antidepressants

However, there are other classifications of antidepressants. For example, it has been proposed to classify antidepressants according to their clinical effect:

1. Sedative antidepressants: trimipramine, doxepin, amitriptyline, mianserin, mirtazapine, trazodone, fluvoxamine
2. Antidepressants with balanced action: maprotiline, tianeptine, milnacipran, sertaline, paroxetine, pyrazidol, clomipramine
3. Antidepressant stimulants: imipramine, desipramine, citalopram, fluoxetine, moclobemide, ademetionine.

Antidepressant classes

Monoamine oxidase inhibitors

Non-selective inhibitors

Nonselective and irreversible monoamine oxidase inhibitors are first generation antidepressants. These drugs irreversibly block both types of monoamine oxidase. These include derivatives of isonicotinic acid hydrazide (GINK), or the so-called “hydrazine” MAOIs - iproniazid (iprazide), isocarboxazid, nialamide, as well as amphetamine derivatives - tranylcypromine, pargyline. Most of the drugs in this group cannot be combined with a number of other drugs due to the inactivation of a number of liver enzymes and require a special diet to prevent the development of tyramine (“cheese”) syndrome.

Currently, non-selective MAO inhibitors are used quite rarely. This is due to their high toxicity.

Selective inhibitors

Newer drugs of this class - selective MAO-A inhibitors (moclobemide, pirlindole, metralindole, befol) or MAO-B (selegiline) are used more widely, as they give significantly fewer side effects, are better tolerated and do not require a special diet. They are compatible with many medications that non-selective MAOIs are not compatible with. However, selective MAO-A and selective MAO-B have significantly weaker antidepressant activity compared to non-selective MAOIs. Their antidepressant effect is somewhat weaker than that of tricyclic antidepressants.

Non-selective monoamine reuptake blockers

Tricyclic antidepressants

Tricyclic antidepressants (TCAs), or tricyclics, are a group of highly effective antidepressants with much fewer side effects compared to MAOIs, which do not require a special diet and do not impose large restrictions on the medications used simultaneously. The reason these drugs are grouped together is that they have three rings joined together in the molecule, although the structure of these rings and the radicals attached to them can be very different.

Within the class of tricyclics, there are two subclasses that differ in the characteristics of their chemical structure - tricyclics, which are tertiary amines ( tertiary amine tricyclics), and tricyclics, which are secondary amines ( secondary amine tricyclics). Many of the tricyclics of the secondary amine subgroup are active metabolites of tertiary amines formed from them in the body. For example, desipramine is one of the active metabolites of imipramine, nortriptyline is one of the active metabolites of amitriptyline.

Tertiary amines

Tertiary amines, as a rule, are distinguished by stronger sedative and anti-anxiety activity than secondary amines, more pronounced side effects (M-anticholinergic, antihistamine, α-adrenergic blocking), stronger antidepressant activity and a more balanced effect on the reuptake of both norepinephrine and serotonin. Typical representatives of tertiary amines are amitriptyline, clomipramine (anafranil), imipramine (melipramine, tofranil), trimipramine (gerfonal), doxepin, dothiepin (dosulepin).

Doxepin is a representative of tertiary amines. Available in the form of film-coated tablets.

Secondary amines

Selective norepinephrine reuptake inhibitors

Selective norepinephrine reuptake inhibitors (SNRIs) are a modern group of antidepressants with minimal side effects and good tolerability. A characteristic property of this group is a pronounced stimulating effect in the absence or low severity of a sedative effect. Well-known representatives of this group are reboxetine (edronax), atomoxetine (straterra). Some studies suggest that these drugs are superior to selective serotonin reuptake inhibitors, at least in treating severe depression.

Selective serotonin and norepinephrine reuptake inhibitors

Selective serotonin and norepinephrine reuptake inhibitors (SSRIs), or “dual-acting” antidepressants ( double-action antidepressants) is a modern group of antidepressants with few or minimal side effects and good tolerability. Drugs in this group are powerful antidepressants, superior in antidepressant activity to selective serotonin reuptake inhibitors, and approaching the strength of tricyclic antidepressants. These drugs are especially effective in treating severe depression. Well-known representatives of this group are venlafaxine (Velaxin, Efevelon), duloxetine (Cymbalta), milnacipran (Ixel).

Selective norepinephrine and dopamine reuptake inhibitors

Selective norepinephrine and dopamine reuptake inhibitors (SSRIs) are a modern group of antidepressants with minimal side effects and good tolerability. The only representative of this class of antidepressants known today is bupropion (Wellbutrin, Zyban). Distinctive features of bupropion are the low probability of phase sign inversion into mania or hypomania and the low probability of provoking a “rapid cycle” - less than that of SSRIs, and much less than that of TCAs or MAOIs and other powerful antidepressants. In this regard, bupropion is especially recommended for patients with bipolar depression who are prone to phase inversion or the development of a “rapid cycle” when treated with various antidepressants. Important features of bupropion are also a pronounced general stimulating and psycho-energizing effect (so pronounced that a number of experts previously classified it not as an antidepressant, but as a psychostimulant, despite the lack of narcotic properties), as well as a disinhibiting effect on libido. In this regard, bupropion is often used as a corrector for the sexual side effects of other antidepressants.

Monoamine receptor agonists

Noradrenergic and specific serotonergic antidepressants

Noradrenergic and specific serotonergic antidepressants (NaSSAs) are a modern group of antidepressants with minimal side effects and good tolerability. They are called specific serotonergic because, by blocking “inhibitory” presynaptic α 2 -adrenergic receptors and increasing the content of norepinephrine and serotonin in synapses, drugs of this group simultaneously strongly block postsynaptic serotonin 5-HT2 and 5-HT3 receptors, responsible for the manifestation of a number of “serotonergic » side effects of SSRI drugs. Such side effects include, in particular, decreased libido, anorgasmia, frigidity in women and inhibition of ejaculation in men, as well as insomnia, anxiety, nervousness, nausea, vomiting, decreased appetite and anorexia.

Well-known representatives of the NaSCA group are the structurally similar drugs mianserin (lerivon, bonserin) and mirtazapine (remeron, mirtazonal).

Specific serotonergic antidepressants

Specific serotonergic antidepressants (SSA) are a group of antidepressants with relatively few side effects and good tolerability. Along with blocking serotonin reuptake and increasing serotonergic neurotransmission, drugs in this group strongly block the “bad” serotonin receptors of the 5-HT2 subtype in the context of treating depression, which explains the low likelihood of sexual side effects, as well as the low likelihood of exacerbation of anxiety, insomnia and nervousness compared to SSRIs. On the contrary, an increase in libido and sexual disinhibition, an improvement in the quality and brightness of orgasm are often observed, and therefore SSAs are sometimes used as correctors for the sexual side effects of other antidepressants.

Drugs in this group include trazodone (Tritico) and its newer derivative nefazodone (Serzone).

The antidepressant activity of these drugs is assessed as moderate. In severe depression, SSAs are ineffective or insufficiently effective.

A specific feature of SSA, especially trazodone, is a strong normalizing effect on the phase structure of sleep and the ability to suppress nightmares by reducing the proportion of REM sleep, which is increased in depression and anxiety. This effect is realized even in small doses that do not have a noticeable antidepressant effect. Therefore, trazodone has become widespread and especially loved by psychiatrists in Western countries as a sleeping pill and sedative for insomnia (not only of depressive origin), as well as as a corrector of insomnia and nightmares during therapy with SSRIs or TCAs.

A specific feature of trazodone is also the ability to improve erectile function in men, up to causing priapism (painful spontaneous erections), which is not associated with antidepressant activity and is realized in any type of functional (non-organic) erectile dysfunction. Due to this property, trazodone is widely used to treat impotence and erectile dysfunction, including those not associated with depression or anxiety.

Unfortunately, soon after the start of its clinical use, nefazodone showed quite significant (1%) hepatotoxicity (liver toxicity), in some cases leading to death, which forced the American FDA to first require a mention of this in large letters in a black frame at the beginning of the tab - annotation for the drug and informed consent of the patient for treatment with nefazodone, and then completely ban the production and distribution of nefazodone in the United States.

After this, the manufacturer of nefazodone announced the recall of the drug from the pharmacy chain in all countries and the cessation of its production. Meanwhile, nefazodone, if not for liver toxicity, would be a very good expansion of the arsenal of antidepressants - it, unlike trazodone, does not cause involuntary painful erections, has a significantly less sedative effect and better tolerability, almost does not reduce blood pressure, and at the same time At the same time, it has strong antidepressant activity.

Indications for the use of antidepressants

Antidepressants are a group of drugs used to treat depression. However, antidepressants are also used in clinical practice to correct other disorders. Among them are panic states, obsessive-compulsive disorders (SSRIs are used), enuresis (TCAs are used as additional therapy), chronic pain syndromes (TCAs are used).

Features of the action

Antidepressants are serious drugs that always require individual selection of a specific drug and dose, and therefore their independent use without a doctor’s prescription is not recommended.

Antidepressants have little or no ability to improve mood in a healthy person, so their recreational use is unlikely or practically impossible. The exceptions are MAOIs, as well as coaxil, which was often used for recreational purposes, which led to its inclusion in the PKU (subject-quantitative) lists.

Antidepressants do not work immediately - it usually takes two to four weeks for them to start working. However, there is often an immediate effect that can be explained by a sedative or, conversely, stimulating effect.

Research has shown that many antidepressants, particularly fluoxetine, may increase the likelihood of suicide in the first months of treatment, especially in children and adolescents. This is due to the rapidly onset stimulating, energizing effect, which occurs before the onset of the true antidepressant effect. Consequently, a still suicidal patient can thus gain enough energy and strength to realize suicidal thoughts against the backdrop of still-lingering bad mood and melancholy. In addition, many antidepressants can cause or worsen anxiety, insomnia, irritability, and impulsivity at the beginning of treatment, which can also lead to an increased risk of suicide.

Taking antidepressants (not only SSRIs, but also SNRIs) can induce hypomania, mania, and psychosis in both patients with bipolar affective disorder and in patients without it. For example, in one study, mania occurred in forty-three of 533 patients taking antidepressants.

Notes

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Selective serotonin and norepinephrine reuptake inhibitors - according to their pharmacokinetic properties, belong to the third generation of antidepressants. Used in the treatment of anxiety disorders and depressive conditions. The body tolerates taking such drugs relatively easily, so some of them are available without prescriptions.

Differing from the TCA group (tricyclic antidepressants), the selective blocker practically does not provoke anticholinergic/cholinergic side effects, only occasionally causing sedation and orthostatic hypotension. In case of overdose of the described drugs, the risk of cardiotoxic effects is lower, therefore such antidepressants are used in many countries.

A selective approach to treatment is justified by the use of SSRIs in general medical practice; they are often prescribed for outpatient treatment. A non-selective antidepressant (tricyclic) can cause arrhythmia, while selective inhibitors are indicated for chronic heart rhythm disturbances, angle-closure glaucoma, etc.

Selective neuronal reuptake inhibitors

For depression, drugs in this group can improve mood through the intensive use by the brain of the chemical components that make up serotonin. They regulate the processes of impulse transmission between neurotransmitters. A sustainable result is achieved by the end of the third week of use, the patient notices emotional improvements. To consolidate the effect, it is recommended to take the selected serotonin uptake inhibitor for 6-8 weeks. If no changes occur, the drug should be replaced.

Antidepressants are not available without a prescription, but some groups of patients are prescribed "by default", for example, women with complaints of postpartum depression. Mothers who breastfeed use Paroxetine or Sertaline. They are also prescribed for the treatment of severe forms of anxiety syndrome, depression in pregnant women and for the prevention of depressive conditions in people at risk.

SSRIs are the most popular antidepressants due to their proven effectiveness and low number of side effects. However, negative consequences of taking are still observed, but quickly pass:

• short-term attacks of nausea, loss of appetite, weight loss;
• increased aggressiveness, nervousness;
• migraines, insomnia, excessive fatigue;
• decreased libido, erectile dysfunction;
• tremor, dizziness;
• allergic reactions (rare);
• sudden increase in body weight (rare).

Patients with epilepsy or bipolar disorders should not take antidepressants, as they aggravate the course of these diseases.

Side effects in infants whose mothers take antidepressants are extremely rare. But such a treatment outcome is quite possible. Women undergoing specific therapy should discuss all risks with their supervising physician in order to prevent the development of negative conditions in the child.

Clinical characteristics

Modern medicine does not have information that antidepressants are absolutely safe. However, there is a list of drugs that cause the least and greatest harm:

• Zoloft is the drug of choice for nursing mothers;
• The intake of Fluoxetine, Citalopram and Paroxetine should be limited. They provoke excessive nervous excitability, irritability, crying attacks, and refusal to eat in children. “Citalopram” and “Fluoxetine” pass into breast milk, but this depends on what time of day the woman took the drug.

There have been several extensive studies examining the condition and behavior of people taking serotonin uptake agents. Antidepressants do not cause any intellectual or emotional problems and do not lead to future health problems. Each product has a package insert that lists all possible side effects.

Relationship between antidepressant use and overall risks

People being treated with antidepressants should be regularly tested for serotonin, which will allow them to be under constant medical supervision and is a direct way to prevent suicidal thoughts. This is especially true for the first stage of treatment and with a sharp change in dosage.

According to the results of studies conducted on the drug "Paxil" and its analogues, it can be argued that taking this medication in the first 3 months of pregnancy increases the risk of birth defects of the fetus.

Concomitant use of selective serotonin/norepinephrine reuptake inhibitors (SSRIs) and headache medications may result in a condition called serotonin syndrome.

Comparison of reuptake inhibitors and tricyclic antidepressants

Treatment of depression in any case involves the prescription of specific drugs that can improve the patient’s emotional background and mood. This effect is due to the effect on various neurotransmitters, primarily the serotonin and norepinephrine systems. All drugs in this series can be classified according to their properties, chemical structure, the possibility of influencing only one or simultaneously several central nervous system systems, the presence of an activating component or signs of sedation.

The more neurotransmitters exposed to an antidepressant, the greater its ultimate effectiveness. However, this same feature also implies an expansion of the range of possible side effects. The first such drugs were drugs with a tricyclic chemical structure, we are talking about Melipramine, Anafranil and Amitriptyline. They influence a wide range of neurotransmitters and show high treatment effectiveness, but when they are taken, the following conditions often occur: dryness of the mucous membranes of the mouth and nasopharynx, constipation, akathisia, swelling of the extremities.

Selective drugs, that is, those with a selective effect, affect only one type of neurotransmitters. This, of course, reduces the likelihood of “targeting” the cause of depression, but is fraught with a minimum of side effects.

An important point when prescribing antidepressants is the presence, in addition to antidepressant, of a sedative effect, along with an activating one. If depression is accompanied by apathy, loss of interest in the social aspect of life, and inhibition of reactions, then remedies with a predominant activating component are applicable. Anxious depression accompanied by mania, on the contrary, requires sedation.

Antidepressants are classified with a focus on the selectivity of their effects on various neurotransmitters, as well as taking into account the possibility of a balanced - harmonizing effect. Side effects are caused by blocking the acetylcholine neurotransmitter system of the brain, as well as the nerve cells of the autonomic nervous system, which are involved in the regulation of the functioning of internal organs. The autonomic nervous system is responsible for the functions of the excretory system, heart rhythm, vascular tone, etc.

Tricyclic antidepressants include Gerfonal, Amitriptyline, Azafen and those that are close to them in chemical formula, for example, Ludiomil. Due to their influence on acetylcholine receptors located in the brain, they can cause memory impairment and inhibition of the thought process, leading to dissipation of concentration. These effects become worse when treating elderly patients.

Action diagram

The basis of the action of such drugs is to block the breakdown of monoamines, such as serotonin, norepinephrine, dopamine, phenylethylamine under the influence of MAO monoamine oxidases and block the reverse neuronal uptake of monoamines.

One of the provoking processes leading to the occurrence of depressive states is a deficiency of monoamines in the synaptic cleft, especially dopamine and serotonin. With the help of depressants, the concentration of these mediators in the synaptic cleft is increased, which helps to enhance their effect.

It is necessary to clearly understand the “antidepressive threshold”, individual for each individual patient. Below this “mark” the antidepressant effect will not manifest itself, expressed only in nonspecific effects: side effects, low stimulation and sedation. In order for third-generation drugs (which reduce the reuptake of monoamines) to exhibit all the antidepressant properties, the uptake itself must be reduced by at least 10 times. The manifestation of antidepressant effects from drugs that inhibit the activity of monoamine oxidases is possible only when it is reduced by 2-4 times.

Research confirms that in practice other mechanisms of antidepressant action can be used. For example, there is an assumption that such drugs can reduce the level of stress hyperactivity of the hypothalamus, adrenal glands and pituitary gland. Some antidepressants, even those that are sold without prescriptions and do not require strict monitoring of intake, are antagonists of NMDA receptors, helping to reduce the toxic effects of glutamates, which are undesirable in a depressive state.

Data have been obtained to judge the interaction of Paroxetine, Mirtazapine and Venlafaxine with opioid receptors. This means that the drugs have an antinociceptive effect. The use of some depressants can reduce the concentration of substance P in the central nervous system, but psychiatrists do not consider this point to be critical, since the most important mechanism for the development of a depressive state, which is affected by any reuptake inhibitors, is insufficient activity.

All the remedies described above are quite effective in treating depressive conditions, and in addition, they can prevent them. However, only a doctor who combines antidepressants and cognitive behavioral therapy can choose the appropriate treatment for the situation. These two methods are considered to be equivalent in terms of effectiveness. Don’t forget about psychotherapy with the support of loved ones; in mild cases of depression, serotonin reuptake inhibitors (drugs based on them) are not always needed. Moderate and severe forms of the disease may require not only medication, but also placement in a clinical hospital.

Interactions with other drugs when taking SSRIs are associated with their ability to affect cytochrome P450 isoenzymes. Combination use with other drugs is one of the main risk factors for undesirable effects of antidepressants in this group. A high risk of drug interactions exists when taking fluoxetine, which interacts with four types of cytochrome P450 isoenzymes - 2 D62, C9/10, 2 C19 and 3 A3/4 - and fluvoxamine, which interacts with isoenzymes 1 A2, 2 C19 and 3 A3/4. Paroxetine is also a powerful inhibitor of liver enzymes. Sertraline is less problematic in this regard, although its effect on enzyme inhibition is dose dependent; Citalopram and escitalopram are relatively safe.
SSRIs should not be combined with MAO inhibitors as this may cause severe serotonin syndrome.
When TCAs are coadministered with an SSRI, tricyclic antidepressants should be used in lower doses and plasma levels monitored as the combination may result in elevated TCA blood levels and an increased risk of toxicity.
The combined use of SSRIs and lithium salts enhances the serotonergic effects of antidepressants, and also increases the side effects of lithium salts and changes their concentrations in the blood.
SSRIs may increase the extrapyramidal side effects of typical antipsychotics. Fluoxetine and paroxetine are more likely than other SSRIs to increase blood levels of typical antipsychotics and therefore increase their side effects or toxicity. Blood concentrations of many atypical antipsychotics also increase when taking SSRIs.
Cimetidine can lead to inhibition of the metabolism of SSRIs, increasing their concentration in the blood with an increase in their main effect and side effects.
SSRIs increase plasma concentrations of benzodiazepines.
Warfarin in combination with SSRIs leads to an increase in prothrombin time and increased bleeding.
When taken simultaneously with SSRIs, aspirin or other non-steroidal anti-inflammatory drugs, as well as anticoagulants and antiplatelet agents, increases the risk of gastrointestinal bleeding. Painkillers of non-steroidal anti-inflammatory drugs (aspirin, ibuprofen, naproxen) may reduce the effectiveness of SSRIs:
In combination with alcohol or sedative-hypnotics, SSRIs lead to an increase in the inhibitory effect of sedative-hypnotics and alcohol on the central nervous system with the development of undesirable effects.
Some drugs may increase the toxicity of SSRIs, such as zolpidem.
SSRIs may potentiate the development of extrapyramidal disorders caused by the use of bupropion and psychostimulants.
Some antibiotics (in particular, erythromycin) can increase the concentration of sertraline and citalopram in the blood and even cause psychosis when combined with fluoxetine (clarithromycin).
In patients taking SSRIs, the analgesic effect of tramadol or codeine may be reduced.
Some SSRIs interact unfavorably with statins - for example, fluoxetine in combination with some statins can cause manifestations of myositis.
SSRIs greatly attenuate the effects of tryptamines (e.g., psilocybin), LSD, 2C-family psychedelics, and almost completely abolish the serotonergic effects of MDxx (e.g., MDMA, methylone, butylone).
Drug interactions of individual SSRIs.
Paroxetine. Sodium valproate slows down the metabolism of paroxetine and increases its concentration in the blood. Paroxetine slows down the metabolism of some antipsychotics (pimozide, etaprazine and) and tricyclic antidepressants and increases their concentration in the blood with a possible increase in their side effects.
Fluvoxamine. Slows down the metabolism of haloperidol (as well as other neuroleptics of the group of butyrophenone derivatives) and increases its concentration in the blood by 2 times (at the same time the concentration of fluvoxamine increases by 2-10 times), as a result of which it can reach a toxic level. When fluvoxamine is combined with atypical antipsychotics olanzapine or clozapine, the metabolism of the antipsychotic also slows down and its concentration in the blood increases (when combined with clozapine - several times). In addition, fluvoxamine slows down the metabolism of some tricyclic antidepressants with a possible increase in their concentration and the development of intoxication; The combined use of fluvoxamine with beta-blockers, theophylline, caffeine, alprazolam, carbamazepine leads to similar effects.
Fluoxetine. Macrolide antibiotics (erythromycin, clarithromycin, etc.) increase the concentration of fluoxetine in the blood with the possible development of toxic effects. Fluoxetine has a similar effect on the metabolism of drugs such as TCAs, trazodone, alprazolam, beta-blockers, carbamazepine, sodium valproate, phenytoin, and barbiturates. Fluoxetine enhances the sedative effect and motor retardation when taking barbiturates and triazolobenzodiazepines (alprazolam, triazolam). Reduces the anti-anxiety effect of buspirone. Lithium enhances both the antidepressant and toxic effects of fluoxetine. Fluoxetine causes an increase in the level of the main metabolite of bupropion - hydrox-bupropion, which can lead to clinical manifestations of the toxic effects of this metabolite: catatonia, confusion and agitation. When fluoxetine was used together with calcium channel blockers (verapamil, nifedipine), headaches, swelling, and nausea were observed.
Sertraline. Slows down the metabolism of desipramine (as well as imipramine) and increases the concentration of this antidepressant in the blood by 50%. Reduces the plasma clearance of diazepam and tolbutamide, slightly increasing their concentrations in the blood. It enhances the side effects of lithium salts, but the effect of sertraline on the concentration of lithium salts in the blood has not been detected.

There are dozens of medications to treat depression. In most cases, the optimal effect can be achieved by combining drugs that relieve symptoms of depression and psychotherapy. The main class of drugs for treating depression are antidepressants. The doctor may also prescribe other medications if deemed necessary.

There are several types of antidepressants. They mainly differ in the method of influencing chemicals produced by the brain - neurotransmitters. The choice of antidepressants is determined by the severity of symptoms, a family history of depression, and any comorbidities that the patient may have. When choosing an antidepressant, you need to be patient. Sometimes you have to change several medications to find the optimal one that really works and does not have severe side effects.

In general, antidepressants are comparable in effectiveness, but some have a higher risk of side effects. Usually, when choosing antidepressants, doctors are guided by the following classification.

First line drugs

Most often, treatment is started with an antidepressant from the SSRI class (selective serotonin reuptake inhibitors). This class of antidepressants is quite effective and has few side effects. SSRIs include fluoxetine (Prozac), paroxetine (Plesil), sertraline (Zoloft), citalopram and escitalopram (Cipralex).

Selective serotonin and norepinephrine reuptake inhibitors (SSRIs), acting on two types of receptors, may be effective in those patients in whom SSRI treatment has failed. Among the SSRIs used in Russia are venlafaxine (Velafax), milnacipran (Ixel) and duloxetine (Cymbalta). According to some psychiatrists, the first of them is especially effective for severe depression. SSRIs have analgesic effects. In particular, duloxetine is widely used in diabetic polyneuropathies.

Reversible monooxidase A inhibitors

Reversible monooxidase A inhibitors (MAO-A inhibitors), such as moclobemide (Auroxis) and perlindole (Pyrazidol), are also highly safe. A feature of this class is its low effect on the cardiovascular system. In particular, they practically do not cause orthostatic hypotension.

Selective norepinephrine reuptake inhibitors/norepinephrine antagonists

Selective norepinephrine reuptake inhibitors/norepinephrine antagonists (SIOZNAN) are represented on the domestic market by two drugs - maprotiline (Lyudiomil) and mianserin (Lerivon). Maprotiline, being a highly effective antidepressant, is often poorly tolerated and has a relatively high incidence of side effects. For this reason, some psychiatrists classify it as a second-line drug.

Antagonists of presynaptic a2-adrenergic receptors and postsynaptic serotonin receptors

Among the antagonists of presynaptic a2-adrenergic receptors and postsynaptic serotonin receptors (AASR), mirtazapine (Remeron) is used. The advantages of this drug are safety in patients with cardiovascular diseases and the absence of a significant effect on sexual function.

Serotonin reuptake inhibitor/serotonin antagonist

The serotonin reuptake inhibitor/serotonin antagonist (SSRI) trazodine (Trittico), unlike most other antidepressants, does not worsen but improves sleep and sexual function.

Tianeptine (Coaxil)

Another safe antidepressant that does not affect sexual function, tianeptine (Coaxil), is a selective serotonin reuptake stimulator.

Second line drugs

Second-line drugs include the class of tricyclic antidepressants. This class of antidepressants was developed even before the advent of SSRIs and SSRIs, but has still not lost its relevance. TCAs are quite effective, but have more pronounced side effects than modern antidepressants. Therefore, TCAs are prescribed only when first-choice drugs are ineffective.

Third line drugs

Irreversible monoamine oxidase inhibitors (MAOIs) fall into this category. Currently, they are used extremely rarely. The low popularity of monoamine oxidase inhibitors is associated with the high severity of side effects associated with their use. When taking these drugs, you must adhere to a strict diet because they may interact with certain food components.

Other treatment strategies

In addition to antidepressants, your doctor may prescribe other medications that can also be used to treat depression. Most often these are drugs from the groups of neuroleptics, tranquilizers, and nootropics. In some cases, your doctor may prescribe two or more antidepressants and other medications to be taken at the same time.

Side effects of antidepressants

All antidepressants have side effects. Tolerance to antidepressants is very individual and difficult to predict in advance. Some patients have no side effects, while others have them so strong that they have to stop taking the drug. Some coping strategies can help mitigate side effects. Typically, after a few weeks of starting antidepressants, side effects become less severe or disappear completely.

If side effects occur, you should consult your doctor, but you should not stop taking the drug until then. When you stop taking some antidepressants, a “withdrawal syndrome” may occur, so you must stop treatment carefully, gradually reducing the dose.

Precautions when taking antidepressants

Clinical studies have shown that modern antidepressants are quite safe, but some precautions should be taken when taking them.

In some cases, antidepressants increase suicidal thoughts in children, adolescents and young adults aged 18-24 years, especially in the first weeks after starting or increasing the dose. In this regard, these groups of patients require special attention from doctors and close relatives while taking medications.

Some antidepressants can, in rare cases, cause dangerous complications such as liver failure or anemia. Although such cases are rare, regular blood tests should be performed while taking antidepressants to monitor the patient's general condition.

If you are taking antidepressants, be aware of the risk of serious side effects you may be exposed to, monitor your health, and get regular tests ordered by your doctor. If you are planning a pregnancy or are breastfeeding, tell your doctor so that he can reduce the risk of side effects for your baby.

Expectation of the effect of antidepressant therapy

Antidepressants begin to work 8-12 weeks after you start taking them, although the first signs of improvement may appear earlier. The effectiveness of an antidepressant is influenced by genetic factors. Sometimes, if an antidepressant does not have the desired effect, the doctor may increase the dose, prescribe another drug at the same time, or change the antidepressant.

This is a modern group of antidepressants with minimal side effects and good tolerability. The only representative of this class of antidepressants known today is bupropion.
Distinctive features of bupropion are the low probability of phase sign inversion into mania or hypomania and the low probability of provoking a “rapid cycle” - less than that of SSRIs, and much less than that of TCAs or MAOIs and other powerful antidepressants. In this regard, bupropion is especially recommended for patients with bipolar depression who are prone to phase inversion or the development of a “rapid cycle” when treated with various antidepressants. Bupropion has the ability to reduce the need and craving for nicotine, as well as the physical and mental symptoms of nicotine withdrawal. In this regard, under the name “Zyban” it is specially proposed to facilitate tobacco withdrawal. Important features of bupropion are also a pronounced general stimulating and psycho-energizing effect (so pronounced that a number of experts previously classified it not as an antidepressant, but as a psychostimulant, despite the lack of narcotic properties), as well as a disinhibiting effect on libido, sexual activity and the quality of orgasm. Due to its libido-disinhibiting effect, bupropion is often used to correct the sexual side effects of TCAs, SSRIs, or SSRIs.
A wide range of antidepressant drugs have been proposed for modern psychiatric practice. A feature of the treatment of depressive disorders is the need for long-term prescription of antidepressants, taking into account the cyclical nature of the mental disorder. Modern drugs produce a clinical effect, as a rule, within several weeks of regular use, and therefore the progress of treatment should be monitored. In many cases, depression develops against the background of a concomitant somatic disease, and antidepressant therapy, as a rule, has a positive effect on the course of the underlying disease, which is clearly demonstrated by the example of cardiovascular pathology. The mortality rate in patients who have suffered a vascular accident and suffering from depression is 3-6 times higher than in patients who have had a heart attack and do not have signs of depression. Accordingly, it is necessary to take into account the peculiarities of the receptor mechanism of action of each group of drugs, especially when prescribing to patients with cardiovascular diseases (drugs that affect adrenergic structures are prescribed with caution). An extremely significant range of doses for various drugs should be taken into account - from units to hundreds of milligrams, which is very important when prescribing to patients with liver and kidney pathologies. All other things being equal, in such situations preference should be given to “low-dose” drugs. The interaction of antidepressants with other drugs remains a pressing problem. An advantage in this situation will be drugs that have little effect on the metabolic systems of the liver (for example, venlafaxine) and, to a lesser extent, interact with blood plasma proteins. The positions of the “gold standard” remain tricyclics (amitriptyline) and SSRIs (fluoxetine), which are effective in the most severe depressive disorders. More modern groups of antidepressants, in some cases not inferior in activity to TCAs and SSRIs, may have advantages in the form of reduced sedation, less pronounced side effects, ease of combination with other drugs, however, as a rule, they are not superior to TCAs and SSRIs in clinical effectiveness .

More on the topic Selective norepinephrine and dopamine reuptake inhibitors (SNRIs):

1. Antidepressants - serotonin reuptake inhibitors (fluoxetine, fluvok-samine, sertraline, paroxetine, citalopram