What is norepinephrine reuptake? Effects of selective serotonin reuptake inhibitors on mood. Indications and contraindications for use

Especially in outpatient practice, relatively new antidepressants are used - selective serotonin reuptake inhibitors (SSRIs), which have significantly fewer side effects than tricyclic antidepressants due to their selective effect on serotonin metabolism (selective inhibition of 5-HT uptake).

SSRIs are represented by drugs such as: fluoxetine (Prozac), fluvoxamine (Fevarin), sertraline (Zoloft, Stimuloton, Asentra), paroxetine (Paxil, Rexetine), cipramil (Citalopram, Cipralex).

Unlike TCAs, a feature of the action of serotonergic antidepressants is their selective effect on the serotonergic system, initially identified in laboratory studies (Wong D., et al., 1974; Fuller R., et al., 1977). The effectiveness of SSRI therapy for depression is at least 65% (Mulrow D., et al., 2000)

Due to the affinity of these drugs and their active metabolites for serotonin receptors, serotonin reuptake is blocked at the level of presynaptic terminals, thereby increasing the concentration of the transmitter in the synaptic cleft, which in turn leads to a decrease in the synthesis and turnover of serotonin (Stark R., et al., 1985).

The selective, but nonspecific for a certain receptor subtype (Stahl S., 1993) action of SSRIs does not always increase the effectiveness of treatment, especially when it comes to the treatment of patients suffering from severe depression (Anderson I., Tomenson B., 1994; Burce M., Prescorn S., 1995).

SSRI drugs have completely different chemical structures and differ from each other in pharmacokinetic parameters, dosages and side effect profiles. The selectivity of 5-HT reuptake inhibition reduces side effects, improves tolerability and reduces drug discontinuation compared with TCAs (Anderson I., Tomenson T., 1994).

Table Comparative characteristics of SSRIsby intensity of antidepressant effect

Note: +++ - significant intensity, ++ - moderate intensity, + - weak effect.

It is necessary to emphasize the relative safety of SSRIs (fewer number and severity of side effects) and greater comfort of treatment (the possibility of carrying out therapy on an outpatient basis).

SSRIs are also characterized by low toxicity (the risk of death in case of poisoning or overdose is almost zero), as well as the possibility of using drugs in this group in patients with contraindications to the use of TCAs (heart rhythm disturbances, difficulty urinating due to prostatic hypertrophy, closed-angle glaucoma) ( Mashkovsky M.D., 1997).

It should be noted that the literature has reported cases of central and peripheral side effects during treatment with SSRIs (Baldessarini R., 1989).

These drugs are more expensive antidepressants than other drugs used to treat depression.

Most selective serotonin reuptake inhibitors (SSRIs) are long-acting and are used in fixed doses. The pharmacokinetics of various representatives of the SSRI group has its own characteristics depending on the age of the patients and somatic burden. Thus, the half-life of fluvoxamine increases slightly in elderly patients and patients with liver pathology (Raghoebar M., Roseboom H., 1988). The half-life of sertraline is also influenced by age (Warrington S.1988), and the effect of fluoxetine is quite significantly affected by the functional capabilities of the liver (Bergstrom M., Lemberg L, et al., 1988).

Clinical trials of SSRIs have demonstrated that they, like TCAs, are an effective treatment for most depressive conditions, including anxiety, sleep disturbances, psychomotor agitation and retardation. (Levine S. et al., 1987, Dunlop S. et al., 1990, Claghorn J., 1992, Kiev A., 1992).

Table Comparative assessment of the additional therapeutic effect of SSRIs

Indications for the use of SSRIs are severe and moderately severe depression (such as simple) with mild anxiety and restlessness (Pujynski S., et al., 1994; Pujynski S., 1996). In addition, SSRIs can be used to treat personality disorders, including anger reactions and impulsivity.

The medical literature emphasizes the sensitivity of vital disturbances to the action of these antidepressants (Laakmann G. et al. 1988).

A number of studies have described that patients in whom melancholy predominated in the structure of the syndrome demonstrated a good therapeutic response when using SSRIs (Reimherr F. et al., 1990, Tignol G. et al., 1992; Mosolov S.N., Kalinin V. .V., 1994).

Considering the good tolerability of these drugs, they are recommended for use in old age.

At the same time, most researchers note a fairly high anxiolytic activity of SSRIs (Amin M. et al., 1989; Kiev A., 1992, Bovin R.Ya., et al. 1995, Ivanov M.V. et al. 1995). At the initial stages of the emergence of SSRIs in the domestic literature, there were indications of low effectiveness, and sometimes even increased anxiety when using SSRIs in patients with anxious depression (Kalinin V.V., Kostyukova E.G., 1994, Lopukhov I.G. et al. , 1994, Mosolov S.N., et al., 1994).

In recent years, studies have been conducted comparing SSRIs with TCAs. Most authors note that the activity of new compounds is comparable to traditional drugs (Guelri J. et al., 1983; Shaw D. et al., 1986; Hale A. et al., 1991, Fontaine R. et al., 1991 ). When comparing SSRIs with TCAs, traditionally used in the treatment of anxiety and depressive conditions, it is usually indicated that the differences in the effectiveness of the studied drugs in their ability to relieve anxiety are not statistically significant (Feighner J., 1985, Laws D. et al., 1990 , Avrutsky G.Ya., Mosolov S.N., 1991, Doogan D., Gailard V., 1992).

According to many authors, SSRIs are effective in some cases when the use of TCAs turned out to be ineffective (Weilburg J.B. et al., 1989, Beasley C.M. et al.. 1990; Ivanov M.V. et al., 1991; Bovin R.Ya. et al. al., 1992; Serebryakova T.V., 1994; Bovin R.Ya., et al. 1995). According to Beasley C., Sayler M. (1990), patients resistant to TCAs are sensitive to new drugs in 50-60% of cases.

It is necessary to emphasize the greater safety of SSRIs compared to TCAs (fewer number and severity of side effects), greater comfort of treatment (the possibility of carrying out therapy on an outpatient basis) (Boyer W. Feighner J., 1996).

When taking TCAs, 30% of patients are forced to abandon treatment due to the severity of side effects, while when new drugs are prescribed, only 15% of patients have to interrupt their medication (Cooper G., 1988).

S. Montgomery, S. Kasper (1995) showed that the frequency of drug discontinuation due to side effects was 14% of patients treated with SSRIs and 19% with TCAs. The advantage of second-generation antidepressants is especially important during long-term therapy (Medavar T. et al., 1987).

R.Ya. Bovin (1989) points to an increased risk of suicide in the early stages of TCA therapy. While in most studies on SSRIs, the authors pay attention to the high anti-suicide nature of these drugs (Fava M. et al., 1991; Cohn D. et al., 1990; Sacchetti E. et al., 1991) .

In addition to the treatment of depression, attempts are increasingly being made to long-term use of antidepressants (fluoxetine, sertraline) to prevent its relapse.

Cohn G.N. et al., (1990), given the good tolerability of SA, recommend their use in gerontopsychiatry.

There is no consensus regarding the speed of onset of effect when using SSRIs. According to foreign authors, the clinical effect of SSRIs is detected later than TCAs (Roose S, et al. 1994). At the same time, domestic scientists indicate that SSRIs tend to have a faster onset of therapeutic effect compared to other antidepressants (Avrutsky G.Ya., Mosolov S.N., 1991).

In the SSRI group, various drugs differ in the strength of their action on receptors and the level of selectivity. Moreover, selectivity and potency do not coincide. It was found that paroxetine is a more potent inhibitor of serotonin return, while citalopram is more selective. Differences in the selectivity and power of action on receptors determine not only the characteristics of the therapeutic effect of a particular drug, but also the presence of side effects (Thopas D., et al., 1987; Hyttel G., 1993).

Other things being equal, relapses of depression are more likely to occur after treatment with fluoxetine than with paroxetine and after treatment with citalopram than with sertraline; with an almost equal number of relapses during treatment with sertraline and paroxetine.

Since fluvoxamine and paroxetine have a pronounced sedative and anti-anxiety effect, their spectrum of activity is similar to drugs such as amitriptyline or doxepin. Most other drugs, especially fluoxetine, more closely resemble the profile of imipramine, as they have a disinhibitory effect and can increase symptoms of anxiety and restlessness (Caley Ch., 1993; Pujynski S., et al., 1994; Montgomery S., Johnson F., 1995 ). In the domestic literature there are also indications of low effectiveness, and sometimes even increased anxiety when using SSRIs in patients with anxious depression (Kalinin V.V., Kostyukova E.G., 1994, Lopukhov I.G. et al., 1994, Mosolov S.N. et al., 1994).

Due to the disinhibiting effect, such drugs should not be used for anxiety, restlessness, motor disinhibition, insomnia, suicidal thoughts and tendencies. According to S. Pujynski (1996), psychotic forms of depression are a relative contraindication to the use of SSRIs. However, Feighner J., Bouer W (1988), on the contrary, note the positive effect of these drugs even in the psychotic version of depression.

The most common side effects when taking serotonin inhibitors are gastrointestinal disorders: nausea and vomiting, constipation and loose stools. A number of patients experience weight loss.

Table Comparative characteristics of SSRIs according to the severity of side effects

Note: +++ - significant severity of side effects, ++ - moderate severity of side effects, + - mild severity of side effects

The next most common side effects are: restlessness, anxiety, insomnia, and less commonly, increased drowsiness.

Patients are especially concerned about sexual disorders that may occur when using these drugs. The most common of them: decreased libido, weak erection and difficulty achieving orgasm. In case of severe sexual disorders that have developed during SSRI therapy, the dosage of drugs is usually reduced or discontinued for several days. In some cases, drugs that are serotonin antagonists (cyproheptadine) or drugs that enhance sexual function (yohimbine) are prescribed.

The most frequently mentioned contraindications to taking SSRIs include: hypersensitivity to the drug, pregnancy (cases of treatment of depression during this period with fluoxetine are known) and breastfeeding (the effect of SSRIs on the fetus and child development has been poorly studied), epilepsy, impaired renal and liver function. Drugs in this group cannot be used for poisoning with alcohol and psychotropic drugs. SSRIs should not be used earlier than 2 weeks after the end of therapy with non-selective MAO inhibitors, as well as together with other drugs with serotonergic action (Feihner J., Boyer W., 1996).

All registered SSRIs can provoke a phase change from depressive to manic in individuals with bipolar disease, but such a phase change occurs less frequently than with the use of TCAs (Kharkevich M.Yu., 1996). In addition, when treated with antidepressants for dysthymia, 10% of patients experience mild mania.

Due to the trend towards wider use of serotonin reuptake inhibitors in the treatment of depression, it makes sense to dwell on the characteristics of individual representatives of this group of drugs.

In his practical work, a psychiatrist in a number of cases encounters difficulties in distinguishing the clinical manifestations of depression from the side effects of SSRIs, SSRI withdrawal syndrome, as well as potentially life-threatening serotonin syndrome.

In the practice of a psychiatrist, differential diagnosis of the withdrawal syndrome of these drugs, their side effects and serotonin syndrome with clinical symptoms is of particular importance in the process of SSRI therapy. SSRI withdrawal syndrome, which occurs in the event of a rapid reduction in the dose of the drug or its abrupt withdrawal, is characterized by symptoms such as dizziness, nausea, anxiety and headache. As noted above, side effects of SSRIs usually appear in the first two weeks of therapy and include asthenia, diarrhea, nausea, anxiety, dizziness, sleep disturbance, nervousness and tremor. For serotonin syndrome, which occurs with an overdose of an SSRI or its combination with a TCA, abdominal cramps, psychomotor agitation, diarrhea, convulsions, tachycardia, hypo or hypertension, sweating, and hyperthermia are typical. In depression, the core of the depressive state is anhedonia.

Fluoxetine

One of the first serotonin reuptake inhibitors was fluoxetine (Prozac), which has been actively used since the early 80s to treat various depressive spectrum disorders. In addition, its positive effect in the treatment of bulimia was noted.

Fluoxetine is prescribed at a dose of 20 mg. once a day in the morning, if necessary, increase the dose to 40-80 mg. (in addition to tablet forms, a special solution of fluosetine 4 mg/ml is used abroad).

The drug is well absorbed when administered orally and is demethylated in the liver to form inactive metabolites and pharmacologically active norfluoxetine. Due to the peculiarities of metabolism, the effect of fluoxetine is quite significantly reflected in the functional capabilities of the liver (Bergstrom M., Lemberg L, et al., 1988). It suppresses the activity of hepatic cytochromes P4502D6, and therefore slows down the metabolism of a number of psychotropic drugs, including TCAs, with an increase in their concentration in plasma, which determines the possibility of toxic effects (Creve N., et.al., 1992).

The maximum concentration in the blood when taking fluoxetine is achieved after 6 hours. It has the longest half-life of all SSRIs, which in this case is two to three days, and the half-life of its active metabolite, norfluoxetine, reaches 7-9 days. This circumstance provides an advantage in the treatment of patients who may occasionally forget to take the next dose, but, on the other hand, it complicates the replacement of the drug with other antidepressants (especially MAOIs). It takes several weeks to achieve a stable concentration of the active substance. It was noted that, despite the anxiolytic effect, fluoxetine can increase the manifestations of anxiety and agitation at the initial stage of therapy.

In terms of its spectrum of action, fluoxetine is more reminiscent of the profile of imipramine, since it has a disinhibitory effect and can, as noted above, increase the manifestations of anxiety and restlessness (Caley Ch., 1993; Pujynski S., et al., 1994; Montgomery S., Johnson F., 1995). There is a point of view according to which, due to the disinhibitory effect, fluoxetine should not be used for anxiety, restlessness, motor disinhibition, insomnia, suicidal thoughts and tendencies, however, recent studies have shown that taking fluoxetine does not increase the risk of suicide (Freemante N., et.al ., 2000).

Fluoxetine (Prozac), compared to other SSRIs, eliminates signs of depression much more slowly (within 2-3 weeks), however, its final effect turned out to be similar to the effect of other drugs of this class (Edwards J., Anderson I., 1999). There are observations that fluoxetine is approximately equal to TCAs in its effectiveness in relieving symptoms of depression (Beasley C., et al., 1991).

At the same time, there is a point of view according to which fluoxetine is inferior to other SSRIs in its ability to relieve general manifestations of depression (Williams J., et al., 2000).

In the first days of using fluoxetine, and possibly also at further stages of treatment, nausea, akathisia, headaches, impaired visual acuity, and allergic skin reactions may be observed. Sexual dysfunctions have been reported when taking fluosetine (Guthrie S., 1991; De Vane C. 1994; Pujynski S., 1996).

Fluvoxamine

Fluvoxamine (fevarin), as a selective serotonin reuptake inhibitor, has a distinctly activating, mood-enhancing effect, it calms, stabilizes the activity of the autonomic system and can be recommended for a combination of depression and anxiety. In addition, the positive aspect of fluvoxamine treatment is its relatively rapid onset and smooth action, which, as a rule, contributes to the establishment of a good relationship between the patient and his attending physician.

Fluvoxamine is prescribed in a dose of 50 mg. per day once in the evening. The dose of the drug can be increased to 100 mg. (average dose of effectiveness) for 5-7 days. If necessary, the dosage of the drug can be further increased at intervals of 2-4 weeks (maximum daily dosage - 500 mg), starting with a dose of 150 mg. the drug is prescribed several times a day.

The active metabolites of fluvoxamine are unknown. The average half-life is 20 hours, plasma concentrations are not proportional to the dose taken

In most cases, symptoms of an anxiety disorder are eliminated earlier than those of a depressive disorder. This was clinically manifested by an improvement in the general condition of the patients, leading them to greater composure, confidence and external calm. The effectiveness of this drug is noted in patients with obsessive disorders and social phobia, in particular in childhood.

Adding fluvoxamine to atypical neuroleptics can reduce the severity of primary negative symptoms in patients with chronic schizophrenia. At the same time, comparative studies have shown that among the group of selective serotonin reuptake inhibitors, it has the greatest number of side effects (Freemante N., et al., 2000), sertraline has the least (Edwards J., Anderson I., 1999 ).

Citalopram

Citalopram has a significantly higher level of selectivity for serotonin transporters compared to norepinephrine and dopamine transporters.

The drug is prescribed in a dose of 20 mg. per day once a day in the morning. For most patients, this dose is the most effective; the maximum daily dose of the drug is 60 mg.

Citalopram practically does not enter into drug interactions, due to the fact that it has little effect on the activity of some liver enzymes (cytochrome P450 enzyme system). Therefore, it is often used in the treatment of depressive conditions that develop as a result of chronic somatic diseases. Interdrug interactions of the drug are minimal. Under the influence of cytochrome P450, citalopram is converted into two main metabolites: demethylcitalopram and didemethylcitalopram. These metabolites have pharmacological activity, but much less than that of citalopram itself. The half-life of citalopram is 30 hours. It is characterized by a linear dependence of plasma concentrations depending on the dose in the therapeutic interval. For the treatment of severe depression, the dose of the drug should be increased.

When prescribing citalopram, the percentage of men with sexual dysfunction, a side effect that is relatively common when prescribing drugs of this group, turned out to be extremely insignificant. Headache and nausea were the most common side effects of citalopram treatment during the first two weeks of treatment.

Sertraline

Sertraline (Zoloft, Stimuloton, Asentra) is characterized by a thymoanaleptic (anxiolytic) effect of moderate severity. There are no vegetative stabilizing, sedative, timerectic, adrenergic and anticholinergic (muscarinic) effects. The drug does not affect psychomotor functions, has a weak antiphobic and very weak hypotensive effect.

Indications for use are mild to moderately severe melancholy depression with secondary anxiety and somatoform disorders. After obtaining a satisfactory effect, continuing treatment with sertraline helps prevent relapse of depression or its subsequent occurrence.

Sertraline is also used to treat obsessive-compulsive disorder (OCD).

As a rule, the antidepressant effect occurs after one week of therapy.

After achieving the initial effect, long-term treatment with sertraline for up to 2 years ensures its sufficient effectiveness and good tolerability. Sertraline is used to treat panic disorders and post-traumatic stress disorder syndrome (PTSD). The initial therapeutic effect in this case may appear within 7 days, but the full effect is usually achieved later - after 2-4 weeks (possibly over a longer period of time, especially with OCD). There is a point of view according to which the drug usually reduces secondary anxiety associated with melancholy depression.

Sertraline (Zoloft, Stimuloton) is a relatively low-toxic antidepressant from the SSRI group; it is used in child psychiatry, as well as in cases of depressive spectrum disorders that develop after an acute episode of schizophrenia.

Sertraline is prescribed in a dose of 50 mg. per day (usually once a day in the morning, regardless of meals). The dose can be increased by 50 mg. in Week. Recommended daily doses: for inpatient treatment of depression - 50-100 mg, for outpatient use - 25-50 mg. If necessary, the dose is increased at intervals of 2-4 weeks (maximum daily dose - 200 mg).

At therapeutic doses, sertraline inhibits the uptake of serotonin by platelets. It is extensively metabolized in the liver, approximately 98% of it is present in the body in protein-bound form, and its main metabolite has weak pharmacological activity. Unlike most antidepressants, it binds preferentially to a1-glycoprotein, whereas other drugs interact primarily with albumin.

The half-life of sertraline is influenced by age. In children, sertraline metabolism is more active (Warrington S.1988). Considering the latter circumstance, it is recommended to use the drug in children in a lower dose to avoid excessive levels of its concentration in plasma. At the same time, according to other authors, the pharmacokinetic profile in adolescents and elderly people does not differ significantly from the profile of patients aged 18 to 65 years.

Sertraline is slowly absorbed over 4-6 hours, eliminated through the gastrointestinal tract and kidneys, the equilibrium concentration of the drug is achieved within one week after the start of treatment.

The average half-life of sertraline is 22-36 hours. Steady-state concentrations of sertraline are established after 1 week of treatment.

Kidney pathology has almost no effect on the clearance of sertraline. At the same time, with liver pathology, the half-life of sertraline in serum, as well as its concentration in plasma, increases by almost 50%.

Side effects: tremor, nausea, dry mouth, diarrhea. Typically, side effects resolve spontaneously by the end of 4 weeks of therapy. Early unwanted side effects are especially common in the treatment of panic disorders.

Contraindications to the use of the drug are liver and kidney diseases with impaired function. After discontinuation of the drug, MAOIs are prescribed no earlier than 5 weeks later.

With chronic use of sertraline, addiction develops to it, since its prolonged use leads to a decrease in the number of its receptors (Anthony P., et al., 2002).

Paroxetine

Paroxetine (Paxil, Rexetine) has the highest affinity for serotonin receptors of all SSRIs. This drug inhibits serotonin reuptake much more actively than sertraline or fluoxetine.

Begin treatment with paroxetine with a daily dose of 20 mg. (once a day). In some cases, the initial dose is 10 mg. Most studies show that this dose becomes effective for most patients treated with this drug. If necessary, it is increased by 10 mg. per day with an interval of 2-4 weeks (maximum daily dose of paroxetine - 50 mg.).

The half-life of paroxetine is 21-24 hours. Therefore, to achieve stable concentrations, one week is enough after the start of treatment.

During the metabolism of this drug, no active substances are formed. Up to 60% of poroxetine present in serum is filtered in the kidneys. With mild or moderate impairment of their function, the maximum concentration of the substance in the serum may double.

This enzyme is easily saturated and as the dose of paroxetine increases, the relationship between its dose and plasma concentration becomes nonlinear. With long-term use of paroxetine, its steady-state plasma concentration is several times higher than what would be expected based on the results of a single dose.

Paroxetine may cause slight weight gain.

There are many groups of medications that are aimed at psychotropic correction in the treatment of anxiety and depressive conditions.

All of them have a common mechanism of action, the essence of which is to control the influence of certain neurotransmitters on the state of the central nervous system, depending on the genesis of the disease. According to research, a central deficiency of serotonin in synoptic transmission has a special effect on the pathogenesis of depression, by controlling which one can regulate mental activity.

Selective serotonin reuptake inhibitors (SSRIs) are third generation drugs that are relatively easily tolerated by patients. They are used for the treatment of depressive disorders and disorders in mono and poly therapy.

This group of medications works by maintaining the continued activity of central serotonergic processes by preventing the uptake of serotonin by brain tissue, as a result of which the mediator, accumulating in the receptor area, exerts its influence on them longer.

The main advantage of SSRIs over other groups is the selective inhibition of only one type of biogenic amines, which helps prevent unwanted side effects on the body. This has a positive effect on the body’s tolerance of this group of drugs, due to which their popularity among patients and specialists is growing every year.

Mechanism of action and pharmacological properties

When serotonin is released from the fibers of the nerve endings in the area of ​​the reticular formation, which is responsible for wakefulness, as well as the limbic system, which is responsible for controlling the emotional state, it enters a space called the synoptic cleft, where it attaches to special serotonin receptors.

During this interaction, the neurotransmitter excites the cell membranes of these structures, thereby increasing their activity. As a result, this substance breaks down under the action of special enzymes, after which its elements are recaptured by the structures through which its initial release was made.

Reuptake inhibitors exert their influence at the stage of enzymatic breakdown of serotonin, preventing its destruction, promoting the subsequent accumulation and prolongation of its stimulating effects.

As a result, the increase in neurotransmitter activity eliminates the pathological processes of depressive and phobic disorders, and compensates for the deficit in emotional behavior and regulation of mental states.

Scope of application

The main purpose of using this group of antidepressants is to suppress various types of depression by providing a stimulating effect on brain structures.

SSRIs are also used in the following cases:

This group of drugs is also effective in the treatment of alcoholism and withdrawal symptoms.

Restrictions and contraindications

Taking SSRI antidepressants is prohibited if there are psychostimulant drugs in the blood or while under the influence of alcohol or drugs.

The combination of several drugs with serotonergic effects is contraindicated. The use of serotonin reuptake inhibitors is also incompatible if there is a history of serotonin reuptake inhibitors.

Hepatic and renal failure, as well as cardiovascular diseases in the decompensation stage are a contraindication to the use of selective inhibitors.

1. Nausea, vomiting, congestion in the intestines and, as a result, constipation.
2. Restless states may occur and develop to the point of insomnia or reversion to increased sleepiness.
3. Increased nervous agitation, appearance, loss of visual acuity, appearance of skin rash are possible, a change in the phase of the disease is possible with a transition from depressive to manic.
4. There may be an appearance, decreased libido, development in the form of, or acute. There is an increase in prolactin production.
5. With long-term use, a phenomenon such as loss of motivation with emotional dulling, which is also known as SSRI-induced apathy syndrome, is possible.
6. Bradycardia may develop, and a decrease in sodium levels in the blood may occur, leading to edema.
7. When taking drugs during pregnancy, spontaneous abortions are possible as a result of a teratogenic effect on the fetus, as well as developmental abnormalities in late pregnancy.
8. In rare cases, it is possible with corresponding mental, autonomic and neuromuscular disorders.

Food for thought

According to recent studies, the treatment of endogenous depression in adolescence is effective and safe when used as therapy with SSRI antidepressants, due to the absence of such side effects as when taking tricyclic drugs.

The predictability of the treatment effect allows us to provide the correct treatment to this group of patients, despite the atypical symptoms of depression at this age associated with neurobiological changes in adolescence.

SSRIs make it possible, already at the initial stages of treatment, to prevent exacerbation of the condition and reduce the relevance of suicidal behavior, which is typical for people suffering from juvenile depression.

Also, serotonin reuptake inhibitors have proven effective in the treatment of postpartum depression and have a positive effect in menopausal syndrome in the form of depression and depressive states, which allows the use of antidepressants as a replacement for hormonal therapy.

TOP 10 popular SSRI drugs

Ten selective serotonin reuptake inhibitors that are deservedly popular among patients and doctors:

Full list of drugs available for 2017

An exhaustive list of SSRIs, which consists of all the active substances of the group, as well as drugs based on them (trade names).

Structural formulas of popular SSRIs (clickable)

Preparations based on;

• Prozac;
• Deprex;
• Flunisan;
• Fluval;
• Profluzak;
• APO-fluoxetine;
• Prodep;
• Flunate;
• Fluxonil;
• Fludak.

This group of drugs has a stimulating and thymoanaleptic effect. Medicines are used for different types of depression.

• Avoxin.

The drugs specifically inhibit serotonin reuptake and have an anxiolytic effect. Used for the prevention and treatment of obsessive-compulsive disorders. They also have an effect on adrenergic, histamine and dopamine receptors.

• Paroxetine;
• Rexitin;
• Serestill;
• Plizil;
• Actaparoxetine;
• Apo-paroxetine.

The group has anxiolytic and sedative properties. The active substance has a bicyclic structure, which distinguishes it from other drugs.

With a long course, the pharmacokinetic properties do not change. The main indications cover endogenous, neurotic and reactive depression.

Preparations based on Sertraline:

• Oprah;
• Pram;
• Sedopram;
• Siozam;
• Moral;
• Citalift;
• Citalorin;
• Cytol;
• Citalopram.

The group has minimal third-party effects on dopamine and adrenergic receptors. The main therapeutic effect is aimed at correcting emotional behavior, leveling feelings of fear and. The therapeutic effect of other groups of antidepressants may be enhanced by simultaneous interaction with Citalopram derivatives.

Medicines based on Escitalopram:

Medicines are used for. The maximum therapeutic effect develops 3 months after starting to take this group of SSRI drugs. Medicines practically do not interact with other types of receptors. Most of the metabolites are excreted by the kidneys, which is a distinctive feature of these derivatives.

General treatment regimen

Drugs from the group of selective serotonin reuptake inhibitors are used once a day. This may be for a different time period, but most often it is taken in the morning before meals.

The medicinal effect occurs after 3-6 weeks of continuous treatment. The result of the body's response to therapy is regression of symptoms of depressive states, after complete suppression of which the therapeutic course is continued for 4 to 5 months.

It is also worth considering that in the presence of individual intolerance or resistance of the body, manifested in the absence of a positive result within 6-8 months, the group of antidepressants is replaced with another. The dosage of the drug per dose depends on the derivative substance; as a rule, it ranges from 20 to 100 mg per day.

Once again about warnings!

Antidepressants are contraindicated for use in cases of renal and liver failure, due to a violation of the elimination of drug metabolites from the body, resulting in toxic poisoning.

Serotonin reuptake inhibitors should be used with caution in people whose work requires high concentration and attention.

In diseases that cause tremor, such as, antidepressants can increase the negative clinical picture, which can negatively affect the patient’s condition.

Taking into account the fact that inhibitors have a teratogenic effect, they are not recommended for use during pregnancy and lactation.

It should be remembered that if the body is severely physically exhausted, drugs in this group cannot be used due to the risk of even greater suppression of appetite.

It is also always worth remembering about withdrawal syndrome, which is a complex of negative symptoms that develop when the course of treatment is abruptly stopped:

However, these drugs have their own disadvantages, which are manifested in incomplete knowledge of all their properties and the presence of certain side effects characteristic only of SSRIs.

Serotonin is an important substance related to the mediators of the nervous system of the human body. People call it the hormone of happiness.

Serotonin received its name due to the activation of positive emotions and a beneficial effect on the psychoneurological state of a person.

The main task of serotonin is to regulate neuronal function. In the central nervous system, this substance has the following effects:

• improves mood;
• improves memory;
• regulates the speed of cognitive reactions;
• normalizes appetite;
• organizes food cravings;
• regulates sexual desire;
• responsible for social behavior.

It is accompanied by muscular, autonomic and mental disorders, which have a high risk of death.

To prevent the syndrome, it is unacceptable to take SSRIs together with MAO inhibitors.

Combinations with the following types of drugs can lead to the same condition:

• tetracyclic antidepressants;
• herbal remedies with the addition of St. John's wort;
• Levodopa;
• antimigraine drugs;
• mood stabilizers;
• atypical antipsychotics.

If you have previously used any medications, you must wait at least two weeks before starting to take an SSRI.

Depending on the type of drug, this period may be changed. Replacing Fluoxetine with Paroxetine requires a break of 2-3 weeks. For older patients, this period increases to 8 weeks.

Comparison of reuptake inhibitors: which is better?

If you seek medical help, a specialist will definitely select the appropriate medicine and tell you how to use it as productively as possible for your health.

Many years of experience in use and consumer reviews allow us to schematically outline the advantages and disadvantages of the drugs.

It is impossible to say for sure which is the best selective serotonin reuptake inhibitor.

All medications have features of use, restrictions and individual dosage regimens.

The doctor will need to see the patient weekly or biweekly to provide support, information, and monitoring for changes in the condition. Phone calls can complement doctor visits. The patient and their loved ones may be distressed by the idea of ​​having a mental disorder. In this situation, a doctor can help by explaining that depression is a serious medical illness caused by biological disorders and requires specific treatment, and that depression most often ends on its own and the prognosis with treatment is good. The patient and his relatives must be convinced that depression is not a character flaw (for example, laziness). Explaining to the patient that the road to recovery will not be easy will help him subsequently cope with feelings of hopelessness and improve cooperation with the doctor.

Encouraging patients to gradually increase activities of daily living (eg, walking, regular exercise) and social interactions should be balanced with acknowledgment of patients' desire to avoid activities. The doctor should advise the patient to avoid self-blame and explain that dark thoughts are part of the disease and they will pass.

Psychotherapy

Individual psychotherapy, often in the form of cognitive behavioral therapy (individual or group), by itself is often effective for mild forms of depression. Cognitive behavioral therapy is increasingly used to overcome the inertia and self-blaming thinking of depressed patients. However, cognitive behavioral therapy is most effective when used in combination with antidepressants to treat moderate to severe depression. Cognitive behavioral therapy can improve coping skills and increase the benefit of support and guidance by addressing cognitive distortions that impede adaptive functioning and by encouraging the patient to gradually regain social and occupational roles. Family therapy can help reduce disharmony and tension between spouses. Long-term psychotherapy is not necessary unless the patient has a protracted interpersonal conflict or does not respond to short-term therapy.

Selective serotonin reuptake inhibitors (SSRIs)

These drugs block the reuptake of serotonin. SSRIs include citalopram, escitalopram, fluoxetine, paroxetine and sertraline. Although these drugs have a similar mechanism of action, differences in their clinical properties make the choice important. SSRIs have wide therapeutic limits; they are relatively easy to administer and rarely require dose adjustment (with the exception of fluvoxamine).

By blocking presynaptic 5-HT retake, SSRIs lead to increased 5-HT stimulation of postsynaptic serotonin receptors. SSRIs act selectively on the 5-HT system, but not specifically on various types of serotonin receptors. Therefore, they not only stimulate 5-HT receptors, which is associated with antidepressant and anxiolytic effects, they also stimulate 5-HT, which often causes anxiety, insomnia, sexual dysfunction, and 5-HT receptors, which usually leads to nausea and headache. Thus, SSRIs may act in paradoxical ways and cause anxiety.

Some patients may appear more agitated, depressed, and anxious for a week after starting SSRI treatment or increasing their dose. The patient and his relatives should be warned about this possibility and instructed to call the doctor if symptoms worsen during treatment. This situation needs to be monitored closely as some patients, especially children and adolescents, are at increased risk of suicide if agitation, increased depression and anxiety are not recognized and treated promptly. Recent research shows that children and adolescents have an increased incidence of suicidal thoughts, actions, and suicide attempts in the first few months of taking SSRIs (similar caution should also be exercised for serotonin modulators, serotonin-norepinephrine reuptake inhibitors, and dopamine-norepinephrine reuptake inhibitors). ; The physician must maintain a balance between clinical need and risk.

Sexual dysfunction (especially difficulty achieving orgasm, decreased libido and erectile dysfunction) is observed in 1/3 or more of patients. Some SSRIs cause excess body weight. Others, especially fluoxetine, cause loss of appetite in the first few months. SSRIs have slight anticholinergic, adrenolytic and cardiac conduction effects. Sedation is minimal or negligible, but during the first weeks of treatment, some patients tend to experience daytime sleepiness. Some patients experience loose stools and diarrhea.

Drug interactions are relatively rare; however, fluoxetine, paroxetine and fluvoxamine may inhibit CYP450 isoenzymes, which may lead to significant drug interactions. For example, fluoxetine and fluvoxamine may inhibit the metabolism of some beta blockers, including propranolol and metoprolol, which may lead to hypotension and bradycardia.

Serotonin modulators (5-HT blockers)

These drugs primarily block 5-HT receptors and inhibit the reuptake of 5-HT and norepinephrine. Serotonin modulators include nefazodone, trazodone, and mirtazapine. Serotonin modulators have antidepressant and anxiolytic effects and do not cause sexual dysfunction. Unlike most antidepressants, nefazodone does not suppress REM sleep and promotes a feeling of rest after sleep. Nefazodone significantly interferes with liver enzymes involved in drug metabolism and its use has been associated with liver failure.

Trazodone is similar to nefazodone, but does not inhibit presynaptic 5-HT reuptake. Unlike nefazodone, trazodone causes priapism (in 1 in 1000 cases) and, as a norepinephrine blocker, can lead to orthostatic (postural) hypotension. It has pronounced sedative properties, so use in antidepressant doses (>200 mg/day) is limited. It is most often prescribed in doses of 50-100 mg at bedtime in depressed patients with insomnia.

Mirtazapine inhibits serotonin reuptake and blocks adrenergic autoreceptors, as well as 5-HT and 5-HT receptors. The result is more effective serotonergic activity and increased noradrenergic activity without sexual dysfunction and nausea. It has no cardiac side effects, minimal interaction with liver enzymes involved in drug metabolism, and is generally well tolerated, with the exception of sedation and weight gain mediated by histamine H receptor blockade.

Such drugs (for example, venlafaxine, duloxetine) have a dual mechanism of action on 5-HT and norepinephrine, just like tricyclic antidepressants. However, their toxicity approaches that of SSRIs; Nausea is the most common problem during the first two weeks. Venlafaxine has some potential advantages over SSRIs: it may be more effective in some patients with severe or refractory depression, and due to its low protein binding and virtually no interaction with liver enzymes involved in drug metabolism, it has a low risk of interactions when administered concomitantly with other drugs. However, when the drug is suddenly stopped, withdrawal symptoms (irritability, anxiety, nausea) are often observed. Duloxetine is similar to venlafaxine in effectiveness and side effects.

Dopamine-norepinephrine reuptake inhibitors

Through not fully understood mechanisms, these drugs have a positive effect on catecholaminergic, dopaminergic and noradrenergic functions. These medications do not affect the 5-HT system.

Currently, bupropion is the only drug in this class. It is effective in depressed patients with concomitant attention deficit hyperactivity disorder, cocaine addiction, and in those trying to quit smoking. Bupropion causes hypertension in a very small number of patients and has no other cardiovascular effects. Bupropion may precipitate seizures in 0.4% of patients taking more than 150 mg three times daily [or 200 mg sustained release (SR) twice daily, or

450 mg extended release (XR) once daily]; the risk is increased in patients with bulimia. Bupropion has no sexual side effects and has few interactions with other drugs, although it inhibits the liver enzymes CYP2D6. Agitation, which is quite common, is reduced when slow or extended release forms are used. Bupropion may cause dose-dependent impairment of short-term memory, which recovers after dose reduction.

Heterocyclic antidepressants

This group of drugs, which previously formed the basis of therapy, includes tricyclics (tertiary amines amitriptyline and imipramine and secondary amines, their metabolites, nortriptyline and desipramine), modified tricyclic and heterocyclic antidepressants. These drugs increase the availability primarily of norepinephrine and, to a certain extent, 5-HT, blocking their reuptake in the synaptic cleft. A long-term decrease in the activity of α-adrenergic receptors of the postsynaptic membrane is possibly a common result of antidepressant activity for them. Despite their ineffectiveness, these drugs are now rarely used, as they are toxic in overdose and have many side effects. The most common side effects of heterocyclic antidepressants are associated with their muscarinic-blocking, histamine-blocking and α-adrenolytic effects. Many heterocyclics have pronounced anticholinergic properties and therefore are not suitable for use in the elderly, patients with benign prostatic hyperplasia, glaucoma or chronic constipation. All heterocyclic antidepressants, especially maprotiline and clomipramine, lower the seizure threshold.

Monoamine oxidase inhibitors (MAOIs)

These drugs inhibit the oxidative deamination of 3 classes of biogenic amines (norepinephrine, dopamine and serotonin) and other phenylethylamines. MAOIs have no or little effect on normal mood. Their main importance is to act effectively when other antidepressants are ineffective (for example, in atypical depression, when SSRIs do not help).

MAOIs registered as antidepressants on the US market (phenelzine, tranylcypromine, isocarboxazid) are irreversible and non-selective (inhibit MAO-A and MAO-B). They can cause hypertensive crises if sympathomimetic drugs or foods containing tyramine or dopamine are simultaneously consumed. This effect is called the cheese reaction because ripened cheese contains a lot of tyramine. MAOIs are not widely used due to fear of such a reaction. More selective and reversible MAOIs (such as moclobemide, befloxatone) that block MAO-A are not yet common in the United States; these drugs practically do not cause such interactions. To prevent hypertensive and febrile crises, patients taking MAOIs should avoid sympathomimetic agents (eg, pseudoephedrine), dextromethorphan, reserpine, meperidine, as well as malt beer, champagne, sherry, liqueurs, and certain foods containing tyramine or dopamine (eg, bananas, beans, yeast extracts, canned figs, raisins, yogurt, cheese, sour cream, soy sauce, salted herring, caviar, liver, heavily marinated meat). Patients should carry chlorpromazine 25 mg tablets with them and, as soon as signs of a hypertensive reaction appear, take 1 or 2 tablets before reaching the nearest emergency department.

Common side effects include erectile dysfunction (less common with granylcypromine), anxiety, nausea, dizziness, pasty legs, and weight gain. MAOIs should not be used in combination with other classical antidepressants; at least 2 weeks (5 weeks for fluxetine, as it has a long half-life) should elapse between taking the two classes of drugs. Use of MAOIs with antidepressants that affect the serotonin system (eg, SSRIs, nefazodone) can cause neuroleptic malignant syndrome (malignant hyperthermia, muscle breakdown, renal failure, seizures, in severe cases, death. Patients taking MAOIs and requiring anti-asthmatic, anti-allergic treatment, local or general anesthesia, should be treated by a psychiatrist and an internist, dentist or anesthesiologist with experience in neuropsychopharmacology.

Selecting and prescribing a drug for the treatment of depression

When choosing a drug, you can be guided by the nature of the response to a previously used specific antidepressant. In other words, SSRIs are the drugs of first choice. Although different SSRIs are approximately equally effective in typical cases, the properties of a particular drug determine their greater or lesser suitability in particular patients.

If one SSRI is not effective, another drug in that class can be used, but other classes of antidepressants are more likely to be effective. Tranylcypromine in high doses (20-30 mg orally 2 times a day) is often effective for refractory depression after sequential administration of other antidepressants; it should be prescribed by a physician experienced with MAOIs. In cases of refractory depression, psychological support for the patient and his loved ones is especially important.

Insomnia, a common side effect of SSRIs, is treated by reducing the dose or adding a small amount of trazodone or another sedating antidepressant. Nausea and loose stools that occur at the beginning of treatment usually go away, but severe headaches do not always go away, requiring the prescription of a drug of a different class. SSRIs should be discontinued in case of agitation (more often when taking fluoxetine). If there is a decrease in libido, impotence, or anorgasmia due to taking SSRIs, reducing the dose or prescribing a drug of a different class may help.

Antidepressants

Serotonin and norepinephrine reuptake inhibitors

Serotonin modulators (5-HT blockers)

Dopamine and norepinephrine reuptake inhibitors

MAOIs - monoamine oxidase inhibitors, TCAs - tricyclic antidepressants, CR - continuous release, XR - extended release, 5-HT - 5-hydroxytryptamine (serotonin), SR - sustained release, XL - extended release.

SSRIs, which tend to stimulate many depressed patients, should be prescribed in the morning. If the full dose of a heterocyclic antidepressant is taken before bedtime, there will be no increased sedation, side effects during the day will be minimized and compliance will improve. MAOIs are usually given in the morning or before lunch to avoid excess stimulation.

The therapeutic response to most antidepressants is observed in weeks 2-3 (sometimes from day 4 to week 8). For the first episode of mild or moderate depression, antidepressants should be taken for 6 months, then gradually tapered over 2 months. If there has been a severe or repeated depressive episode or a significant suicidal risk, a dose that promotes complete remission should be taken during maintenance treatment. For psychotic depression, maximum doses of venlafaxine or heterocyclic antidepressants (eg, nortriptyline) should be prescribed for 3-6 weeks; if necessary, antipsychotics may be added (eg, risperidone, starting at 0.5-1 mg orally twice daily, gradually increasing to 4-8 mg once daily, olanzapine, starting at 5 mg orally once daily, and gradually increasing to 10-20 mg 1 time per day, quetiapine, starting with 25 mg orally 2 times a day and gradually increasing to 200-375 mg orally 2 times a day). To prevent the development of tardive dyskinesia, the antipsychotic should be prescribed at the minimum effective dose and discontinued as soon as possible.

To prevent exacerbations, maintenance therapy with antidepressants is usually necessary for 6 to 12 months (up to 2 years in patients over 50 years of age). Most antidepressants, especially SSRIs, should be tapered off gradually (25% dose reduction per week) rather than abruptly; immediate withdrawal of SSRIs can lead to serotonin syndrome (nausea, chills, muscle pain, dizziness, anxiety, irritability, insomnia, fatigue).

Some patients use herbal remedies. St. John's wort may be effective for mild depression, although the evidence is conflicting. St. John's wort may interact with other antidepressants.

Electroconvulsive therapy in the treatment of depressive disorder

In the treatment of severe depression with suicidal ideation, depression with agitation or psychomotor retardation, depression during pregnancy, in case of ineffectiveness of previous therapy, electroconvulsive therapy is often used. Patients who refuse to eat require electroconvulsive therapy to prevent death. Electroconvulsive therapy is also effective for psychotic depression. The effectiveness of 6-10 sessions of electroconvulsive therapy is high, and this method can be life-saving. After electroconvulsive therapy, exacerbations occur, so maintenance drug therapy is necessary after the end of electroconvulsive therapy.

, , , , , , [

Phototherapy may be used in patients with seasonal depression. Treatment can be carried out at home using lamps of 2500-10,000 lux at a distance of 30-60 cm for 30-60 minutes per day (longer with less intense light sources). For patients who go to bed late at night and wake up late in the morning, phototherapy is most effective in the morning, sometimes with an additional 5-10 minutes of exposure between 3 and 7 p.m.

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

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