From Wiki Drugs

Antidepressants are psychotropic drugs used, primarily, to treat depression. For depressed patients they improve mood, reduce or relieve depression, lethargy, apathy, anxiety and emotional stress, increase mental alertness, and normalize the phase structure and duration of sleep and appetite.

The main effect of antidepressants is to block the breakdown of monoamines (serotonin, nor epinephrine, dopamine, phenethylamine, etc. ) under the action of monoamine oxides (MAO) or block neuronal capture of monoamines.

It should be noted the existence of so-called «antidepressant threshold», which is individual for each patient. If below this threshold, antidepressant effect does not exist and there are non-specific effects only, including undesirable effects, sedative and stimulating characteristics.

Current data indicate that for the manifestation of antidepressant action with the drugs reducing the reuptake of monoamine, you need to reduce the capture in 5-10 times. To detect the antidepressants effect of the drugs that reduce the activity of MAO, it is necessary to bring the activity down approximately in 2 times.

However, contemporary research shows that there are other mechanisms of antidepressants action. For example, they assume that antidepressants reduce stress hyper reactivity of the hypothalamic-pituitary-adrenal system.

Contemporary studies indicate that some antidepressants reduce the concentration of substance P in the central nervous system. But these days the most important mechanism of depression, which affects all antidepressants, is considered the lack of monoamines activity.

History

Isolation antidepressant means (antidepressant) in an independent pharmacological group occurred in 1950 with the discovery of synthetic drugs as iproniazid and imipramine, with thymoanaleptic action. Before that, as antidepressants, they used various natural and synthetic opiates amphetamines, which have disappeared from usage in connection with a large number of side effects, as well as alkaloids, isolated from plant Rauvolfia, and hypericum, which is currently assigned to other ATC groups.

Iproniazid and imipramine

In 1951, New York (USA) there began clinical tests of two new anti-TB drugs - isoniazid and iproniazid. Firstly, these tests were subjected to only patients with poor prognosis, however, and their preparations have proven high effect. In addition, the researchers noted that patients in treatment with these drugs experienced a slight excitement, began to show an excess of force, and some even began to violate public order in the hospital. Drugs were found interesting for global health community, so, they were actively discussed. They were interested in the influence of drugs on the mood of patients as well. In 1952, the French psychiatrist Jean Delahey reported positive results in treating depression with the drug named isoniazid. In the same year following the case of Delahey, American doctor, Max Lurie decided to try usage of isoniazid for the correction of doldrums. The following year, Lurie and his colleague, Harry Seltzer reported that 60% of the drug was effective and successfully corrected the depression. Lurie and G. Seltzer were first who asked to call the effect hereinafter as antidepressant.

Some years before the Americans discovery, in 1948, in the laboratories of the Swiss company «Geigy» there was synthesized the founder of tricyclic antidepressants, imipramine. In 1950, the drug clinical research started, but until 1954 the drug was motionless, while the impressive results obtained by applying a similar chemical structure, tricyclic compounds - antipsychotic chlorpromazine, attracted attention to that drug. From 1954 to 1957, imipramine treated over 500 patients in the clinic of R. Kuhn in Switzerland. Later imipramine entered into widespread usage, it has been synthesized to generics.

The first synthetic antidepressants were introduced into medical practice in mid-1950 and were allowed only on medical prescription. That time it was considered that depression affected only 50-100 people in a million inhabitants, so the drug companies showed no expression of interest to antidepressants. Sales of these drugs in 1960 were not comparable in volume with sales of antipsychotic and benzodiazepine drugs.

Classification

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

1. Supplies blocking neuronal capture of monoamines 2.

• Indiscriminative ones blocking of neuronal serotonin reuptake and nor epinephrine (imizin, amitriptyline)

• Selective ones

o Blocking neuronal serotonin reuptake (fluoxetine) 

o Blocking neuronal capture of nor adrenaline (Maprotiline) 

2. Inhibitors of monoamine oxides (MAO)* Indiscriminate inhibit MAO-A and MAO-B (Nialamide, transamin)

• Selective, inhibit MAO-A (moclobemide).

3. Monoamine receptor agonists

• Noradrenergic and specific serotonergic antidepressant

• The specific serotonergic antidepressant

There are other classifications of antidepressants. For example, they asked to classify the clinical effect of antidepressants:

1. Antidepressant-sedates: trimipramin, doxepin, amitriptyline, mianserin, mirtazapine, trazodone, fluvoxamine

2. Balanced action of antidepressants: Maprotiline, tianeptine, Milnacipran, sertraline, paroxetine, pirazidol, clomipramine

3. Antidepressants - stimulants: imipramine, desipramine, citalopram, fluoxetine, moclobemide, ademetionin.

Selective serotonin reuptake inhibitors

«Prozac» - trade name for fluoxetine. This is a typical representative of the selective serotonin reuptake inhibitors.

Selective serotonin reuptake inhibitors (SSRIs) are a modern and relatively easily portable group of antidepressants. Today, the drugs in this group are appointed by the most. In light and medium depression, selective serotonin reuptake inhibitors are comparable in efficiency with tetra cyclic antidepressants. In severe depression, they are less effective. Well-known representatives are as follows: fluoxetine (Prozac, portal, PRODEP, fontecs, seromecs, Serono, Saraf), paroxetine (Paxil, actaparocsetin, recsetin, paxet, Seroxat, aropacs), citalopram (Vicodin, tsipramil, emocal, Oprah, SEPREM), escitalopram (Lexapro, tsipralecs), sertraline (Zoloft, deprefolt, lyustral, stimuloton), fluvoxamine (fevarin, lyuvocs, favoxil, faverin).

The most common undesirable effects of SSRIs are the follows: insomnia, extrapyramidal disorder (restless restlessness, increased parkinsonism, or his appearance, muscle hypertonicity, lockjaw, dystonia, acute dyskinesia), headache, dizziness, nausea and vomiting, diarrhea, lack or loss of appetite, physical weakness, fatigue, sleepiness, tremor, sweating, weakening of libido or potency, braking (deceleration) ejaculation or anorgasmia, frigidity, exacerbation of anxiety. It is also possible the following effects: irritability, aggressiveness, irritability and nervousness, dysphoria, the inversion of the mark phase of depression into mania or hypomania, or frequency and acceleration of the cycle with the formation of «rapid cycle».

Reuptake inhibitor of nor epinephrine

Reuptake inhibitor of nor adrenaline (SIOZN) is a modern group of antidepressant drugs with minimal undesirable effects and good tolerability. The characteristic feature of this group is expressed by the stimulating effect in the absence or low expression of sedative action. Well-known representatives of this group are as follows: reboxetin (edronacs) atomoxetin (straterra). According to some studies, these drugs are superior to the effectiveness of selective serotonin reuptake inhibitors, at least in the treatment of severe depression.

Specific serotonergic antidepressant (PAS) is a group of antidepressants with relatively small undesirable effects and good tolerability. In addition to blocking the reuptake of serotonin and increasing in serotonergic neurotransmission, the drugs in this group strongly can block the «bad», in the context to treat depression with serotonin receptor with subtype 5-HT2, and it explains the low probability of sexual undesirable effects, and low probability of high anxiety, insomnia and nervousness compared with SSRIs. There frequently observed, in contrast, increasing libido and sexual disinhibition, improving the quality and intensity of orgasm, in connection with this effect sometimes the PAS is used as correctors of sexual undesirable effects of other antidepressants.

Chemical structure of trazodone

This group of drugs includes trazodone (tritiko) and its newer derivative nefazodone (serzon).

Anti-depression activity of these drugs is assessed as moderate. In severe depression PAS is ineffective or inadequate.

The specific feature of the PAS, especially trazodone, is a strong normalizing effect on the phase structure of sleep and the ability to suppress the nightmares by reducing the proportion of REM-sleep, in case it is increased with depression and anxiety. This effect is realized even in small dosage, having a non-significant antidepressant effect. Therefore, trazodone has been widely disseminated, and special love of psychiatrists in the Western world as sleeping pills and sedatives for insomnia (not depressive origin only), as well as a proofreader insomnia and nightmares in the therapy of SSRIs or TCAs.

The specific feature of trazodone is also the ability to improve erectile function in men, up to induce priapism (painful spontaneous erections). This activity is not associated with antidepressant activity and it is implemented with any type of functional (non-organic) erectile dysfunction. Thanks to this property, trazodone is widely used to treat impotence, erectile dysfunction, including those that are not associated with depression or anxiety.

Indication for antidepressants indications administration

Antidepressants are the group of drugs used to treat depression. However, antidepressants are used in clinical practice to correct other violations. They are as panic states, obsessive-compulsive disorders (used SSRIs), enuresis (TCA used as an additional therapy), chronic pain syndromes (used SSRIs and TCAs). There have been reports of effective usage of antidepressants as part of adjunctive therapy in the treatment of bulimia, smoking, early ejaculation. Also, antidepressants successfully used for the correction of sleep structure.

Features of the action

Antidepressants are the «serious» drugs that always require individual selection of a particular drug and dosage, and therefore, their self-administration without medical prescription is not recommended.

Antidepressants do not act immediately. Usually it shall go through two to four weeks before they start working. However, An immediate effect can present, which can be attributed to a sedative or, conversely, stimulating effect.

Side effects of different groups of antidepressants

As different antidepressants have different chemical structure and mechanism of action, undesirable effects from drugs of different groups are different. Among the common side effects with the shown dosage, as well as overdoses, we can allocate insomnia, agitation, mania, hallucinations may be developed. To correct these conditions usually there applied Mood stabilizers, antipsychotics and other drugs.

Appointment of antidepressants is contraindicated with certain concomitant diseases, among which there is great importance of epilepsy and thyrotoxicosis. It is also necessary to keep in mind the interaction of antidepressants with other drugs. Antidepressant drugs should not be combined with sympathomimetics and thyroidin, as in such interaction there may be developed tachycardia and its undesirable consequences.

Antidepressants (not just SSRIs, but SIOZSiN) can induce hypomania, mania, psychosis in patients with and without bipolar affective disorder. For example, in one study mania occurred in 43 of the 533 patients taking antidepressants.

Medicine Links

• Antidepressant medicines