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Antidepressants are the psychotropic medications used for the treatment of depression, melancholy, and apathy. For several weeks antidepressants produce “happiness” hormones in the body, that is how they help to get rid of depression. Adrenaline, Serotonin, and Dopamine are the main hormones that give the perception of the world. Adrenaline produces energy, Serotonin produces euphoria, Dopamine produces motivation.
The hormones of depression appear in the body by themselves, but the problem might be in their small amount, or in too fast utilization of hormones. Antidepressants slowly flatten out hormonal levels, giving back to the patient the happiness of life. The effect of antidepressants is shown in the reduction of the feeling of melancholy, the forming of cheerfulness, growth of the-efficiency, initiative.
The experimental estimate of the effect of antidepressants is especially hard because we are talking about the invisible feelings, emotions, and mood of a person. Nevertheless, several effective techniques can be used for these goals. There was a series of experiments in the USSR. It showed the work of antidepressants. Such models help to define the spectrum of action of psychotropic medications and predict their efficiency more accurately.
Two mice are placed in flasks with water, one of the mice was injected with an antidepressant. In this stalemate, the control (sober) mouse quickly loses her hope to escape and stops fighting back. An antidepressant mouse continues to struggle in order to find a way out and is eventually survived as a reward for tenacity.
It is possible to imitate a state similar to depression in animals somehow. For example, a cat is injected with reserpine, a medicine that runs down the reserves of monoamines, the central nervous system. The cat is apathetic, is not interested in anything, his motor activity is unsteady, instincts are put down. Antidepressants restore the metabolism of monoamines, and the behavior of the animal is normalized.
Experiments on highly organized animals help to appreciate the spectrum of action of antidepressants even more accurately. A pair of monkeys were taught to press the lever during the sound signal and get a delight as a reward. Separating the monkeys can cause disturbance of higher nervous activity in one of them. The male left alone began to develop mental and autonomic disorders. If you check the individual reactions, this monkey has clear signs of depression, an antidepressant was injected, and it helped to recover the mental state of the animal.
Selective serotonin reuptake inhibitors (SSRIs)
Citalopram (Celexa, Tsipramil)
Escitalopram (Lexapro, Cipralex)
Fluoxetine (Prozac, Sarafem)
Fluvoxamine (Luvox, Faverin)
Paroxetine (Paxil, Seroxat)
Sertraline (Zoloft, Lustral)
Serotonin and norepinephrine reuptake inhibitors (SNRIs)
Milnacipran (Ixel, Savella)
Serotonin Modulator and Stimulants (SMS)
Serotonin antagonists and reuptake inhibitors (SARI)
Nefazodone (Dutonin, Nefadar, Serzone) – canceled / discontinued in most countries
Norepinephrine reuptake inhibitors (NRIs)
Atomoxetine (Strattera) – NRI Approved for ADHD
Tenyloxazine (Lucelan, Metatone) – also a 5-HT 2A receptor antagonist
Although marketed as an antidepressant, a meta-analysis showed reboxetine to be ineffective and potentially harmful.
Norepinephrine and dopamine reuptake inhibitors (NDRIs)
Bupropion (Wellbutrin) is a weak NDRI, although its dopaminergic actions are controversial; can act as a norepinephrine-dopamine releasing agent (NDRA), alternatively or additionally; also a non-competitive antagonist of nicotinic acetylcholine receptors
Tricyclic antidepressants (TCAs)
Amitriptyline (Elavil, Endep)
Amitriptyline oxide (amioxide, ambivalone, equilibrin)
Desipramine (Norpramin, Pertofrane)
Dibenzepine (Noveril, Victoril)
Doxepin (Adapin, Sinequan)
Lofepramine (Lomont, Gamanil)
Melitracen (Dixeran, Melikseran, Trausabun)
Nortriptyline (Pamelor, Aventyl)
Noxiptyline (Agedal, Elronon, Nogedal)
Pipofezin (Azafen / Azafen)
Tetracyclic antidepressants (TeCAs)
Mianserin, mirtazapine, and setiptyline are also sometimes referred to as noradrenergic and serotonergic specific antidepressants (NaSSA).
Monoamine oxidase inhibitors (MAOIs)
Selective for MAO-B
Selegiline (Eldepril, Zelapar, Emsam)
Caroxazone (Surodil, Timostenil) was previously used as an antidepressant, but its use has been discontinued.
Selective for MAO-A
Moclobemide (Aurorix, Manerix)
These drugs are sometimes called reversible MAO-A inhibitors (RIMA).
Eprobemide (Betol) and minaprine (Brantur, Kantor) were also previously used as antidepressants, but their use has been discontinued.
Bifemelan (Alnert, Celeport) – RIMA, irreversible MAO-B inhibitor and weak NRI
Agomelatine (Valdoxan) – 5-HT 2C receptor antagonist and MT 1 and MT 2 – receptor – agonist
Esquetamin (Spravato) is a non-competitive NMDA receptor antagonist
Ketamine (Ketalar) – a non-competitive NMDA receptor antagonist – not specifically approved for the treatment of depression (misused)
Tandospirone (Sediel) is a partial agonist of the 5-HT 1A receptor. Tianeptine (Stablon, Coaxil) is a weak and atypical agonist of μ-opioid receptors
Out of production
α-methyltryptamine [αMT] (Indopan) – a non-selective serotonin receptor agonist, serotonin-norepinephrine-dopamine antiadhesive (SNDRA), and mild RIM
Etryptamine [α-ethyltryptamine (αET)] (monase) – non-selective serotonin receptor agonist, SNDRA and weak RIMA Indeloxazine (Elen, Noin) – serotonin releasing agent (SRA), NRI and NMDA receptor antagonist
Medifoxamine (Clédial, Gerdaxyl) – a weak serotonin and dopamine reuptake inhibitor (SDRI) and an antagonist of 5-HT 2A and 5-HT 2C receptors
Oxaflozan (Conflictan) is an agonist of 5-HT 1A, 5-HT 2A and 5-HT 2C receptors
Pivagabin (Tonerg) – unknown / unclear mechanism of action
The following antidepressants are available both prescription and over-the-counter:
Ademethionine [S-adenosyl-L-methionine (SAMe)] (Heptral, Transmethyl, Samil) is a cofactor in the biosynthesis of monoamine neurotransmitters.
Hypericum perforatum [St. St. John’s wort (SJW)] (Jarsin, Kira, Movina) – TRPC6 activator and various other actions.
Oxytriptan [5-hydroxytryptophan (5-HTP)] (Tsinkopharm, Levotim, Tryptum) is a precursor in serotonin biosynthesis.
Rubidium chloride [RbCl] (Rubinorm) – unknown / unclear mechanism of action
Tryptophan (Triptan, Optimax, Aminomin) is a precursor of serotonin biosynthesis.
Amisulpride (Solian) – Specifically approved in low doses as monotherapy for dysthymia.
Aripiprazole (Abilify) – Specifically approved as an adjuvant in major depressive disorder.
Brexiprazole (Rexulti) – Specifically approved as an adjuvant in major depressive disorder.
Lurasidone (Latuda) – Specially approved for depressive episodes of bipolar disorder
Olanzapine (Zyprexa) – Specifically approved as an adjuvant in major depressive disorder.
Quetiapine (Quetiapine) – Approved as an adjuvant for both major depressive disorder and depressive episodes of bipolar disorder.
Risperidone (Risperdal) – not specifically approved for major depressive disorder (misused)
Buspirone (Buspar) – a partial agonist of the 5-HT 1A receptor – not specifically approved for the treatment of depression (used for other purposes)
Lithium (Eskalith, Lithobid) – mood stabilizer (mechanism of action unknown / unclear) – not specifically approved for the treatment of depression (used for other purposes)
Modafinil – marketed as an eugeroic or wakefulness drug, a mild dopamine reuptake inhibitor with other pharmacodynamic effects important for improving depressive symptoms, misused
Thyroxine (T 4) – Thyroid hormone (thyroid hormone receptor agonist) – not specifically approved for the treatment of depression (used for other purposes)
Triiodothyronine (T 3) – Thyroid hormone (thyroid hormone receptor agonist) – not specifically approved for the treatment of depression (used for other purposes)
Minocycline, a microglial inhibitor (tetracycline antibiotics) – total size of antidepressant effect compared to placebo was -0.78 (95% CI: -0.4 to -1.33, P = 0.005) in meta-analysis. – not specifically approved for the treatment of depression (misused).
Amitriptyline / Chlordiazepoxide – TCA and Benzodiazepine (Limbitrol)
Amitriptyline / Perphenazine (Etaphron) – TCAs and a typical combination of antipsychotics
Flupentixol / Melitracene (Deanxit) – TCA and a typical combination of antipsychotics
Olanzapine / fluoxetine (Symbiax) – SSRIs and an atypical combination of antipsychotic drugs – specifically approved as monotherapy for depressive episodes in bipolar disorder and therapy-resistant depression
Tranylcypromine / trifluoperazine (Parstelin, Parmodalin, Yatrosom N, Stelapar) – MAOIs and a typical combination of antipsychotics