Antidepressants, also known as thymoleptics, are a class of chemically different drugs that are used to treat depressive disorders, anxiety disorders, obsessive-compulsive disorder and chronic pain and have very different efficacy profiles. Their effect is based on a brightening of the mood and an increase in drive, which is also accompanied by a reduction in the physical symptoms of depression. In principle, there is no potential for dependence.
The first antidepressant was imipramine, which was discovered in 1957 by the Swiss psychiatrist R. Kuhn. Previously, depressive patients were treated with opium or somnifen and barbiturates to induce prolonged sleep. Since the discovery of imipramine, numerous other tricyclic, tetracycline and novel antidepressants have been launched.
Pharmacology and Biochemistry
The mechanisms of action of antidepressants were of great importance for the theoretical understanding of the development of depressive diseases. It could be shown that antidepressants increase the concentration of the neurotransmitters norepinephrine and serotonin in the synaptic cleft. This is done either by inhibiting reuptake or by inhibiting enzymatic degradation.
Studies have shown that the neurotransmitters norepinephrine and serotonin are present in a disbalance or lowered in some of the depressive patients. The long-term application of antidepressants also leads to changes in the sensitivity of the postsynaptic receptors, in the sense of a β down regulation or 5-HT up regulation. This could also explain the clinical effect of antidepressants. The connections between the influenced transmitter system and the acute effect are not always clear. Imipramine seems to inhibit the reuptake of norepinephrine and thus contribute to an increase in propulsion.
In amitriptyline, on the other hand, the inhibition of serotonin reuptake is in the foreground, which seems to be responsible for the attenuating effect. Fluoxetine, however, is a selective serotonin reuptake inhibitor and does not have a sedative effect.
The name tricyclic antidepressants is based on their hydrophobic three-member ring system. The group of tricyclic and tetracyclic antidepressants has no selective affinity to a specific neurochemical transmitter system, but acts on the norepinephrine and serotonin system in other ways. They also act on peripheral receptors for acetylcholine and histamine. Typically, tricyclic antidepressants are classified according to their clinical-therapeutic profile.
Dual mechanism antidepressants
This group includes modern antidepressants whose mode of action is based on a serotonin and norepinephrine reuptake inhibition, a norepinephrine serotonin-specific effect or a dual-serotonergic effect.
Venlafaxine inhibits the reuptake of serotonin, norepinephrine and also dopamine. It is interesting to note that serotonin reuptake inhibition is predominant in the low dose range and norepinephrine reuptake is additionally blocked in higher doses. Therefore, high doses of venlafaxine are particularly suitable for the treatment of depression in combination with an anxiety disorder.
Mirtazapine inhibits central α2-noradrenergic receptors, which indirectly increases noradrenergic and serotonergic neurotransmission. On the other hand, a postsynaptic serotonin receptor antagonism causes an increased release of serotonin. Mirtazapine is traditionally taken before sleep, as it has a dampening effect and regulates the rhythm of sleep.
Substances: serotonin noradrenalin reuptake inhibitors: venlafaxine; serotonin noradrenalin-specific antidepressants: mianserin, mirtazapine.
Duloxetine a serotonin noradrenaline reuptake inhibitor with special position
Duloxetine is intended for a relatively specific indication, namely urinary incontinence in depressive women due to stress. The effect is based on influencing the onus nucleus in the sacral marrow, which is the area of origin of the motor fibres of the pudendal nerve.
Monoamine oxidase inhibitors
Monoamine oxidases catalyse the breakdown of neuroactive and vasoactive amines. Monoamine oxidase A deaminates norepinephrine, serotonin and dopamine, monoamine oxidase B deaminates phenylethylamine, benzylamine and dopamine. A distinction is made between irreversible nonselective and reversible selective monoamine oxidase inhibitors. The non-selective MAO inhibitors inhibit monoamine oxidase A and B and are particularly rich in side effects, so they should only be considered as the second choice.
Furthermore, the intake of tyramine must be restricted during ingestion, otherwise serotonin syndrome with fever, muscle twitching, hypertensive derailment, sweating, nausea and hallucinations may occur. Foods containing tyramine include chocolate, red wine, bananas and mature cheese, which is why they are called the cheese-effect. In the case of reversible MAO inhibitors, the symptoms caused by the intake of tyramine cannot be observed, as they only inhibit the monoamine oxidase A. The MAO inhibitors are also known as the cheese effect.
MAO inhibitors have a predominantly drive-increasing effect – not a mood-enhancing effect, which is why they are also called thymeretics. The area of indication is limited to depressions with a severe lack of drive and depression in old age.