Thymoleptic, English: antidepressant
An antidepressant is a psychotropic drug with antidepressant effects. Besides depression, it is also used in the treatment of e.g. anxiety and obsessive-compulsive disorders, panic attacks, chronic pain, eating disorders, listlessness, sleep disorders and post-traumatic stress syndrome. There are many different classes of active ingredients, which differ in their mechanism of action as well as their main effect, side effects and interactions with other drugs.
For example, an antidepressant can brighten the mood and increase drive, but also have an anxiety-relieving and calming effect. Antidepressants are classified according to their mechanisms of action. Tri- and tetracyclic antidepressants” (TZA) are an exception.
They are named after their chemical structure. In their function they are so-called “non-selective monoamine reuptake inhibitors” (NSMRI). Only the most important classes are listed.
- Tri- and tetracyclic antidepressants (TZA): Amitriptyline Clomipramine Doxepin Imipramine Nortriptyline
- Selective serotonin reuptake inhibitors (SSRI): Citalopram Fluovoxamine Fluoxetine Paroxetine Sertraline
- Norepinephrine and serotonin reuptake inhibitors (NSRI): Duloxetine Venlafaxine
- Beta2-adrenoceptor antagonists: Mianserin Mirtazapine
- MAO (monoaminooxidase) inhibitor: tranylcypromine moclobemide
The tri- and tetracyclic antidepressants are non-selective monoamine reuptake inhibitors (NSMRIs). They are divided into these two groups based on their characteristic chemical structure. By blocking transmitter channels, they non-specifically inhibit the reuptake of norepinephrine and serotonin from the synaptic cleft into the nerve cells.
Depending on the preparation, they show a stronger effect on the norepinephrine or serotonin transporters. The resulting increased concentrations of the transmitters in the synapses enhance signal transmission and thus have a boosting (mainly through norepinephrine) and mood-lifting (mainly through serotonin) effect. At the same time, the preparations also bind to numerous other receptors, which explains their broad spectrum of side effects.
The tricyclic antidepressants include amitriptyline, clomipramine and nortriptyline. While amitriptyline has an additional sleep-promoting effect and is mainly used in depressive patients with sleep disorders, clomipramine has a strong anxiety-reducing effect and nortriptyline a strong stimulant effect. The tetracyclic antidepressants include maprotilin, mianserin and mirtazapine.
In addition to the antidepressant effect, the latter mainly has a sleep-inducing effect. The selective serotonin reuptake inhibitors (SSRIs) only prevent the reuptake of serotonin from the synaptic cleft, which is why they have a strong mood-lifting effect. Since they do not bind to numerous other receptors at the same time, they have a smaller spectrum of side effects and better tolerability in contrast to the tri- and tetracyclic antidepressants.
This is why they are now among the antidepressants of first choice. They can also be used to treat anxiety, compulsive and eating disorders. SSRIs include citalopram, escitalopram, fluoxetine, paroxetine and sertraline.
The most commonly prescribed SSRI in Germany is citalopram. It is superior to the other drugs, especially with regard to its weaker interactions with other drugs. Citalopram belongs to the group of selective serotonin reuptake inhibitors (SSRIs).
It is the most frequently prescribed antidepressant in Germany in recent years. Citalopram binds to serotonin transporters of nerve cells that are responsible for the reuptake of the transmitter. As a result, higher concentrations of serotonin are obtained in the synaptic cleft, which corresponds to a mood-lifting and antidepressant effect.
Furthermore, they do not bind to other receptors in the central nervous system, which explains the significantly smaller spectrum of side effects compared to tricyclic antidepressants. Nevertheless, gastrointestinal complaints (with nausea, vomiting and diarrhoea) as well as a loss of libido (sexual desire) may occur during the course of therapy. Numerous other side effects are possible.
In addition, the patient’s sense of anxiety can initially be significantly increased during the first days of therapy. Due to a simultaneous stimulating effect, there is an increased risk of suicide for the patient at the beginning of therapy. The drug Cipralex® contains the active ingredient escitalopram.
Escitalopram belongs to the group of selective serotonin reuptake inhibitors (SSRIs) and is structurally similar to citalopram. In addition to its use in depression, Cipralex® can also be prescribed for the treatment of panic, anxiety and obsessive-compulsive disorders. For successful treatment, therapy must be continued for several months.
Escitalopram works by increasing serotonin levels in the central nervous system by blocking the serotonin transporters of nerve cells. The increased serotonin levels have a mood-lifting effect. At the same time, the side effects that occur are largely due to the altered serotonin concentrations.
Similar to citalopram and fluoxetine, weight changes (due to a change in appetite), headaches, sleep disorders, dizziness, (diarrhoea, constipation, nausea, vomiting) and sexual dysfunction (ejaculation disorders, impotence) are possible. Fluoxetine is a selective serotonin reuptake inhibitor (SSRI). The active substance leads to an increase in the serotonin level in the central nervous system, which results in a mood-lifting effect.
Compared to the tricyclic antidepressants used for a long time, SSRIs are characterised by a greater therapeutic breadth (lower risk of massive side effects in the event of overdose) and a smaller spectrum of side effects. Common side effects are sexual dysfunction (loss of libido) and gastrointestinal complaints (nausea, vomiting). At the beginning of the therapy, the increased serotonin levels can also cause an increased sense of fear and drive.
Due to the delayed onset of a mood-lifting effect after a few weeks, there is an increased risk of suicide for the patient. Regular checks by the treating physician are urgently required. The selective serotonin and norepinephrine reuptake inhibitors (SSNRIs) only block the serotonin and norepinephrine transporters that are responsible for the reuptake of transmitters from the synaptic cleft.
They do not or only very weakly bind to other receptors. For this reason, they have a smaller spectrum of side effects and better tolerability compared to the tri- and tetracyclic antidepressants. Together with SSRIs, they are therefore the first choice for the treatment of depression.
They are primarily indicated in patients who have a mood-lifting as well as a drive-enhancing indication. However, it should be borne in mind that the mood-enhancing effect can occur before the mood-lifting effect, which increases the risk of suicide at the beginning of therapy. For this reason, regular check-ups by the attending physician should take place, especially at the beginning of therapy with SSNRIs.
SSNRIs include mainly venlafaxine and duloxetine. Similar to SSRIs, they can be used in addition to antidepressant therapy to treat anxiety, compulsive and eating disorders. Venlafaxine belongs to the group of selective serotonin noradrenalin reuptake inhibitors (SSNRIs).
Besides blocking serotonin and noradrenalin transporters, it does not bind to other receptors and thus causes fewer side effects than tricyclic antidepressants. Due to the additional binding to norepinephrine transporters, it has a strong boosting effect. It is therefore indicated primarily in patients with a drive-enhancing indication and is the drug of choice.
In addition to its use in the treatment of depression, it can also be prescribed specifically for anxiety disorders (generalized anxiety disorder, social anxiety disorder, panic disorder). The side effects of treatment with venlafaxine are similar to those of treatment with SSRIs. Very often patients experience dizziness, headaches, nausea and dry mouth.
Other possible side effects include loss of appetite (possibly with weight loss), sexual dysfunction, gastrointestinal problems, and visual and sleep disturbances. The activated alpha2-receptors usually ensure a reduced release of neurotransmitters. The so-called a2-adrenoreceptor antagonists block the alpha2-receptors, which causes them to lose their activity and thus their inhibitory effect on the release of transmitters.
As a result, there is an increased release of neurotransmitters. The group of α2 adrenoreceptor antagonists includes Mianserin and Mirtazapine. In addition to this effect via α2 receptors, they can also directly lead to increased amounts of serotonin and noradrenalin by blocking the channels for reuptake of the transmitters.
They are therefore also considered to be tetracyclic antidepressants. A special property of these active ingredients is their strong sleep-inducing effect. This is why they are mainly prescribed to depressed patients with an accompanying sleep disorder.
Mirtazapine belongs to the class of tetracyclic antidepressants because of its chemical structure. In addition to slightly blocking serotonin and norepinephrine transporters to reabsorb the transmitters into the nerve cells, it also binds to α2 receptors on nerve cells, thereby increasing the release of transmitters (including norepinephrine, serotonin and histamine). The increased release of norepinephrine and serotonin into the synaptic cleft has a stimulating and mood-enhancing effect.
Due to the strong binding of mirtazapine to α2 receptors of histaminergic nerve cells (nerve cells that release histamine) it has a strong sleep-inducing effect. Mirtazapine is therefore the first choice for treating depression with accompanying sleep disorders and is frequently prescribed. Compared with other antidepressants, mirtazapine is better tolerated and has fewer side effects.
Nevertheless, numerous side effects are possible, especially due to the increased serotonin levels. While side effects such as sleep disorders, restlessness, loss of appetite and sexual dysfunction occur significantly less frequently, patients often report an increase in appetite and weight, severe fatigue and dry mouth. MAO inhibitors act by inhibiting monoaminooxidase.
Monoaminooxidase is an enzyme widely distributed in the body that is responsible for the breakdown of many transmitters (including norepinephrine, serotonin, dopamine). There are two different forms of monoaminooxidases (A/B), depending on their affinity to the transmitters. Due to the inhibited degradation of the transmitters in the central nervous system, a larger quantity of the transmitters can be released in the course of signal transmission.
Two different agents are used to treat depression: tranylcypromine and moclobemide. Due to their broad spectrum of side effects, they are mainly used for the treatment of therapy-resistant (with the above-mentioned groups of active ingredients) depression. Tranylcypromine irreversibly inhibits MAO-A and MAO-B and therefore has a particularly strong effect.
There is an increase in all transmitter concentrations. Instead, moclobemide only leads to a reversible inhibition of MAO-A. For this reason, the breakdown of the transmitters noradrenalin and serotonin is inhibited, which corresponds to an antidepressant effect.
- Lithium salts: Lithium salts such as lithium carbonate, lithium acetate, lithium sulphate, lithium citrate and lithium orotate are used therapeutically for various affective disorders such as bipolar disorder or even depression. – St. John’s wort: The ingredients of St. John’s wort hypericin and hyperforin are also believed to have antidepressant effects. All antidepressants are characterised by a wide range of potential side effects.
These mainly occur at the beginning of a therapy and subside during the course of treatment. Since an antidepressive effect only occurs with a delay of several weeks, these side effects are a frequent reason for premature discontinuation of therapy. A particularly large number of side effects, some of them serious, are found in treatment with tricyclic antidepressants (amitriptyline, clomipramine, nortriptyline).
This is due to the fact that these drugs bind to numerous other receptors in the body in addition to their affinity to the serotonin and norepinephrine transporters. As a result, disturbances in heart function, deviations in blood pressure, a strong increase in weight (by increasing appetite) as well as dry mouth, constipation and numerous other side effects are possible. In contrast, the remaining reuptake inhibitors bind exclusively to the serotonin and norepinephrine transporters of the body.
Consequently, their side effects can only be explained by the increased transmitter concentrations. Frequently occurring side effects are sexual dysfunction (with a loss of libido), gastrointestinal complaints, fatigue and a change in weight. MAO inhibitors, which are mainly used for depressions that are difficult to treat, are also characterised by a wide range of side effects, as they influence a large proportion of all transmitters.