The principle of drug treatment of depression is based on the assumption that the underlying cause of the disease is a lack of serotonin. In addition, noradrenalin is also believed to be responsible for at least the (motor) drive weakness. Antidepressants make use of these findings by increasing the concentration of both messenger substances in the synaptic cleft.
For very interested laypersons: This is the space between two synapses which must be overcome by these messenger substances in order to be able to transmit a signal. When the so-called presynapse is excited by a signal, it releases neurotransmitters into the synaptic cleft. These then travel the distance by diffusion to the subsequent synapse, the so-called post-synapse. The transmitters bind to the receptors located on the surface. The postsynapse is then also excited and can then transmit the signal.
Increase in the concentration of the messenger substances
An increase in concentration can be achieved in three ways: 1. inhibition of the neuronal monoamine transporters:These transporters normally ensure the reabsorption of norepinephrine/serotonin from the synaptic cleft into the presynapses, so that the transmitted signal ends. The following antidepressants inhibit this process: tricyclic antidepressants, selective serotonin reuptake inhibitors, norepinephrine and serotonin reuptake inhibitors. 2. increase in release from the presynapse:Usually the release of the specific transmitter is limited by activation of so-called auto-receptors on their neurons.
Antidepressants that inhibit these receptors thus achieve an increased release and consequently also an increased concentration in the synaptic cleft: ?2-adrenergic receptor antagonists 3. Inhibition of monoaminooxidase A:The enzyme monoaminooxidase A normally degrades “our” neurotransmitters again after transmission in the synaptic cleft. By inhibiting it, less serotonin and noradrenalin are broken down and instead are absorbed more into the presynaptic stores.
The now “overfilled” memories subsequently release a larger quantity of transmitters. The following antidepressants have this effect: MAO-inhibitorsIt is important for the therapy, however, to know that the concentrations of the neurotransmitters already change directly after the start of therapy and thus possible undesired effects start almost immediately. In contrast, the desired antidepressive effect only sets in after 1-3 weeks.
The drug inhibition of the transporters is responsible for this. This is because the permanently increased concentration of the neurotransmitters in the synaptic cleft causes the synapse to react by releasing them at a reduced rate. An antidepressive effect cannot therefore occur at this point.
Prolonged inhibition leads to a downregulation (desensitization) of the auto-receptors, which are responsible for limiting the release from the presynapse. This gradually leads to a slow increase in release. As a result, the patient must be aware of the fact that these “adaptive changes” require a certain amount of time. This is because premature discontinuation of therapy often occurs, as the patient complains about side effects early on and the desired effect is supposedly not achieved. Furthermore, it is worth knowing that antidepressants have no addictive potential and the side effects are often only temporary due to tolerance development.